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AbstractsPoster Abstracts

Falk FoundationDr. Falk Pharma Symposium 217

West Meets East: Functional Meets Organic in Gastrointestinal Diseases

November 29–30, 2019Parkroyal on Beach RoadSingapore

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21664_Falk_Singapore_Symp_217_Abstracts_US.indd 2 14.10.19 16:14

Abstracts of Invited Lectures Poster Abstracts

Symposium 217

WEST MEETS EAST: FUNCTIONAL MEETS ORGANIC GASTROINTESTINAL DISEASES

Singapore, Singapore November 29 – 30, 2019

Scientific Organization: Kok Ann Gwee, Singapore (Singapore)

Scientific Co-Organization: G. Barbara, Bologna (Italy)G. Holtmann, Brisbane (Australia)W. Kruis, Cologne (Germany)C.J. Ooi, Singapore (Singapore)

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CONTENTS

page Session I

Frontiers in functional and organic GI diseases

Chair: K.A. Gwee, Singapore G. Holtmann, Brisbane

State-of-the-Art Lecture: The irritable bowel syndrome – What is functional? What is organic? S.M. Collins, Hamilton 17

Gluten – From Celtic to China: An anthropological journey W. Lee, Singapore 18

Biosensors – Exploring the dark depths of the GI tract P.R. Gibson, Melbourne 19

Gastroesophageal reflux: Beyond acid and PPI Y. Xiao, Guangzhou 20

Session II

Overlapping IBS

Chair: J. Liu, WuhanR.A. Raja Ali, Kuala Lumpur

Irritable bowel syndrome and tropical sprue overlap U.C. Ghoshal, Lucknow 23

Inflammatory bowel disease E.M.M. Quigley, Houston 24

Overlap between celiac disease and irritable bowel syndrome G.K. Makharia, New Delhi 25

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Oral Poster Presentation Predictive value of the “DICA” endoscopic classification on the outcome of diverticular disease of the colon: An analysis from the international, multicenter, prospective study G. Brandimarte, A. Tursi, F. Di Mario, W. Elisei,M. Picchio, L. Allegretta et al. Rome, Andria, Parma,Albano Laziale, Velletri, Galatina 26 – 27

Oral Poster Presentation Variation of the mucosa-associated microbiome along the human gastrointestinal tract in health and disease A. Shah, G. Tyson, J. Zaugg, P. Hugenholtz, M. Morrison,G. Holtmann, Chermside, Brisbane 28 – 29

Session III

Gastritis, duodenitis and dyspepsia

Chair: K.-L. Goh, Kuala Lumpur K. Sugano, Tochigi

State-of-the-Art Lecture: Helicobacter pylori: From Ötzi the iceman to Asia in the 21st century K.-G. Yeoh, Singapore 33

Post-infectious dyspepsia J. Tack, Leuven 34

Gastritis – East-West perspectives H. Suzuki, Isehara 35 – 36

Duodenosis, where functional dyspepsia meets irritable bowel syndrome – Pathologies in the duodenum in FD and IBS M.M. Walker, Newcastle 37 – 39

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Session IV Food and FGIDs beyond orthodox

Chair: Y.Y. Lee, Kota Bharu P.J. Whorwell, Manchester

State-of-the-Art Lecture: The interplay of the intestinal and extraintestinal environment in FGID G. Barbara, Bologna 43

Grain intolerance: Celiac disease, atypical allergy and ATI-sensitivity D. Schuppan, Mainz 44 – 45

Is traditional Chinese diet better for FGID than the healthy Western diet? V. Tan, Hong Kong 46

Food intolerance and food allergy, How are they different? R.C. Spiller, Nottingham 47 – 48

Session V Eosinophils in GI diseases

Chair: M. Aw, Singapore T.K.H. Lim, Singapore

Eosinophilic esophagitis J. Molina-Infante, Cáceres 51

Eosinophilic gastroenteritis N.J. Talley, Callaghan 52

Atopy, eczema, asthma and IBS M. Simrén, Gothenburg 53

Oral Poster Presentation Eosinophilic esophagitis in children of the North-Eastern Poland K. Zdanowicz, M. Kucharska, U. Daniluk, D. Lebensztejn, Bialystok 54

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Oral Poster Presentation Particularities of celiac disease in masculine population E. Bel Hadj Mabrouk, S. Ayadi, M. Ayari, Y. Zaimi,L. Mouelhi, R. Dabbèche, Tunis 55

Session VI

Diverticular disease

Chair: J.D. Sollano, ManilaA. Tursi, Andria

State-of-the-Art Lecture: Diverticular disease: A disorder of Westernized lifestyle W. Kruis, Cologne 59 – 60

Location of diverticular disease is associated to the irritable bowel syndrome and bowel habit: A multicenter study in Japan A. Nakajima, Yokohama 61

SUDD and IBS, what’s the difference? S. Papagrigoriadis, London 62

Chronic diverticulitis – To operate or not W.A. Bemelman, Amsterdam 63

Session VII

Immune enterocolitides

Chair: N.I. Hilmi, Kuala LumpurK.L. Ling, Singapore

Autoimmune enteropathy C. Langner, Graz 67 – 68

Microscopic colitis A. Münch, Linköping 69

Tandem talk: Behcet’s disease Asia J.H. Cheon, Seoul 70

Turkey A.F. Celik, Istanbul 71

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Oral Poster Presentation Increasing evidence for macroscopic abnormalities in collagenous colitis K. Dabos, P. Fineron, A. Koulaouzidis, Edinurgh 72

Oral Poster Presentation Emerging role of gut microbiota and SIBO in NAFLD development K. Kvit, N. Kharchenko, U. Dorofeeva, O. Chornenka, Lviv 73 – 74

Session VIII Inflammatory bowel disease

Chair: W.K. Leung, Hong Kong C.J. Ooi, Singapore

State-of-the-Art Lecture: Where are we heading to in pharmacotherapy of IBD? R.J. Xavier, Boston 77

Tandem talk: De-escalating biologics

Western perspectives M.A. Kamm, Melbourne 78

Asian perspectives (no abstract) R. Banerjee, Hyderabad

The role of newer biologics and small molecules in infection endemic areas W.K. Leung, Hong Kong 79

Closing remarks C.J. Ooi, Singapore

List of Chairpersons, Speakers and Scientific Organizers 80 – 84

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Poster Abstracts 1. Validity and reliability of the Malay language-translated Bloating Severity and

Quality of Life Questionnaire (BSQoL-M) N. Abdullah, Y. Kueh, G. Kuan, F. Yahaya, M. Wong, N. Abd Samat, Y. Lee (Kota Bharu, Kota Bharu, MY)

2. Conservative treatment of patients after excision of chronic anal fissure

P. Andreev, O. Davydova (Samara, RU) 3. Recurrence of primary biliary cholangitis after liver transplantation: A single-

center experience L. Bajer, K. Chmelova, J. Brezina, P. Macinga, P. Taimr, J. Spicak, P. Drastich (Prague, CZ)

4. Evaluation of undiagnosed HCC (without any typical imaging features) by

percutaneously tru-cut core biopsy: A single-centre experience M. Basaranoglu (Istanbul, TR)

5. Particularities of celiac disease in masculine population

E. Belhadj Mabrouk, S. Ayadi, M. Ayari, Y. Zaimi, L. Mouelhi, R. Dabbèche (Tunis, TN)

6. Thrombosis in celiac disease: Retrospective study

E. Belhadj Mabrouk, S. Ayadi, M. Ayari, Y. Zaimi, L. Mouelhi, R. Dabbèche (Tunis, TN)

7. Predictive value of the “DICA” endoscopic classification on the outcome of

diverticular disease of the colon: An analysis from the international, multicenter, prospective study G. Brandimarte, A. Tursi, F. Di Mario, W. Elisei, M. Picchio, L. Allegretta, M. Annunziata, M. Astegiano, M. Bafutto, F. Baldi, G. Bassotti, M. Bianco, R. Colucci, R. Conigliaro, S. Danese, D. Dumitrascu, R. Escalante, R. Faggiani, S. Fiorella, G. Forti, M. Franceschi, G. GianMarco, S. Grad, M. Graziani, M. Lai, F. Lammert, G. Latella, D. Lisi, G. Maconi, M. Murphy, G. Nardone, L. Oliveira Camara De Castro, E. Oliveira Chaves, A. Papa, S. Papagrigoriadis, A. Penna, A. Pietrzak, S. Pontone, P. Portincasa, T. Poskus, G. Pranzo, M. Reichert, G. Rizzo, S. Rodinò, J. Regula, G. Scaccianoce, F. Scaldaferri, L. Schiffino, I. Stundiene, R. Vassallo, M. Walker, C. Zampaletta, A. Zullo (Rome, Andria, Parma, Albano Laziale, Velletri, Galatina, San Donato Milanese, Turin, Tarquinia, Perugia, Torre Del Greco, Spoleto, Baggiovara, Rozzano, Viterbo, Vasto, Latina, Santorso, Cagliari, L'Aquila, Milan, Naples, Bari, Martina Franca, Brindisi, Catanzaro, Ostia, Palermo, IT; Goiânia, Rio De Janeiro, BR; Cluj-Napoca, RO; Caracas, VE; Homburg, DE; Mount Pleasant, US; London, GB; Warsaw, PL; Vilnius, LT; Newcastle, AU)

8. A national survey of IBD clinician’s perspectives on the use of faecal microbiota

transplantation S. Chandler, A. Cunningham, M. Hitchings, D. Harris (Swansea, GB)

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9. A diagnostic value of indirect and direct markers of liver fibrosis in non-alcoholicfatty liver disease patientsH. Cichoż-Lach, A. Michalak, M. Guz, J. Kozicka, M. Cybulski, A. Stepulak(Lublin, PL)

10. Hematological scales – Potential non-invasive tools in the assessment of liverfibrosis in alcoholic liver cirrhosis – A single-center experienceH. Cichoż-Lach, A. Michalak, M. Guz, J. Kozicka, M. Cybulski, A. Stepulak(Lublin, PL)

11. Platelet indices reflect dynamic changes in the extracellular matrix –The observation of alcoholic liver cirrhosis patientsH. Cichoż-Lach, A. Michalak, M. Guz, J. Kozicka, M. Cybulski, A. Stepulak(Lublin, PL)

12. The challenges in developing a faecal transplantation bank for thetreatment of IBDA. Cunningham, S. Chandler, M. Hitchings, D. Harris (Swansea, GB)

13. Increasing evidence for macroscopic abnormalities in collagenous colitisK. Dabos, P. Fineron, A. Koulaouzidis (Edinburgh, GB)

14. Celiac disease and Crohn’s disease: An association not to be disregardedO. Daboussi, A. Benkhemmar, M. Luwawu, A. Herber (Le Coudray, FR)

15. A validated score assessing the risk for intra-abdominal abscess in patients withCrohn's disease presenting at the Emergency DepartmentS. Daher, T. Khoury, M. Massarwa, D. Hakimian, A. Benson, E. Viener,R. Farah, A. Mari, W. Hazou, A. Kadah, W. Sbeit, M. Mahamid, E. Israeli(Jerusalem, Naharia, Safed, Nazareth, IL)

16. Macrophage activation syndrome: Rare cause of acute liver failure withuncertain prognosisP. Drastich, J. Brezina, L. Bajer, J. Spicak (Prague, CZ)

17. The contribution of lower GI alarm symptoms as predictors for organic boweldiseases and exclusion factors for functional bowel diseasesY. He (Wuhan, CN)

18. Profile of diverticular disease at Dr. Soetomo General HospitalSurabaya IndonesiaT. Imroati, T. Sugihartono, B. Widodo, U. Kholili, U. Maimunah, H. Purbayu,P. Setiawan, I. Nusi (Surabaya, ID)

19. Comparison of the quality of life in patients with IBD and IBSM. Konecny (Olomouc, CZ)

20. Emerging role of gut microbiota and SIBO in NAFLD developmentK. Kvit, N. Kharchenko, U. Dorofeeva, O. Chornenka (Lviv, UA)

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21. Gut microbiota, SIBO and NAFLD – The risk and protective factors K. Kvit, N. Kharchenko, U. Dorofeeva, O. Chornenka (Lviv, Kiev, UA)

22. Red blood cell distribution width and its derivatives as markers of liver fibrosis in

non-alcoholic fatty liver disease patients H. Lach, A. Michalak, M. Guz, J. Kozicka, M. Cybulski, A. Stepulak (Lublin, PL)

23. Usefulness of fecal calprotectin and C-reactive protein as disease activity

biomarkers according to disease location in Crohn’s disease patients requiring surgical interventions of intestine L. Lozynska, R. Lozynskyy, O. Precel, M. Lozynska, O. Lukavetskyy (Lviv, UA)

24. The role of APC gene mutations in early onset of familial adenomatous

polyposis and colorectal cancer in patients from Ukraine M. Lozynska, L. Lozynska, A. Plavski, I. Vitvytskyy, R. Lozynskyy (Lviv, UA; Poznan, PL)

25. Optimal treatment option for anti-Helicobacter therapy in patients with

Helicobacter-associated gastritis and concomitant diabetes mellitus type 2 G. Maslova, I. Skrypnyk, T. Radionova (Poltava, UA)

26. Hematological scales in the assessment of liver fibrosis in non-alcoholic liver

disease patients A. Michalak, H. Cichoż-Lach, M. Guz, J. Kozicka, M. Cybulski, A. Stepulak (Lublin, PL)

27. Indirect and direct markers of liver fibrosis – A study on alcoholic liver cirrhosis

A. Michalak, H. Cichoż-Lach, M. Guz, J. Kozicka, M. Cybulski, A. Stepulak (Lublin, PL)

28. Platelet indices as potential markers of liver fibrosis in the course of non-

alcoholic fatty liver disease A. Michalak, H. Cichoż-Lach, M. Guz, J. Kozicka, M. Cybulski, A. Stepulak (Lublin, PL)

29. Red blood cell distribution width and its derivatives as predictors of fibrosis and

clinical outcome in alcoholic liver cirrhosis patients A. Michalak, H. Cichoż-Lach, M. Guz, J. Kozicka, M. Cybulski, A. Stepulak (Lublin, PL)

30. Case report: A patient from Moscow with unclear abdominal pain

A. Mitroshkin (Baden-Baden, DE) 31. Exploitation of deubiquitinylase A20 as novel biomarker for prognosis of gastritis

M. Naumann (Magdeburg, DE) 32. Human leukocyte antigens celiac haplotypes: From etiological factors to

diagnostic approaches in Romanian patients R. Nemteanu, A. Plesa, P. Cianga, A. Trifan, A. Clim, L. Gheorghe, I. Ciortescu (Iasi, RO)

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33. Intestinal recovery after treatment with a gluten-free diet among adult patientswith celiac diseaseR. Nemteanu, A. Plesa, C. Gorincioi, C. Sfrijan, B. Mazilu, A. Clim, A. Trifan(Iasi, RO)

34. Evaluation of mindfulness-based cognitive therapy in patients with functionaldyspepsia in a tertiary referral center in SingaporeY. Ng, A. Ong, Y. Hao, K. Doshi, Y. Wang (Singapore, SG)

35. Evaluation of MCAM protein in gastric cancer with correlation of Helicobacterpylori infectionM. Nizioł, J. Zińczuk, K. Zaręba, W. Ustymowicz, M. Misiura, K. Guzińska-Ustymowicz, A. Pryczynicz (Białystok, PL)

36. Cutaneous manifestations of Waldenström’s macroglobulinemia and hepatitis Cvirus – Clinical caseA. Plesa, C. Gorincioi, C. Sfrijan, B. Mazilu, A. Clim, R. Nemteanu (Iasi, RO)

37. Expression of VDR receptor in inflammatory bowel diseasesA. Pryczynicz, M. Nizioł, J. Zińczuk, K. Zaręba, W. Ustymowicz, K. Guzińska-Ustymowicz(Bialystok, PL)

38. The role of serum S100A12 (calgranulin C) as a diagnostic marker in Egyptianpatients with irritable bowel syndrome and ulcerative colitisY. Rashid (Sohag, EG)

39. Hemophagocytic syndrome – A rare cause of dyspepsia and hepatopathy: CasereportK. Režonja, D. Majc, M. Šeruga, M. Gerič (Murska Sobota, SI)

40. CRP in IBD flare: How predictive is it? Single-centred retrospective analysisA. Ruban, E. Lam, G. Mahir, L. Ruprai, C. Tai, N. Thoua (London, GB)

41. A prospective, controlled study exploring the pathophysiology of non-celiacwheat sensitivity in patients with chronic unexplained gastrointestinal symptomsA. Shah, N. Talley, A. Do, E. Shanahan, M. Walker, N. Koloski, M. Jones,S. Keeley, M. Morrison, G. Holtmann(Chermside, Newcastle, Brisbane, Sydney, AU)

42. Diagnostic yield of symptom severity, visceral sensory testing, small intestinal,bacterial load and gastric emptying for the diagnosis of functionalgastrointestinal disordersA. Shah, M. Morrison, N. Koloski, T. Hansen, M. Walker, M. Jones, N. Talley,G. Holtmann (Chermside, Brisbane, Newcastle, Sydney, AU)

43. Enteric methane or hydrogen production in patients with unexplainedgastrointestinal symptoms: Associations with age, symptoms and proton-pumpinhibitorsA. Shah, N. Koloski, M. Morrison, G. Holtmann (Chermside, Brisbane, AU)

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44. Variation of the mucosa-associated microbiome along the human gastrointestinal tract in health and disease A. Shah, G. Tyson, J. Zaugg, P. Hugenholtz, M. Morrison, G. Holtmann (Chermside, Brisbane, AU)

45. Aeroallergen sensitization is associated with irritable bowel syndrome-like

symptoms in atopic patients K. Siah, A. Santosa, C. Cheung, P. Bigliardi (Singapore, SG; Hong Kong, CN; Minneapolis, US)

46. The assessment of risk factors for functional constipation

I. Skrypnyk, G. Maslova, O. Gopko, I. Kryvoruchko (Poltava, UA) 47. Rising incidence of colonic diverticulosis in a westernized multiethnic Asian

community Y. Soh, S. Ooi, Y. Chan, S. Lee, T. Siah, W. Lee, F. Zhu, K. Yeoh, K. Gwee (Singapore, SG)

48. Helicobacter pylori (HP) resistance in North East London: Are we treating HP

with appropriate antibiotics? C. Tai, A. Jepson, L. Marelli (London, GB)

49. MMP-7 expression in patients with colitis ulcerosa and Crohn’s disease

W. Ustymowicz, Z. Justyna, A. Pryczynicz, K. Guzinska-Ustymowicz, K. Zaremba (Bialytsok, PL)

50. Eosinophilic esophagitis in children of the North-Eastern Poland

K. Zdanowicz, M. Kucharska, U. Daniluk, D. Lebensztejn (Bialystok, PL) 51. Can survivin may be responsible for inflammatory process in patients with

ulcerative colitis? J. Zińczuk, K. Zaręba, M. Nizioł, W. Ustymowicz, K. Guzińska-Ustymowicz, J. Matowicka-Karna, A. Pryczynicz (Białystok, PL)

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Session I

Frontiers in functional and organic GI diseases

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State-of-the-Art Lecture The irritable bowel syndrome – What is functional? What is organic? S.M. Collins Farncombe Family Digestive Health Research Institute, McMaster University Hamilton Ontario Canada The term functional has several interpretations in the context of Irritable Bowel Syndrome (IBS) and include “a disorder of function” as well as “idiopathic” and “psychosomatic”. The term organic implies an understood pathophysiology, structural damage and the availability of biomarkers. With the availability of high-resolution structural analyses and molecular-based investigation, these terms are becoming redundant. There is increasing evidence of innate immune activation in IBS patients, and this can be driven centrally by stress or behavioral disorders such as depression, or peripherally by gut contents that include dietary antigens or resident/pathogenic bacteria. The link with TNSF15 polymorphism introduces a genetic component to immune activation in IBS, as the gene product TL1A contributes to immunological homeostasis in the intestine. The microbiota from IBS-D patients has been shown to induce and an IBS-like phenotype in mice, including innate immune activation and changes in gut permeability, transit and secretion. The microbiota from IBD-D patients with psychiatric comorbidity induces behavioral changes in recipient mice that are associated with innate immune activation. IBS microbiota produce chemotactic factors that increase IELs and induce intestinal mastocytosis in recipient mice. Dietary intoler-ances are very common in IBS and recent work has demonstrated evidence of IgE-independent immune activation and structural changes following exposure to common dietary antigens. Microbiota from FODMAP-intolerant IBS patients induces mast cell-mediated changes in pain signaling in recipient mice. Thus, while IBS is indeed a disorder of function, the identification of mechanisms leading to altered gut and brain function as well as the recent identification of diet-induced structural and immunol-ogical changes prompt reconsideration of the use of the term “functional” as a blanket descriptor of this condition.

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Gluten – From Celtic to China: An anthropological journey

W. LeeCamden Medical Center, Singapore, Singapore

Celiac disease is a multi-system autoimmune condition characterized by specific serological and histological profiles triggered by gluten ingestion in genetically predis-posed individuals. The clinical presentation includes gastrointestinal problems such as chronic diarrhea, abdominal distention, malabsorption, and loss of appetite while extra-intestinal symptoms are common in both children and adults and include chronic fatigue, nutrient deficiencies, failure to thrive, short stature, anemia, delayed puberty, dental enamel hypoplasia, reduced bone density, oral ulcers, liver and biliary disease, and dermatitis herpetiformis. Many children present with behavioral disturbances and reduced educational performance, while adults with celiac disease are at higher risk of anxiety disorders, depression and bipolar disorder. Celiac disease should be sought in people with Hashimoto thyroiditis, type 1 diabetes, autoimmune liver disease, neuro–pathy and ataxia. Nonceliac gluten sensitivity is diagnosed in individuals who do not have celiac disease or wheat allergy but who have intestinal symptoms, extraintestinal symptoms, or both, related to ingestion of gluten-containing grains, with symptomatic improvement on their withdrawal. Celiac disease was originally associated with Western populations (e.g. those with Celtic ancestry) but has been found worldwide in the countries of the Middle East, Africa and Asia. While previously seen as a disease of children, the disease is now more commonly diagnosed in older children and adults. Wheat consumption is substantial among Asian nations and the HLA DQB1 *02:01 and *03:08 alleles associated with celiac disease are actually widespread in Asian popul-ations. Going by serological studies and biopsy proven series, celiac disease is notrare in Asia, and arguably the celiac disease patients in China and India and SouthEast Asia, while often not recognized and diagnosed, may outnumber those in theWest. If we include the patients with atypical presentations and those with positiveserology but no obvious histological changes of celiac disease, a different epi-demiological picture may emerge. Non celiac wheat sensitivity or “gluten intolerance”has many overlapping features with celiac disease, and may occur in families withknown celiac patients. The rise of celiac disease worldwide has also been accom-panied by a rise in gluten intolerance and a rise in inflammatory bowel disease andtype 1 diabetes mellitus. Is this a coincidence?

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Biosensors – Exploring the dark depths of the GI tract P.R. Gibson Monash University and Alfred Health, Melbourne, Australia Biotelemetry was science fiction until, in 1957, a dog called Laika, was sent into space on Sputnik to study the physiological effects of zero-gravity. 62 years later, wireless communication is second nature. Advances in semi-conductor microelectronics and microfabrication have enabled what was science fiction at its most ridiculous in the 1966 classic, Fantastic Voyage, to evolve into reality. Nowhere in the body are such technologies needed more than the GI tract. Gastroenterologists have good access to the each end, but the small intestine and proximal colon in the free-living ambulant human in terms of the function, microenvironmental milieu including the microbiota, and its modulation by, for example, diet and drugs have been relatively inaccessible. Advances in battery technology and microprocessing in addition to miniaturization has enabled capsules the size of a large vitamin pill with amazing capabilities to be built. The real challenges now are threefold. First, biosensors that can detect biologically relevant molecules and their concentrations need to be developed. There has been success with H+ (pH) and simple gases such as oxygen and H2 using methodology that can sample fluids throughout the GI tract. There is an expectation that other volatile molecules will soon be reliably detected (including H2S, short-chain fatty acids) and novel techniques of detecting specific biomolecules have been published (such as a system that used engineered bioluminescent bacteria). The second challenge is to be able localise where in the GI tract the signal is being generated. It has been simple knowing when the capsule leaves the body via temperature drop, but defining the transition of a capsule from major regions (e. g., stomach to duodenum, ileum to colon) carries more challenges and defining position within a region (e. g., where in the very long small intestine) the greatest challenges. Use of physiological steps such as changes in pH or oxygen content have the greatest value to date as they are localising mechanisms that reside within the capsule and are measured concurrently with the molecule(s) of interest. Imaging techniques carry different limitations. The third chal-lenge is to be able to sample fluid or tissue at specific sites for more detailed analysis (e. g., microbial profiling). The development of osmotic sampling for instance is promis-ing. Progress will be associated with the close liaison of clinicians with bioengineers.

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Gastroesophageal reflux: Beyond acid and PPI

Y. XiaoDepartment of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen Uni-versity, Guangzhou, China

Proton-pump inhibitors (PPIs) are the first-line medicines for gastroesophageal reflux disease (GERD), which have shown efficacy for alleviating reflux symptoms and pro-moting mucosal healing of erosive esophagitis. However, more than one-third of GERD patients report poor response to PPI treatment. What’s more, there is growing concern regarding the potential risks of long-term PPI treatment. The current lecture is about alternatives to acid suppression for GERD.

Firstly, lifestyle modifications such as bed head elevation were proved to reduce reflux and relief symptoms. Secondly, the acid pocket is considered associated with in-creased esophageal acid exposure. Alginate can form a physical barrier at the proximal stomach, leading to significantly lower distal acid exposure in GERD patients. Thirdly, transient lower esophageal sphincter relaxation (tLESR) is one of the common patho-genesis of GERD, and baclofen was found to inhibit the incidence of tLESR and reduce postprandial reflux events. Furthermore, prokinetic agents including itopride, acoti-amide, and revexepride were also found to improve GERD symptoms and reduce acid reflux events. What’s more, mucosal protective compounds such as sucralfate were recommended for treating esophagitis patients. Sucralfate also showed efficacy for NERD patients in a recent randomized, double-blind trial. Increased esophageal sensi-tivity is thought to contribute to the perception of reflux symptoms, and traditional pain modulators may help to relief symptoms in GERD.

Fundoplication is a common surgery for the treatment of GERD, however, it also faces some technical problems and adverse effects. Electrical stimulation of the lower eso-phageal sphincter (LES) is a new technique, which enhances anti-reflux barrier func-tion, and it has been proved to provide significant symptom improvement and reduction of esophageal acid exposure over a 3-year follow-up. Moreover, magnetic sphincter augmentation is also a novel technique that shows long-term safety and efficacy in reduction of esophageal acid as well as symptom improvement for GERD.

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Session II

Overlapping IBS

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Irritable bowel syndrome and tropical sprue overlap

U.C. GhoshalDepartment of Gastroenterology, Sanjay Gandhi Postgraduate Institute of MedicalSciences, Lucknow 226014, India, E-Mail: udayghoshal@gmail.com

Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be predom-inantly related to psychological factors, has a micro-organic basis in a subset of patients with the disease. Postinfectious IBS (PI IBS), commonly of the diarrhea-predominant or mixed subtypes (defined as new development of IBS following acute infectious diarrhea), is one such condition known to occur in up to 10–30% individuals after acute gastroenteritis. However, following acute infectious gastroenteritis, patients can also develop postinfectious malabsorption syndrome (PI MAS), popularly known as tropical sprue. As there is hardly any study on PI IBS that has rigorously excluding tropical sprue by appropriate investigations including small intestinal biopsy, the frequency of tropical sprue among patients with PI IBS is not much known. In a recent study from our group from Bangladesh, PI-MAS, diagnosed by abnormal results in at least two of the three tests (D-xylose, fecal fat, duodenal biopsy), was present in 9% with PI-IBS. PI-IBS and PI-malabsorption have similar etiological agents and pathophysiological mechanisms. Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated with IBS in general, and in particular diarrhea-predominant IBS, including PI IBS. SIBO is also known to be associated with tropical sprue. As both IBS, particularly the subset probably associated with SIBO, and tropical sprue improve with antibiotic treatment, these disorders might be linked. More studies are needed on this issue.

References:

1. Ghoshal UC, Srivastava D, Verma A, Ghoshal U. Tropical sprue in 2014: the newface of an old disease. Curr Gastroenterol Rep. 2014;16(6):391.

2. Ghoshal UC, Gwee KA. Post-infectious IBS, tropical sprue and small intestinalbacterial overgrowth: the missing link. Nat Rev Gastroenterol Hepatol.2017;14(7):435–41.

3. Mathan VI, Baker SJ. Epidemic tropical sprue and other epidemics of diarrhea inSouth Indian villages. Am J Clin Nutr. 1968;21(9):1077–87

4. McCarroll MG, Riddle MS, Gutierrez RL, Porter CK. Infectious Gastroenteritis asa Risk Factor for Tropical Sprue and Malabsorption: A Case-Control Study. DigDis Sci. 2015;60(11):3379–85.

5. Rahman MM, Ghoshal UC, Sultana S, Kibria MG, Sultana N, Khan ZA, et al.Long-Term Gastrointestinal Consequences are Frequent Following SporadicAcute Infectious Diarrhea in a Tropical Country: A Prospective Cohort Study. AmJ Gastroenterol. 2018;113(9):1363–75.

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Inflammatory bowel disease

E.M.M. QuigleyDivision of Gastroenterology and Hepatology, Lynda K and David M UnderwoodCenter for Digestive Disorders, Houston Methodist Hospital and Weill Cornell MedicalCollege, Houston, Texas, USA

Irritable bowel syndrome (IBS)-type symptoms are common among patients with inflammatory bowel disease who, by every available measure, appear to be in clinical, endoscopic and histological remission. The pathogenesis of these symptoms continues to generate scientific controversy and the interpretation and management of these symptoms, so distressing to the sufferer, represent major challenges for the clinician. On the one hand, these symptoms often satisfy Rome IV criteria for IBS and their occurrence correlates highly with anxiety, a known trigger for IBS. Could it be that such symptoms represent no more than the coincident occurrence of IBS in an individual who happens to have IBD – prevalence studies suggest otherwise by documenting higher than expected rates of IBS in IBD sufferers. On the other hand, recent studies have shown that many of these patients exhibit subtle inflammatory changes and experimental observations have shown how and infectious or inflam-matory insult, in a susceptible individual and in tandem with certain environmental factors, can lead to long-standing perturbations in the intestinal neuro-muscular apparatus. These observations beg the question: are these symptoms “true” IBS superimposed on IBD, or an active but sub-clinical form of IBD? While it is certain that earlier studies failed to detect subclinical inflammation, it is also evident that even with the use of sensitive biomarkers for inflammation, such as calprotectin and lactoferrin backed up by pan-endoscopy and biopsy to exclude ongoing inflammatory activity in its most subtle form, the prevalence of IBS-type symptoms remains higher than expected in the IBD patient. These are critical clinical issues – one certainly does not want to persist with anti-inflammatory strategies if inflammation is not an issue. Pending further definition of its etiology and pathology, the term irritable inflammatory bowel syndrome (IIBS) has been coined to refer to this phenomenon. Here we explore the risk factors for this entity, sift through clues to its pathogenesis and attempt to provide, albeit bereft of a robust evidence base, an approach to its management.

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Overlap between celiac disease and irritable bowel syndrome G.K. Makharia All India Institute of Medical Sciences, New Delhi, India The spectrum of manifestations of celiac disease is wide and ranges from classic gastrointestinal manifestations such as diarrhea, weight loss, or malnutrition to non-classical manifestations such as short stature, anemia, infertility, liver manifestations, osteopenia/osteoporosis or ataxia. Furthermore, while in some patients with celiac dis-ease the disease phenotype of the disease is fully expressed, in many however the disease is expressed only in the milder form to have only mild gastrointestinal symp-toms. Many such patients with celiac disease having mild gastrointestinal symptoms may fulfill the criteria for the diagnosis of irritable bowel syndrome (IBS) and they may be diagnosed and treated as irritable bowel syndrome in the general clinical practice. In a recent meta-analysis involving 22 studies the pooled prevalence of celiac disease in 6991 patients with IBS was 3.3% (95% CI: 2.3%, 4.5%). However, all but one study involved in this systematic review were from secondary or tertiary care referral centers. Thus, it is unclear if there is utility to screening for celiac disease in individuals with IBS in the primary care settings or the general population. The prevalence of celiac disease in patients with IBS might vary with geographic region. The pooled prevalence of celiac disease also varies significantly with IBS subtype. As expected, the prevalence of celiac disease is the highest in patients with diarrhea predominant IBS (pooled prevalence of 5.4%, 95% CI: 3.3–7.8%) suggesting that all patients with diarrhea predominant IBS should be screened for celiac disease. The pooled prevalence of celiac disease among patients with constipation predominant IBS and mixed form of IBS were 1.8% (95% CI: 0.9–3.0%) and 3.1% (95% CI: 1.7–5.1%). In another study from India including 362 patients with IBS, we observed that only 3 (0.8%) patients had biopsy confirmed celiac disease and 19 had potential celiac disease. Additionally, 28.7% of them had a positive anti-gliadin antibody suggesting presence of some form of gluten sensitivity in them. A study from China has also reported occurrence of celiac disease in Chinese patients with IBS.

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Oral Poster Presentation

Predictive value of the “DICA” endoscopic classification on the outcome of diverticular disease of the colon: An analysis from the international, multicenter, prospective study

G. Brandimarte (Rome, IT), A. Tursi (Andria, IT), F. Di Mario (Parma, IT),W. Elisei (Albano Laziale, IT), M. Picchio (Velletri, IT), L. Allegretta (Galatina, IT),M.L. Annunziata (San Donato Milanese, IT), M. Astegiano (Turin, IT),M. Bafutto (Goiânia, BR), F. Baldi (Tarquinia, IT), G. Bassotti (Perugia, IT),M.A. Bianco (Torre del Greco, IT), R. Colucci (Spoleto, IT),R. Conigliaro (Baggiovara, IT), S. Danese (Rozzano, IT),D. Dumitrascu (Cluj-Napoca, RO), R. Escalante (Caracas, VE),R. Faggiani (Viterbo, IT), S. Fiorella (Vasto, IT), G. Forti (Latina, IT),M. Franceschi (Santorso, IT), G. GianMarco (Rome, IT), S. Grad (Cluj-Napoca, RO),M.G. Graziani (Rome, IT), M.A. Lai (Cagliari, IT), F. Lammert (Homburg, DE),G. Latella (L'Aquila, IT), D. Lisi (Rome, IT), G. Maconi (Milan, IT),M.M. Murphy (Mount Pleasant, US), G. Nardone (Naples, IT),L. Oliveira Camara De Castro (Rio de Janeiro, BR), E. Oliveira Chaves (Goiânia, BR),A. Papa (Rome, IT), S. Papagrigoriadis (London, GB), A. Penna (Bari, IT),A. Pietrzak (Warsaw, PL), S. Pontone (Rome, IT), P. Portincasa (Bari, IT),T. Poskus (Vilnius, LT), G. Pranzo (Martina Franca, IT), M. Reichert (Homburg, DE),G.L. Rizzo (Brindisi, IT), S. Rodinò (Catanzaro, IT), J. Regula (Warsaw, PL),G. Scaccianoce (Bari, IT), F. Scaldaferri (Rome, IT), L. Schiffino (Ostia, Rome, IT),I. Stundiene (Vilnius, LT), R. Vassallo (Palermo, IT), M. Walker (Newcastle, AU),C. Zampaletta (Viterbo, IT), A. Zullo (Rome, IT)

Introduction: The endoscopic classification called “DICA” (Diverticular Inflammation and Complication Assessment) has been recently developed in order to have an objective endoscopic description of the colon harboring diverticula. Aim of this multi-center, international, prospective study was to assess the predictive value of this classification in term of acute diverticulitis and surgery occurrence on a 1-year observa-tional follow-up period.

Methods: 2215 prospective patients at the first diagnosis of diverticular disease were enrolled after exclusion of radiological signs of acute diverticulitis; inflammatory bowel diseases; ischemic colitis; prior colonic resection; patients with severe liver failure (Child-Pugh C) or severe kidney failure; pregnant women; patients who are currently using or who have received any laxative agents or mesalazine or probiotics or anti-biotics < 2 weeks prior to the enrollment; inability to comply with study protocol and to give informed consensus to the procedure; patients with or history of cancer, of any origin, within 5 years before enrollment; history of alcohol, drug, or chemical abuse. All patients were classified according to DICA classification.

Results: 1377 (62.15%) patients were classified as DICA 1, 599 (27.04%) as DICA 2, and 239 (10.80%) as DICA 3.

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The risk of acute diverticulitis occurrence/recurrence, as well as the risk of surgery, were significantly linked to the severity of DICA score at entry. Overall, acute diverticulitis occurred in 79 (3.6%) patients: it occurred in 17 (1.38%) DICA 1, 30 (5.11%) DICA 2 and 30 (12.82%) DICA 3 patients respectively (p < 0.0001). Overall, surgery occurred in 29 (1.3%) patients: it occurred in 2 (0.14%) DICA1, 11 (1.87%) DICA 2 and 16 (6.83%) DICA 3 patients respectively (p < 0.0001). Discussion/Conclusion: The 1-year results of this prospective study seems to con-firm that DICA endoscopic classification has a significant prognostic role on the risk of acute diverticulitis occurrence/recurrence and on the risk of surgery in people having colonic diverticulosis detected at colonoscopy.

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Oral Poster Presentation

Variation of the mucosa-associated microbiome along the human gastrointestinal tract in health and disease

A. Shah (Chermside, AU), G. Tyson (Brisbane, AU), J. Zaugg (Brisbane, AU),P. Hugenholtz (Brisbane, AU), M. Morrison (Brisbane, AU),G. Holtmann (Brisbane, AU)

Introduction: Very little is known about the variation in the mucosa-associated micro-biota (MAM) along the human gastrointestinal (GI) tract. Thus, we aimed to determine the bacterial communities in different parts of the GI tract and compare patients without gastrointestinal disease with patients with Crohn’s disease (CD) and ulcerative colitis (UC).

Methods: We recruited 72 patients undergoing upper GI endoscopy and colonoscopy for the assessment of a positive FOBT with normal results of the endoscopic investiga-tions (other than small adenoma) and no symptoms reported utilising a standardised assessment of gastrointestinal symptoms (SAGIS). In addition, we recruited 44 patients with CD and 50 patients with UC. Utilising the Brisbane Aseptic Biopsy Device, we obtained biopsies from the proximal small intestine, terminal ileum, ascending colon and rectum without cross contamination from luminal contents or other regions of the GI tract. Biopsy samples were immediately placed under aseptic conditions into a sterile tube containing RNA later (Qiagen). Samples were allowed to incubate at room temperature for 30 minutes, then frozen and stored at -80°C. Total DNA was extracted from biopsies, and sample free reagent controls, using a repeated bead-beating based method. Samples were profiled by high-throughput amplicon sequencing with dual-index barcoding using the Illumina MiSeq platform, targeting the V6–V8 region of the gene encoding 16S ribosomal RNA. The libraries were sequenced on an Illumina MiSeq platform and the data were quality assessed, trimmed and filtered, then proces-sed using the Quantitative Insights into Microbial Ecology version 2 (QIIME2) software. Microbiota and statistical analyses were performed in QIIME2 and R. Significant differ-ences in Shannon and Chao1 alpha diversity metrics between sample types, and be-tween disease states for each sample type, were calculated using Kruskal-Wallis and unpaired Wilcox rank sum tests. Differentially abundant taxa were identified with DESeq2 using a likelihood ratio test while correcting for age, BMI and gender.

Results: Across all patient groups, the three most abundant genera in the duodenum were Streptococcus, Pseudomonas and Prevotella. However, in the terminal ileum, right colon and rectum, Faecalibacterium, Bacteroides, and Escherichia-Shigella were the three most abundant bacterial taxa. There were significant differences in the Shannon and Chao1 diversity scores of the mucosa-associated microbiota (MAM) present in the duodenum and terminal ileum (p < 0.001–0.05) between UC and CD, and UC and controls, with greater diversity found for the control subjects. In the right colon and rectum, significantly lower Shannon diversities were observed in UC and CD vs. controls (p < 0.05).

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Discussion/Conclusion: There are marked differences in the three most abundant bacteria in the upper and lower gut. Similarly, MAM from different parts of the human GI tract reveal distinct characteristics in the relation to the most prevalent bacterial taxa and the alpha diversity observed at these sites. Interestingly, both UC and CD patients have different MAM profiles in both proximal and distal sites of the GI, and these are different from those observed for healthy asymptomatic controls.

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Session III

Gastritis, duodenitis and dyspepsia

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State-of-the-Art Lecture Helicobacter pylori: From Ötzi the iceman to Asia in the 21st century K.-G. Yeoh Department of Medicine, National University of Singapore, Singapore The evolutionary relationship of Helicobacter pylori with its host is thought to have begun 100,000 years ago, when it first colonized human stomachs. A high mutation rate and frequent exchange of genetic material between strains contribute to the genetic diversity of H. pylori. Genotyping of H. pylori strains from human populations around the world reveal phylogeographic patterns, which closely mirror human migra-tion out of Africa 60,000 years ago and subsequent geographic and ethnic separation between human groups. H. pylori infection is known to play a role in several gastrointestinal diseases such as peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. In Asian popula-tions like China, Korea and Japan, where gastric cancer (GC) incidence is among the highest in the world, H. pylori prevalence is similarly high, around 50%. The ‘Indian enigma’ describes the incongruence between high seroprevalence of H. pylori but low GC incidence, suggesting H. pylori is necessary but not sufficient to cause GC. H. pylori genotype has demonstrated correlation with clinical outcomes. The carcino-genic effects of H. pylori infection have been linked to its virulence factors, such as the cytotoxin-associated gene A (cagA) and the vacuolating cytotoxin gene A (vacA). The high GC incidence in Asia is believed to be due to the EPIYA-D motif in cagA. Treatment of H. pylori eradicates peptic ulcer disease, and reduces future GC risk. GC is a major cause of death in Asia. Even after H. pylori eradication, patients may remain at risk of GC due to pre-malignant lesions such as intestinal metaplasia (IM). We per-formed extensive genomic profiling of IM, and identified 3 genomic alterations associated with disease progression of IM to GC. Going forwards this could be em-ployed in a molecular test to identify very-high-risk IM patients for targeted endoscopic surveillance and secondary prevention of GC.

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Post-infectious dyspepsia

J. TackTARGID, University of Leuven, Belgium

A subset of patients with functional dyspepsia report an acute onset of their symptoms, accompanied by flu-like symptoms (low grade fever, myalgia, etc...), and subsequent persistence of dyspeptic symptoms in the absence of demonstrable ongoing infection. These elements suggest a “post-infectious” type dyspepsia (PD), as opposed to “un-specified onset” dyspepsia (UD). In tertiary care cohorts, patients with PD were signif-icantly younger, had more prevalent early satiety, nausea and vomiting, had less heart-burn had suffered major weight loss. PD and UD patients did not differ in Helicobacter positivity, gastric emptying rate, prevalence of delayed emptying, sensitivity to gastric distention and prevalence of hypersensitivity to gastric distention. However, impaired gastric accommodation to a meal was significantly more prevalent in PD (56% vs. 31%, p < 0.01). In animal models, post-inflammatory dysmotility is attributable to a loss of nitrergic motor control, and observations in PD patients support a similar mechanism underlying the loss of gastric accommodation. In addition, PD was characterized by duodenal mucosal lymphoid aggregates and by eosinophil cell infiltrates. The link between duodenal mucosal alterations, impaired accommodation and the symptom pattern requires further studies. No specific therapies for PD have been established, but in FD with weight loss, treatment with mirtazapine has shown benefit through improvement of nutrient tolerance, control of nausea and recovery of lost body weight.

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Gastritis – East-West perspectives H. Suzuki Professor, Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara, Kanagawa, Japan The incidence of gastric cancer in Asia (East) is higher than that in Europe and Northern America (West). Helicobacter pylori infection is the most important factor for the development of atrophic gastritis and gastric cancer [1]. The geographical distribution of the prevalence and virulence factors of H. pylori is important to understand the gastritis East and West perspectives. Severity of gastritis is known to be related to the risk of gastric cancer, and the severity of gastritis is more advanced especially in East Asia. From the viewpoint of the virulence factors of H. pylori, the East Asian CagA-positive strain with (EPIYA motif ABD type) is peculiar in East Asia [2, 3]. Considering comprehensively the geographical distribution of H. pylori subtypes is the most important factor among all prospected risk factors for the incidence of gastric cancer and the rate of development of gastritis2. On the other hand, H. pylori are also considered to cause symptomatic gastritis, that is, dyspepsia. The Kyoto global consensus meeting concluded that dyspepsia whose symptoms were ameliorated several months after eradication was diagnosed as H. pylori-associated dyspepsia (HpD) and should be a distinct entity different from functional dyspepsia even in Rome IV criteria [4-7]. There is evidence that chronic gastritis caused by reactive oxygen species (ROS) is associated with dyspepsia severity in individuals with H. pylori infection. ROS production is characteristic during innate immune responses such as neutrophil attack to H. pylori and facilitates the establishment of persistent infection. We have recently identified a polymorphism in H. pylori neutrophil-activating protein A (NapA) closely associated with this H. pylori-associated dyspepsia [8]. While eating habits, such as salty foods, vegetables and fruits, might influence the progression of histological and symptomatic gastritis, such factors could also be responsible for the geographic heterogeneity of gastritis. In this symposium, I would like to discuss gastritis in an East-West comparison. References: 1. Suzuki H, Mori H. World trends for H. pylori eradication therapy and gastric

cancer prevention strategy by H. pylori test-and-treat. J Gastroenterol. 2018;53(3):354–61.

2. Suzuki H, Mori H. Different Pathophysiology of Gastritis between East and West? An Asian Perspective. Inflamm Intest Dis. 2016;1(3):123–8.

3. Tsugawa H, Suzuki H, Saya H, Hatakeyama M, Hirayama T, Hirata K, et al. Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells. Cell Host Microbe. 2012;12(6):764–77.

4. Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64(9):1353–67.

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5. Suzuki H, Moayyedi P. Helicobacter pylori infection in functional dyspepsia. NatRev Gastroenterol Hepatol. 2013;10(3):168–74.

6. Suzuki H, Mori H. Helicobacter pylori: Helicobacter pylori gastritis – a noveldistinct disease entity. Nat Rev Gastroenterol Hepatol. 2015;12(10):556–7.

7. Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al.Gastroduodenal Disorders. Gastroenterology. 2016;150(6):1380–92.

8. Matsuzaki J, Tsugawa H, Kashiwazaki Y, Mori H, Yamamoto Y, Kameyama H, etal. Neutrophil-activating Protein Polymorphism of Helicobacter pylori Determinesthe Host Risk of Dyspepsia. Cell Mol Gastroenterol Hepatol. 2019;8(2):295–7.

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Duodenosis, where functional dyspepsia meets irritable bowel syndrome – Pathologies in the duodenum in FD and IBS M.M. Walker Professor of Anatomical Pathology, School of Medicine & Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia, marjorie.walker@newcastle.edu.au In functional gastrointestinal disorders (FGIDs), “functional” indicates no organic cause for symptoms in dyspepsia (FD) or irritable bowel syndrome (IBS) [1, 2]. Conversely, a more relevant descriptive term for these disorders is dysfunctional, as recent studies have shown that there is tangible pathology in FD and IBS, which likely causes symp-toms [3]. FD is subdivided into post-prandial distress syndrome (PDS) and epigastric pain syn-drome (EPS), characterized by meal-induced gastroduodenal centered dyspeptic symptoms [1]. In IBS, symptoms are of recurrent abdominal pain associated with defecation or a change in bowel habits, which may be disordered – constipation, diarrhea, or a mix of these [2]. This marked symptom variability in FGIDs suggests heterogeneous disease complexes, with differing etiopathogenesis, currently being explored. Recent studies show epidemiological links and mechanistic pathways in FGIDs that point to immune activation. Population studies link FD and IBS to both autoimmune and atopic disease [4], which suggests disturbance in innate immune pathways. Microbial-immune interactions are implicated in FGIDs – post-infectious FD [5] and post-infectious IBS are recognized [6], alongside specific small intestinal infections, Giardia lamblia [7], tropical sprue [8] and SIBO [9]. Recognition of symptom response to successful Helicobacter pylori eradication defines H. pylori associated dyspepsia [1, 10]. There are specific duodenal microbiome signatures in FD [11]. Importantly, food intake is key in many cases of FD and IBS – a low FODMAP diet can relieve IBS symptoms as can a gluten free diet in both FD and IBS [12]. Non-celiac gluten or wheat sensitivity (NCWS) may have FD symptoms [12]. Tangible duodenal pathology, duodenal eosinophilia, is evident in PDS-FD and is now described worldwide [13]. Mast cells are increased in the duodenum in FD [14] and IBS [15]. There are neuronal alterations associated with eosinophilia [16] and intra-epithelial lymphocytes are increased in IBS [17] and NCWS [18]. New onset anxiety is linked to duodenal eosinophilia, linking duodenal pathology to stress [19] – a significant pathway associated with FGIDs [20]. Understanding these networks may underpin using relevant medications that treat, rather than merely alleviate symptoms [3. 21].

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References:

1. Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al.Gastroduodenal Disorders. Gastroenterology. 2016;150(6):1380–92.

2. Mearin F, Lacy BE, Chang L, Chey WD, Lembo AJ, Simren M, et al. BowelDisorders. Gastroenterology. 2016.

3. Keely S, Walker MM, Marks E, Talley NJ. Immune dysregulation in the functionalgastrointestinal disorders. Eur J Clin Invest. 2015;45(12):1350–9.

4. Koloski N, Jones M, Walker MM, Veysey M, Zala A, Keely S, et al. Populationbased study: atopy and autoimmune diseases are associated with functional dys-pepsia and irritable bowel syndrome, independent of psychological distress.Aliment Pharmacol Ther. 2019;49(5):546–55.

5. Futagami S, Itoh T, Sakamoto C. Systematic review with meta-analysis: post-infectious functional dyspepsia. Aliment Pharmacol Ther. 2015;41(2):177–88.

6. Spiller R. Postinfectious functional dyspepsia and postinfectious irritable bowelsyndrome: different symptoms but similar risk factors. Gastroenterology.2010;138(5):1660–3.

7. Dormond M, Gutierrez RL, Porter CK. Giardia lamblia infection increases risk ofchronic gastrointestinal disorders. Trop Dis Travel Med Vaccines. 2016;2:17.

8. Ghoshal UC, Srivastava D, Verma A, Ghoshal U. Tropical sprue in 2014: the newface of an old disease. Curr Gastroenterol Rep. 2014;16(6):391.

9. Ghoshal UC, Gwee KA. Post-infectious IBS, tropical sprue and small intestinalbacterial overgrowth: the missing link. Nat Rev Gastroenterol Hepatol.2017;14(7):435–41.

10. Suzuki H, Mori H. Helicobacter pylori: Helicobacter pylori gastritis – A noveldistinct disease entity. Nat Rev Gastroenterol Hepatol. 2015;12(10):556–7.

11. Zhong L, Shanahan ER, Raj A, Koloski NA, Fletcher L, Morrison M, et al.Dyspepsia and the microbiome: time to focus on the small intestine. Gut.2017;66(6):1168–9.

12. Potter MDE, Walker MM, Keely S, Talley NJ. What's in a name? 'Non-coeliacgluten or wheat sensitivity': controversies and mechanisms related to wheat andgluten causing gastrointestinal symptoms or disease. Gut. 2018;67(12):2073–7.

13. Talley NJ, Ford AC. Functional Dyspepsia. N Engl J Med. 2015;373(19):1853–63.

14. Vanheel H, Vicario M, Vanuytsel T, Van Oudenhove L, Martinez C, Keita AV, etal. Impaired duodenal mucosal integrity and low-grade inflammation in functionaldyspepsia. Gut. 2014;63(2):262–71.

15. Walker MM, Talley NJ, Prabhakar M, Pennaneac'h CJ, Aro P, Ronkainen J, et al.Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis aspossible disease markers in the irritable bowel syndrome and functional dys-pepsia. Aliment Pharmacol Ther. 2009;29(7):765–73.

16. Cirillo C, Bessissow T, Desmet AS, Vanheel H, Tack J, Vanden Berghe P.Evidence for neuronal and structural changes in submucous ganglia of patientswith functional dyspepsia. Am J Gastroenterol. 2015;110(8):1205–15.

17. Aziz I, Evans KE, Hopper AD, Smillie DM, Sanders DS. A prospective study intothe aetiology of lymphocytic duodenosis. Aliment Pharmacol Ther. 2010;32(11–12):1392–7.

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18. Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, et al. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled chal-lenge: exploring a new clinical entity. Am J Gastroenterol. 2012;107(12):1898–906; quiz 907.

19. Ronkainen J, Aro P, Agréus L, Andreasson A, Walker MM, Talley NJ. Functional dyspepsia and duodenal eosinophilia are associated with new-onset anxiety: prospective 10-year follow-up of the Kalixanda study. Gastroenterology 2019 156, S-780.

20. Jones MP, Tack J, Van Oudenhove L, Walker MM, Holtmann G, Koloski NA, et al. Mood and Anxiety Disorders Precede Development of Functional Gastrointestinal Disorders in Patients but Not in the Population. Clin Gastroenterol Hepatol. 2017;15(7):1014-20 e4.

21. Potter MDE, Goodsall TM, Walker MM, Talley NJ. Dual histamine blockade for the treatment of adult functional dyspepsia: a single centre experience. Gut. 2019 Apr 30. [Epub ahead of print]

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Session IV

Food and FGIDs beyond orthodox

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State-of-the-Art Lecture

The interplay of the intestinal and extraintestinal environment in FGID

G. BarbaraDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, Italy,E-Mail: giovanni.barbara@unibo.it

The focus of studies on the pathophysiology of functional gastrointestinal disorders (FGIDs) has shifted over the years from the role of stress, to the participation of the enteric neuromuscular apparatus and the gut-brain axis to the potential importance of the luminal and extra-luminal environment. The descriptions of FGID-type symptoms developing de novo in the aftermath of an enteric infection has generated new para-digms in our understanding of FGIDs and the discovery that FGID are associated with numerous microscopic abnormalities in the structure of the gastrointestinal tract. Acute infectious gastroenteritis represents the strongest known risk factor for IBS develop-ment, a condition known as postinfectious IBS (PI-IBS). Approximately 10% of those with intestinal infection who respond to survey questionnaires endorse symptoms consistent with PI-IBS. These estimates have varied with the type of pathogen involved, and some studies have shown estimates as high as 35–45% for PI-IBS devel-opment. The exact burden of PI-IBS is hard to assess: There is poor recall of intestinal infections, and no biomarkers have been identified. Conservative estimates suggest that PI-IBS contributes to as much as 9% of the overall number of IBS cases in the community. There is much interest now on the understanding of the human gut micro-biota and microbe-host interactions, including immune and metabolic responses and their potential relevance for FGIDs. Clinical experience has also informed us of the relevance of food as a symptom precipitant. Nonetheless, there is yet little information on the interactions of diet and/or the products of digestion in the FGID pathophysiology.

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Grain intolerance: Celiac disease, atypical allergy and ATI-sensitivity

D. SchuppanInstitute of Translational Immunology, Center for Celiac, Small Intestinal andAutoimmune Diseases, University Medical Center, Mainz Germany; Division ofGastroenterology and Celiac Center, Beth Israel Deaconess Medical Center, HarvardMedical School, Boston, MA, USA

Wheat has become the most important staple food worldwide, with China and India being the largest producers worldwide. There are 3 defined inflammatory conditions that are caused by wheat and related grains: 1. Celiac disease (prevalence ~1%); 2. Atypical wheat allergies (prevalence ~5%); 3. ATI-sensitivity (prevalence~10%).

Celiac disease is a still underdiagnosed small intestinal inflammatory reaction to the gluten proteins of wheat (including barley, rye, and old wheat variants like einkorn, emmer and spelt). Patients present from asymptomatic to a broad spectrum of abdom-inal and extra-abdominal symptoms. If undetected and untreated, severe com-plications including intestinal lymphoma and adenocarcinoma may develop. Diagnosis is by the transglutaminase-Ab test and typical findings on upper endoscopy. The therapy is a strict gluten free diet.

Classical wheat allergies with an immediate reaction to inhaled or ingested wheat are rare. However, atypical allergies (IgE and skin test negative), prominently to wheat, followed by yeast, milk and soy, are frequent. Patients run under the diagnosis of “irritable bowel syndrome” (IBS). They display a delayed reaction, with abdominal com-plaints occurring hours after allergen ingestion, which makes diagnosis difficult. Investi-gation with confocal laser endo-microscopy demonstrates an inflammatory reaction within 3 minutes after duodenal allergen challenge. With identification and exclusion of the allergen, these IBS patients usually become symptom-free. The atypical food allergies affect ~10% of most populations.

ATI (amylase trypsin inhibitors) are a minor protein component of wheat and other gluten containing grains, where they play a role in parasite defense and grain maturation. ATI are resistant to intestinal digestion and heat. They activate intestinal immune cells (macrophages, dendritic cells) via the TLR4 pathway. Once activated by ATI, these immune cells leave the gut towards the periphery, where they promote inflammatory diseases, especially autoimmune diseases, such as biliary diseases, rheumatoid arthritis, lupus, and multiple sclerosis), but also metabolic inflammation, such as type 2 diabetes, and steatohepatitis and fibrosis. ATI-sensitivity is therefore defined by worsening of these diseases with consumption of wheat and related grains. Currently, we perform several randomized and controlled clinical studies in patients with these diseases on a normal, ATI-containing, vs. ATI-free diet, to confirm our preclinical and clinical data on a broader basis.

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References: 1. Ashfaq-Khan M, Aslam M, Qureshi MA, Senkowski MS, Weng SY, Strand D,

et al. Dietary wheat amylase trypsin inhibitors promote obesity and non-alcoholic fatty liver disease. Sci Rep. [in press]

2. Bellinghausen I, Weigmann B, Zevallos V, Maxeiner J, Reißig S, Waisman A, et al. Wheat amylase-trypsin inhibitors exacerbate intestinal and airway allergic immune responses in humanized mice. J Allergy Clin Immunol. 2019;143(1): 201–12.

3. Caminero A, McCarville JL, Zevallos VF, Pigrau M, Yu XB, Jury J, et al. Lactobacilli Degrade Wheat Amylase Trypsin Inhibitors to Reduce Intestinal Dysfunction Induced by Immunogenic Wheat Proteins. Gastroenterology. 2019; 156(8):2266–80.

4. Fasano A, Sapone A, Zevallos V, Schuppan D. Nonceliac gluten sensitivity. Gastroenterology. 2015;148(6):1195–204.

5. Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Röcken C, Brasch J, et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014; 147(5):1012–20.

6. Fritscher-Ravens A, Pflaum T, Mösinger M, Ruchay Z, Röcken C, Milla PJ, et al. Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies Not Associated With Immunoglobulin E. Gastroenterology. 2019;157(1):109–18.

7. Junker Y, Zeissig S, Kim SJ, Barisani D, Wieser H, Leffler DA, et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med. 2012;209(13):2395–408.

8. Lundin KE, Sollid LM. Advances in coeliac disease. Curr Opin Gastroenterol. 2014;30(2):154–62.

9. Pickert G, Wirtz S, Heck R, Rosigkeit S, Thies D, Ashfaq-Khan M, et al. Wheat consumption aggravates experimental colitis by amylase trypsin inhibitor (ATI)-mediated dysbiosis. Gastroenterology. [in press]

10. Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology. 2009;137(6):1912–33.

11. Schuppan D, Zevallos V. Wheat amylase trypsin inhibitors as nutritional activators of innate immunity. Dig Dis. 2015;33(2):260–3.

12. Zevallos VF, Raker V, Tenzer S, Jimenez-Calvente C, Ashfaq-Khan M, Rüssel N, et al. Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflam-mation via Activation of Myeloid Cells. Gastroenterology. 2017;152(5): 1100–13.

13. Zevallos VF, Raker VK, Maxeiner J, Scholtes P, Steinbrink K, Schuppan D. Dietary wheat amylase trypsin inhibitors exacerbate murine allergic airway inflammation. Eur J Nutr. 2019;58(4):1507–14.

All-encompassing book on the wheat sensitivities, for experts and affected subjects, including commented case reports: Detlef Schuppan and Kristin Gisbert-Schuppan. Wheat Syndromes: When Wheat, Gluten and ATI Cause Disease. Springer Medicine, London. October 2019 (155 pages).

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Is traditional Chinese diet better for FGID than the healthy Western diet?

V. TanClinical Associate Professor, University of Hong Kong; Chief Medical Officer,Gleneagles Hospital Hong Kong

East and South East Asia is one of the most populous regions of the world. It is a region that despite significant cultural diversity has significant commonalities including the belief in Chinese Nutrition Therapy, the diet (where the traditional diet is dominated by the cereal grain rice), healthcare systems and crowded living conditions. The low FODMAP diet has been proven to be effective in irritable bowel syndrome in multiple western countries but its efficacy in the Far East remains to be proven. Dietary management of FGID in this region presents a challenge due to the prevalence of lactose intolerance/malabsorption, the cultural belief paradigms surrounding Chinese Nutrition Therapy and of course the fundamental differences in the diet between East and West. An examination of the core elements surrounding diet, dietary belief systems and lactose intolerance/malabsorption in East and South East Asia finds that the traditional Chinese diet may just as easily be an exacerbating factor as the healthy Western diet.

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Food intolerance and food allergy, how are they different? R.C. Spiller NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, UK Many patients report onset of symptoms soon after eating but food is complex and there are many different mechanism of action underlying such intolerances, which are difficult for both patient and physician to understand. Patient reports from Scandinavia suggest dairy products, pulses, wheat, certain stone fruits along with food rich in biogenic amines and fatty foods were commonly implicated in adverse reactions to food [1]. IgE mediated food allergy is well recognised but appears uncommon in general gastroenterology clinics by the gold standard of either endoscopic allergen provocation or double blind food challenge [2]. Indeed in most cases double blind food challenge fails to elicit any response, though a nocebo effect is clear in randomised clinical trials of food challenge. While varying IgG food antibodies have been reported as elevated in IBS their significance is unclear and there is no clear link to symptoms [3]. Specialist clinics describe a selected group in which atopy and food intolerance is common and associated with increased numbers of IgE positive cells in the duodenal mucosa (Lillestol, 2010). Furthermore recent studies using confocal laser endoscopy, in selected IBS patients who were believed to have food intolerance, showed increased leakage of fluorescent probe on exposure to wheat, milk, soy, yeast or egg white, possibly mediated via eosinophil activation. More than half such patients have a personal or family history of atopic disorders and elevated duodenal intra-epithelial lymphocytes and the response appears to predict a response to elimination diets [4]. How common such reactions awaits confirmation by other groups but non-immunolog-ical reactions are also likely to be important in non-atopic patients. Genetically deter-mined lactose malabsorption is well recognised to cause symptoms by osmotic effects within the small bowel and subsequent fermentation of unabsorbed lactose in the colon. Irritable bowel patients show evidence of visceral hypersensitivity with symptoms at lower doses and a correlation with anxiety and other psychological factors [5]. A wide range of poorly absorbed but readily fermentable carbohydrates (FODMAPs) have been shown to cause symptoms in IBS patients. The low molecular weight molecules (lactose, fructose and polyols) trap water in the small bowel and deliver increased fluid and carbohydrate to the colon where they are rapidly fermented. Larger polymers have minimal effect in the small bowel but also reach the colon where they produce substantial increases in colonic gas [6]. Real food contains a complex mixture of FODMAPs in widely varying matrix, which alters the fermentation process. Work is ongoing to see if adding less fermentable substances can improve the tolerability of high fibre diets in the treatment of functional GIDs.

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References:

1. Bohn L, Störsrud S, Törnblom H, Bengtsson U, Simren M. Self-reported food-related gastrointestinal symptoms in IBS are common and associated with moresevere symptoms and reduced quality of life. Am J Gastroenterol. 2013;108(5):634–41.

2. Bischoff SC, Herrmann A, Manns MP. Prevalence of adverse reactions to food inpatients with gastrointestinal disease. Allergy. 1996;51(11):811–8.

3. Zuo XL, Li YQ, Li WJ, Guo YT, Lu XF, Li JM, et al. Alterations of food antigen-specific serum immunoglobulins G and E antibodies in patients with irritablebowel syndrome and functional dyspepsia. Clin Exp Allergy. 2007;37(6):823–30.

4. Fritscher-Ravens A, Pflaum T, Mösinger M, Ruchai Z, Röcken C, Milla PJ, et al.Many Patients With Irritable Bowel Syndrome Have Atypical Food Allergies NotAssociated With Immunoglobulin E. Gastroenterology. 2019;157(1):109–18.

5. Yang J, Deng Y, Chu H, Cong Y, Zhao J, Pohl D, et al. Prevalence andpresentation of lactose intolerance and effects on dairy product intake in healthysubjects and patients with irritable bowel syndrome. Clin Gastroenterol Hepatol.2013;11(3):262–8.

6. Murray K, Wilkinson-Smith V, Hoad C, Costigan C, Cox E, Lam C, et al.Differential effects of FODMAPs (fermentable oligo-, di-, mono-saccharides andpolyols) on small and large intestinal contents in healthy subjects shown by MRI.Am J Gastroenterol. 2014;109(1):110–9.

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Session V

Eosinophils in GI diseases

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Eosinophilic esophagitis J. Molina-Infante Department of Gastroenterology, University Hospital San Pedro de Alcantara, Cáceres, Spain Eosinophilic esophagitis (EoE), is a novel and unique form of non IgE-mediated chronic allergic disorder of the esophagus, first described in the early 90s, predominantly affecting children and young adults. The incidence of EoE has increased substantially over the past two decades, coinciding with the so-called allergy epidemic. Updated prevalence figures in both children and adults in US and Spain are over 1 in 1000 inhabitants, and growing cases are being reported out of Western countries. Inter-actions between genetic predisposition, early-life, infectious, and geographic factors, along with environmental factors (modern chemicals, food additives and processing changes) might conceivably trigger a local aberrant Th2 response. Consensus diagnostic criteria have been recently redefined, suggesting that PPIs are better classified as a treatment for EoE rather than a diagnostic asset. Accordingly, current treatment options consist of drug therapy (PPIs, topical corticosteroids), dietary inter-ventions, and endoscopic dilatation. Being EoE a relatively young disease, several unmet needs are to be solved, as finding non-invasive diagnostic and disease-monitoring tools, ascertaining different disease phenotypes with distinct natural history, developing novel food allergy testing to detect triggering foods, and elucidating doses required for induction and maintenance therapy, aside from safety issues with long-term maintenance therapy.

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Eosinophilic gastroenteritis

N.J. Talley The University of Newcastle, Australia

Eosinophilic gastroenteritis (EG) is a rare disease (prevalence 5 per 100,000) affecting adults usually in their 3rd to 5th decade. There is infiltration of eosinophils into the intes-tinal tract at any site, most often in the mucosal layer. Typically there are more than 20 eosinophils per high power field on biopsy, and in many cases eosinophils are present in dense sheets. Presenting symptoms include abdominal pain (2/3), early satiety, full-ness, nausea, vomiting, or diarrhea depending on the site affected, with waxing and waning symptoms. Mucosal layer EG may initially be misdiagnosed as a functional GI disorder such as functional dyspepsia. Muscle layer disease can present with intestinal obstruction, and serosal disease with eosinophilic ascites. Peripheral eosinophilia is common (80%) but not universal in EG. Endoscopy may be normal or show erythema, nodularity or ulceration. Diagnosis depends on taking multiple biopsies at endoscopy, remembering disease may be patchy or deep, not mucosal. The differential diagnosis includes parasites, drugs, vasculitis and hypereosinophilic syndrome (HES). The pathogenesis is postulated to be related to food allergy, often non-IgE driven, followed by tissue damage from eosinophil degranulation; the role of the microbiome is unknown. Treatment options include an elimination diet, corticosteroids (e. g. budeso-nide or prednisolone), montelukast (eosinophil stabilizer) and antihistamines, and monoclonal antibodies. Maintenance therapy is often needed to maintain disease remission.

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Atopy, eczema, asthma and IBS M. Simrén Professor, Senior Consultant, Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden; Adjunct Professor of Medicine, University of North Carolina School of Medicine, UNC, Chapel Hill, USA Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, affecting approximately 10% of the adult population. The disease is characterized by recurrent abdominal pain and altered bowel habits. The pathophysiology of IBS is incompletely understood, but gut-brain interactions are suggested to be of relevance for symptom generation in these patients. Atopic disease has been identified as a comorbid condition with symptoms that overlap with IBS. Mast cells have a primary role in atopic disease and release inflammatory mediators, e.g. cytokines, histamine and proteases, when cell-bound IgE are cross-linked by allergens. Various studies suggest that allergen exposure, whether ingested or inhaled, may lead to IBS manifestations in atopic individuals. Several research groups have reported increased numbers of mucosal mast cells, within proximity to nerve endings, in IBS patients. Thus, the increased presence and activity of mucosal mast cells in atopic disease and IBS proposes a link between these disorders, and may therefore play a unique role in a subgroup of IBS patients. The presence of allergy has been suggested to correlate with more severe IBS symptoms and atopic IBS has been proposed as a new IBS subgroup with allergic manifestations, even though not all studies come to the same conclusion. In this lecture, the evidence linking atopy, eczema and asthma with IBS will be reviewed and potential mechanisms explaining this association will be further discussed. Furthermore, the potential role of local allergy-like reactions in the gut as an explanation for food-related symptoms in IBS will be presented.

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Oral Poster Presentation

Eosinophilic esophagitis in children of the North-Eastern Poland

K. Zdanowicz (Bialystok, PL), M. Kucharska (Bialystok, PL), U. Daniluk (Bialystok, PL),D. Lebensztejn (Bialystok, PL)

Introduction: The aim of the retrospective study was the evaluation of the clinical symptoms and endoscopic and pathological changes of EoE in children and adoles-cence from the North-Eastern part of Poland.

Methods: The study included 433 pediatric patients with EoE (n = 36, 8.31%) and non-eosinophilic esophagitis (non-EoE) (n = 397; 91.7%) diagnosed based on endoscopic and histological examination between January 2015 and December 2018. Histological criteria for EoE were fulfilled when at least 15 eosinophils per high power field were found on esophageal biopsy. Moreover, the evaluation included the reported symp-toms, the patient’s medical history, eosinophil count in CBC, the coexistence of Helico-bacter pylori infection, endoscopic lesions and body mass index (BMI).

Results: The mean age of children with EoE was statistically lower comparing to non-EoE (9.6 ± 4.3 years vs. 12.17 ± 4.23; p < 0.001) with male predominance (77.78% vs. 49.62%; p = 0.002). Among symptoms, only dysphagia was more often reported in EoE group (22.2% vs. 7.30%; p = 0.02). No difference in BMI was found between groups. Eosinophilia was observed more frequently in EoE (529 cells/ul vs. 188 cells/ul; p < 0.001). The most significant endoscopic lesions found in EoE were the linear fissuring, decrease vascular pattern, trachealization, whitish exudates. Co-existing allergy was reported mainly in children with EoE (47.2% vs. 18.14%; p < 0.001) and no association with other diseases, also Helicobacter pylori infection, were noted.

Discussion/Conclusion: Our results confirmed the previous reports that EoE in pediatric population affects more often males, appears in early childhood, coexists with allergy and manifests with dysphagia, eosinophilia, and typical endoscopic lesions. These common features are helpful in differentiating patients with EoE from non-EoE.

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Oral Poster Presentation Particularities of celiac disease in masculine population E. Bel Hadj Mabrouk (Tunis, TN), S. Ayadi (Tunis, TN), M. Ayari (Tunis, TN), Y. Zaimi (Tunis, TN), L. Mouelhi (Tunis, TN), R. Dabbèche (Tunis, TN) Introduction: Celiac disease (CD) is a chronic autoimmune disease with a prevalence of 2% in the world. Few studies were interested in the particularities in a masculine population. Methods: It is a retrospective study from January 2000 to December 2017. All patients hospitalized for a CD were included. 69 patients were studied. The diagnosis of CD was confirmed by the positivity of endomysial antibody as well as duodenal biopsy showing villous atrophy. The charts of all patients of masculine sex were studied. Results: 23 were men. Mean age was 38 years old (15–68). Family history of CD was found in 17.4%. The main discovery circumstance were diarrhea (87%) and iron deficiency anemia (52.2%). A deficiency syndrome made of anemia, low cholesterol and low albumin was found in 82.6% of the patients. Gastrointestinal endoscopy showed mosaic pattern in 56.5%, atrophic mucosa (8.7%) and mucosal ulceration (4.3%). Biopsies found total atrophy of the gland in 43.5%. 8 patients had autoimmune manifestations: type 1 diabetes (n = 3), Biermer anemia (n = 2), vitiligo (n = 2), hypo-thyroid (n = 1) and autoimmune hepatitis (n = 1). Bone densitometry showed abnor-malities in 32.6% of the cases. The evolution was favorable in 73.9% with gluten-free diet. Discussion/Conclusion: Autoimmune diseases are not frequent in masculine popu-lations. Our study suggests that CD in masculine population is correlated to deficiency syndrome and to villous atrophy. These data requires larger sample to confirm our results.

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Session VI

Diverticular disease

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State-of-the-Art Lecture Diverticular disease: A disorder of Westernized lifestyle W. Kruis Professor of Medicine, University of Cologne, Cologne, Germany Outpouching of colonic mucosa defined as diverticula (diverticulosis) is common in humans and can induce a variety of clinical presentations. Diverticula with related symptoms and clinical signs are called Diverticular Disease (DD), which can be combined with signs of inflammation (diverticulitis). Prevalence of diverticulosis and incidence of DD vary considerably around the world. Simple diverticulosis is asymptomatic, which makes accurate estimates of the true prevalence difficult. Approximately 25% of individuals with asymptomatic diverticulosis will eventually develop symptomatic uncomplicated DD and an even smaller proportion develop acute diverticulitis. In Western countries, most (90%) cases of colonic diverticulosis are located in the sigmoid or left colon, whereas diverticulosis occurs more frequently in the ascending or right colon (75–85% of cases) in Japan and South Korea (75–85%). The prevalence of diverticulosis on colonoscopy has also increased in Asia, from 13% between in the period 1990–2000 to 24% between in the period 2001–2010 (11). Furthermore, recent data suggest that right-sided diverticulosis may also be increasing in Western countries. It is of interest, that black individuals living in Western countries have a higher proportion of diverticula in the right colon compared to Caucasian individuals, which points to a non exclusive influence of environment but also to race. DD is highly frequent in some Western countries but also in “Eastern” countries. Though occurrence of DD is highest in some “Western” countries in other “Western” countries epidemiology is significantly lower. In some developing countries frequency of DD increases in parallel to the changing environment. The highest reported prevalence of DD has been reported in Japan (13–28 cases/per million individuals), the USA (12–22 cases per million individuals) and Western Europe where DD has been estimated between 13–28, 12–22 and (8–12 cases/per million individuals) respectively. Conversely, the prevalence is low (0.1–5 cases/per million individuals) in Africa and Asia (with the exception of Japan). In Europe, there are some differences between countries, but they do not follow any geographical pattern. The lowest prevalence has been reported in Italy, Austria and Sweden, whereas Germany, France and the United Kingdom show the highest reported prevalence. However, these differences may, at least in part, be due to differences in the methodology adopted used to collect the informations. One study found that Swedish immigrants to Sweden from non-Western countries had a decreased risk of hospitalization compared to individuals born in Sweden, but that the risk grew soon after a short period of acculturation to the new environment.

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Those different epidemiological numbers indicate environment and lifestyle as factors of the as yet not fully understood pathogenesis. Usually, “Western lifestyle” is suggest-ed to be such a factor. Increasing frequency of DD in different continents rather point to the hypothesis that not “Western lifestyle” but developing industrialization, and economic wealth with changing eating and living attitudes may be of significance.

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Location of diverticular disease is associated to the irritable bowel syndrome and bowel habit: A multicenter study in Japan A. Nakajima Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama City, Japan One major difference between colonic diverticular disease (DD) in the West and Asia is the predominant location. In European and US populations, DD arises mainly in the distal colon, with 90% of patients having sigmoid colon involvement and only approxi-mately 15% having right-sided disease. No previous reports have shown an association between location of DD and the irritable bowel syndrome (IBS). We included 1,009 consecutive patients undergoing total colonoscopy in seven centers in Japan. IBS was diagnosed using Rome III criteria, and diverticulosis was diagnosed by colonoscopy with transparent soft-short-hood. Left-sided colon was defined as sigmoid colon, descending colon, and rectum. Right-sided colon was defined as cecum, ascending colon, and transverse colon. We divided the patients into IBS and non-IBS groups and compared characteristics. Right sided DD was identified in 21.6% of subjects. Left-sided and bilateral DD was identified in 6.6 and 12.0% of subjects, respectively. IBS was observed in 7.5% of subjects. Multiple logistic regression analysis showed left-sided DD (odds ratio [OR] = 3.1; 95% confidence interval [CI]: 1.4–7.1; p = 0.0060) and bilateral DD (OR = 2.6; 95% CI: 1.3–5.2; p = 0.0070) were independent risk factors for IBS. Right-sided DD was not a risk factor for IBS. Our data showed that the presence of left-sided and bilateral DD, but not right-sided disease, was associated with a higher risk of IBS, indicating that differences in pathological factors caused by the location of the DD are important in the development of IBS. Clarifying the specific changes associated with left-sided DD could provide a better understanding of the pathogenic mechanisms of IBS. Furthermore, we investigated the association between DD and bowel habits. The study evaluated 1066 Japanese subjects. After adjusting for age and sex, the presence of constipation was associated with a significantly reduced likelihood of DD (OR = 0.70; 95% CI: 0.52–0.93). When assessed according to the location of DD, the presence of constipation was associated with a significantly decreased likelihood of left-sided (OR = 0.39; 95% CI: 0.16–0.93), but not right-sided (OR = 1.10; 95% CI: 0.48–2.53), DD. Furthermore, stool form was not correlated with the presence or absence of DD. The wide-spread hypothesis that constipation is associated with colonic DD was not supported. Rather, the absence of DD was associated with constipation, suggesting the need to reassess the etiology of colonic DD. In conclusion, investigation of changes in left-sided colonic DD may lead to better understanding of the DD in association with IBS and constipation.

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SUDD and IBS, what’s the difference?

S. PapagrigoriadisHonorary Consultant Surgeon, King’s College Hospital, London, UK; Director of Rectaland Pelvic Surgery, Metropolitan General Hospital, Athens, Greece

Irritable Bowel Sydrome (IBS) is one of the commonest and more studied intestinal conditions. On the other hand, even though diverticulosis of the colon is very common, the specific variety of Symtomatic Uncomplicated Diverticular Disease (SUDD) has only recently been recognised and its definition and characteristics are still work in progress. Although the two conditions were of different natural history and patho-genesis in traditional textbooks, there is recently an increased recognition of inflam-matory factors contributing to IBS. Similarly, there is a recognition of chronic functional symptoms in SUDD which remind of IBS. Research has shown an overlap of the two conditions as a group of SUDD patients fulfill the Rome criteria for IBS as well. The role of serotonin is established in IBS and recent reports claim abnormalities of the serotonin system in SUDD. There is an increasing understanding of the contribution of microbiota in IBS. Similarly there is a start of appreciation of the therapeutic role of probiotics in SUDD. Chronic abdominal pain is a landmark feature of IBS. Well documented motility abnormality of the bowel outside the periods of inflammation also is proven in SUDD, and those abnormalities are associated with chronic pain without inflammation markers. Given all these similarities there is recent debate as to the overlapping ground and the distinction lines between IBS and SUDD. The two conditions still have many differences and should remain distinct however research may prove a common background. Recent endoscopic ultrasound identification of thickening of colonic muscularis may help to distinguish between early diverticular disease and IBS. Clinicians should keep an open mind.

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Chronic diverticulitis – To operate or not W.A. Bemelman Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands Diverticulitis presents itself in many ways. Acute diverticulitis with abscesses and free perforation and chronic diverticulitis presenting as recurrent attacks, smoldering dis-ease and complications e.g. fistula and stenosis. Decision making whether to operate or not is relatively simple when symptomatic complications has occurred. More difficult are the patients who present with recurrent attacks or ongoing complaints, particularly because these symptoms can also be caused by IBS. In this talk a typical case will be presented and decision making moments will be dis-cussed. The decision making steps and examples will be based on the latest literature and the ESCP diverticulitis guideline which is currently being finalized. Finally, a short video will demonstrate a best practice of laparoscopic sigmoidectomy for diverticulitis.

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Session VII

Immune enterocolitides

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Autoimmune enteropathy C. Langner Diagnostic and Research Institute of Pathology, Medical University of Graz, Austria; Advanced Training Center of Gastrointestinal Pathology, European Society of Pathology Although autoimmune enteropathy was initially believed to be a condition of chronic diarrhea and malabsorption restricted to the pediatric age group, cumulating evidence indicates that the disorder may in fact occur in all age groups. Diagnostic criteria are still vaguely defined. Anti-enterocyte antibodies have been identified a subset of pa-tient, their value however appears limited. The disease is most prominent in the small intestines and the majority of patient de-monstrates villous blunting, crypt hyperplasia, mononuclear cell inflammatory expan-sion of the lamina propria and crypt apoptosis. The remaining patients showed marked intraepithelial lymphocytosis reminiscent of celiac disease. Acute cryptitis and crypt abscesses may be present obscuring the presence of apoptosis. The absence of Paneth cells, goblet cells or both has been recognized as an additional important histological finding (Singhi et al. 2014). Masia et al. (2014) described four different patterns of small bowel injury • Active chronic inflammation (IBD-like) • Intraepithelial lymphocytosis (celiac disease-like) • Apoptotic enteropathy/colonopathy (GvHD-like) • Mixed (no predominant pattern) In that study, changes to the stomach mucosa were documented in 86%, changes to the colon in 64% of cases respectively. Accumulating evidence proved that autoimmune enteropathy can no longer be regarded as a single entity. In fact, the disease may occur in five different setting (Umetsu et al. 2018). • Primary (sporadic) autoimmune enteropathy (pediatric) • Syndromic autoimmune enteropathy (pediatric), e.g. within IPEX or APECED

syndrome • Primary (sporadic) autoimmune enteropathy of adults (often in association with

other autoimmune conditions) • Paraneoplastic autoimmune enteropathy (TAMA, Thymoma-associated multi-

organ autoimmunity) • Secondary autoimmune enteropathy of adults (usually associated with certain

drugs, such as immune checkpoint inhibitors [ipilimumab, nivolumab and pembrolizumab], idelalisib etc.)

The improvement of endoscopic techniques, in particular the introduction of device-assisted enteroscopy has set small-bowel histology on a new level. Among the “typical” causes of mucosal inflammation and/or atrophy autoimmune enteropathy has become

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more prevalent than previously thought. Still, the disease remains a “puzzle” (Elli et al. 2019) composed by serological, endoscopic, histological and molecular markers, requiring exclusion of other causes of villous atrophy in order to reach a certain diag-nosis.

This diagnosis is of eminent clinical importance for clinical management, in that possible triggers of the disease, such as drugs are identified (and potentially elimi-nated) and the appropriate treatment (usually immunosuppressive agents) is initiated.

References:

1. Singhi AD, Goyal A, Davison JM, Regueiro MD, Roche RL, Ranganathan S.Pediatric autoimmune enteropathy: an entity frequently associated withimmunodeficiency disorders. Mod Pathol. 2014;27(4):543–53.

2. Masia R, Peyton S, Lauwers GY, Brown I. Gastrointestinal biopsy findings ofautoimmune enteropathy: a review of 25 cases. Am J Surg Pathol.2014;38(10):1319–29.

3. Umetsu SE, Brown I, Langner C, Lauwers GY. Autoimmune enteropathies.Virchows Arch. 2018;472(1):55–66.

4. Elli L, Ferretti F, Vaira V. Demystifying autoimmune small bowel enteropathy.Curr Opin Gastroenterol. 2019;35(3):243–9.

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Microscopic colitis A. Münch President of the European Microscopic Colitis Group (EMCG), Department of Gastro-enterology/Hepatology, University Hospital, Linköping, Sweden Microscopic colitis (MC) is an inflammatory bowel disease that consists of two sub-groups: collagenous colitis (CC) and lymphocytic colitis (LC). MC is characterized clinically by chronic, watery, non-bloody diarrhea leading to urgency and fecal inconti-nence, abdominal pain and weight loss. Macroscopically, the mucosa has a normal or nearly normal appearance with colonoscopy, however, it is mandatory to take segmen-tal biopsies of the colon. The diagnosis is then made by finding the typical histopathol-ogy. MC has been recognized as a common IBD with increasing incidence rates over the last decades up to approximately 25/100.000 inhabitants in certain geographic areas. It affects mainly the elderly population, especially females. Although MC is not linked to increased mortality or risk for colon cancer, the patients’ quality of life (QoL) is significantly deteriorated with active disease. The pathogenesis of MC is unknown but is certainly multifactorial including genetics, associations with drugs intake (e.g. PPI, NSAID, SSRI), environmental factors (e.g. smoking) microbial dysbiosis and mucosal barrier dysfunction. Empirical data have shown that some patients with MC can be successfully treated with antidiarrheal treatment (loperamide, cholestyramine). Although, budesonide is the only treatment tested in numerous randomized controlled studies and it has proven to be highly effective in inducing remission in both CC and LC with remission rates of roughly 80%. However, approximately 60% of these responders experience a relapse after budesonide cessation which indicates that the disease course is not changed. Maintenance treatment with budesonide can be given trying to find the lowest dose which keeps patients in clinical remission. When budesonide treatment fails, immunosuppressive drugs and treatment with bio-logicals (anti-TNF, vedolizumab) have been tested to be beneficial in some patients. Surgery (ileostomy) is seldom necessary.

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Tandem talk: Behcet’s disease – Asia

J.H. Cheon1,2 1Department of Internal Medicine, Yonsei University College of Medicine; 2Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea

Behçet's disease (BD) is a multi-systemic inflammatory disorder of an unknown etiology and shows a chronic recurrent clinical course. Intestinal Behçet's disease, commonly accepted as a type of inflammatory bowel disease (IBD), could be diag-nosed when patients with BD have objectively documented gastrointestinal symptoms and intestinal ulcerations. While any part of the gastrointestinal tract can be involved, the most common location of intestinal BD is the ileocecal area. A few, large, deep ulcerations with discrete border are characteristic endoscopic findings of intestinal BD. there is no single gold standard test or pathognomonic finding of intestinal BD. Intes-tinal BD is more frequently reported in East Asian countries than in Western or Middle Eastern countries. Similar to IBD, intestinal BD has an unpredictable disease course with relapse and remission and is often related to a poor prognosis. As intestinal BD shares a lot of characteristics with IBD, including genetic background, clinical manifes-tations, and therapeutic strategies, distinguishing between the two diseases in clinical practice is quite difficult. It is important to distinguish and treat those two disease entities separately from the standpoint of precise medicine. Clinicians should require comprehensive knowledge regarding the similarities and differences between intestinal BD and inflammatory bowel disease for making an accurate clinical decision.

Currently, there is no single gold standard for assessment of the disease activity of intestinal BD, and its diagnosis and management depend heavily on expert opinions. The Korean IBD Study Group recently developed novel diagnostic criteria based on colonoscopy findings and clinical manifestations using a modified Delphi process to overcome drawbacks of previously used consensus for the diagnosis of intestinal BD. In addition, the recently developed disease activity index for intestinal BD, consisting of a relatively simple 8-point index, could also help in determining treatment strategies and monitoring therapeutic responses.

The management of intestinal BD has not yet been properly established. Intestinal BD patients with a severe clinical course experience frequent disease aggravations and often require recurrent corticosteroid and/or immunomodulatory therapies, or even surgery. However, a considerable number of patients with intestinal BD are often refractory to conventional therapies such as corticosteroids and immunomodulators. Administration of anti-tumor necrosis factor-α, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal BD has been accumulating. Recently, a line of evidence suggests that bio-logics such as infliximab and adalimumab are effective in treating intestinal BD. More-over, new biologics targeting proteins other than tumor necrosis factor α are emerging and are under active investigation.

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Tandem talk: Behçet’s disease – Turkey A.F. Celik Department of Gastroenterology, Cerrahpaşa Medical Faculty, Istanbul, Turkey Although Behçet’s Disease (BD) is accepted as an all size vessel vasculitis, general-ized inflammatory activity including gastrointestinal(GI) mucosa makes it as a unique and bridging disease between vasculitis and inflammatory diseases. Most of the BD cases present with muco-cutaneous signs, like oral and genital ulcers. Diagnosis has to rely on the fully fill of the criteria, but different criteria use, low sensitivity and time dependent appearance of signs and symptoms may create difficulties and make the close follow up necessary. This diagnostic dilemma is especially seen in the Inflam-matory Bowel Disease (IBD) clinics of BD endemic countries. In general, BD may have some regional differences, like having more frequent vascular thrombotic events in Turkey in contrast to more eye involvement in Japan. There are also some geographical differences in the frequency of Gastrointestinal Behçet’s Disease (GIBD), like having relatively high GI prevalence in Asia, in contrast to less than 1% in Anatolia (Turkey), where the geographically ancient silk way end. Different prevalence of GIBD in different geographies may arise from diagnostic biases as well as some regional realities. Both in Asia and Europa, BD experts have an agreement on the diagnostic value of the morphological specifications and distribution of GIBD ulcers. In general, the young males have the worst prognosis, especially in the form of throm-botic disease pattern. High risk complications, like perforation and bleeding are com-mon in up to 1/3 of the patients with GIBD. This may create and excuse why GIBD differentiation needs a necessary attention in IBD clinics. Although GIBD treatment mainly extrapolated from IBD clinical experiences, there may be some different implications between Asian and European experts, like steroid vs AZA use in uncomplicated persistent ulcers. Biologics, mainly anti-TNFs are success-ful in resistant cases. Very limited case reports with anti-integrins and IL-12/23 blockers may encourage their use in unresponsive conditions.

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Oral Poster Presentation

Increasing evidence for macroscopic abnormalities in collagen-ous colitis

K. Dabos (Edinburgh, GB), P. Fineron (Edinburgh, GB),A. Koulaouzidis (Edinburgh, GB)

Introduction: The definition of collagenous colitis (CC) includes a normal colonoscopy and histological findings. A thick collagen submucosal band is the histological hallmark of the disease. However there is increase evidence that endoscopic findings are asso-ciated with the histological diagnosis of CC. These include erythema, oedema and nodularity of the mucosa, lacerations of the mucosa, linear scarring, subtle changes in the vascular pattern and pseudomembranes.

Methods: The aim of the study was to evaluate the frequency and type of endoscopic findings in collagenous colitis in the Lothian region of Scotland in the UK. This was a retrospective study; the database of hospitals in the region was interrogated for patients diagnosed with CC between January 2013 and December 2018. Endos-copy reports and images were retrieved and reviewed; data on lesions, and endos-copist experience were extracted. Categorical data are reported as mean ± SD.

Results: 280 patients (40 male, mean age 62.8 ± 13.4 years) were diagnosed with CC. A total of 64/280 (22.86%) patients had one or more suggestive endoscopic find-ings: mucosal erythema/oedema 46/280 (16.4%), linear colonic mucosal defects 6/280(0.02%), mucosal scarring 8/280 (0.03%), loss of subtle vascular patterns 4/280(0.014%). From the 40 male patients only one exhibited lacerations and the rest of thecolonoscopies were normal. Eighteen different endoscopists performed all theprocedures in four hospitals in the region. Five endoscopists reported > 80% of theabnormal findings.

Discussion/Conclusion: A significant minority of patients with collagenous colitis exhibit macroscopical findings. Increasing awareness of that between endoscopists will increase the number of findings and might lead to the conclusion that collagenous colitis is not so microscopic after all.

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Oral Poster Presentation Emerging role of gut microbiota and SIBO in NAFLD develop-ment K. Kvit (Lviv, UA), N. Kharchenko (Lviv, UA), U. Dorofeeva (Lviv, UA), O. Chornenka (Lviv, UA) Introduction: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disease worldwide. NAFLD patients are typically characterized with small intestine bacterial overgrowth (SIBO) that may impair the intestinal tight junction and subsequently increase intestinal permeability. The studies, dedicated to the microbiota composition in patients with NAFLD are insufficient. Hence, there is an interest in exploring the fatty infiltration as the result of the syndrome, that includes bacterial com-position disturbance, with profound analysis of preventive and aggressive factors that impact on liver disease occurrence and progress. The aim of this study was to analyze the gut microbiota composition in patients with NAFLD with possible examination of aggressive and protective factors, including SIBO existence and biochemical markers. Methods: 43 patients with hyperlipidemia with average age 46.97 ± 2.53. and BMI 27.43 ± 0.74 were examined in “Medicover Ukraine” (Lviv, Ukraine). The average waist circumference in main group was 91.6 ± 1.09 cm (in men), 83.3 ± 0.65 cm (in women). The exclusion criteria for both groups were – diabetes mellitus, viral hepatitis and auto-immune hepatitis during the last 10 years. All patients underwent biochemical evaluation – lipid profile, C-reactive protein, ALT, AST, GGTP, CRP, bilirubin (total, direct, indirect), apolipoprotein B, apolipoprotein A1. Determination of microbial com-position at the level of major microbial phyla was carried out by identification of total bacterial DNA, and DNA of Bacteroidetes, Firmicutes and Actinobacteria was performed with quantitative real-time PCR (qRT-PCR), using gene-targeted primers. Ultrasound examination was proved to all patients. The criteria for fatty infiltration existence was a diffuse increase in the echogenicity of the liver parenchyma, decreas-ed attenuation on the liver and ratio between the brightness level of the liver and the right kidney that was calculated for the hepato-renal index (HRI) determination. All subjects were examined by a lactulose breath test (LBT). Results: The prevalence of SIBO in patients with NAFLD was 51.2%. The percent composition of microbiota included next proportions of bacteria – Bacteroidetes – 16.7 ± 2.99, Firmicutes – 45.3 ± 2.99, Actinobacteria – 25.9 ± 1.9, Firmicutes/ Bacteroi-detes ratio (F/B) – 6.47 ± 1.55.). Strong negative correlation between Bacteroidetes and Firmicutes (r = -0.93), Bacteroidetes and Firmicutes/Bacteroidetes index (r = -0.65) and Bacteroidetes and Actinobacteria (r = -0.89) was marked. Moreover, there was strong positive correlation among F/B index and triglycerides (r = 0.42) and ALT (r = 0.4). Additionally, there was middle-strong correlation between SIBO existence and Firmicutes increasing in patients with NAFLD (r = 0.39). According to different data, there are contradictory facts about F/B index in patients with NAFLD. However, most of the studies, show the potential exacerbating influence Firmicutes on the fatty infiltration progression. Some of the data suggests to include the F/B index to the list

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of early markers of NAFLD presence. Regarding the previous data about the theory of “two-hit” theory, where tri-glycerides play one of the most essential roles, we’ve paid the attention to the fact of possible relationship between the part of microbes in this process. Moreover, there is an interesting point in SIBO existence and its connection with Firmicutes by widely-spread fact that SIBO is associated with gram-negative microflora, to which Firmicutes do not belong. So, we’ve tried to compare the group of patients with NAFLD and SIBO and NAFLD without SIBO with idea to find some features in gut microbiota composition, that could explain this relationship. There was no difference between these groups. Thus, we can suggest, that there is a violation in composition of some species of bacteria, not phyla, that are leading to SIBO occur-rence especially in the background of NAFLD and it could be not only gram-negative bacteria, but gram-positive, that are associated with NAFLD.

Discussion/Conclusion: The prevalence of SIBO in patients with NAFLD was 51.2%. The decreasing of Bacteroidetes leads to Firmicutes and Actinobacteria increasing, with F/B growth, that provokes triglycerides and ALT level raise in patients with NAFLD. The increasing of Firmicutes is associated with SIBO presence. F/B index could be the marker of NAFLD presence, while the Bacteroidetes are potentially preventive factors for NAFLD progression.

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Session VIII

Inflammatory bowel disease

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State-of-the-Art Lecture Where are we heading to in pharmacotherapy of IBD? R.J. Xavier Kurt Isselbacher Professor of Medicine, Harvard Medical School Director, Center for Computational and Integrative Biology, MGH Core member, Broad Institute, Boston, MA, USA The current understanding of Inflammatory Bowel Disease (IBD) pathogenesis impli-cates a complex interaction between host genetics, host immunity, microbiome and environmental exposures. Mechanisms gleaned from genetics and molecular patho-genesis offer clues to the critical triggers of mucosal inflammation and guide the devel-opment of therapeutic interventions. A complex network of interactions between host genetic factors, microbes, and microbial metabolites governs intestinal homeostasis, making classification and mechanistic dissection of involved pathways challenging. In this presentation I will discuss these challenges, areas of active translation, and oppor-tunities for development of next-generation therapies.

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Tandem talk: De-escalating biologics – Western perspectives

M.A. KammProfessor of Gastroenterology, St Vincent’s Hospital and University of Melbourne,Melbourne, Australia

Biologic therapies are valuable, but a variety of circumstances may necessitate stopping their use. In other circumstances it is possible to dose reduce.

Dose reduction can be undertaken when drug levels are high, especially if remission has been achieved. Intermittent therapy when symptomatic or short term induction therapy only are usually not recommended to due drug sensitization, subsequent allergic reactions, and inability to re-use the drug later.

Voluntary stopping may relate to cost, patient preference, concern about drug side effects, desire to get pregnant off therapy, or the patient wants to travel.

Stopping the biologic may also be a necessity, due to drug-related side effects, devel-opment of cancer, allergic drug reaction, or complete loss of response.

Stopping can be undertaken with a traditional immune suppressant in place to maintain therapy.

Each patient should be considered on their own merits. Stopping a biologic is more viable when the past history was not too severe or recurrent, when the disease is in endoscopic remission, and when other disease parameters such as calprotectin and haemoglobin are normal.

When a biologic is stopped after combination therapy about 50% of patients are still in remission 2 years later, although this decreases with time. Relapse after stopping a biologic can usually be successfully re-induced in the short term.

In pregnancy biologics can sometimes be stopped around week 22 if the disease is in remission and they are on another medication to maintain remission.

For fistulizing Crohn’s disease healing (including MRI) should probably be achieved before stopping the biologic, but even then some will have a recurrence.

Large real-life case series suggests that about a third of patients will crease their bio-logic drug in the medium term. A strategy needs to be in place to maintain remission. Patients should be monitored for disease relapse.

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The role of newer biologics and small molecules in infection endemic areas W.K. Leung Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong The incidence and prevalence of inflammatory bowel disease (IBD) are rising rapidly in Asia, which is associated with a parallel increase in the usage of biologics for treat-ment of IBD. Unlike western countries, some infections such as tuberculosis and viral hepatitis are still endemic in Asia, which may pose additional risk to our patients who are on biologics. In particular, anti-TNFs are associated with higher risk of tuberculosis. In a recent population-based study from Hong Kong, it was shown that treatment with infliximab had a nearly 26-time higher risk of tuberculosis compared with general popu-lation. The risk was particularly increased for infliximab than adalimumab. With the availability of new biologics for treatment of IBD, the potential risk of infection may be lower. Vedolizumab, the gut-selective integrin inhibitor, may have less systemic side effects and hence risk of systemic infections. Recent data also did not show an increase in risk of enteric infections with vedolizumab. While the IL-12 pathway is potentially important in regulating the immunity to tuberculosis, ustekinumab, the new anti IL-12/23, did not appear to pose higher risk of tuberculosis. In the combined analysis of 5 trials of ustekinumab-treated patients with psoriasis, 23.7% of Asian patients who were also diagnosed with latent tuberculosis were co-treated with isoniazid prophylaxis. None of these patients concomitantly treated with ustekinumab and isoniazid had reactivation of tuberculosis. The PSOLAR study that analyzed 11,466 patients with psoriasis also found a lower risk of infection with ustekinumab than other anti-TNFs. On the other hand, reappearance of HBV DNA in patients with chronic HBV had been reported on ustekinumab. The oral JAK kinase inhibitor, tofacitinib, was shown in a recent meta-analysis to be associated with a higher risk of infection by 1.4-fold, particularly herpes zoster. In the integrated analysis of global trials of that involved 6,194 patients treated with tofacintinib, the risk of herpes zoster was 3.9 per 100 patient-years. The infection risks were higher with combination therapy than mono therapy with tofacitinib in patients with rheumatoid arthritis. More data are needed to establish the safety of these newer agents for treatment of IBD in Asia, an infection endemic area.

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List of Chairpersons, Speakers and Scientific Organizers

Prof. Dr. Marion Aw Department of Pediatrics National University of Singapore NUHS Tower Block Level 12 1E Kent Ridge Road Singapore 119228 Singapore

Dr. Rupa Banerjee Department of Medical Gastroenterology Asian Institute of Gastroenterology 6-3-661, Somajiguda, HyderabadIndia

Prof. Dr. Giovanni Barbara Department of Medical and Surgical Sciences University of Bologna St. Orsola-Malpighi Hospital Pavilion 5 Via Massarenti, 9 Bologna, 40138 Italy

Dr. Emna Bel Hadj Mabrouk Gastroenterology Charles Nicole Hospital 09 rue de Rabat cité Erriadh Ezzahra 2034 Tunis Tunisia

Prof. Dr. Willem A. Bemelman Department of Surgery Tytgat Institute for Liver & Intestinal Research University of Amsterdam Meibergdreef 9 1105 AZ Amsterdam The Netherlands

Prof. Dr. Aykut F. Celik Department of Gastroenterology Cerrahpasa Medical Faculty 34098 Istanbul Turkey

Prof. Dr. Jae H. Cheon Department of Internal Medicine Institute of Gastroenterology Yonsei University College of Medicine 50-1 Yonsei-ro, Seodaemun-guSeoul 03722Korea

Prof. Dr. Stephen M. Collins Farncombe Family Digestive Health Research Institute Faculty of Health Sciences Room 3N8B McMaster University Medical Centre Hamilton, ON L8N 3Z5 Canada

Dr. Konstantinos Dabos Department of Hepatology Royal Infirmary of Edinburgh 51 Little France Crescent Edinburgh EH16 4SA Great Britain

Dr. Walter Elisei Division of Gastroenterology ASL Roma 6 Via Borgo Garibaldi, 12 00041 Albano Laziale Italy

Prof. Dr. Uday C. Ghoshal Department of Gastroenterology Sanjay Gandhi Postgraduate Institute of Medical Sciences Raebareli Road Lucknow, Uttar Pradesh 226014 India

Prof. Dr. Peter R. Gibson Department of Gastroenterology Alfred Hospital and Monash University Melbourne VIC 3004 Australia

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Dr. Khean-Lee Goh Emeritus Professor Department of Medicine Faculty of Medicine University of Malaya 50603 Kuala Lumpur Malaysia Prof. Dr. Kok Ann Gwee Stomach, Liver and Bowel Clinic Gleneagles Hospital Suite #05-37 6 A Napier Road Singapore 258500 Singapore Prof. Dr. Normila I. Hilmi Department of Medicine Faculty of Medicine University Malaysia 50603 Kuala Lumpur Malaysia Prof. Dr. Gerald Holtmann Gastroenterology & Hepatology Princess Alexandra Hospital Ipswich Road, Woollongabba Brisbane QLD 4102 Australia Prof. Dr. Michael A. Kamm Department of Gastroenterology St. Vincent‘s Hospital University Department of Medicine Victoria Parade Melbourne VIC 3065 Australia Prof. Dr. Wolfgang Kruis University of Cologne Am Dorfplatz 1 50259 Freimersdorf Germany Dr. Khrystyna Kvit Medical University Lviv 69, Pekarska Str. 79010 Lviv Ukraine

Prof. Dr. Cord Langner Abteilung für Pathologie Pathologisches Institut Medizinische Universität Graz Auenbruggerplatz 25 8036 Graz Austria Dr. Warren Lee Camden Medical Centre One Orchard Boulevard #02-06 Singapore 248649 Singapore Prof. Dr. Yeong Y. Lee Department of Gastroenterology, Hepatology & Internal Medicine School of Medical Sciences University Sains Malaysia Kota Bharu Malaysia Prof. Dr. Wai K. Leung Department of Medicine University of Hong Kong Queen Mary Hospital 102 Pokfulam Road Hong Kong Prof. Dr. Tony K.H. Lim Anatomical Pathology Singapore General Hospital Outram Road Singapore 169608 Singapore Dr. Khoon L. Ling Kl Ling Gastroenterology and Liver Clinic 3, Mount Elizabeth #16-04 Mount Elizabeth Medical Centre Singapore 228510 Singapore

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Dr. Jinsong Liu Gastroenterological Department Wuhan Union Hospital Huazhong Science & Technology University Jiefang Road 1277# 430022 Wuhan, Hubei China

Prof. Dr. Govind K. Makharia Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences Ansari Nagar New Delhi 110029 India

Dr. Javier Molina-Infante Department of Gastroenterology Hospital Universitario San Pedro de Alcantara Avenida Pablo Naranjo, s/n 10003 Cáceres Spain

Prof. Dr. Mark Morrison Translational Research Institute (TRI) The University of Queensland Diamantina Institute Level 7, 37 Kent St Woolloongabba, QLD 4102 Australia

Dr. Andreas Münch Department of Medicine Department of Gastroenterology & Hepatology School of Medicine Linköping University Hospital 581 85 Linköping Sweden

Prof. Dr. Atsushi Nakajima Department of Gastroenterology & Hepatology Fukuura Campus Yokohama City University Hospital Kanazawa-ku 3-9 Kanagawa Yokohama 236-0004 Japan

Dr. Choon J. Ooi Gastroenterology Clinic #10-02 Gleneagles Medical Centre 6 Napier Road Singapore 258499 Singapore

Dr. Savvas Papagrigoriadis King’s College Hospital Department of Colorectal Surgery Denmark Hill London SE5 9RS Great Britain

Eamonn M.M. Quigley, M.D. Professor of Medicine Division of Gastroenterology and Hepatology Clinical Sciences Building The Methodist Hospital 6565 Fannin St., SM1201 Houston, TX 77030 USA

Prof. Dr. Raja A. Raja Ali UKM Medical & Specialist Centers The National University of Malaysia Jalan Yaacob Latiff 56000 Cheras, Kuala Lumpur Malaysia

Prof. Dr. Dr. Detlef Schuppan Translationale Immunologie Universitätsmedizin der Johannes Gutenberg-Universität Langenbeckstr. 1 55131 Mainz Germany

Prof. Dr. Magnus Simrén Department of Internal Medicine & Clinical Nutrition Institute of Medicine Sahlgrenska Academy University of Gothenburg 40530 Gothenburg Sweden

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Prof. Dr. Jose D. Sollano Faculty of Medicine and Surgery University of Santo Tomas España Boulevard 1099 Manila Philippines Prof. Dr. Robin C. Spiller Biomedical Research Unit Nottingham Digestive Diseases Centre Queen‘s Medical Centre E floor West Block Clifton Boulevard Nottingham NG2 7UH Great Britain Prof. Dr. Kentaro Sugano Department of Internal Medicine Division of Gastroenterology Jichi Medical University 3311-1 Yakushiji, Shimotsuke Tochigi 329-0498 Japan Prof. Dr. Hidekazu Suzuki Department of Gastroenterology and Hepatology Tokai University School of Medicine Isehara Kanagawa 259-1193 Japan Prof. Dr. Jan Tack Department of Clinical and Experimental Medicine University Hospital Leuven Herestraat 49 3000 Leuven Belgium Prof. Dr. Nicholas J. Talley Newcastle University HMRI Building University Drive Callaghan NSW 2308 Australia

Prof. Dr. Victoria Tan Department of Gastroenterology & Hepatology University of Hong Kong Hong Kong Prof. Dr. Antonio Tursi Servizio di Gastroenterologia Territoriale DSS n°4, Barletta - ASL BAT 70031 Andria Italy Prof. Dr. Marjorie M. Walker School of Medicine & Public Health Faculty of Health and Medicine University of Newcastle Callaghan NSW 2308 Australia Prof. Dr. Peter J. Whorwell Wythenshawe Hospital M23 9LT Manchester Great Britain Ramnik J. Xavier, M.D. Professor of Medicine GI Unit School of Medicine Massachusetts General Hospital 55 Fruit Street Boston, MA 02114-2696 USA Dr. Yinglian Xiao Department of Gastroenterology The First Affiliated Hospital of Sun Yat-Sen University 58 Zhongshan Road ll Guangzhou 510080 China Dr. Khay-G. Yeoh National University Health System 1E Kent Ridge Road NUHS Tower Block, Level 13 Singapore 119228 Singapore

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Katarzyna Zdanowicz Department of Pediatrics, Gastroenterology, Hepatology University Children‘s Clinical Hospital Waszygtona 17 15-274 BialystokPoland

POSTER ABSTRACTS Poster Numbers 1 – 51

Author Index to Poster Abstracts

1   

Validity and reliability of the Malay language-translated Bloating Severity and Quality of Life Questionnaire (BSQoL-M) Nurzulaikha Abdullah (Kota Bharu, MY), Yee Cheng Kueh (Kota Bharu, MY), Garry Kuan (Kota Bharu, MY), Fatan Hamamah Yahaya (Kota Bharu, MY), Mung Seong Wong (Kota Bharu, MY), Nor Aslina Abd Samat (Kota Bharu, MY), Yeong Yeh Lee (Kota Bharu, MY) Introduction: The Bloating Severity and Quality of Life Questionnaire (BSQoL) is among the limited few and valid tools to determine disease activity of bloating. Our aim was to validate the Malay-translated version of BSQoL (BSQOL-M) among bloating individuals with functional gastrointestinal disease (FGID). Methods: This cross-sectional study recruited Malay-speaking participants with FGIDs and bloating. The BSQOL (17 items) has three components i.e. severity in general (SevGen, 7 items), severity past 24 hours (Sev24, 5 items) and quality of life (QoL, 5 items). Exploratory factor analysis (EFA) was used to explore the construct validity of the three components of BSQOL-M separately. Internal consistency (Cronbach’s alpha) for reliability was determined for each component. Additional hypothesis-testing validity was done by examining the correlation (Pearson, r) between SevGen with Sev24 and QoL. Results: Of 162 screened FGID individuals, 1d50 (mean age: 31.27 years; females: 68.3%) were eventually included. In EFA, all items have factor loading passing the threshold value, which is 0.40 except for two items in SevGen (i.e., SevG1 and SevG2) (Table 1). The average variance extracted for SevGen, Sev24 and QoL were 0.31, 0.66 and 0.59 respectively. For internal consistency, the Cronbach’s alpha values for SevGen, Sev24, QoL were 0.64, 0.86, and 0.81 respectively. The correlation between SevGen and QoL was good (r = 0.654, p < 0.001), relatively poor between SevGen and Sev24 (r = 0.275, p = 0.001) and no correlation seen between Sev24 and QoL (r = 0.107, p = 0.192). Discussion/Conclusion: While BSQOL-M is a valid and reliable tool but the components were poorly correlated especially Sev24.

2

Conservative treatment of patients after excision of chronic anal fissure Pavel Andreev (Samara, RU), Olga Davydova (Samara, RU) Introduction: Anal fissure have been reported in 11–15% of patients with pathology of the colon. Methods: The main group (group I) consisted of 52 patients (50%), which is 7 days after excision of chronic anal fissures with the anal sphincter divulsa was appointed a suppos-itory Salofalk® worth us scheme is 250 mg 2 times a day for 14 days. The control group (group II) accounted for 52 patients (50%), which is 7 days after excision of chronic anal fissures with the anal sphincter divulsa was appointed a suppository natalise scheme 2 times a day for 14 days. Statistically significant differences between groups of patients by sex (χ2 = 1,44; p < 0.05), age (t = 0.01; p < 0.05) were not fixed. Patients with chronic anal fissure was considered cured after complete epithelization of the surgical wound. Results: The level of pain on a visual-analog scale for the seventh day in group I – 3.6 ± 0.4 and group II – 5.6 ± 0.6, statistical difference t = 2.77; p < 0.05; on the 14th day in group I – 0.96 ± 0.33 and group II – 3.9 ± 0.63, statistical difference t = 4.13; p < 0.05; on the 28th day in group I – 0 ± 0.005 and group II – 0.45 ± 0.33, statistical difference t = 1.36; p = 1.05. In the main group of patients on the 28th day complete epithelization of wound was noted in 37 (74%) patients, while in patients of the control group – 27 (54%). Discussion/Conclusion: Epithelization of wounds in the early stages, as well as faster relief of manifestations such as blood in the chair, pain syndrome, create an advantage for both patients and coloproctologists in the use of Salofalk® suppository after surgical treatment of chronic anal fissure.

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Recurrence of primary biliary cholangitis after liver transplan-tation: A single-center experience Lukas Bajer (Prague, CZ), Klara Chmelova (Prague, CZ), Jan Brezina (Prague, CZ), Peter Macinga (Prague, CZ), Pavel Taimr (Prague, CZ), Julius Spicak (Prague, CZ), Pavel Drastich (Prague, CZ) Introduction: Primary biliary cholangitis (PBC) may progress to end-stage disease requiring orthotopic liver transplantation (OLT). Recurrent form of PBC (rPBC) appears in significant proportion of patients after OLT and is usually characterized by mild clinical course. The aim of this study was to evaluate outcome of OLT for PBC in our center and to identify recipient risk factors for rPBC. Methods: A total number of 82 OLTs for PBC were performed in our center between 1995–2017. We retrospectively analyzed all relevant medical records from our computed database. Input statistical data were analyzed using JMP software. Survival ratio was determined from Kaplan-Meier curves. Pearson’s chi-squared test and Fisher’s exact test were used to assess the potential risk factors for rPBC. Results: Out of 82 patients with median 158 (23–261) months of follow-up, 73 (89%) were female and 9 (11%) were male with median age of 56.9 (36–71) at the time of OLT. 3/82 (3.7%) had hepatocellular carcinoma (HCC) in the liver explant. 1-, 3-, 5-years patient survival was 92.7%, while 10-years survival was 84.6%. Graft survival was 91.7% at 1, 3 and 5 years and 83.7% at 10 years. 3 (3.7%) patients received re-transplant: 1 (1.2%) for primary graft dysfunction and 2 (2.4%) for rPBC. Out of 74 analyzed patients (after applying exclusion criteria), 45 (54.9%) developed rPBC after median time of 46 (11–239) months. None of the potential risk factors (age, sex, type of immunosuppression, features of AIH prior OLT, AMA and ANA positivity prior OLT) were significantly associated with rPBC (p > 0.1). However, the rate of rPBC had statistical tendency to be higher in patients who had HCC in their explants (p = 0.056). Discussion/Conclusion: Recurrent PBC is frequent but usually not serious clinical con-dition. In our cohort, rPBC rate was relatively high, presumably due to long median follow-up after OLT.

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Evaluation of undiagnosed HCC (without any typical imaging features) by percutaneously tru-cut core biopsy: A single-centre experience Metin Basaranoglu (Istanbul, TR) Introduction: In the diagnostic strategy of liver masses, two scenarios are examined 1: (1) incidentally discovered solid lesions or masses in a cirrhotic patient. The most likely diagnosis is HCC, followed by high and low-grade dysplastic nodule. Lesions > 2 cm are diagnosed by imaging techniques, lesions of 1–2 cm require histology if imaging modalities are atypical, and lesions < 1 cm require US follow-up every three months. His-tology is required when the lesion is doubtful. In this study, we aimed to evaluate patients with undiagnosed HCC without any typical imaging features, previously investigated by multidisciplinary approach and tru-cut core biopsy performed by transabdominal ultrasound approach. Methods: We retrospectively evaluated 123 patients, the years 2011, 2012 and 2013. A single gastroenterologist who is very well experienced performed all biopsies. Results: A single well-experienced radiologist retrospectively reevaluated all records and found 27 pts with HCC that were shown in Table 1 according to the BCLC Staging System. Distribution of the patients by hepatitis serology and the serum levels of α-FP and finally follow-up results were also shown in Table 1. Relation between the hepatitis serology and serum α-FP levels shown in Table 2. Table 1: Stage HCC (A) HCC (B) HCC (C) Number of the pts 8 pts 9 pts 10 pts α-FP (↑) in 4 pts (7.4–181) 4 pts (9.5–300) 4 pts (14–300) HBV 4 pts 2 pts 5 pts HCV 2 pts 3 pts none Seronegative: 2 pts 4 pts 5 pts Exitus 2 pts 5 pts 7 pts

Table 2: Number of the pts HBV6 HCV 2 HBV; α-FP (↑) 6 HCV; α-FP (↑) 2 HBV (-), HCV (-) 4 HBV (-), HCV (-); α-FP (↑) 6 HBV (-), HCV (-); α-FP: un-known 1 Discussion/Conclusion: In the majority of patients, a proper diagnosis can be made based on the characteristics on imaging modalities (Lesions size < 1.0 cm are usually benign). For diagnostic purposes, liver masses should be divided into those occurring with and without cirrhosis. A liver mass in a cirrhotic liver should be viewed as HCC until proven otherwise. Multiple liver masses in a cirrhotic liver indicate diffuse HCC or high-grade dysplastic nodules. Benign liver lesions are found in more than 20% of the general population, including hemangioma, focal nodular hyperplasia (FNH) and hepatic adenomas. Multiple liver lesions in a normal liver usually indicate liver metastasis, but could be cysts or hemangiomas. Liver metastasis is a rare finding in a cirrhotic liver. Multiple liver lesions of a benign nature such as hemangiomas or focal nodular hyperplasia are not uncommon in a normal liver. In conclusion, tru-cut core biopsy might be required, but biopsy of potentially operable lesions should be avoided.

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Particularities of celiac disease in masculine population

Emna Belhadj Mabrouk (Tunis, TN), Shema Ayadi (Tunis, TN), Myriam Ayari (Tunis, TN), Yosra Zaimi (Tunis, TN), Leila Mouelhi (Tunis, TN), Radhouène Dabbèche (Tunis, TN)

Introduction: Celiac disease (CD) is a chronic autoimmune disease with a prevalence of 2% in the world. Few studies were interested in the particularities in a masculine popu-lation.

Methods: It is a retrospective study from January 2000 to December 2017. All patients hospitalized for a CD were included. 69 patients were studied. The diagnosis of CD was confirmed by the positivity of endomysial antibody as well as duodenal biopsy showing villous atrophy. The charts of all patients of masculine sex were studied.

Results: 23 were men. Mean age was 38 years old (15–68). Family history of CD was found in 17.4%. The main discovery circumstance were diarrhea (87%) and iron deficiency anemia (52.2%). A deficiency syndrome made of anemia, low cholesterol and low albumin was found in 82.6% of the patients. Gastrointestinal endoscopy showed mosaic pattern in 56.5%, atrophic mucosa (8.7%) and mucosal ulceration (4.3%). Biopsies found total atrophy of the gland in 43.5%. 8 patients had autoimmune manifestations: type 1 diabetes (n = 3), Biermer anemia (n = 2), vitiligo (n = 2), hypothyroid (n = 1) and autoimmune hepatitis (n = 1). Bone densitometry showed abnormalities in 32.6% of the cases. The evolution was favorable in 73.9% with gluten-free diet.

Discussion/Conclusion: Autoimmune diseases are not frequent in masculine popu-lations. Our study suggests that CD in masculine population is correlated to deficiency syndrome and to villous atrophy. These data requires larger sample to confirm our results.

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Thrombosis in celiac disease: Retrospective study Emna Belhadj Mabrouk (Tunis, TN), Shema Ayadi (Tunis, TN), Myriam Ayari (Tunis, TN), Yosra Zaimi (Tunis, TN), Leila Mouelhi (Tunis, TN), Radhouène Dabbèche (Tunis, TN) Introduction: Celiac disease (CD) is an autoimmune disorder caused by gluten. During the last decades, extra-digestive manifestations became at the first plan. Among these manifestations; we are interested in studying the clinical aspects of venous thrombosis (VT) in celiac disease. Methods: It is a descriptive, retrospective study from January 2000 to December 2017. All patients hospitalized for a CD were included. 69 patients were studied. The diagnosis of CD was confirmed by the positivity of endomysial antibody as well as duodenal biopsy showing villous atrophy. Patients who had presented a VT were studied. Results: Five cases of thrombosis were found: prevalence = 7.2%. 3 were women and 2 were men. Mean age was 37 years old (23–48). No risk factors of thrombosis were found. The thrombotic manifestations were diagnosed before the CD in 1 case. 3 patients presented profound venous thrombosis of the inferior members. In the fourth case, it was a thrombosis of the superior mesenteric venous and the portal venous with portal cavernoma and portal hypertension. In the fifth case it was a cerebral thrombophlebitis complicated by hemiplegia. Thrombophilia tests were performed. Abnormalities were found in 2 cases: defect in protein S (n = 1) and in activated protein C (n = 1). The evolution was favorable with anticoagulant treatment and gluten-free diet. Discussion/Conclusion: The association of venous thrombosis and celiac disease are rare yet not exceptional. Diagnosis must be suspected whenever thrombotic manifes-tations remain unexplained. Screening and correcting the risk factors is required.

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Predictive value of the “DICA” endoscopic classification on the outcome of diverticular disease of the colon: An analysis from the international, multicenter, prospective study

Giovanni Brandimarte (Rome, IT), Antonio Tursi (Andria, IT), Francesco Di Mario (Parma, IT), Walter Elisei (Albano Laziale, IT), Marcello Picchio (Velletri, IT), Leonardo Allegretta (Galatina, IT), Maria Laura Annunziata (San Donato Milanese, IT), Marco Astegiano (Turin, IT), Mauro Bafutto (Goiânia, BR), Fabio Baldi (Tarquinia, IT), Gabrio Bassotti (Perugia, IT), Maria Antonia Bianco (Torre del Greco, IT), Raffaele Colucci (Spoleto, IT), Rita Conigliaro (Baggiovara, IT), Silvio Danese (Rozzano, IT), Dan Dumitrascu (Cluj-Napoca, RO), Ricardo Escalante (Caracas, VE), Roberto Faggiani (Viterbo, IT), Serafina Fiorella (Vasto, IT), Giacomo Forti (Latina, IT), Marilisa Franceschi (Santorso, IT), Giorgetti GianMarco (Rome, IT), Simona Grad (Cluj-Napoca, RO), Maria Giovanna Graziani (Rome, IT), Maria Antonia Lai (Cagliari, IT), Frank Lammert (Homburg, DE), Giovanni Latella (L'Aquila, IT), Daniele Lisi (Rome, IT), Giovanni Maconi (Milan, IT), Maria Margarita Murphy (Mount Pleasant, US), Gerardo Nardone (Naples, IT), Laura Oliveira Camara De Castro (Rio de Janeiro, BR), Enio Oliveira Chaves (Goiânia, BR), Alfredo Papa (Rome, IT), Savvas Papagrigoriadis (London, GB), Antonio Penna (Bari, IT), Anna Pietrzak (Warsaw, PL), Stefano Pontone (Rome, IT), Piero Portincasa (Bari, IT), Tomas Poskus (Vilnius, LT), Giuseppe Pranzo (Martina Franca, IT), Matthias Reichert (Homburg, DE), Giovanni Luca Rizzo (Brindisi, IT), Stefano Rodinò (Catanzaro, IT), Jaroslaw Regula (Warsaw, PL), Giuseppe Scaccianoce (Bari, IT), Franco Scaldaferri (Rome, IT), Luigi Schiffino (Ostia, Rome, IT), Ieva Stundiene (Vilnius, LT), Roberto Vassallo (Palermo, IT), Marjorie Walker (Newcastle, AU), Costantino Zampaletta (Viterbo, IT), Angelo Zullo (Rome, IT)

Introduction: The endoscopic classification called “DICA” (Diverticular Inflammation and Complication Assessment) has been recently developed in order to have an objective endoscopic description of the colon harboring diverticula. Aim of this multicenter, inter-national, prospective study was to assess the predictive value of this classification in term of acute diverticulitis and surgery occurrence on a 1-year observational follow-up period.

Methods: 2215 prospective patients at the first diagnosis of diverticular disease were enrolled after exclusion of radiological signs of acute diverticulitis; inflammatory bowel diseases; ischemic colitis; prior colonic resection; patients with severe liver failure (Child-Pugh C) or severe kidney failure; pregnant women; patients who are currently using or who have received any laxative agents or mesalazine or probiotics or antibiotics < 2 weeks prior to the enrollment; inability to comply with study protocol and to give informed consensus to the procedure; patients with or history of cancer, of any origin, within 5 years

before enrollment; history of alcohol, drug, or chemical abuse. All patients were classified according to DICA classification. Results: 1377 (62.15%) patients were classified as DICA 1, 599 (27.04%) as DICA 2, and 239 (10.80%) as DICA 3. The risk of acute diverticulitis occurrence/recurrence, as well as the risk of surgery, were significantly linked to the severity of DICA score at entry. Overall, acute diverticulitis occurred in 79 (3.6%) patients: it occurred in 17 (1.38%) DICA 1, 30 (5.11%) DICA 2 and 30 (12.82%) DICA 3 patients respectively (p < 0.0001). Overall, surgery occurred in 29 (1.3%) patients: it occurred in 2 (0.14%) DICA1, 11 (1.87%) DICA 2 and 16 (6.83%) DICA 3 patients respectively (p < 0.0001). Discussion/Conclusion: The 1-year results of this prospective study seems to confirm that DICA endoscopic classification has a significant prognostic role on the risk of acute diverticulitis occurrence/recurrence and on the risk of surgery in people having colonic diverticulosis detected at colonoscopy.

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A national survey of IBD clinician’s perspectives on the use of faecal microbiota transplantation

Sue Chandler (Swansea, GB), Andrew Cunningham (Swansea, GB), Matthew Hitchings (Swansea, GB), Dean Harris (Swansea, GB)

Introduction: Interest in the use of faecal microbiota transplantation (FMT) is steadily increasing since the approval of FMT in the management of recurrent C.difficile infections (rCDI) in 2014 by NICE and the explosion of international literature regarding the micro-biome. Gut dysbiosis is considered to have a central role in the pathogenesis of inflam-matory bowel disease (IBD). FMT as a treatment in IBD appears promising but is unproven. The aim of this survey was to assess the perceptions of clinicians potentially involved in patients who could benefit from the treatment of FMT.

Methods: A web-based survey was distributed through email to Consultant General Surgeons and Gastroenterologists practicing in Wales.

Results: The questionnaire was completed by Consultants from varying specialties in-cluding gastroenterology, general surgery and gastrointestinal surgery. 58.8% of those were currently based in a district general hospital and 21.2% (7/35) claimed an academic interest. The majority (72.7%) stated that they had limited knowledge on FMT, with only 15.2% ever had a patient either request FMT treatment or made a FMT referral. Over 87% would consider referring patients for FMT treatment with rCDI being the most common indication. Over 90% feel FMT has a place in clinical practice, 78.8% would refer patients for FMT but 56.3% would like more evidence before it is introduced into routine clinical practice. 12% of respondents believe there is a significant infection risk despite the vigorous donor screening regime and over 71% believe the ‘Yuck’ factor. It is encouraging to report that 62.5% state that they have an interest in learning how to process and administer FMT so that if necessary they could arrange necessary treatment.

Discussion/Conclusion: This survey highlights that the majority recognise FMT as a potential therapeutic option, however increasing literature and accessibility is required before the routine introduction of FMT in Wales.

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A diagnostic value of indirect and direct markers of liver fibrosis in non-alcoholic fatty liver disease patients Halina Cichoż-Lach (Lublin, PL), Agata Michalak (Lublin, PL), Małgorzata Guz (Lublin, PL), Joanna Kozicka (Lublin, PL), Marek Cybulski (Lublin, PL), Andrzej Stepulak (Lublin, PL) Introduction: A diagnostic accuracy of indirect and direct markers of liver fibrosis in the course of non-alcoholic fatty liver disease (NAFLD) constitutes an important issue. Methods: The aim was to compare serological indices of liver fibrosis in NAFLD patients. One hundred sixty persons were included to the study: 92 with NAFLD and 68 volunteers in control group. Indirect markers of liver fibrosis were assessed: AAR, APRI, FIB-4 and GPR (GGT to PLT ratio). Among direct indices of liver fibrosis, procollagen I carboxy-terminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin were obtained. NAFLD fibrosis score and BARD score were assessed too. Achieved results were compared to controls. Diagnostic value of assessed parameters together with a proposed cut-off in research group were measured with AUC. Results: APRI, FIB-4 and GPR values were higher compared to controls (p < 0.0001); AAR level was lower (p < 0.05). TGF-α and laminin values were lower (p < 0.0001); PICP, PIIINP and PDGF-AB concentrations did not differ significantly. NAFLD fibrosis score correlated positively with: APRI (p < 0.01), FIB-4 (p < 0.0001) and BARD score (p < 0.0001). A positive relationship between BARD score and FIB-4 (p < 0.05) was noted. There were positive dependencies between PICP and both: APRI (0.01) and GPR (p < 0.001). PDGF-AB correlated negatively with AAR (p < 0.05) and TGF-α with NAFLD fibrosis score (p < 0.005). AUC values and proposed cut-offs for the most powerful indirect and direct indices of liver fibrosis were: GPR (0.839; > 0.316), APRI (0.842; 0.31), laminin (0.760; < 509.31 ng/ml) and TGF-α (0.739; < 68.96 pg/ml). Discussion/Conclusion: Indirect parameters of liver fibrosis compared to direct indices turned out to be more powerful markers.

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Hematological scales – Potential non-invasive tools in the assessment of liver fibrosis in alcoholic liver cirrhosis – A single-center experience Halina Cichoż-Lach (Lublin, PL), Agata Michalak (Lublin, PL), Małgorzata Guz (Lublin, PL), Joanna Kozicka (Lublin, PL), Marek Cybulski (Lublin, PL), Andrzej Stepulak (Lublin, PL) Introduction: Mean platelet (PLT) volume (MPV) to PLT ratio (MPR), neutrophil to lymphocyte ratio (NLR) and PLT to LYM ratio (PLR) are potential markers of liver fibrosis. Methods: The aim of our investigation was to evaluate the diagnostic accuracy of MPR, NLR and PLR in the assessment of liver fibrosis in alcoholic liver cirrhosis (ALC) patients and to compare it with serological markers of liver fibrosis. We tried to assess correlations between above-mentioned hematological indices and clinical progression of ALC (MELD score). Two hundred ten participants were recruited to the study: 142 patients with ALC and 68 healthy volunteers in control group. Hematological indices (MPR, NLR and RLR) were measured in each person. Indirect markers of liver fibrosis were also obtained: AAR, APRI, FIB-4 and GPR (GGT to PLT ratio). Among direct indices of liver fibrosis, procollagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal propep-tide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin were assessed. Results: MPR and NLR values in ALC patients were higher in comparison to controls (p < 0.0001); PLR level was lower (p < 0.0001). MPR and PLR correlated positively with indirect markers of liver cirrhosis (APRI, FIB-4; p < 0.001). Positive relationships were found between NLR and both: AAR and GPR (p < 0.05). MPR correlated negatively with PDGF-AB (p < 0.0001); positive relationship was observed between PLR and PDGF-AB (p < 0.01). NLR correlated negatively with PIIINP (p < 0.05). MELD score correlated positively with NLR (p < 0.0001) and negatively - with PLR (p < 0.001). AUC values and proposed cut-offs for MPR, NLR and PLR in ALC patients were: 0.929 (> 0.048), 0.821 (> 2.227) and 0.675 (< 70.445), respectively. Discussion/Conclusion: MPR and NLR seem to be promising parameters in the assessment of liver fibrosis in ALC patients.

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Platelet indices reflect dynamic changes in the extracellular matrix – The observation of alcoholic liver cirrhosis patients Halina Cichoż-Lach (Lublin, PL), Agata Michalak (Lublin, PL), Małgorzata Guz (Lublin, PL), Joanna Kozicka (Lublin, PL), Marek Cybulski (Lublin, PL), Andrzej Stepulak (Lublin, PL) Introduction: Platelet (PLT) indices have been proposed as potential markers in liver disorders. Methods: The aim of our study was to verify PLT indices in the evaluation of liver fibrosis in the course of alcoholic liver cirrhosis (ALC) and to compare them with serological markers of liver fibrosis. Another goal was to assess the relationship between PLT indices and clinical progression of liver failure (MELD score). Two hundred ten persons were enrolled to the study: 142 patients with ALC and 68 healthy volunteers in control group. Hematological indices were measured: mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT). Indirect markers of liver fibrosis were assessed: AAR, APRI, FIB-4 and GPR (GGT to PLT ratio). Among direct indices of liver fibrosis, pro-collagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin were obtained. Results: PDW value in ALC group was higher in comparison to controls (p < 0.0001), level of PCT was lower (p < 0.0001) and MPV value did not differ significantly. PLT indices correlated positively with indirect indices of liver fibrosis: MPV with: APRI, FIB-4 and GPR (p < 0.001), PDW with: APRI and FIB-4 (p < 0.0001). There were negative relationships between PCT and both: APRI and FIB-4 (p < 0.0001). Positive correlations were noted between PCT and direct markers of liver fibrosis: PDGF-AB (p < 0.001) and TGF-α (p < 0.05). MELD score correlated with PLT indices; positively with: MPV and PDW (p < 0.001) and negatively with PCT (p < 0.05). AUC values and proposed cut-offs for MPV, PDW and PCT in ALC patients were: 0.458 (> 11.1 fl), 0.764 (> 59.3%) and 0.839 (< 0.17%), respectively. Discussion/Conclusion: PLT indices are closely related to serological markers of liver fibrosis. PCT seems to be the most powerful parameter.

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The challenges in developing a faecal transplantation bank for the treatment of IBD Andrew Cunningham (Swansea, GB), Sue Chandler (Swansea, GB), Matthew Hitchings (Swansea, GB), Dean Harris (Swansea, GB) Introduction: Faecal Microbiota Transplantation (FMT) was first recorded over 2000 years ago for the treatment of severe diarrhoea. FMT is an infusion of a faecal suspension from a healthy individual to the GI tract of a recipient patient, in order to treat a disorder associated with an alteration of gut microbiota. It is proposed that Ulcerative Colitis (UC) is caused by a bacteria or group of bacteria within the microbiome interacting with genetically susceptible individuals to cause chronic relapsing inflammation of the colon. Increasing evidence has shown frozen faecal infusions from unrelated donors are as effective as related donors which has provided an opportunity for a better standardised approach for donor selection, screening, and treatment preparation. Methods: Faecal donors were recruited from the local area through multiple advertising campaigns including visual posters, social media, word of mouth and oral presentations. Donors were extensively screened according to British guidelines for eligibility. Successful volunteers were invited for interview and if deemed appropriate underwent both blood and stool testing for transmissible diseases prior to donation. Further questionnaires were completed on the day of donation prior to in-house sample processing. Results: Fifty-one volunteers registered initial interest in partaking in the faecal donor programme of which fifteen (29.4%) were eligible for screening. Reasons for eligibility failure included healthcare students, recent/current use of antibiotic and excludable medical disorders. Of the eligible volunteers, ten (66.7%) were suitable to supply donations. Positive infectious screens included hepatitis E, Amoeba, Clostridium perfringens, EBV and CMV. Previous but not active EBV and CMV infections were not excluded but matched to recipients also showing evidence of past infection. Discussion/Conclusion: We report the ongoing success of implementing a non-related frozen FMT donor stool bank for the experimental treatment of UC and highlight common pitfalls in current donor recruitment.

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Increasing evidence for macroscopic abnormalities in collagenous colitis Konstantinos Dabos (Edinburgh, GB), Paul Fineron (Edinburgh, GB), Anastasios Koulaouzidis (Edinburgh, GB) Introduction: The definition of collagenous colitis (CC) includes a normal colonoscopy and histological findings. A thick collagen submucosal band is the histological hallmark of the disease. However there is increase evidence that endoscopic findings are associated with the histological diagnosis of CC. These include erythema, oedema and nodularity of the mucosa, lacerations of the mucosa, linear scarring, subtle changes in the vascular pattern and pseudomembranes. Methods: The aim of the study was to evaluate the frequency and type of endoscopic findings in collagenous colitis in the Lothian region of Scotland in the UK. This was a retrospective study; the database of hospitals in the region was interrogated for patients diagnosed with CC between January 2013 and December 2018. Endoscopy reports and images were retrieved and reviewed; data on lesions, and endoscopist experience were extracted. Categorical data are reported as mean ± SD. Results: 280 patients (40 male, mean age 62.8 ± 13.4 years) were diagnosed with CC. A total of 64/280 (22.86%) patients had one or more suggestive endoscopic findings: mucosal erythema/oedema 46/280 (16.4%), linear colonic mucosal defects 6/280 (0.02%), mucosal scarring 8/280 (0.03%), loss of subtle vascular patterns 4/280 (0.014%). From the 40 male patients only one exhibited lacerations and the rest of the colonoscopies were normal. Eighteen different endoscopists performed all the procedures in four hospitals in the region. Five endoscopists reported > 80% of the abnormal findings. Discussion/Conclusion: A significant minority of patients with collagenous colitis exhibit macroscopical findings. Increasing awareness of that between endoscopists will increase the number of findings and might lead to the conclusion that collagenous colitis is not so microscopic after all.

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Celiac disease and Crohn’s disease: An association not to be disregarded Oussama Daboussi (Le Coudray, FR), Amine Benkhemmar (Le Coudray, FR), Murphy Luwawu (Le Coudray, FR), Anne Herber (Le Coudray, FR) Introduction: Celiac disease is one of common causes of malabsorption. The association with Crohn’s disease is possible although rare. This association should be kept in mind when diagnosis is not clear or the patient is not improving on appropriate therapy. Methods: We report a case of 49-year-old male who presented diarrhea and weight loss. He was initially diagnosed as celiac disease but later we notice recurrence of diarrhea. Results: A 49-year-old male was evaluated for weight loss and watery voluminous diarrhea. Serology showed raised anti-tTG Ig A and IgG. An upper gastrointestinal endoscopy was performed and distal duodenum biopsies showed features of severe villous atrophy. He was advised gluten-free diet (GFD), which showed marked improvement of his symptoms. Seven years later, he was admitted for diarrhea, abdominal pain and weight loss although he was strictly compliant with GFD. The anti-tTG titers were markedly decreased. Gastroscopy showed gastric erosions in the antropyloric region and aphtous ulcerations of the duodenum with a lumen narrowing. Colonoscopy was performed and showed erythematous mucosa with discontinious distribution of small aphtous ulcerations of the terminal ileum. Biopsies showed chronic active inflammation with epithelioid granuloma. The histopathological findings were suggestive of Crohn’s disease. Diagnosis of ileal Crohn’s disease with upper gastro-intestinal involvement was made. He was started steroids, proton-pump inhibitor and aza-thioprine, in addition to GFD. Diarrhea improved and he gained 4 kg of body weight over 3 months. Discussion/Conclusion: The association of Crohn’s disease with celiac disease is rare. Crohn’s disease is a diagnosis that must be considered in case of resistance to well-conducted GFD. Accordingly, colonoscopy should be performed in a systematic way.

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A validated score assessing the risk for intra-abdominal abscess in patients with Crohn's disease presenting at the Emergency Department Saleh Daher (Jerusalem, IL), Tawfik Khoury (Naharia, IL), Muhammad Massarwa (Jerusalem, IL), David Hakimian (Jerusalem, IL), Ariel Benson (Jerusalem, IL), Elez Viener (Jerusalem, IL), Raymond Farah (Safed, IL), Amir Mari (Nazareth, IL), Wadi Hazou (Jerusalem, IL), Anas Kadah (Naharia, IL), Wisam Sbeit (Naharia, IL), Mahmud Mahamid (Nazareth, IL), Eran Israeli (Jerusalem, IL) Introduction: A majority of acutely-ill Crohn’s disease (CD) patients who present to Emergency Department (ED) will undergo an abdominal CT to rule out disease compli-cations. We aimed to generate a simple non-invasive scoring model to predict the presence of an intra-abdominal abscess in CD patients in the ED. Methods: We performed a retrospective case control study at two Israeli hospitals from January 1st 2010 to May 30th 2018. Inclusion criteria included patients with an established diagnosis of CD that had cross-sectional abdominal imaging performed in the emergency room. Three hundred and twenty-two patients were included, of these eighty-one patients (25%) were diagnosed with an intra-abdominal abscess. Results: In univariate analysis, ileo-colonic location (OR = 1.88, p = 0.0148), perianal CD (OR = 7.01, p = 0.0004), fever (OR = 1.88, p = 0.0247), neutrophil-to-lymphocyte ratio (OR = 1.12, p < 0.0001), and C-reactive protein (OR = 1.10, p < 0.0001) were significantly associated with abscess formation, while, current use of corticosteroids was negatively associated with abscess formation (OR = 0.46, 95% CI: 0.2–0.88, p = 0.0192). We developed a diagnostic score that included the 5 parameters that were significant on multi-variate regression analysis, with assignment of weights for each variable according to the co-efficient estimate. A low cut-off score ≤ 7 was associated with a negative predictive value (NPV) of 93% for abscess formation, while a high cut-off score > 9 was associated with positive predictive value of 65%. We validated this score with an independent cohort with AUC of 0.881 and NPV of the low cut-off score of 98.5%. Discussion/Conclusion: We recommend incorporating this score as an aid for stratifying acutely-ill CD patients in the ED with low or high probability for presence of an intra-abdominal abscess.

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Macrophage activation syndrome: Rare cause of acute liver failure with uncertain prognosis Pavel Drastich (Prague, CZ), Jan Brezina (Prague, CZ), Lukas Bajer (Prague, CZ), Julius Spicak (Prague, CZ) Introduction: Macrophage activation syndrome (MAS), also known as secondary hemo-phagocytic lymphohistiocytosis (HLH) is poorly described life-threatening condition. It is caused by excessive activation of immune system with subsequent pro-inflammatory environment resulting in hemophagocytic macrophages appearance in various organs. Clinically, MAS is characterized mainly by fever, cytopenia, hepatosplenomegaly and elevated levels of circulating ferritin. MAS can develop into acute liver failure (ALF) with poor prognosis. Methods: We retrospectively analyzed patients referred to our transplantation center with ALF in which the diagnosis of MAS was confirmed by histology. The analysis was focused on diagnosis leading to MAS, survival, transplantation outcome and clinical, laboratory and histological findings. Results: From January 2005 to November 2018, we found five patients with MAS referred to our center with ALF. The primary cause was Epstein-Barr virus (EBV) infection in three cases and adult Still disease in two cases. All five patients had highly elevated levels of circulating ferritin (in average 20208 μg/l), leukocytosis and thrombocytopenia. All patients had at least one negative bone marrow or lymph node examination prior to definitive diagnosis of MAS. All five patients were treated with high-dose corticosteroids. Three patients met King's College criteria for urgent liver transplantation. Two of them were transplanted. Despite intensive therapy based on mechanical ventilation, continuous renal replacement therapy and circulation support, their clinical condition further deteriorated and all three patients died on average 38 days after symptom onset. At the autopsy, hemophagocytic macrophages have been identified in multiple organs. Two patients who responded to corticosteroid therapy are in long-term remission after specialized hemato-logical treatment with etoposide. Discussion/Conclusion: Macrophage activation syndrome as a rare cause of acute liver failure has high mortality, it is difficult to diagnose and even more difficult to treat. Our case studies suggest that when the patients with MAS meet King's College criteria, their prognosis is uncertain despite the successful liver transplant. Therefore, it is important to carefully consider liver transplantation in the case of MAS diagnosis. Supported by Ministry of Health of the Czech Republic, grant nr. 16-27449A. All rights reserved.

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The contribution of lower GI alarm symptoms as predictors for organic bowel diseases and exclusion factors for functional bowel diseases Yunduan He (Wuhan, CN) Introduction: To examine the utility of the individual lower gastrointestinal (GI) alarm symptoms as well as the combinations of these in predicting organic bowel diseases (OBDs) and/or excluding functional bowel diseases (FBDs) in the patients with symptoms compatible with FBDs. Methods: We collected data prospectively from 1005 adult patients with lower gastro-intestinal symptoms who completed colonoscopic evaluation. When necessary, histo-pathology was confirmed via biopsy specimens from colorectal lesion. The assessors were blinded to symptoms status. Calculate p value, sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) for individual alarm symptom as well as the combinations of them between OBDs and FBDs individuals. Results: There were 412 patients confirmed with OBDs. The sensitivities of six selected individual alarm symptoms which were statistically significant (p ≤ 0.001) via chi-square test ranged from 4.1% (recurrent fever) to 53.4% (age ≥ 50) and specificities from 61.2% (age ≥ 50) to 99.2% (recurrent fever). PPV for rectal bleeding was excellent (90.6%) and for age ≥ 50 was poor (48.9%). Combinations of the selected alarm symptoms had higher specificities and PPVs, but lower sensitivities. In addition, we found that the percentage of patients with an organic bowel disease was gradually increasing with more number of alarm symptoms and the difference was statistically significant. On the other hand, 31 of 129 (19.4%) with IBS symptoms meeting Rome IV criteria was confirmed as OBDs, but that of patients meeting Rome III criteria was slightly lower (17.4%) while no statistical significance existed. Discussion/Conclusion: The combinations of alarm symptoms improved specificity and PPV with low sensitivity. With the increase of the number of positive alarm symptoms, the possibility of OBDs increases accordingly.

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Profile of diverticular disease at Dr. Soetomo General Hospital Surabaya Indonesia Tri Asih Imroati (Surabaya, ID), Titong Sugihartono (Surabaya, ID), Budi Widodo (Surabaya, ID), Ulfa Kholili (Surabaya, ID), Ummi Maimunah (Surabaya, ID), Herry Purbayu (Surabaya, ID), Poernomo Setiawan (Surabaya, ID), Iswan Nusi (Surabaya, ID) Introduction: Diverticular disease and its complications have become a health burden throughout the world, and this disease is the most common condition in the Western world. Diverticulosis is a frequent finding in colonoscopy, and its prevalence is increasing with age. The purpose of this study was to determine the profile of patients with diverticular disease in Dr. Soetomo General Hospital Surabaya Indonesia. Methods: The data was taken from the patient's medical record at Gastrointestinal Endos-copic Center of Dr. Soetomo Teaching Hospital Surabaya in the period February 2018 to June 2019, who underwent upper or lower gastrointestinal tract endoscopy. Results: From 2309 endoscopies, we found that 49 patients had diverticulosis (2.12%). Women were more than men (65.31% vs. 34.69%). The youngest age was 30 years old, the oldest was 89 years old, with an average age of 59.86 ± 11.10 years. Diverticulosis was found most in patients with hematochezia complaints (28.57%), followed by com-plaints of abdominal pain (14.29%). Most diverticulosis was found in all colorectal segments (42.31%), then in the ascending colon (13.46%). The most common abnor-malities with diverticulosis were colitis/gastritis (37.73%). The most mucosal biopsy results around diverticulosis showed active chronic colitis (39.13%). Discussion/Conclusion: The prevalence of diverticulosis in Dr. Soetomo General Hospital Surabaya Indonesia was 2.12%. More women than men, with an average age of 59.86 ± 11.10 years. Most complaints of diverticulosis were hematochezia and abdominal pain. Diverticulosis was found in all segments of the colorectal, with the most common abnormalities that exist together was colitis/gastritis, with the most common anatomic histopathology results was active chronic colitis.

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Comparison of the quality of life in patients with IBD and IBS Michal Konecny (Olomouc, CZ) Introduction: Monitoring the quality of life (QoL), both in patients with IBD (inflammatory bowel disease) and IBS (irritable bowel syndrome), is currently an essential part of the assessment of patients' health condition and the effect of treatment. The aim of this study is to compare the QoL of patients with IBD with the QoL of patients with IBS. Methods: Patients aged 18–65 years were asked to complete the Item Health Survey (SF-36) in the course of an outpatient check-up. The questionnaire is made up of 36 questions divided into 8 dimensions (comparison to the condition a year ago, physical limitations, physical pain, general health, vitality, social functioning, emotional problems, mental health). The overall score below 50 points (maximum is 100) is considered to be below standards in a general population. A univariate and multivariate regression analysis was performed to evaluate the relationship between selected indicators of the quality of life. All factors with p < 0.05 in the univariate analysis were included in the multivariate model. Results: The survey was attended by 107 patients with an average age of 49.2 years, mostly from the Olomouc region. 56 patients had IBD (32 Crohn's disease, 24 ulcerative colitis), 51 patients had IBS (5 IBS-C, 31 IBS-D, 15 IBS-M). The statistically significant difference between IBD and IBS was in the dimension of body pain (worse QoL in IBD) and in the dimension of social functioning and emotional problems (worse QoL in IBS). There was no statistically significant difference when comparing the overall questionnaire scores for both patient groups (34.6 points for IBD versus 30.4 points for IBS). Discussion/Conclusion: Both IBD and IBS significantly reduce the QoL. The IBD pa-tients primarily suffer from abdominal pain and are limited in physical performance and the IBS patients suffer from psychological problems are lower possibility of integration into normal work and life.

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Emerging role of gut microbiota and SIBO in NAFLD development

Khrystyna Kvit (Lviv, UA), Natalia Kharchenko (Lviv, UA), Uliana Dorofeeva (Lviv, UA), Olga Chornenka (Lviv, UA)

Introduction: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disease worldwide. NAFLD patients are typically characterized with small intestine bacterial overgrowth (SIBO) that may impair the intestinal tight junction and sub-sequently increase intestinal permeability. The studies, dedicated to the microbiota com-position in patients with NAFLD are insufficient. Hence, there is an interest in exploring the fatty infiltration as the result of the syndrome, that includes bacterial composition disturbance, with profound analysis of preventive and aggressive factors that impact on liver disease occurrence and progress. The aim of this study was to analyze the gut micro-biota composition in patients with NAFLD with possible examination of aggressive and protective factors, including SIBO existence and biochemical markers.

Methods: 43 patients with hyperlipidemia with average age 46.97 ± 2.53. and BMI 27.43 ± 0.74 were examined in “Medicover Ukraine” (Lviv, Ukraine). The average waist circum-ference in main group was 91.6 ± 1.09 cm (in men), 83.3 ± 0.65 cm (in women). The exclusion criteria for both groups were – diabetes mellitus, viral hepatitis and autoimmune hepatitis during the last 10 years. All patients underwent biochemical evaluation - lipid profile, C-reactive protein, ALT, AST, GGTP, CRP, bilirubin (total, direct, indirect), apolipo-protein B, apolipoprotein A1. Determination of microbial composition at the level of major microbial phyla was carried out by identification of total bacterial DNA, and DNA of Bacte-roidetes, Firmicutes and Actinobacteria was performed with quantitative real-time PCR (qRT-PCR), using gene-targeted primers. Ultrasound examination was proved to all patients. The criteria for fatty infiltration existence was a diffuse increase in the echo-genicity of the liver parenchyma, decreased attenuation on the liver and ratio between the brightness level of the liver and the right kidney that was calculated for the hepato-renal index (HRI) determination. All subjects were examined by a lactulose breath test (LBT).

Results: The prevalence of SIBO in patients with NAFLD was 51.2%. The percent composition of microbiota included next proportions of bacteria – Bacteroidetes – 16.7 ± 2.99, Firmicutes – 45.3 ± 2.99, Actinobacteria – 25.9 ± 1.9, Firmicutes/Bacteroidetes ratio (F/B) – 6.47 ± 1.55.). Strong negative correlation between Bacteroidetes and Firmicutes (r = -0.93), Bacteroidetes and Firmicutes/Bacteroidetes index (r = -0.65) and Bacteroidetes and Actinobacteria (r = -0.89) was marked. Moreover, there was strong positive correlation among F/B index and triglycerides (r = 0.42) and ALT (r = 0.4). Additionally, there was middle-strong correlation between SIBO existence and Firmicutes increasing in patients with NAFLD (r = 0.39). According to different data, there are contra-dictory facts about F/B index in patients with NAFLD. However, most of the studies, show the potential exacerbating influence Firmicutes on the fatty infiltration progression. Some of the data suggests to include the F/B index to the list of early markers of NAFLD

 

presence. Regarding the previous data about the theory of “two-hit” theory, where tri-glycerides play one of the most essential roles, we’ve paid the attention to the fact of possible relationship between the part of microbes in this process. Moreover, there is an interesting point in SIBO existence and its connection with Firmicutes by widely-spread fact that SIBO is associated with gram-negative microflora, to which Firmicutes do not belong. So, we’ve tried to compare the group of patients with NAFLD and SIBO and NAFLD without SIBO with idea to find some features in gut microbiota composition, that could explain this relationship. There was no difference between these groups. Thus, we can suggest, that there is a violation in composition of some species of bacteria, not phyla, that are leading to SIBO occurrence especially in the background of NAFLD and it could be not only gram-negative bacteria, but gram-positive, that are associated with NAFLD. Discussion/Conclusion: The prevalence of SIBO in patients with NAFLD was 51.2%. The decreasing of Bacteroidetes leads to Firmicutes and Actinobacteria increasing, with F/B growth, that provokes triglycerides and ALT level raise in patients with NAFLD. The increasing of Firmicutes is associated with SIBO presence. F/B index could be the marker of NAFLD presence, while the Bacteroidetes are potentially preventive factors for NAFLD progression.

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Gut microbiota, SIBO and NAFLD – The risk and protective factors Khrystyna Kvit (Lviv, UA), Natalia Kharchenko (Kiev, UA), Uliana Dorofeeva (Lviv, UA), Olga Chornenka (Lviv, UA) Introduction: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disease worldwide. In addition to the well-established “two-hit” theory, the alteration of gut microbiota also promotes the development of NAFLD by mediating processes of inflammation. Moreover, the gut microbiota may affect all risk factors for the development of NAFLD by disturbing energy homeostasis, enhancing IR, increasing oxidative stress and evoking violation of bile acids and choline level. NAFLD patients are typically characterized with small intestine bacterial overgrowth (SIBO). Disturbances in the homeostasis between bacteria and host at the intestinal epithelial cell level may lead not only to altered intestinal barrier but also promote bacterial translocation from the gut into the portal circulation, with further inducing liver damage. The aim of this study was to analyze the gut microbiota composition in patients with NAFLD with possible exploration of aggressive and protective factors, including association of SIBO presence and bio-chemical markers correlational relationship. Methods: 43 patients with hyperlipidemia with average age 46.97 ± 2.53. and BMI 27.43 ± 0.74 were examined in “Medicover Ukraine” (Lviv, Ukraine). Biochemical evaluation in-cluded lipid profile, C-reactive protein, ALT, AST, GGTP, CRP, bilirubin (total, direct, in-direct), apolipoprotein B, apolipoprotein A1. Determination of microbial composition at the level of major microbial phyla was carried out by identification of total bacterial DNA, and DNA of Bacteroidetes, Firmicutes and Actinobacteria was performed with quantitative real-time PCR (qRT-PCR), using gene-targeted primers. Ultrasound examination was proved to all patients. The criteria for fatty infiltration existence was a diffuse increase in the echogenicity of the liver parenchyma, decreased attenuation on the liver and ratio between the brightness level of the liver and the right kidney that was calculated for the hepato-renal index (HRI) determination. All subjects were examined by a lactulose breath test (LBT). Results: In 51.2% of NAFLD patients the SIBO was diagnosed. The percent composition of microbiota included next proportions of bacteria – Bacteroidetes – 16.7 ± 2.99, Firmicutes – 45.3 ± 2.99, Actinobacteria – 25.9 ± 1.9, Firmicutes/Bacteroidetes ratio (F/B) – 6.47 ± 1.55.). Strong negative correlation between Bacteroidetes and Firmicutes (r = -0.93), Bacteroidetes and Firmicutes/Bacteroidetes index (r = -0.65) and Bacteroi-detes and Actinobacteria (r = -0.89) was marked. Moreover, there was strong positive correlation among F/B index and triglycerides (r = 0.42) and ALT (r = 0.4). Surprisingly, there was no correlational relationship between BMI and any of bacteria phyla. Discussion/Conclusion: The prevalence of SIBO on the background of NAFLD is 51.2%. The Firmicutes increasing leads to ALT and TG level growth, that is the factor of NASH risk. Simultaneously, the Firmicutes decreasing are strongly connected with Actino-

 

bacteria amount reduction, with Bacteroidetes increasing. Thus, Bacteroidetes could be the preventing factor of NAFLD progression, while the F/B index is potential marker of NASH progression in patients with NAFLD.

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Red blood cell distribution width and its derivatives as markers of liver fibrosis in non-alcoholic fatty liver disease patients Halina Lach (Lublin, PL), Agata Michalak (Lublin, PL), Małgorzata Guz (Lublin, PL), Joanna Kozicka (Lublin, PL), Marek Cybulski (Lublin, PL), Andrzej Stepulak (Lublin, PL) Introduction: An elevated level of red blood cell distribution width (RDW) was proposed to be a marker of liver fibrosis, however a little data concerns non-alcoholic fatty liver disease (NAFLD). Methods: The aim of our study was to verify the role of RDW, RDW to platelet ratio (RPR) and RDW to lymphocyte ratio (RLR) in the assessment of liver fibrosis in NAFLD patients. One hundred sixty persons were included to the study: 92 patients with NAFLD and 68 volunteers in control group. Hematological indices (RDW, RPR and RLR) were obtained from each participant. Indirect markers of liver fibrosis were also measured: AAR, APRI, FIB-4 and GPR (GGT to PLT ratio). Among direct indices of liver fibrosis, procollagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin were obtained. NAFLD fibrosis score and BARD score were calculated too. Achieved results were compared to controls. Then a correlation between evaluated indices was performed. Diagnostic value of each assessed hematological parameter together with a proposed cut-off in research group were measured with AUC (area under the curve). Results: RDW, RPR and RLR values were higher in NAFLD patients compared to controls (p < 0.05, p < 0.0001, p < 0.0001, respectively). RDW correlated positively with FIB-4 (p < 0.05) and RPR - with APRI (p < 0.0001). There was also a strong relationship between RPR and NAFLD fibrosis score (p < 0.0001). There were no correlations between RDW derivatives and direct markers of liver fibrosis. AUC values and proposed cut-offs for RDW, RPR and RLR in NAFLD patients were: 0.606 (> 12.8%), 0.724 (> 0.047%) and 0.691 (> 6.25%), respectively. Discussion/Conclusion: RDW derivatives could serve a role of potential markers of liver fibrosis in NAFLD patients.

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Usefulness of fecal calprotectin and C-reactive protein as disease activity biomarkers according to disease location in Crohn’s disease patients requiring surgical interventions of intestine Lyubov Lozynska (Lviv, UA), Rostyslav Lozynskyy (Lviv, UA), Orest Precel (Lviv, UA), Mariya Lozynska (Lviv, UA), Oleksiy Lukavetskyy (Lviv, UA) Introduction: Fecal calprotectin (FC) measured in feces can be helpful in differentiating functional from organic bowel disorders and has a good overall diagnostic precision in discriminating IBD from non-IBD diagnosis. The diagnostic usefulness of FC has been proven in several studies and may vary depending on the Crohn's disease (CD) location. C-reactive protein (CRP) is a serologic activity marker in CD, but it may be less useful in evaluating CD activity in patients with ileal location of the disease. The patients with ileal disease had significantly higher postoperative recurrence of CD rates compared to patients with ileocolonic or colonic disease. Our aim was to determine levels of CRP and FC as a disease activity markers in CD patients according to different disease localization in the patients needs surgical interventions of intestine. Methods: Ukrainian patients CD patients from of the Surgery Department of a single hospital were evaluated. Disease activity was assessed by using Crohn's Disease Activity Index (CDAI). Diagnosis of CD was based on the results of physical examination, labora-tory studies, endoscopic investigations – ileocolonoscopy, MR enterography and CT en-terography. The clinical phenotype of CD was evaluated according to the Montreal classifi-cation. The CRP test was performed in 47 patients and FC-test was carried out in 28 patients. FC concentration was assessed in single stool samples by using the ELISA method. Results: The elevated level of CRP was observed in 44.7% patients with ileocolonic involvement localization of the disease (L3), in 40.4% patients with colonic localization (L2) in comparing with 14.9% patients with terminal ileitis (L1) (p < 0.01). The average level of CRP was 34.2 ± 6.2 ml/l in the group of patients with CDAI > 150. In all patients with ileocolonic (L3) and colonic (L2) location an elevated CRP level were associated with elevated erythrocyte sedimentation rate (ESR) (p < 0.05). The surgical interventions underwent of 87.2% patients with elevated level of CRP. In all patients with CDAI > 150 higher levels of FC, CRP and ESR were detected. Among these patients 28.6% had ileal, 21.4% had colonic, and 50.0% had ileocolonic CD. The average level of FC in the patients with CDAI > 150 was 148.3 ± 10.5 mcg/g and with CDAI > 220 was 437.8 ± 71.8 mcg/g. FC concentration was highest among patients with CDAI > 220 with combined small and large bowel involvement (L3) – 480.9 ± 347.6 mcg/g when compared with both colonic (L2) – 431.1 ± 107.2 mcg/g and small bowel CD (L1) – 393.6 ± 122.6 mcg/g, but difference statistically not significant. The surgical interventions on intestine undewent in 85.7% of patients with higher initial level of FC and the rest of the patients also requiring surgical interventions on intestine.

Discussion/Conclusion: CRP level was highest among patients with ileocolonic involve-ment localization of the disease and with colonic localization when compared with terminal ileitis with statistical significance (p < 0.01). There are not statistically significant difference of FC concentration in CD patients with different disease location. FC equally useful in all СD locations. After treatment more often stable elevated level of FC, but not CRP and ESR was observed.

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The role of APC gene mutations in early onset of familial adenomatous polyposis and colorectal cancer in patients from Ukraine Mariya Lozynska (Lviv, UA), Lyubov Lozynska (Lviv, UA), Andrzej Plavski (Poznan, PL), Ihor Vitvytskyy (Lviv, UA), Rostyslav Lozynskyy (Lviv, UA) Introduction: Adenomatous polyposis syndromes of the colorectum are precancerous conditions characterized by the presence of hundreds to thousands of polyps. The major inherited monogenic form of adenomatous polyposis is familial adenomatous polyposis (FAP), caused by germline mutations in APC gene. Mutations within APC gene are con-sidered to be initiating events in colorectal tumorigenesis. In FAP patients, the risk of developing colorectal cancer (CRC) before age 20 is very low; however, up to 1.5% of CRC occur between 11 and 20 years of age. The goal of colorectal neoplasia manage-ment in FAP patients is to prevent CRC. Our aim was to study the correlation of APC gene mutations with FAP and CRC onset in patients and in their relatives, to estimate the individuals of the risk group. Methods: Diagnosis of FAP in probands is based on a suggestive family history, clinical findings and colonoscopy. Among 47 patients with FAP, including 25 probands and 22 relatives of the probands with FAP, 60.9% were males and 39.1% were females. The clinical diagnosis should be confirmed by genetic testing. The molecular genetic analysis of the peripheral blood was carried out. The amplified fragments of the APC gene were screened for the mutations using heteroduplex analysis (HD), detection of single-stranded conformational polymorphism (SSCP) and multiplex ligation-dependent probe amplifi-cation (MLPA) method. The anticipation index (A) was calculated. Results: The age of FAP onset was 36.0 ± 1.4 years in males, while in females the disease manifested earlier – at the age of 29.5 ± 2.4 years (p < 0.01). CRC was observed in 72.3% of patients among them were 73.5% males and 26.5% females. The average age at CRC diagnosis was 39.7 ± 1.9 years in males and 39.3 ± 3.6 years in females (p > 0.05). The APC mutations, including four novel mutations, were found in 36.0% of patients. The lowest average age of FAP onset was 23.7 ± 8.1 years observed in the family members carriers of the mutation с.3927_3931delAAAGA p.Q1309fs. The average age at CRC diagnosis was 37.0 ± 2.5 years (range 24–59 years) in patients with mutations, and in patients without mutations the disease diagnosis was established at the age of 40.5 ± 2.0 years (range 32–45 years) (p > 0.05). The youngest patient diagnosed with CRC was 24 years old female carrier the new mutation с.3931_3946delATTGGAACTAGGTCG, and the 25-year-old male carrier another new mutation с.3343delA p.R1114fs. The average age difference between FAP onset in the parents and their offspring was 12.0 ± 1.7 years. The anticipation index in FAP was 18.0%. In 3 of 4 families with new mutations carriers predominance of males (12:4) and antici-pation phenomenon were observed. The strongest age correlations of FAP onset were found in mother-offspring pairs (r = 0.80) and parents-son pairs (r = 0.58).

 

Discussion/Conclusion: There was no statistically significant difference between average age of the FAP and CRC onset in the patients carriers of APC mutations and in the patients without the mutations. The lowest age of CRC onset was observed in the patients with novel mutations of APC gene. In offsprings with FAP the reduced age of disease onset compared to the parents was revealed irrespective of the presence of the APC mutations. Accounting anticipation allows estimating the approximate average age at FAP onset during genetic counselling, and therefore timely to carry out targeted prevention.

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Optimal treatment option for anti-Helicobacter therapy in patients with Helicobacter-associated gastritis and concomitant diabetes mellitus type 2 Ganna Maslova (Poltava, UA), Igor Skrypnyk (Poltava, UA), T. Radionova (Poltava, UA) Introduction: Patients with diabetes mellitus (DM) type 2 are referred to the category with high risk of antibiotic resistance formation, which is the leading cause for anti-Helicobacter pylori therapy (AHT) inefficacy. Aim: to substantiate the choice of the optimal AHT scheme for the treatment of Helicobacter pylori-associated (HP+) gastritis in patients with DM type 2. Methods: 84 patients with DM type 2 and concomitant HP+ chronic gastritis were examined. The ratio of men and women was 41 (48.8%) / 43 (51.2%), mean age – 56.1 ± 10.8 years. The duration of DM type 2 was 9.4 ±4.31 years, DM type 2 was at the stage of subcompensation: the level of НBА1с ≤ 7.5%, without ketoacidosis. Correction of carbohydrate metabolism was performed by combination of oral hypoglycemic agents. On the basis of prescribed AHT regimen the patients were subdivided onto 4 groups: І (n = 20) – pantoprazole 80 mg/day, amoxicillin 2000 mg/day, clarithromycin 1000 mg/day – for 10 days; II (n = 22) – pantoprazole 80 mg/day, amoxicillin 2000 mg/day, clarithromycin 1000 mg/day – for 14 days; III (n = 20) – pantoprazole 80 mg/day, tetracycline 2000 mg/day, metronidazole 1500 mg/day, colloidal bismuth subcitrate 480 mg/day – for 10 days; IV (n = 22) – pantoprazole 80 mg/day, tetracycline 2000 mg/day, metronidazole 1500 mg/day, colloidal bismuth subcitrate 480 mg/day – for 14 days. The control of AHT efficacy was conducted in 4 weeks after it had been completed. Results: In patients with DM type 2 and associated HP+ chronic gastritis, who underwent standard triple AHT according to Maastricht V Consensus, in 28 days HP eradication was achieved in 12 (60%) patients of the group I and in 16 (72.2%) patients of the group II. Thus, prolongation of triple AHT from 10 to 14 days leads to increased efficacy of HP eradication for 12.2% (р > 0.05). Among the patients who took quadruple AHT according to Maastricht V Consensus, in 4 weeks HP eradication was achieved in 14 (70%) patients of the group ІІІ and in 20 (90.9%) patients of the group ІV, therefore prolongation of quadruple AHT from 10 to 14 days allows to improve efficacy of HP eradication for 20.9% (р < 0.05). To summarize, prescription of the quadruple regimen of AHT, according to the Maastricht V Consensus, for 14 days in patients with DM type 2 and concomitant HP (+) gastritis significantly increases an efficacy of HP eradication in comparison to the triple AHT for 10 days (RR = 1.5; 95% CI: 1.03–2.21; p < 0.05). Discussion/Conclusion: Quadruple regimen of the Maastricht V Consensus with optimal treatment duration for 14 days should be recommended to the patients with DM type 2 and concomitant HP (+) chronic gastritis as an AHT option.

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Hematological scales in the assessment of liver fibrosis in non-alcoholic liver disease patients Agata Michalak (Lublin, PL), Halina Cichoż-Lach (Lublin, PL), Małgorzata Guz (Lublin, PL), Joanna Kozicka (Lublin, PL), Marek Cybulski (Lublin, PL), Andrzej Stepulak (Lublin, PL) Introduction: Mean platelet (PLT) volume (MPV) to PLT ratio (MPR), neutrophil to lymphocyte ratio (NLR) and PLT to LYM ratio (PLR) have been discussed as potential markers of liver fibrosis, recently. Methods: The goal of our survey was to verify the diagnostic accuracy of MPR, NLR and PLR in the assessment of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) patients and to compare it with serological: indirect and direct markers of liver fibrosis. One hundred sixty participants were enrolled to the study: 92 with NAFLD and 68 healthy volunteers in control group. Hematological indices (MPR, NLR and RLR) were measured in each person. Indirect markers of liver fibrosis were also obtained: AAR, APRI, FIB-4 and GPR (GGT to PLT ratio). Among direct indices of liver fibrosis, procollagen I carboxy-terminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin were assessed. NAFLD fibrosis score and BARD score were calculated too. Results: NLR level in NAFLD patients was higher in comparison to controls (p < 0.0001). MPR and PLR values did not differ significantly. MPR correlated positively with indirect markers of liver fibrosis - APRI (p < 0.0001), FIB-4 (p < 0.0001) and GPR (p < 0.01). A strong positive relationship between MPR and NAFLD fibrosis scale was noted, too (p < 0.0001). No correlations between assessed hematological indices and direct marker of liver fibrosis were found. AUC values and proposed cut-offs for MPR, NLR and PLR in NAFLD patients were: 0.547 (> 0.038), 0.725 (> 2.034%) and 0.528 (> 97.101%), respec-tively. Discussion/Conclusion: Diagnostic accuracy of NLR in the assessment of liver fibrosis in examined NAFLD patients turned out to be quite accurate.

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Indirect and direct markers of liver fibrosis – A study on alcoholic liver cirrhosis Agata Michalak (Lublin, PL), Halina Cichoż-Lach (Lublin, PL), Małgorzata Guz (Lublin, PL), Joanna Kozicka (Lublin, PL), Marek Cybulski (Lublin, PL), Andrzej Stepulak (Lublin, PL) Introduction: Investigations comparing the usefulness and diagnostic accuracy of indirect and direct markers are still required in hepatology. Methods: We aimed to compare diagnostic accuracy of indirect and direct indices of liver fibrosis in alcoholic liver cirrhosis (ALC) patients. Two hundred ten persons were enrolled to the survey: 142 patients with ALC and 68 volunteers in control group. Indirect markers of liver fibrosis were measured: AAR, APRI, FIB-4 and GPR (GGT to PLT ratio). Among direct indices of liver fibrosis, procollagen I carboxyterminal propeptide (PICP), procolla-gen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin were obtained. MELD score was calculated too. Achieved results were compared to controls. Diagnostic value of assessed parameters together with a proposed cut-off in research group were measured with AUC. Results: The level of Indirect markers was significantly higher in ALC group compared to controls (p < 0.0001). PIIINP (p < 0.01), PDGF-AB (p < 0.001) and TGF-α (p < 0.0001) values were lower in comparison to controls and laminin level was higher (p < 0.05). PICP value did not differ significantly. PDGF-AB correlated negatively with FIB-4 (p < 0.005). Negative relationships were observed between TGF-α and both: APRI (p < 0.05) and FIB-4 (p < 0.01). Laminin correlated positively with AAR (p < 0.005). MELD score corre-lated positively with indirect markers (p < 0.0001). Negative dependence was found between MELD score and PIIINP (p < 0.01). AUC values and proposed cut-offs for the most powerful indirect and direct indices of liver fibrosis in ALC were: GPR (0.992; > 0.553), FIB-4 (0.980; > 1.396), PDGF-AB (0.663; < 25,171.82 pg/ml) and PIIINP (0.630; < 28.65 ng/ml). Discussion/Conclusion: Indirect markers of liver fibrosis in examined ALC patient had significantly greater diagnostic value than direct markers.

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Platelet indices as potential markers of liver fibrosis in the course of non-alcoholic fatty liver disease Agata Michalak (Lublin, PL), Halina Cichoż-Lach (Lublin, PL), Małgorzata Guz (Lublin, PL), Joanna Kozicka (Lublin, PL), Marek Cybulski (Lublin, PL), Andrzej Stepulak (Lublin, PL) Introduction: Platelet (PLT) indices have been proved to correlate with the progression of liver fibrosis. Methods: The goal of our survey was to verify PLT indices in the evaluation of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) patients and to compare them with serological indices of liver fibrosis. One hundred sixty persons were enrolled to the study: 92 with NAFLD and 68 healthy volunteers in control group. Hematological indices were assessed: mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT). Indirect markers of liver fibrosis were also assessed: AAR, APRI, FIB-4 and GPR (GGT to PLT ratio). Among direct indices of liver fibrosis, procollagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin were obtained. NAFLD fibrosis score and BARD score were calculated too. Achieved results were compared to controls and between ALC and NAFLD groups. Then a correlation between evaluated indices was performed. Diagnostic value of each assessed parameter together with a pro-posed cut-off in research group were measured with AUC. Results: MPV and PDW values in NAFLD group were higher (p < 0.0001 and p < 0.01, respectively) and PCT - lower (p < 0.01). PDW correlated positively with indirect markers of liver fibrosis (APRI and FIB-4; p < 0.05) and PCT - negatively (APRI - p < 0.01, FIB-4 - p < 0.0001). There were negative relationships between: PCT and NAFLD fibrosis score (p < 0.0001) and between PCT and laminin (p < 0.05). AUC values and proposed cut-offs for MPV, PDW and PCT in NAFLD patients were: 0.808 (< 7.9 fl), 0.643 (> 52.8%) and 0.622 (< 0.23%), respectively. Discussion/Conclusion: MPV was found to have the greatest clinical accuracy in the examined NAFLD patients.

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Red blood cell distribution width and its derivatives as predictors of fibrosis and clinical outcome in alcoholic liver cirrhosis patients Agata Michalak (Lublin, PL), Halina Cichoż-Lach (Lublin, PL), Małgorzata Guz (Lublin, PL), Joanna Kozicka (Lublin, PL), Marek Cybulski (Lublin, PL), Andrzej Stepulak (Lublin, PL) Introduction: Higher values of red blood cell distribution width (RDW) and its derivatives have been proposed as predictors of poor survival in cirrhotic patients, recently. Methods: The aim of our survey was to assess the utility of RDW, RDW to platelet ratio (RPR) and RDW to lymphocyte ratio (RLR) in the evaluation of liver fibrosis in alcoholic liver cirrhosis (ALC) patients. We also aimed to assess a relationship between above-mentioned parameters and clinical progression of ALC (MELD score). Two hundred ten persons were included to the study: 142 patients with ALC and 68 volunteers in control group. Hematological indices (RDW, RPR and RLR) were obtained from each participant. Indirect markers of liver fibrosis were also measured: AAR, APRI, FIB-4 and GPR (GGT to PLT ratio). Among direct indices of liver fibrosis, procollagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin were obtained. Achieved results were compared to controls. Diagnostic value of each assessed hematological parameter together with a proposed cut-off in research group were measured with AUC. Results: RDW, RPR and RLR values were higher in ALC patients compared to controls (p < 0.0001). There were strong positive correlations between RPR and indirect markers of liver fibrosis - FIB-4 and RPR (p < 0.0001). RDW and RPR correlated negatively with PDGF-AB (p < 0.01 and p < 0.0001, respectively). Positive relationship was observed between RPR and MELD score (p < 0.01). AUC values and proposed cut-offs for RDW, RPR and RLR in ALC patients were: 0.912 (> 14.2%), 0.965 (> 0.075) and 0.914 (> 8.684), respectively. Discussion/Conclusion: RDW and its derivatives seem to be powerful diagnostic markers of liver fibrosis in ALC patients. They might also reflect a decompensation of liver function in this group.

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Case report: A patient from Moscow with unclear abdominal pain Andrey Mitroshkin (Baden-Baden, DE) Introduction: A 59-year-old lady with a history of chronic low back pain presented to our hospital with crampy, intermittent abdominal pain for a second opinion. The complaints have been steadily increasing over the last six months. Three months before the current presentation a colonoscopy, gastroscopy, ultrasonography and abdominal CT scan have been performed, no abnormalities have been revealed. Blood levels of electrolytes, liver enzymes and lipase were normal, as were the complete blood count, LDH and CRP. We performed an abdominal MRI incl. MR-angiography, which did not show any pathological findings, except for an activated lumbal spondylarthrosis and L4/5 disc herniation. Especially no stenosis of the abdominal vessels could be detected. As the patient already visited many internationally renowned hospitals and underwent numerous examinations incl. repeated GI-endoscopy, CT-scans and functional tests, which all could not explain the chronically progredient symptoms, we decided to perform an intestinal capsule endoscopy. It revealed multiple small bowel strictures. The patient confirmed high-dose NSAID-intake due to the low back pain over the last two years. We diagnosed NSAID-induced enteropathy. The patient reported a significant improvement 12 weeks after discontinuation of NSAID’s and orthopedical treatment. Results: Non-steroidal anti-inflammatory drugs are some of the most frequently prescribed drugs in the world; they are well known to be associated with various upper gastrointestinal complications. The adverse events can also affect the small intestine and colon. New endoscopic techniques such as capsule endoscopy can help in detecting the small bowel injuries. Recent data suggest that NSAID-induced enteropathy may be as frequent as upper GI complications. The pathogenesis of NSAID-induced small bowel injuries is complex, effective prevention measures have not been yet found. NSAID-induced enteropathy should be always ruled out in patients with unclear abdominal symptoms*. *In addition to case report, the poster will summarize the current data on epidemiology, pathogenesis, clinical manifestations, differential diagnosis, and treatment strategies of NSAID-induced enteropathy. QR-Code will allow the colleagues to see a YouTube-video with the typical small bowel lesions detected by the capsule endoscopy,

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Exploitation of deubiquitinylase A20 as novel biomarker for prognosis of gastritis Michael Naumann (Magdeburg, DE) Introduction: Gastritis represents an abundant inflammatory disease. Herein, high salt diet, sedentary lifestyle and other circumstances represent high risk factors for the development of gastritis, but also gastric cancer. Another risk factor is the microbial pathogen Helicobacter pylori which colonizes the gastric epithelial cells. The incidence of H. pylori infection is > 50% in the world. Colonization of gastric cells of the pit- and gland types in gastric foveolae by the human pathogen H. pylori impairs gastric barrier function and represents a risk factor for chronic gastritis, cellular dysplasia, and gastric cancer. H. pylori, but also a number of other environmental factors trigger the activation of the immediate early response factor nuclear factor kappa B (NF-κB), which could lead to inflammation in the gastric mucosa. Continuous inflammation causes chronic gastritis and NF-κB regulated cell survival genes could promote the development of neoplasia and gastric adenocarcinoma. Thus, apart of a healthy diet, also suitable novel predictive bio-markers, and therapeutic lead structures are requested to support diagnosis and therapeutic medication. Methods: Within a systems wide siRNA screen we identified a number of deubiquitinyla-ses (DUBs), molecules which affect the activity of NF-κB and inflammation in gastric epithelial cells. Molecular studies (Immunoblot, immunoprecipitation, electrophoretic mobilty shift, PCR etc.) in cell lines, and the analysis of patient samples by immunohisto-chemistry defined the role of these DUBs in gastritis. Results: Based on our long standing experience in H. pylori and gastric research we discovered within a systems wide siRNA screen a number of molecules which affect the activity of NF-κB and cell survival in gastric cells. Prominently, NF-κB is regulated by covalent conjugated proteins, e.g. ubiquitin or NEDD8. These modifications are directed by E3 ligases and counteracted by deubiquitinylases (DUBs), which control the trans-criptional activity of NF-κB. We studied the function of the DUB molecule A20 and in human gastric biopsies we observed in “H. pylori gastritis” and “adenocarcinoma” groups, 48.6% and 79.5% of specimens, respectively, were strongly positive for A20. Discussion/Conclusion: Overall, our studies provide novel insights in the molecular pathogenesis of gastritis, which allowed the definition of DUBs as novel predictive bio-markers.

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Human leukocyte antigens celiac haplotypes: From etiological factors to diagnostic approaches in Romanian patients Roxana Nemteanu (Iasi, RO), Alina Plesa (Iasi, RO), Petru Cianga (Iasi, RO), Anca Trifan (Iasi, RO), Andreea Clim (Iasi, RO), Liliana Gheorghe (Iasi, RO), Irina Ciortescu (Iasi, RO) Introduction: Celiac disease (CD) is an autoimmune enteropathy caused by gluten ingestion in genetically susceptible individuals. Genetic susceptibility to CD has been associated with human leukocyte antigen (HLA)-DQ2 heterodimer, encoded by the DQA1*05 and DQB1*02 genes. Our aim was to investigate whether the DQB1*02 allele could influence anti-tissue transglutaminase (tTG) titres in adult patients with CD. Methods: A total of 75 patients with established CD, tested for tTG antibodies at diag-nosis, were typed for HLA-DQA1, and -DQB1 genes, and divided according to the number of DQB1*02 alleles: group 1, homozygous; group 2, heterozygous; group 3,no gene. Results: We report that the mean of tTG antibody indexes was not significantly higher in group 1 patients than in group 2 (118.90 ± 93.98 versus 142.45 ± 100.24, p = 0.529), or group 3 patients (90.74 ± 91.87 versus 142.45 ± 100.24, p = 0.221). Nevertheless, patients in group 1 showed more severe histological lesions (Marsh3a–c) compared to those in the other groups. When assessing disease phenotype, the carriage of 2 copies was associated with the presence of anemia, abdominal pain, weight loss, and chronic diarrhea. Discussion/Conclusion: The study demonstrates that tTG titres are not significantly influenced by the number of HLA-DQB1*02 copies. Moreover, individuals with at least 1 HLA-DQB1*02 allele tend to have a higher degree of histological damage and different clinical features compared to those carrying other alleles.

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Intestinal recovery after treatment with a gluten-free diet among adult patients with celiac disease Roxana Nemteanu (IASI, RO), Alina Plesa (Iasi, RO), Cristina Gorincioi (Iasi, RO), Cristina Sfrijan (Iasi, RO), Bogdan Mazilu (Iasi, RO), Andreea Clim (Iasi, RO), Anca Trifan (Iasi, RO) Introduction: A small subset of celiac disease (CD) patients becomes refractory to a gluten-free diet with persistent intestinal villous atrophy (VA). We aim to assess the prevalence of RCD in a cohort of CD patients. Methods: The study included adult patients with biopsy proven CD evaluated at a tertiary referral center between October, 2012- October, 2018. Follow-up biopsy were dichoto-mized into persistent VA (Marsh 3a–c class) or improvement (Marsh 0–2). RCD can be classified as type 1 (normal intraepithelial lymphocyte phenotype), or type 2 (defined by the presence of abnormal (clonal) intraepithelial lymphocyte phenotype). Results: The initial histopathology showed complete VA (Marsh 3c) in 34 (33.3%), subtotal (Marsh 3b) in 18 (17.6%) cases, partial VA (Marsh3a) in 27 (26.5%) cases, while the reminder had mild enteropathy (Marsh I, II) in 23 (22.5%) cases. Ninety-three (91.2%) patients underwent a follow-up appointment. Among them, approximately two-thirds (n = 68, 66.7%) of patients had at least one follow-up biopsy. Among the 68 of 102 patients with a follow-up biopsy after initiation of GFD, 25 (59.5%) had some degree of intestinal villous atrophy (Marsh type 3). Total VA was confirmed in 3 (7.1%) of patients. Follow-up biopsy demonstrated persistent VA in 14 (56%) patients. Patients with partial VA on the initial diagnostic biopsy were less likely to have persistent VA on follow-up biopsy than those who originally had total/subtotal VA (p = 0.003). Discussion/Conclusion: It is currently unknown whether mucosal recovery or complete mucosal healing is actually linked to survival among patients with CD. Intact mucosa has remained a desirable goal of the therapy.

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Evaluation of mindfulness-based cognitive therapy in patients with functional dyspepsia in a tertiary referral center in Singapore

Yi Kang Ng (Singapore, SG), Andrew Ming Liang Ong (Singapore, SG), Ying Hao (Singapore, SG), Kinjal Doshi (Singapore, SG), Yu Tien Wang (Singapore, SG)

Introduction: Functional dyspepsia (FD) is a disorder of the brain-gut axis characterized by symptoms of abdominal discomfort. Mindfulness-based therapies use meditation and relaxation to achieve a state of consciousness, mindfulness, during which one consciously attends to his or her moment-to-moment experience. Its efficacy for FD treatment is uncertain.

Methods: To determine the effectiveness of group mindfulness based intervention in im-proving the symptoms and quality of life in patients with functional dyspepsia. We per-formed an assessor-blinded randomized treatment-as-usual waitlist controlled trial. Patients who fulfilled Rome-3 FD were prospectively recruited from a tertiary care gastro-enterology unit in Singapore and randomized to undergo Mindfulness Based Cognitive Therapy (MBCT) or Treatment-as-Usual (TAU). Subjects in the MBCT arm underwent weekly 2-hour-long standardised MBCT sessions for 8 weeks and 1 half-day retreat conducted by 2 accredited psychologists. Outcomes were assessed using Short Form Nepean Dyspepsia Index (NDI-SF) and the EuroQOL VAS scale which were administered pre and post treatment by assessors blinded to the treatment assignment. The primary outcome was change in NDI-SF and EuroQoL at end of treatment compared to baseline. Ethics Board review was obtained.

Results: Fifty-three patients were referred and 27 (59.9%) patients were recruited over 3 months. Amongst those who did not agree to recruitment, 10 were not fluent in English, 10 cited time constraints and unsuitability of the MBCT schedules, and 6 had no cited reasons. 21 of 27 patients (78%) completed the intervention. Of those who withdrew, 5 found difficulty in attending the intervention schedule due to time commitments, 1 had difficulty in following with the intervention instructions, 1 lost interest, and 2 were unable to complete “homework” due to time constraints. There was significant difference in change of NDI-SF at end of treatment compared to baseline between MBCT and TAU (mean change: -11.33 [7.53] vs. -2.0 [9.16], p < 0.01) (see table) indicating that partic-ipants in the MBCT arm experienced a greater symptom improvement as compared to those in the TAU arm. There was no significant difference in change of EuroQOL VAS scale between baseline and post-treatment assessment between groups.

Discussion/Conclusion: FD patients who underwent MBCT experienced a greater im-provement in their symptoms compared to those in the TAU arm. Language proficiency and time constraints were the major barriers to attendance of MBCT. Modifications to the intervention to address these limitations and careful patient selection should be con-sidered in future studies.

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Evaluation of MCAM protein in gastric cancer with correlation of Helicobacter pylori infection Marcin Nizioł (Białystok, PL), Justyna Zińczuk (Białystok, PL), Konrad Zaręba (Białystok, PL), Wiktoria Ustymowicz (Białystok, PL), Magdalena Misiura (Białystok, PL), Katarzyna Guzińska-Ustymowicz (Białystok, PL), Anna Pryczynicz (Białystok, PL) Introduction: Helicobacter pylori is recognized as a first class carcinogen in the develop-ment of gastric cancer. Its presence in the stomach mucosa causes the inflammation, ulceration and, as a consequence, the development of cancer. The MCAM protein is an adhesion molecule. It is expressed in many cancers, including gastric cancer. In addition, the presence of this protein has been found on CD4+ and CD8+ T lymphocytes. Mainly CD4+ lymphocytes are recruited to the inflammation of the gastric mucosa caused by H. pylori infection. Methods: The aim of the study was to evaluate the MCAM protein expression in gastric cancer and to investigate the correlation between MCAM expression and varying grades of H. pylori infection. The research was performed on a group of 87 patients diagnosed with gastric cancer. Expression of the MCAM protein was evaluated using the immuno-histochemical method. The presence of protein in ≥ 10% of tumor cells was considered as a positive reaction. Expression was correlated with the 4 grades of H. pylori infection. Results: Positive expression of MCAM was observed in 42.5% of patients with gastric cancer. Positive reaction for MCAM protein was detected in 37.88% of patients without H. pylori infection, 53.85% of patients with medium-grade infection and in 83.33% of patients with a high-grade infection (p = 0.037). Discussion/Conclusion: The result of the presented studies shows that the positive expression of MCAM protein is observed more often in patients with a higher degree of H. pylori infection. It suggests that presence of expression of this protein is associated with a higher risk of developing gastritis, and consequently, progression to gastric cancer. Moreover, this result may indicates that the MCAM protein may be involved in the develop-ment of cancer. However, in-depth research is needed to discover the mechanism of this reaction.

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Cutaneous manifestations of Waldenström’s macroglobulinemia and hepatitis C virus – Clinical case Alina Plesa (Iasi, RO), Cristina Gorincioi (Iasi, RO), Cristina Sfrijan (Iasi, RO), Bogdan Mazilu (Iasi, RO), Andreea Clim (Iasi, RO), Roxana Nemteanu (Iasi, RO) Introduction: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by the accumulation of malignant immunoglobulin Type M (IgM)-producing lymphocytes, and lymphoplasmacytic and plasma cells. Dermatologic conditions with WM are rare appearing in only about 5% of cases, and the skin should be surveyed looking for purpura, rash, or bruising. Methods: A 63-year-old female presented with bilateral neck swelling, intermittent fever, and fatigue of 3-year duration. She had a history of viral C hepatitis and pruritic papules and plaques of the face, trunk and extensor areas for which she was seen by different medical experts. Routine laboratory studies and a patch test were performed, but no specific findings were noted, except for mild anemia as hemoglobin (Hb) 10.6 g/dl. Liver function tests including viral load were normal, but high levels of serum IgM were noted. Results: A complete CT scan was performed but no masses or tumors were identified. Lymphocytosis was shown on the peripheral blood smear, the serum IgM level was elevated, and serum electrophoresis revealed a monoclonal peak at the β1 region (M-protein 27%, 2.6 g/dl). Bone marrow biopsy revealed 80% cellularity showing lymphoid cell aggregation with CD20+, CD79a+, and CD5-. A skin biopsy was also performed and it showed an atypical lymphocytic proliferation. Discussion/Conclusion: Hepatitis C virus is more weakly associated with Walden-ström’s macroglobulinemia, T-cell lymphomas, and other monoclonal gammopathies. The clinical presentation is variable and may include symptomatic cytopenias, hyperviscosity, extramedullary disease, and patient management requires regular evaluation with a multi-disciplinary team.

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Expression of VDR receptor in inflammatory bowel diseases Anna Pryczynicz (Bialystok, PL), Marcin Nizioł (Bialystok, PL), Justyna Zińczuk (Bialystok, PL), Konrad Zaręba (Bialystok, PL), Wiktoria Ustymowicz (Bialystok, PL), Katarzyna Guzińska-Ustymowicz (Bialystok, PL) Introduction: Crohn's disease (CD) and ulcerative colitis (UC) are classified as non-specific inflammatory bowel diseases (IBD). Both of these disease are chronic and the etiopathogenesis is not fully known. Vitamin D is one of the vitamins that belong to the fat-soluble group. Its primary function in the body is regulation of homeostasis of calcium and phosphate metabolism, which translates into the correct functioning of the intestines, bones and kidneys. The biological activity of vitamin D depends on the presence of the VDR receptor. This receptor can be found primarily in the intestinal epithelium, bones or renal tubules but also in the skin, skeletal muscle, brain, large intestine, nipple, prostate. It acts as a transcription factor. VDR is important in the action of vitamin D on the human body by regulating the expression of many genes involved in the calcium-phosphate economy and the genes involved in differentiation, cell proliferation and immune response. The aim of the study was the immunohistochemical evaluation of the receptor for vitamin D in inflammatory bowel diseases. Methods: We analyzed 29 cases of ulcerative colitis and 11 cases of CD. In the endo-scopic preparations the expression of the vitamin D receptor was assessed by immuno-histochemistry. The staining reaction was observed in the glandular epithelium and was assessed as weak (present in single glandular cells or in < 10 positive cells in the field of view) or strong (diffuse reaction or ≥ 10 positive cells in the field of view) in UC. Whereas in CD reaction was absent, weak (reaction of VDR protein present in < 5 cells in the field of view) or medium (reaction of VDR protein present in ≥ 5 cells in the field of view). Expression of VDR was correlated with age, sex and GUPTA classification. Results: In UC the expression of VDR receptor was rather strong (75.9% positive cases), whereas in CD expression of VDR was absent in 9.1% cases, weak in 63.6% cases and medium in 27.3% cases. There were no correlations between expression of VDR expres-sion and sex or age of patients. A significant relationship was observed between VDR expression and GUPTA classification in UC. VDR receptor expression was more likely to be strong in patients with active inflammation, while poor VDR expression was more common in people with inactive inflammation. Discussion/Conclusion: There is noticeable different expression of the VDR receptor in ulcerative colitis compared to Crohn's disease. In UC, expression was dispersed, whereas in CD expression was observed in single cells, which may indicate a different mechanism of these inflammations. In ulcerative colitis, inflammation activity according to GUPTA classification may affect the increase of VDR receptor expression in the glandular cells of the intestinal mucosa.

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The role of serum S100A12 (calgranulin C) as a diagnostic marker in Egyptian patients with irritable bowel syndrome and ulcerative colitis Yasser Rashid (Sohag, EG) Introduction: S100A12, a proinflammatory protein secreted by granulocytes, is known to be elevated in different diseases of inflammatory origin, including inflammatory bowel disease (IBD). Aims: To evaluate the role of serum S100A12 as a diagnostic marker in patients with irritable bowel syndrome (IBS) and IBD. Methods: A cross-sectional study was conducted on 70 persons who fulfilled the designed inclusion criteria and were classified into four groups: group I included 10 healthy persons; group II included 20 patients known to have IBS; group III included 20 patients known to have ulcerative colitis (UC) in remission; and group IV included 20 patients known to have UC in active state. Serum S100A12 level was measured in all patients using a highly sensitive enzyme-linked immunosorbent assay. Results: The mean serum S100A12 level for UC patients in exacerbation was 83.93 ± 30.78 pg/ml, UC patients in remission 64.03 ± 19.87 pg/ml, the mean value of serum S100A12 was 47.73 ± 11.15 pg/ml in the IBS group, and the mean value for the control group was 45.32 ± 8.60 pg/ml. So, there is a significant high level of serum S100A12 in UC groups compared with the IBS group and the control group. Serum S100A12 levels were significantly higher in active UC patients compared with IBS/healthy controls (p < 0.01). Serum S100A12 levels were significantly higher in UC in remission compared with the IBS and control groups (p < 0.05). Serum S100A12 levels were significantly higher in active UC compared with UC in remission (p < 0.05). There is no significant difference between the IBS group and the control group regarding serum S100A12 levels (p > 0.05). The performed analysis also focused on the determination of a cutoff for UC prediction that would exhibit the highest possible sensitivity and specificity. This optimal cutoff was estimated at 52.8 pg/ml with a sensitivity and a specificity of 80 and 75%, respectively. Discussion/Conclusion: Serum S100A12 can be used as a non-invasive marker to distinguish UC from IBS. Discussion: IBD remains a diagnostic challenge for the clinician who faces a repertoire of diverse and fluctuating symptoms and signs. It is mainly due to a subtle or atypical presentation that in some cases the discrimination of Crohn’s disease (CD) or UC, from other diseases of the alimentary tract, especially from IBS, becomes rather problematic [12].Around one-third of patients with IBD experience persistent gastrointestinal tract symptoms similar to IBS in the absence of objective evidence of disease activity [13].

 

The presenting symptoms of IBS and IBD can be similar, distinguishing them on the basis of clinical signs and symptoms can be difficult until recently colonoscopy was often used to rule out IBD [14].Several markers are used for diagnostic purposes. A simple, economic, and reliable test as an alternative to more complex procedures for IBD diagnosis is still under investigation [15]. IBD has been long ago recognized as a systemic inflammatory entity and, as such, it is anticipated to induce changes exceeding the boundaries of bowel mucosa, being reflected in a broader spectrum of tissues, including blood [5]. Intestinal inflammation in UC is characterized by an influx of neutrophils into the intestinal mucosa, thereby altering the intestinal barrier function during IBD [16]. S100A12 is a calcium-binding protein with proinflammatory properties. It is secreted by activated neutrophils and interacts with the multiligand receptor for advanced glycation end products (RAGE) [17]. There are numerous studies examining the significance of several fecal, serum, or mucosal markers including members of the S100 protein family such as S100A8/9 and S100A12 [9]. The vast majority of available literature is focused on S100A8/9 [10] and to a lesser extent on S100A12 and their role in IBD [11]. Our aim in the current case-control study was to investigate serum S100A12 levels in patients with UC during exacerbation and remission and comparing with those obtained from patients with IBS, and control persons and to detect its sensitivity and specificity as a non-invasive biomarker in the identification of such patients. The results of our study have shown that there was a significant high level of serum S100A12 in UC groups compared with the IBS group and the control group as the mean serum S100A12 level for UC patients in exacerbation was 83.93 ± 30.78 pg/ml, UC patients in remission 64.03 ± 19.87 pg/ml, and the mean value of serum S100A12 was 47.73 ± 11.15 pg/ml in the IBS group and the mean value for the control group was 45.32 ± 8.60 pg/ml. The performed analysis also focused on the determination of a cutoff for UC prediction that would exhibit the highest possible sensitivity and specificity. This optimal cutoff was estimated at 52.8 pg/ml. These results support the role of serum S100A12 in differentiating between UC and IBS. Our results are in agreement with those conducted by Manolakis et al. [18], who found that there was significantly higher serum S100A12 in the IBD group compared with the IBS group. Manolakis et al. [18] determined the serum S100A12 in a total of 201 patients of whom 64 patients were with UC, 64 with CD, and 73 with IBS patients, who are sex-matched and age-matched with the IBD groups. The study reported that a significant elevation in serum S100A12 levels which correlated well with IBD but not with IBS. The median values of serum S100A12 levels were 68.2 ng/ml (range, 43.4–147.4 ng/ml) in UC, 70 ng/ml (range, 41.4–169.8 ng/ml) in CD, and 43.4 ng/ml (range, 34.4–74.4 ng/ml) in IBS patients. UC and CD patients had significantly higher serum S100A12 levels compared with IBS patients, thus allowing the distinction between the two entities. The optimal cutoff was estimated at 54 ng/ml and was shown to predict both CD and UC with a sensitivity of 66.7% and a specificity of 64.4%. Although, our performance is superior to the one reported by Manolakis et al. [18], our study was carried out on a small sample size and on UC only and 50% of our patients was selected in exacerbating condition besides the different best cutoff point and laboratory methods. In addition to studies performed by Manolakis et al. [18], Brinar et al. [19] evaluated serum S100A12 in 300 adults with IBD (150 CD and 150 UC), 100 non-IBD inflammatory controls (including diverticulitis, infectious enterocolitis, and ischemic colitis) and 143 healthy controls. Significantly elevated serum S100A12 concentrations were seen in both IBD groups (median 242 ng/ml for CD and median 223 ng/ml for UC) and non-IBD inflammatory controls (median, 94.7 ng/ml) compared with healthy individuals (53.5 ng/ml).

 

Also Leach et al. [20] undertook a cohort study to determine serum S100A12 concentrations in 39 children with IBD 29 with CD (four with UC and six with IBD unclassified) and 33 age-matched non-IBD controls. Serum S100A12 concentrations were greater in the IBD group compared with the non-IBD group [median, 196 (13–810) ng/ml vs. median, 82 (15–4242) ng/ml]. Although serum S100A12 was significantly increased in the children with CD [median, 239 (27–14 810) ng/ml], the median level was higher in those with UC [median, 750 (247–1391) ng/ml] and not elevated in the IBD unclassified group [median, 94 (40–294) ng/ml]. This may reflect the small numbers of patients in the latter two groups. Similarly Foell et al. [17] demonstrated an elevated serum S100A12 in a study of 74 adult patients with IBD. Forty of these patients were diagnosed with CD and 34 with UC. High levels of S100A12 were seen in active CD (470 ± 125 ng/ml) and active UC (401 ± 20 ng/ml) compared with healthy individuals (75 ± 15 ng/ml). Although these studies generally agreed with our work regarding elevated serum level S100A12 in IBD patients, they were different from our study with respect to the age of IBD patients, some of their patients were children. using different enzyme-linked immunosorbent assay and furthermore they did not discriminate specifically between IBD and IBS regarding the serum level of S100A12 unlike the current study. In contrast to the results of our study, Sidler et al. [21] demonstrated no significant difference in serum S100A12 level between children with IBD and children with other gastrointestinal disorders. Therefore, serum S100A12 level does not appear to accurately detect children with gastrointestinal inflammation, similar to standard inflammatory markers. The non-IBD group in their study included children with a range of gastrointestinal disorders such as Helicobacter pylori infection and various systemic inflammatory processes. The median value for serum S100A12 in the IBD group was 270 ng/ml and the median value for serum S100A12 in the non-IBD group was 141 ng/ml. They reported that serum S100A12 had lower test utility, with a sensitivity of 21% and a specificity of 81%. Although variations in assay procedures and differences between adults and children must also be taken into account and furthermore they did not discriminate specifically between IBD and IBS regarding the serum level of S100A12. As regards CRP levels in UC patients, in our study we demonstrated a positive CRP in the IBD group compared with the IBS group. Similarly Bakir et al. [2] study showed a highly significant positive correlation between IBD cases and positive CRP in comparison to IBS cases. In addition to studies performed by Bakir et al. [2], Schoepfer et al. [8] found that CRP had 64% sensitivity and 92% specificity in discriminating IBD (n = 64) from IBS (n = 30). Shine et al. [22] were the first to show that a CRP increase can be used to differentiate IBD from functional bowel disorders. In 82 patients with chronic abdominal symptoms, 19 were diagnosed with CD, 22 with UC, and 41 with a functional bowel disorder. All of the 19 patients with CD and 59% of the 22 patients with UC showed increases in CRP compared with none of the 41 patients with functional symptoms. In our study, we found positive correlations between S100A12 and a well-known marker of inflammation CRP. Our results are in agreement with those con-ducted by Manolakis et al. [18]. As regards ESR in UC patients, according to our study there was a positive, statistical correlation between serum S100A12 levels in UC patients and ESR. This can be explained by a study of Desai et al. [23] who reported that ESR is an indirect measurement of plasma acute-phase protein concentration and is influenced by the morphology of erythrocytes as well as some plasma constituents such as immuno-globulins. As the concentrations of many serum proteins vary in patients with IBD and as some have long lives, the ESR is not rapidly responsive to change in clinical status (the

 

ESR may take several days to decrease even when rapid clinical improvement occurs). Hence, the ESR is a crude assessment of disease activity. In UC, where clinical, endo-scopic, and histological activity is used to assess the overall disease, the correlation between ESR and disease activity is good. However, it may be normal in proctitis and proctosigmoiditis. In our study S100A12 serum levels of UC patients with active and inactive disease were both higher than those of IBS individuals. Mean serum S100A12 level for UC patients in exacerbation was 83.93 ± 30.78 pg/ml, UC patients in remission was 64.03 ± 19.87 pg/ml, and the mean value of serum S100A12 was 47.73 ± 11.15 pg/ml in the IBS group and the mean value for the control group was 45.32 ± 8.60 pg/ml. In our study serum S100A12 exhibits a significant positive correlation with CAI as the mean value of serum S100A12 in patients with inactive disease status according to CAI was 64.03 ± 19.87 pg/ml, in patients with mild disease activity it was 51.66 ± 7.06 pg/ml, in patients with moderate activity 70.41 ± 7.26 pg/ml, and in patients with severe disease activity was 115.91 ± 20.06 pg/ml. Also there is a significant positive correlation between serum S100A12 and the histological picture regarding the degree of activity in UC patients as the mean value of serum S100A12 in patients with normal colonoscopic finding was 47.73 ± 11.15 pg/ml, in patients with inactive disease activity in colonoscopy was 64.03 ± 19.87 pg/ml, in patients with mild disease activity in colonoscopy was 51.66 ± 7.06 pg/ml, in patients with moderate disease activity in colonoscopy was 70.41 ± 7.26 pg/ml, and in patients with high disease activity in colonoscopy was 15.91 ± 20.06 pg/ml. Similarly Brinar et al. [19] reported that S100A12 was higher in endo-scopically active UC compared with inactive disease (357 ng/ml vs. 121 ng/ml). The authors concluded that S100A12 could not be used as an accurate biomarker of inflammation but this data was resulted as the study was conducted on IBD patients both UC and CD and patients were chosen regardless of the disease activity, but in our study patients were only UC patients and disease activity was taken in consideration as 50% of patients were in exacerbation and this could be explained by a study of Foell et al. [17], who reported that serum levels of S100A12 were higher in CD than in UC. The correlation of S100A12 levels with disease activity indices was lower in CD than in UC. Even in patients with inactive CD, they found significantly elevated S100A12 serum levels com-pared with controls. Foell et al. [17] explained that by the more systemic nature of immuno-logical disturbances in CD compared with UC and even in inactive disease, a few neutro-phils remain in the intestinal tissue which might be responsible for elevated serum levels in these patients. S100A12 may therefore be a very sensitive parameter of residual dis-ease activity [17]. As the neutrophil influx is a very early event during the inflammatory process of IBD, S100A12 may also be a useful marker in determining relapse of IBD. It is also conceivable that Crohn’s disease activity index (CDAI) scores may have been falsely low in their patients who were consequently regarded to be in remission, despite having residual disease activity [17]. Brignola et al. [24] found altered laboratory parameters in 55% of patients with inactive disease according to CDAI scores. The results of the present study agreed partially with that of Manolakis et al. [18] who demonstrated that S100A12 serum levels of IBD patients with active and inactive disease were both higher than those of the IBS group, but no significant correlations between its level and CAI and CDAI [18]. Conclusion: Serum S100A12 can be used as a non-invasive marker to distinguish IBD from IBS. The increase in serum S100A12 was correlated with the classical marker of inflammation CRP. The levels of serum S100A12 varied significantly with disease severity in patients with UC, so it can be used in monitoring disease activity in such patients without the need for recurrent endoscopic interventions.

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Hemophagocytic syndrome – A rare cause of dyspepsia and hepatopathy: Case report Katja Režonja (Murska Sobota, SI), Dejan Majc (Murska Sobota, SI), Maja Šeruga (Murska Sobota, SI), Miran Gerič (Murska Sobota, SI) Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by an overactive and ineffective immune response. Diagnostic criteria (5/8) help us to make a diagnosis. Methods: A 52-year-old woman was admitted to our hospital for dyspepsia and progres-sive weight loss of 1 years' duration. In this period she often had malaise, no appetite, a bitter taste in the mouth and upper abdominal pain. Before admission to hospital she vomited and had fever (above 38ºC). Clinical examination was, with exception of paleness and wheezing (she was long-term smoker), within normal limits. With abdominal ultrasound we detected small gallstones, esophagogastroduodenoscopy showed insufficient gastric cardia, reflux esophagitis grade A and signs of gastro-duodenitis. Rapid urease test was negative. The biopsy confirmed reactive, chemical, H. pylori negative gastritis. During hospitalization we treated her for pneumonia. We also confirmed active infection with EBV. Results: In laboratory tests we found leukopenia (1.7 x 109/l) with moderate normocytic anemia (97 g/l), elevated liver enzymes (AST [12.48 µkat/l], ALT [7.39 µkat/l], gamma GT [2.08 µkat/l] and AF [1.37 µkat/l]), elevated PCT (2.3 µg/l), CRP was normal (below 5 mg/l). Ferritin (4776 µg/l) and LDH (10.78 µkat/l) were highly elevated. Triglycerides (2.2 mmol/l), tumor markers CEA (5.4 µg/l) and CA 15-3 (41.6 E/ml) were mildly elevated. Fibrinogen was normal (2.7 g/l). Hepatitis markers and HIV were negative. Based on laboratory tests and clinical manifestation we suspected on hemophagocytic syndrome. Tested NK cells activity was low and soluble receptor for IL2-sCD25 was increased to the level, sufficient for diagnosis of hemophagocytic syndrome. We also performed bone marrow biopsy, which showed non-specific morphological changes, no hemophagocytosis. Discussion/Conclusion: We have had 6 of 8 criteria for hemophagocytic syndrome: fever, cytopenia, hypertriglyceridemia, low NK cells activity, hyperferritinemia and elevat-ed sCD25 (we lacked only hepatosplenomegaly and hemophagocytosis). On dexametha-son orally clinical condition improved and laboratory tests normalized.

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CRP in IBD flare: How predictive is it? Single-centred retrospective analysis Aruchuna Ruban (London, GB), Erika Lam (London, GB), Gheed Mahir (London, GB), Leanna Ruprai (London, GB), Chehkuan Tai (London, GB), Nora Thoua (London, GB) Introduction: The clinical presentation of an inflammatory bowel disease (IBD) flare is often non- specific and overlaps with both gastroenteritis and functional gastrointestinal disorders. CRP can be a predictive marker of inflammation in IBD and is associated with clinical disease activity and endoscopic inflammation [1, 2]. The objective of this single-centred study in an acute NHS London trust was to investigate if CRP levels help in pre-dicting whether an admission is related to acute flare versus other causes. Methods: This was a retrospective study of all inpatient IBD admissions in 2018 over a 7 month period to our trust. The CRP on admission and diagnosis on discharge summary were recorded. Elective admissions and pregnant patients were excluded. Statistical analysis was performed using Microsoft excel. Results: A total of 127 in-patient IBD admissions occurred during the 7 month period with a mean age of 51 years and included 66 (52%) patients with CD and 61 (48%) with UC. The mean CRP value recorded on admission was 55 mg/l. 55% of admissions were directly IBD related (Figure 1). IBD related admissions had a mean CRP of 56 mg/l com-pared with 54 mg/l in the IBD unrelated admissions. 10% of CD and 9% of UC patient had a normal CRP (< 5mg/l). In the non IBD related admissions, 15 patients had bacterial infections (including LRTI and UTI) with a mean CRP of 109 mg/l and 4 patients had a diagnosis of gastroenteritis with a mean CRP of 13 mg/l. Discussion/Conclusion: The mean CRP for IBD related admissions including a flare are similar to non IBD related admissions although IBD patients presenting with bacterial in-fections had marked raised CRPs compared with those having an IBD flare. Our study shows that CRP level is not a good discriminator of predicting those patients presenting with an IBD flare.

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A prospective, controlled study exploring the pathophysiology of non-celiac wheat sensitivity in patients with chronic unexplained gastrointestinal symptoms Ayesha Shah (Chermside, AU), Nicholas Talley (Newcastle, AU), Anh Do (Brisbane, AU), Erin Shanahan (Brisbane, AU), Marjorie Walker (Newcastle, AU), Natasha Koloski (Brisbane, AU), Mike Jones (Sydney, AU), Simon Keeley (Newcastle, AU), Mark Morrison (Brisbane, AU), Gerald Holtmann (Brisbane, AU) Introduction: In patients with otherwise unexplained (functional) gastrointestinal symp-toms (also referred to as patients with functional gastrointestinal disorders (FGID), alter-ations of gastrointestinal sensory, motor or immune function as well changes of the gastro-intestinal microbiome and psychological comorbidities occur. While some patients with FGID report a link of symptoms and the consumptions of wheat products, it is unknown how symptoms related to the consumption of wheat products are linked to the above abnormalities. Methods: We recruited 40 patients with chronic or relapsing gastrointestinal (functional) symptoms, and 20 control patients referred for the diagnostic work-up of a positive fecal occult blood test with normal upper and lower endoscopy. Validated instruments were used to assess gastrointestinal, extraintestinal symptoms and psychological comorbid-ities, and symptoms triggered by gluten ingestion assessed in a structured interview. Gastric emptying (C13 octanoic acid) and nutrient challenge testing were performed and peripheral blood mononuclear cells (PBMCs) isolated by density centrifugation and T-cells quantified by flow cytometry. Duodenal 16S ribosomal RNA were targeted and the abundance of three previously identified microbiome factors of the duodenal mucosa-associated microbiome compared. Stepwise binary regression analysis was used to identify variables associated with unexplained (functional) and wheat related symptoms. Results: 20/40 patients with chronic unexplained (functional) gastrointestinal symptoms reported symptoms that were related to wheat consumption compared to 2/20 controls. Patients with unexplained GI symptoms had an increased symptom response (p < 0.02) to the standardised nutrient challenge but no alterations of gastric emptying. Patients with NCWS had significantly increased gut homing immune cells, compared to controls or FGID patients without NCWS. Discussion/Conclusion: Altered visceral sensory function is the key feature of patients with unexplained (functional) GI symptoms while in patients with NCWS there is activation of the mucosal immune system is activated. The data suggest that patients with NCWS are a distinct subgroup of patients with otherwise unexplained GI symptoms who are characterized by mucosal immune activation.

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Diagnostic yield of symptom severity, visceral sensory testing, small intestinal, bacterial load and gastric emptying for the diag-nosis of functional gastrointestinal disorders Ayesha Shah (Chermside, AU), Mark Morrison (Brisbane, AU), Natasha Koloski (Brisbane, AU), Teressa Hansen (Brisbane, AU), Marjorie Walker (Newcastle, AU), Mike Jones (Sydney, AU), Nicholas Talley (Newcastle, AU), Gerald Holtmann (Brisbane, AU) Introduction: Patients presenting with functional gastrointestinal disorders (FGIDs) frequently report debilitating symptoms which may be more severe than symptoms experi-enced by patients with organic intestinal disease. While presence or absence (i.e. symp-tom pattern) is generally used to categorise patients with FGIDs, the role of symptom intensity to categorise and diagnose patients has not been tested. In addition, alterations of gastrointestinal sensory function, altered motility and bacterial dysbiosis are considered to play key roles in FGID pathophysiology. Methods: In this study we aimed to explore the diagnostic yield of severity of self-reported GI symptoms, visceral sensory testing, qPCR to quantify small intestinal mucosal bacterial load and gastric emptying in differentiating functional from organic GI disease. We recruited 284 patients (150 female, 95 patients with FGID [68 functional dyspepsia (FD)/IBS overlap, 21 FD, 3 IBS], 118 organic disease [43 Crohn’s disease, 48 ulcerative colitis (UC), 16 UC/primary sclerosing cholangiopathy (PSC), 4 PSC alone, 9 other] and 71 patients with a positive stool occult blood test without structural lesions). After informed consent, type and severity of GI symptoms were recorded using a standardized valid questionnaire (SAGIS). Patients underwent a nutrient challenge test and the cumulative symptom response to a standardised test meal (Ensure, 600 cc) were recorded. In addition, gastric emptying of a solid test meal was measured utilising 13C-octanoic breath testing. During endoscopy, mucosal tissue samples were collected utilising the Brisbane Aseptic Biopsy Forceps (MTW, Germany) to avoid the luminal and working channel contamination of tissue, and total DNA was extracted. Tissue bacterial density was normalised to human DNA by qPCR using Bacteria-Domain 16S rRNA gene- and beta-actin gene-specific primers, respectively. Based upon on all available clinical data, patients were categorised as FGID or non-FGID. The FGID and non-FGID groups were compared utilising non parametric testing, and Spearman correlation to determine the relationships between disease category and the respective variables. In addition, Receiver Operator Curves (ROC) for the variables that were significantly different for FGID and non-FGID provided areas under the curve for comparison. Results: SAGIS-Score, Nutrient challenge score, bacterial load (ratio) and Gastric emptying (t-lag[min]) were 30.6 (± 15.1), 458 (± 399),0.20 (± 0.5), and 115.8 (± 29.3) respectively for FGID patients and 10.8 (± 12.9), 204 (± 190),0.04 (± 0.11) and 116.0 (± 37.3) respectively for Non -FGID patients. SAGIS symptom scores, the symptom response to the nutrient challenge, and the tissue bacterial load were all significantly

 

greater (all p < 0.005) in FGID patients as compared to non FGID patients, however, there was no difference with regard to gastric emptying. SAGIS score (r = 0.62, p < 0.001), nutrient challenge score (r = 0.41, p < 0.001) and bacterial load (r = 0.342, p < 0.001) were linked to FGID, whereas gastric emptying was not (r = 0.024, p > 0.8). For the total SAGIS score the AUC was 0.892 (95% CI: 0.83–0.954), for the nutrient challenge score 0.74 (95% CI: 0.64–0.83), bacterial load (0.71 (95% CI: 0.61–0.80). Discussion/Conclusion: In patients referred to a tertiary setting for assessment and treatment, self-reported symptom severity, response to a standardised nutrient challenge and small intestinal bacterial load but not gastric emptying rate differentiate patients with functional and non-functional symptoms. Further studies need to explore the utility of these simple tests to better tailor diagnostic and therapeutic interventions for patients presenting with chronic unexplained GI symptoms.

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Enteric methane or hydrogen production in patients with unex-plained gastrointestinal symptoms: Associations with age, symptoms and proton-pump inhibitors Ayesha Shah (Chermside, AU), Natasha Koloski (Brisbane, AU), Mark Morrison (Brisbane, AU), Gerald Holtmann (Brisbane, AU) Introduction: In humans, enteric methane (CH4) and hydrogen (H2) production is highly variable and related to the gastrointestinal microbiome. Proton-pump inhibitors (PPI) and statins are thought to affect the microbiome and their metabolic functions. We aimed to determine the effect of age, PPI and statin use on breath CH4 and H2 and we also assessed their association with symptoms in patients with otherwise unexplained gastrointestinal (GI) symptoms. Methods: After comprehensive diagnostic work-up and exclusion of relevant structural causes of symptoms, consecutive patients with unexplained (functional) GI symptoms underwent a combined H2/CH4 breath test after ingestion of 75 g of glucose. H2 and CH4 were measured by Breath tracker microlyser (Quintron, USA). GI symptoms were assessed utilising the (Structured Assessment of Gastrointestinal Symptoms Instrument [SAGIS]). The association between H2/CH4 exhalation and age, medication use and symptoms during the 2 weeks prior the test was evaluated using a non-parametric test. Results: 313 consecutive patients (55% female), aged 52.2 ± 15.1 yrs (mean ± SD) were included. Baseline and peak CH4 was correlated with age (r = 0.22 and r = 0.19, p < 0.001). Baseline and peak CH4 inversely correlated with the SAGIS diarrhea score (r < -0.25, p all < 0.01) while CH4 exhalation was not associated with self-reported constipation (r < 0.1, p > 0.4). PPI treatment was significantly associated with the baseline and peak methane exhalation (r = 0.1, p, 0.05 and r = 0.15, p < 0.02). Discussion/Conclusion: CH4, but not H2 production increases with age. Specific GI symptoms are linked to the CH4 exhalation. PPI therapy appears to be associated with an increased methane production. While this is a potential risk factor for constipation, increased CH4 may improve symptoms of diarrhea. These data provide further evidence that specific metabolites of the gut microbiome can alter gastrointestinal functions. These data suggest that CH4 or metabolic products from CH4 producing microbes modulate human gut function.

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Variation of the mucosa-associated microbiome along the human gastrointestinal tract in health and disease Ayesha Shah (Chermside, AU), Gene Tyson (Brisbane, AU), Julian Zaugg (Brisbane, AU), Phil Hugenholtz (Brisbane, AU), Mark Morrison (Brisbane, AU), Gerald Holtmann (Brisbane, AU) Introduction: Very little is known about the variation in the mucosa-associated microbiota (MAM) along the human gastrointestinal (GI) tract. Thus, we aimed to determine the bacterial communities in different parts of the GI tract and compare patients without gastrointestinal disease with patients with Crohn’s disease (CD) and ulcerative colitis (UC). Methods: We recruited 72 patients undergoing upper GI endoscopy and colonoscopy for the assessment of a positive FOBT with normal results of the endoscopic investigations (other than small adenoma) and no symptoms reported utilising a standardised assess-ment of gastrointestinal symptoms (SAGIS). In addition, we recruited 44 patients with CD and 50 patients with UC. Utilising the Brisbane Aseptic Biopsy Device, we obtained biopsies from the proximal small intestine, terminal ileum, ascending colon and rectum without cross contamination from luminal contents or other regions of the GI tract. Biopsy samples were immediately placed under aseptic conditions into a sterile tube containing RNA later (Qiagen). Samples were allowed to incubate at room temperature for 30 minutes, then frozen and stored at -80°C. Total DNA was extracted from biopsies, and sample free reagent controls, using a repeated bead-beating based method. Samples were profiled by high-throughput amplicon sequencing with dual-index barcoding using the Illumina MiSeq platform, targeting the V6–V8 region of the gene encoding 16S ribosomal RNA. The libraries were sequenced on an Illumina MiSeq platform and the data were quality assessed, trimmed and filtered, then processed using the Quantitative Insights into Microbial Ecology version 2 (QIIME2) software. Microbiota and statistical analyses were performed in QIIME2 and R. Significant differences in Shannon and Chao1 alpha diversity metrics between sample types, and between disease states for each sample type, were calculated using Kruskal-Wallis and unpaired Wilcox rank sum tests. Differentially abundant taxa were identified with DESeq2 using a likelihood ratio test while correcting for age, BMI and gender. Results: Across all patient groups, the three most abundant genera in the duodenum were Streptococcus, Pseudomonas and Prevotella. However, in the terminal ileum, right colon and rectum, Faecalibacterium, Bacteroides, and Escherichia-Shigella were the three most abundant bacterial taxa. There were significant differences in the Shannon and Chao1 diversity scores of the mucosa-associated microbiota (MAM) present in the duodenum and terminal ileum (p < 0.001–0.05) between UC and CD, and UC and controls, with greater diversity found for the control subjects. In the right colon and rectum, significantly lower Shannon diversities were observed in UC and CD vs. controls (p < 0.05).

 

Discussion/Conclusion: There are marked differences in the three most abundant bacteria in the upper and lower gut. Similarly, MAM from different parts of the human GI tract reveal distinct characteristics in the relation to the most prevalent bacterial taxa and the alpha diversity observed at these sites. Interestingly, both UC and CD patients have different MAM profiles in both proximal and distal sites of the GI, and these are different from those observed for healthy asymptomatic controls.

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Aeroallergen sensitization is associated with irritable bowel syndrome-like symptoms in atopic patients

Kewin Tien Ho Siah (Singapore, SG), Amelia Santosa (Singapore, SG), Cynthia Cheung (Hong Kong, CN), Paul Lorenz Bigliardi (Minneapolis, US),

Introduction: Multiple studies investigated the link between Irritable Bowel Syndrome (IBS) and allergic diseases. Studies showed that IBS patients had increased atopy and aeroallergen sensitization compared to healthy controls. It was not known if the associ-ation with aeroallergen was confounded by atopic status or specific aeroallergen sensiti-zation. We aimed to investigate within an atopic cohort if the presence of IBS-like symptom was associated with specific aeroallergen sensitization.

Methods: We recruited consecutive atopic Chinese patients from the allergy clinic of a tertiary hospital. Subjects completed bowel questionnaires and skin prick test (SPT). Blood was drawn for serum histamine, total serum immunoglobulin E (IgE) and tested with Immuno CAP ISAC IgE multiplex assay.

Results: We recruited sixty-nine patients in total. Twenty-eight (41%) atopic patients fulfilled ROME III IBS criteria (Atopy-IBS group). There was no difference in gender, age, total serum IgE, food allergen sensitization by SPT or IgE between Atopy-IBS group and non-IBS group. We found that Atopy-IBS group had a significantly higher proportion of asthma (42.9% vs. 14.6%, p = 0.014), positive sensitization for cat dander (64.3% vs. 24.4%, p < 0.001), Fel d1 IgE (21.4% vs. 2.4%, p = 0.029), dog dander (64.3% vs. 41.5%, p = 0.015) and weed/herb (32.1% vs. 14.6%, p = 0.05) compared to Atopy-non-IBS group. Multivariate analyses showed that asthma (OR = 4.38), cat dander (OR = 5.58) and Fel d1 (OR = 10.90) were independently associated with IBS-like symptoms in atopic patients.

Discussion/Conclusion: We demonstrated an association between cat allergen sensiti-zation and IBS-like symptoms in atopic patients. This observation warrants further study to assess the clinical relevance of such sensitization, and whether these patients define a subset of IBS patients with immune dysfunction or allergic bowel disease who could benefit from anti-allergic therapy.

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The assessment of risk factors for functional constipation Igor Skrypnyk (Poltava, UA), Ganna Maslova (Poltava, UA), Olexandr Gopko (Poltava, UA), Ivan Kryvoruchko (Poltava, UA) Introduction: The problem of functional gastrointestinal (GI) disorders, including function-al constipation (FC), has been becoming more relevant for the past decades. Detailed analysis of its causes and mechanisms may allow optimizing therapeutic approaches in this category of patients. Aim: To study significance of some risk factors (gender, lifestyle, dietary characteristics, psycho-emotional stress, antibacterial therapy, changes in intestinal microflora) for FC formation. Methods: 40 patients who were made diagnosis of FC according to Rome IV criteria (2016) were examined. The ratio of males and females was 5 (12.5%)/35 (87.5%), age range – 32–60 years, average age of the patients – 48.1 ± 6.1 years. Average duration of FC was 13.6 ± 5.2 years. According to the survey, role of different factors (lifestyle, dietary characteristics, psycho-emotional stress, antibacterial therapy) in development of FC was assessed. During physical examination height and weight of the patients were deter-mined, body mass index (BMI) was calculated with the formula: BMI = weight (kg)/ height (m2). Hydrogen breath test (HBT) with lactulose was performed: the concentration of hydrogen in the exhaled air was measured before the lactulose intake and on 15th, 30th, 60th, 90th and 120th minutes after. The composition of large intestinal microflora was also assessed. Statistical analysis of results was made with GraphPad Prism version 5.00 with the use of arithmetic means (М) and their deviations (m), confidence interval (95% CI). Results: According to the questionnaire, irregular meals took place in 29 (72.5%) patients, irrational diet with lack of alimentary fibers, consumption of small amount of fluid per day – in 17 (42.5%), sedentary lifestyle – in 34 (85%), psycho-emotional stress – in 36 (90%), intake of medical preparations (antibiotics) – in 5 (12.5%) patients. During the physical examination an overweight, namely BMI > 25 kg/m2, was found only in 7 (17.5%) patients with FC. According to the HBT, hydrogen concentration before lactulose intake was 6.79 ± 1.69 (95% CI: 3.1–10.3) ppm. Increase of lactulose concentration for 10 ppm (18.51 ± 4.13 [95% CI: 10.9–24.3] ppm) was observed on the 90th minute of investigation, which corresponds to intestinal hypofunction. Elevation of hydrogen for more than 20 ppm among all 40 (100%) patients was not observed, which indicates on absence of small intestinal bacterial overgrowth. While studying bacteriogram of the patients’ fecal masses, significant changes of intestinal microbiota were not detected. However, the overall Escherichia coli concentration was 4.29 ± 0.37 х 107 (95% CI: (3.4–5.17) CFU/g and was within reference limits (4 x 106–108 CFU/g). Fungi Candida were found in 5 (12.5%) patients, Klebsiella pneumoniaе – in 10 (25%) patients, Enterobacter aerogenes – in 7 (17.5%) patients.

 

Discussion/Conclusion: Significance for FC formation had the next factors: female gender, irregular meals, sedentary lifestyle and psycho-emotional stress.

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Rising incidence of colonic diverticulosis in a westernized multi-ethnic Asian community Yu Sen Alex Soh (Singapore, SG), Shu Qin Delicia Ooi (Singapore, SG), Yiong Huak Chan (Singapore, SG), Soh-Ee Lee (Singapore, SG), Tien-Ho Kewin Siah (Singapore, SG), Wei Jie Jonathan Lee (Singapore, SG), Feng Zhu (Singapore, SG), Khay Guan Yeoh (Singapore, SG), Kok-Ann Gwee (Singapore, SG) Introduction: Singapore is a multiethnic country that has undergone rapid development over the last few decades, with increasing influence of western culture, and also faces a rapidly aging population. Previously, a varying prevalence of colonic diverticulosis (CD) was reported by a few small studies. This study aims to evaluate the incidence of CD in Singapore, and to identify associations with common gastrointestinal symptoms and potential risk factors. Methods: We reviewed data of consecutive 20,395 colonoscopies performed from 2006 to 2016 for indications of screening, diarrhea, constipation and abdominal pain. Results: The incidence of CD has progressively increased from 2006 to 2016 (14.9% vs. 23.9%, adjusted trend < 0.001). Overall, patients with CD were older and had higher BMI. CD was significantly more prevalent in Chinese compared to Malay and Indian races (20.5% vs. 18.9% vs. 15.5%, p < 0.05), and in males compared to females (21.5% vs. 17.6%, p < 0.05). Right-sided CD was more common than left-sided or pan-diverticulosis (16.2% vs. 8.3% vs. 4.8%, p < 0.05). Age (odds ratio [OR], 1.060; 95% confidence interval [CI], 1.052–1.068), BMI (OR, 1.051; 95% CI, 1.028–1.075), male gender (OR, 1.317; 95% CI, 1.084–1.600), and abdominal pain (OR, 1.409; 95% CI, 1.168–1.699) were positively, while constipation was negatively, associated with CD (OR, 0.566; 95% CI, 0.452–0.709). Discussion/Conclusion: The overall incidence of CD in Singapore from 2006 to 2016 was 19.6%. Age, male gender, elevated BMI, and abdominal pain symptom were posi-tively associated with CD, while constipation was negatively associated with CD.

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Helicobacter pylori (HP) resistance in North East London: Are we treating HP with appropriate antibiotics? Cheh Kuan Tai (London, GB), Annette Jepson (London, GB), Laura Marelli (London, GB) Introduction: Public Health England guidelines advises HP testing and treatment if positive, in patients without alarm symptoms who have uncomplicated dyspepsia unres-ponsive to lifestyle change and antacids. However, the suggested antibiotic therapy is incongruent with the latest Maastricht V/Florence consensus report which suggest bis-muth containing quadruple therapy in regions with high metronidazole and clarithromycin resistance (> 15%). Previous published data from London showed overall resistance to metronidazole at 59%, clarithromycin 11% and both at 8% with non-UK birth being main risk factor for resistance. Homerton University Hospital serves the local borough of City and Hackney. 31% of Hackney’s population consist of black and ethnic minorities. We aimed to look at our local HP resistance data and compare the antibiotics regimes used in different trusts within London. Methods: A list of all gastroscopies with CLO testing over a year between October 2017–18 was generated by the information team. We performed a review of a 100 cases to assess whether patients had symptoms or endoscopic findings suggestive of HP. A list of all HP isolates sent to the microbiology lab over a 2-year period from January 2016 to December 2018 was generated. We performed a search of HP antibiotic regimes for trusts within London. Results: Between October 2017 to September 2018, 27.5% of gastroscopies performed out of a total of 5000 had CLO testing. A review of 100 patients showed that 100% of patients had indication of dyspepsia or endoscopic findings suggestive of HP infection such as gastritis. Between 2016–2018, 36 isolates of HP were received by the lab. 35 were resistant to metronidazole, 26 to clarithromycin, 10 to levofloxacin, 1 to tetracycline and none to amoxicillin. Other antibiotic sensitivities were not assessed. We found antibiotics guidelines for 6 London trusts. None of the trusts used antibiotic duration of 10–14 days as recommended by Maastrict V. 4 of the 6 trusts recommend quadruple bismuth therapy as second line treatment or first line where penicillin allergy is a factor. Discussion/Conclusion: Patients in whom we send HP resistance testing have high resistance rates to conventional first line antibiotics. Given that these patients are likely to have previously failed at least one treatment regime, the results are inevitable skewed towards resistant isolates. While the NICE and PHE guidelines are appropriate for some populations, in areas of London which are at risk of higher resistance rates due to the local demographic, the local guidelines should move towards Maastricht. In patients with previous treatment failure, we recommend a 10 day course of bismuth-containing quadruple therapy as second line.

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MMP-7 expression in patients with colitis ulcerosa and Crohn’s disease Wiktoria Ustymowicz (Bialytsok, PL), Zińczuk Justyna (Bialystok, PL), Anna Pryczynicz (Bialystok, PL), Katarzyna Guzinska-Ustymowicz (Bialystok, PL), Konrad Zaremba (Bialystok, PL) Introduction: The extracellular matrix (ECM) is a specific matrix participating in the migration, cell adhesion, differentiation, and intercell interactions. Remodeling of the ECM is important in the development of many disease processes. A key mechanism is metallo-proteinases activity (MMPs) which has the capacity to its degradation and remodeling. One of the proteins belonging to the MMPs is matrix metalloproteinase 7 (MMP-7) whose overexpression was observed in inflammatory and neoplastic processes. Therefore, the aim of this study was to analyze the expression of MMP-7 matrilysin in inflammatory bowel disease. Methods: The study group consisted of 41 patients diagnosed with ulcerative colitis and 10 with Crohn's disease. The biopsy slices were used as the study material in which the expression of MMP-7 protein was determined by immunohistochemical method with the use of monoclonal antibodies and standard immunoperoxidase technique. The staining reaction in a 4-point scale was assessed as absent, weak, medium and strong. Results: The expression of MMP-7 protein in normal epithelial cells and inflammatory cells was observed. In patients with ulcerative colitis in epithelial cells, the reaction was absent in 54.9%, weak in 29% and medium in 16.1% of cases, while in patients with Crohn's disease the expression was defined as weak in 50%, medium in 40% and strong in 10% of cases. The expression of MMP-7 was higher in inflammatory cells than in epi-thelial cells of patients with ulcerative colitis that was shown as absent in 6.4% of cases, weak in 35.5%, medium in 32.3%, and strong in 25.8% of cases. In the cases of Crohn's disease it was weak at 20%, medium in 20% and strong in 60%. Statistical analysis showed that increased expression of MMP-7 protein in epithelial cells in patients with ulcerative colitis was associated also with its growth in inflammatory cells (p < 0.000). Discussion/Conclusion: The overexpression of MMP-7 in epithelial cells in patients with Crohn's disease was found to correlate with the location of the disease in the rectum (p < 0.000).

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Eosinophilic esophagitis in children of the North-Eastern Poland

Katarzyna Zdanowicz (Bialystok, PL), Magdalena Kucharska (Bialystok, PL), Urszula Daniluk (Bialystok, PL), Dariusz Lebensztejn (Bialystok, PL)

Introduction: The aim of the retrospective study was the evaluation of the clinical symp-toms and endoscopic and pathological changes of EoE in children and adolescence from the North-Eastern part of Poland.

Methods: The study included 433 pediatric patients with EoE (n = 36, 8.31%) and non-eosinophilic esophagitis (non-EoE) (n = 397; 91.7%) diagnosed based on endoscopic and histological examination between January 2015 and December 2018. Histological criteria for EoE were fulfilled when at least 15 eosinophils per high power field were found on esophageal biopsy. Moreover, the evaluation included the reported symptoms, the patient’s medical history, eosinophil count in CBC, the coexistence of Helicobacter pylori infection, endoscopic lesions and body mass index (BMI).

Results: The mean age of children with EoE was statistically lower comparing to non-EoE (9.6 ± 4.3 years vs. 12.17 ± 4.23; p < 0.001) with male predominance (77.78% vs. 49.62%; p = 0.002). Among symptoms, only dysphagia was more often reported in EoE group (22.2% vs. 7.30%; p = 0.02). No difference in BMI was found between groups. Eosinophilia was observed more frequently in EoE (529 cells/ul vs. 188 cells/ul; p < 0.001). The most significant endoscopic lesions found in EoE were the linear fissuring, decrease vascular pattern, trachealisation, whitish exudates. Coexisting allergy was reported mainly in children with EoE (47.2% vs. 18.14%; p < 0.001) and no association with other dis-eases, also Helicobacter pylori infection, were noted.

Discussion/Conclusion: Our results confirmed the previous reports that EoE in pediatric population affects more often males, appears in early childhood, coexists with allergy and manifests with dysphagia, eosinophilia, and typical endoscopic lesions. These common features are helpful in differentiating patients with EoE from non-EoE.

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Can survivin may be responsible for inflammatory process in patients with ulcerative colitis?

Justyna Zińczuk (Białystok, PL), Konrad Zaręba (Białystok, PL), Marcin Nizioł (Białystok, PL), Wiktoria Ustymowicz (Białystok, PL), Katarzyna Guzińska-Ustymowicz (Białystok, PL), Joanna Matowicka-Karna (Białystok, PL), Anna Pryczynicz (Białystok, PL)

Introduction: Apoptosis is a physiological cell death process that contributes to the development and maintenance of healthy cells and tissues. It has been proven that apoptosis plays a significant role in the regulation of homeostasis in intestinal epithelium and controls the cellular immune response to the pathogenic agent. Increased epithelial cell apoptosis induces the loss of epithelial continuity in UC patients. In cancers, increased expression of the proapoptotic protein procaspase 3 may cause upregulation of surviving transcription (which is inhibitor of apoptosis), but it has been not confirmed in inflammatory diseases. Therefore, the aim of our study was to evaluate the expression of procapase-3 and survivin in patients with ulcerative colitis.

Methods: The study included 30 patients diagnosed with ulcerative colitis (UC). The expression of procaspase-3 and survivin proteins in tissue sections was assessed by immunohistochemical methods. The color reaction was defined as a negative (lack of expression), weak (< 10% of positive cells), medium (10–50% of positive cells) and strong (> 50% of positive cells).

Results: The color reaction of procaspase-3 was observed in cytoplasm whereas survivin in nuclei in dysplastic glandular tubes and inflammatory cells. In patients with UC it was observed the absence and the weak procaspase-3 expression in normal glands (41.9% and 32.3%), predominant weak and medium reactions in dysplastic glands and (33.3% and 50.0%) and weak in the inflammatory cells (58.0%). In normal glandular tubes, the expression of survivin was a weak, moderate and strong in 37.5%, 12.5% and 21.8% of cases, respectively. Moreover, it was observed a weak and strong reaction of survivin in the inflammatory cells of 50% cases with UC. Higher expression of procaspase-3 in dys-plastic glands correlated with higher survivin expression in inflammatory cells (p = 0.036). Simultaneously, higher expression of survivin in dysplastic glands was associated with higher procaspase-3 expression in inflammatory infiltration (p = 0.008).

Discussion/Conclusion: Overexpression of survivin may stimulate the inflammatory pro-cess in patients with UC. Moreover, it can cause inhibition of procaspase-3 activity and cell death in patients with ulcerative colitis.

Author Index to Poster Abstracts (Name - Poster Number)

Abd Samat, N. 1 Abdullah, N. 1 Allegretta, L. 7 Andreev, P. 2 Annunziata, M. 7 Astegiano, M. 7 Ayadi, S. 5, 6 Ayari, M. 5, 6 Bafutto, M. 7 Bajer, L. 3, 16 Baldi, F. 7 Basaranoglu, M. 4 Bassotti, G. 7 Belhadj Mabrouk, E. 5, 6 Benkhemmar, A. 14 Benson, A. 15 Bianco, M. 7 Bigliardi, P. 45 Brandimarte, G. 7 Brezina, J. 3, 16 Chan, Y. 47 Chandler, S. 8, 12 Cheung, C. 45 Chmelova, K. 3 Chornenka, O. 20, 21 Cianga, P. 32 Cichoż-Lach, H. 9, 10, 11, 26,

27, 28, 29 Ciortescu, I. 32 Clim, A. 32, 33, 36 Colucci, R. 7 Conigliaro, R. 7 Cunningham, A. 8, 12 Cybulski, M. 9, 10, 11, 22,

26, 27, 28, 29 Dabbèche, R. 5, 6 Dabos, K. 13 Daboussi, O. 14 Daher, S. 15 Danese, S. 7 Daniluk, U. 50 Davydova, O. 2 Di Mario, F. 7

Do, A. 41 Dorofeeva, U. 20, 21 Doshi, K. 34 Drastich, P. 3, 16 Dumitrascu, D. 7 Elisei, W. 7 Escalante, R. 7 Faggiani, R. 7 Farah, R. 15 Fineron, P. 13 Fiorella, S. 7 Forti, G. 7 Franceschi, M. 7 Gerič, M. 39 Gheorghe, L. 32 GianMarco, G. 7 Gopko, O. 46 Gorincioi, C. 33, 36 Grad, S. 7 Graziani, M. 7 Guz, M. 9, 10, 11, 22, 26,

27, 28, 29 Guzińska-Ustymowicz, K. 35, 37,

49, 51 Gwee, K. 47 Hakimian, D. 15 Hansen, T. 42 Hao, Y. 34 Harris, D. 8, 12 Hazou, W. 15 He, Y. 17 Herber, A. 14 Hitchings, M. 8, 12 Holtmann, G. 41, 42, 43, 44 Hugenholtz, P. 44 Imroati, T. 18 Israeli, E. 15 Jepson, A. 48 Jones, M. 41, 42 Justyna, Z. 49

Kadah, A. 15 Keeley, S. 41 Kharchenko, N. 20, 21 Kholili, U. 18 Khoury, T. 15 Koloski, N. 41, 42, 43 Konecny, M. 19 Koulaouzidis, A. 13 Kozicka, J. 9, 10, 11, 22,

26, 27, 28, 29 Kryvoruchko, I. 46 Kuan, G. 1 Kucharska, M. 50 Kueh, Y. 1 Kvit, K. 20, 21

Lach, H. 22 Lai, M. 7 Lam, E. 40 Lammert, F. 7 Latella, G. 7 Lebensztejn, D. 50 Lee, S. 47 Lee, W. 47 Lee, Y. 1 Lisi, D. 7 Lozynska, L. 23, 24 Lozynska, M. 23, 24 Lozynskyy, R. 23, 24 Lukavetskyy, O. 23 Luwawu, M. 14

Macinga, P. 3 Maconi, G. 7 Mahamid, M. 15 Mahir, G. 40 Maimunah, U. 18 Majc, D. 39 Marelli, L. 48 Mari, A. 15 Maslova, G. 25, 46 Massarwa, M. 15 Matowicka-Karna, J. 51 Mazilu, B. 33, 36 Michalak, A. 9, 10, 22, 26,

27, 28, 29 Misiura, M. 35 Mitroshkin, A. 30 MIchalak, A. 11 Morrison, M. 41, 42, 43, 44 Mouelhi, l. 5, 6

Murphy, M. 7

Nardone, G. 7 Naumann, M. 31 Nemteanu, R. 32, 33, 36 Ng, Y. 34 Nizioł, M. 35, 37, 51 Nusi, I. 18

Oliveira Camara De Castro, L. 7 Oliveira Chaves, E. 7 Ong, A. 34 Ooi, S. 47

Papa, A. 7 Papagrigoriadis, S. 7 Penna, A. 7 Picchio, M. 7 Pietrzak, A. 7 Plavski, A. 24 Plesa, A. 32, 33, 36 Pontone, S. 7 Portincasa, P. 7 Poskus, T. 7 Pranzo, G. 7 Precel, O. 23 Pryczynicz, A. 35, 37, 49, 51 Purbayu, H. 18

Radionova, T. 25 Rashid, Y. 38 Regula, J. 7 Reichert, M. 7 Režonja, K. 39 Rizzo, G. 7 Rodinò, S. 7 Ruban, A. 40 Ruprai, L. 40

Santosa, A. 45 Sbeit, W. 15 Scaccianoce, G. 7 Scaldaferri, F. 7 Schiffino, L. 7 Šeruga, M. 39 Setiawan, P. 18 Sfrijan, C. 33, 36 Shah, A. 41, 42, 43, 44 Shanahan, E. 41 Siah, K. 45 Siah, T. 47

Skrypnyk, I. 25, 46 Soh, Y. 47 Spicak, J. 3, 16 Stepulak, A. 9, 10, 11, 22,

26, 27, 28 Stundiene, I. 7 Sugihartono, T. 18

Tai, C. 40, 48 Taimr, P. 3 Talley, N. 41, 42 Thoua, N. 40 Trifan, A. 32, 33 Tursi, A. 7 Tyson, G. 44

Ustymowicz, W. 35, 37, 49, 51

Vassallo, R. 7 Viener, E. 15 Vitvytskyy, I. 24

Walker, M. 7, 41, 42 Wang, Y. 34 Widodo, B. 18 Wong, M. 1

Yahaya, F. 1 Yeoh, K. 47

Zaimi, Y. 5, 6 Zampaletta, C. 7 Zaręba, K. 35, 37, 49, 51 Zaugg, J. 44 Zdanowicz, K. 50 Zhu, F. 47 Zińczuk, J. 35, 37, 51 Zullo, A. 7

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AbstractsPoster Abstracts

Falk FoundationDr. Falk Pharma Symposium 217

West Meets East: Functional Meets Organic in Gastrointestinal Diseases

November 29–30, 2019Parkroyal on Beach RoadSingapore

21664_Falk_Singapore_Symp_217_Abstracts_US.indd 1 14.10.19 16:14