Tu1004 Ursodeoxycholic Acid Therapy Improves Survival of Non-Caucasian Patients With Primary Biliary...
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serum alkaline phosphatase (ALP) .1.5x ULN who received fenofibrate 160mg/day for 6 months. Wilcoxon Signed-Rank Test was used to compare changes in serial liver chemistries from baseline to the end of 6 months of therapy. Liver biochemistries were again measured at 9 weeks after drug discontinuation. Results: Eight patients (7 male, 1 female, median age 41) with established PSC received fenofibrate 160mg/d for 6 months. Four (50%) had associated inflammatory bowel disease, one of whom also had psoriasis. Median serum alkaline phosphatase (ALP) at baseline was 290 IU/dL (range 216-850) and decreased to 165.5 IU/dL (104-273) at month 6, p=0.008. The median drop in ALP was of 47% (range 21-70%). Serum alanine aminotransferase (ALT) also decreased significantly (108 [40-205] vs. 75 [34-119], p= 0.04). There were no significant changes in serum bilirubin, alanine aminotransferase, albumin or prothrombin time. Mayo risk score did not change between baseline and 6 months: median -0.41 (-0.71 to 1.4) vs. -0.46 (-0.96 to 1.8), p=0.46. To further demonstrate the effect of fenofibrate, liver biochemistries were measured again at 9 weeks after drug discontinuation. Median serum ALP was 165 (104-273) at month 6 on the drug and increased to 340 (264-670) after drug discontinuation, p= 0.02, demonstrating a clear rebound in ALP levels. Serum ALT increased from 75 (34-119) to 123 (45-191), but this was not statistically significant (p=0.11). The only adverse event was worsening of psoriasis in one study participant which did not require drug discontinuation. Conclusion: Use of fenofibrate 160 mg/d in patients with PSC appears safe and efficacious in reducing serum levels of ALP and ALT. Further studies are warranted. Tu1003 Primary Non-Response to Ursodeoxycholic Acid Is Associated With Lower Vitamin D Levels in Patients With Primary Biliary Cirrhosis Kate D. Williamson, Said Al Mamari, Roger W. Chapman Background and aims Ursodeoxycholic acid (UDCA) is the only licensed proven effective treatment in PBC. 20-40% of patients do not have a "good biochemical response" to UDCA which is associated with a worse clinical outcome. A lower vitamin D level has been shown to be a poor prognostic indicator in various liver diseases. Additionally, the vitamin D receptor has been shown to be upregulated in the biliary epithelium in patients with PBC on UDCA, and postulated to play a role in the therapeutic effect of UDCA. The aim of this study was to determine if low Vitamin D levels was associated with primary non-response to UDCA in PBC. Methods A retrospective audit was performed of patients with PBC who had been treated with UDCA (13-15mg/kg/day). Patients who discontinued UDCA due to intolerance, or who did not have an available vitamin D level were excluded. The earliest vitamin D level on record was used and biochemical and demographic features were collected. Patients were defined as responders according to Barcelona criteria (ALP drop by 40% or normalisation at one year of UDCA). The median Vitamin D level was compared between responders and non-responders. Results 42 patients with PBC who were treated with UDCA had an available vitamin D level, of whom 9 were excluded due to intolerance to UDCA or no response data available. 33 patients were included in the analysis, with 30 patients (91%) being female, median age at diagnosis 53.0y (31.1-75.5y), and median ALP at diagnosis 633U/L (2.1xULN) (305-2528U/L). 11/33 patients (33%) were non-responders. The median Vit D level was lower in non-responders (33.2nmol/L, IQR 36.7-84.9) compared with responders (56.3nmol/L, IQR 36.7-84.9, p=0.020). However, using stepwise logistic regres- sion analysis, vitamin D was not a significant predictor of response. Additionally, there was a trend towards lower age and AMA-negativity in the non-responder group as compared with responders (55.5y (IQR 47.7-67.1y) vs 46.9y (IQR 35.0- 55.9), p=0.070), as well as a trend for AMA-negativity (27.3% vs 4.5%, p=0.097). Conclusions Patients with PBC who had a primary non-response to UDCA had lower vitamin D levels compared with those who responded. The fact that vitamin D was not identified as an independent predictor of response may be due to small numbers in the study, however, this study is ongoing. These data provide the basis for future research into the impact of Vitamin D on response to therapy with UDCA. Tu1004 Ursodeoxycholic Acid Therapy Improves Survival of Non-Caucasian Patients With Primary Biliary Cirrhosis With Limited Liver Transplantation Availability Yazmin K. Melchor-Mendoza, Segundo Moran, Aline Mina Hawat, Gustavo Rodriguez- Leal, Aldo Torre, Misael Uribe Introduction: The natural history of primary biliary cirrhosis (PBC) has greatly improved in the last 25 years, do to the introduction of ursodeoxycholic acid (UDCA) treatment; the survival further improved once the liver transplantation became an option for rescue those PBC patients who deteriorate; however, survival improvement in those studies were per- formed in developed countries mainly in Caucasian population and in less degree in Japanese patients. Survival information of PBC patients is limited in non-Caucasian population particu- larly in Latin American countries where the number of liver transplants performed remains scarce in patients with advanced liver disease who fulfill criteria for liver transplantation, we therefore decided to review our single center experience. Aim: To compare the survival of non-Caucasian patients with PBC using UDCA vs. the survival of patients who received any other treatment prescribed before UDCA era. Patients and Methods: A retrospective study was performed including 93 patients [Female n=(85): Male (n=8)] with PBC, who were diagnosed with clinical, histological and immunological (antimitochondrial/Antibody) criteria. Patients were followed at least for 5 years after the initial diagnosis and death related to liver disease was recorded during this time. Patients were divided into two groups: Group I (n=55) received treatment with UDCA (15 mg/kg/per day); Group II (n=38) received other treatment (Colchicine, Cholestyramine, Penicillamine, Azathioprine, or Prednisolone) before introduction of UDCA in Mexico. Statistical analysis: Results are expressed as means ± standard deviation and median (minimum-maximum values). For survival analysis, Kaplan Meier method was used for survival curves, log-rank test for univariate comparisons, and Cox proportional hazard model for multivariate analysis. Results: The mean age in Group I was 45.0±12.6 yr and 48.4±10.5 yr in Group II. Eighteen percent of Group I had cirrhosis at the moment of diagnosis and thirteen percent of the Group II. No differences were found at baseline in cholestatic clinical and biochemical characteristics. After one month of S-1029 AASLD Abstracts treatment, the Group I show response at the very early period of treatment, having a significant decrease of the levels of bilirubin and AST; while in both groups the concentrations of ALT diminish. (Table 1) After 5 years of follow-up, the survival probability was 82.6% in patients treated with UDCA while was only 42.5% in patients who received any other treatment (p=0.0001) (Figure 1). Treatment different to UDCA was a predictive variable for mortality in the patients with PBC (HR 4.339, 95% CI: 1.89-9.9; p= 0.0001) Conclusions: The study suggests that the use of UDCA improves survival in patients with PBC in Latin population even though transplantation is not generally available in Latin America. Tu1005 Hispanics With Primary Biliary Cirrhosis Have More Overlap Syndrome With Autoimmune Hepatitis Christin Giordano, Jahnavi Naik, Amar Mandalia, Paul Martin, Cynthia Levy Background and aims: An Overlap Syndrome (OS) of primary biliary cirrhosis (PBC) with autoimmune hepatitis (AIH) is recognized in 2-20% of patients with PBC and is implicated in worse clinical outcomes. We aimed to evaluate the impact of Hispanic ethnicity on the prevalence, presentation, and outcomes of OS. Methods: Retrospective study utilizing a database of patients with PBC seen between 01/01/2001 and 8/31/2011. Patients with PBC who scored ≥6 in the simplified AIH criteria or who met the Poupon criteria were designated as having OS. A comparison was made between patients with and without Hispanic ethnicity. Results: Of 204 patients with PBC, 70 (34%) were of Hispanic origin. While Hispanic subjects were more likely to be male (13% vs. 5%, p=0.06), no differences were seen in age at diagnosis, race, BMI or AMA positivity. Prevalence of OS was significantly higher in Hispanics (22/70, 31% vs. 17/134, 12.8%, p=0.002). Among patients with OS, Hispanics were more likely to have pruritus (47% vs. 12.5%, p=0.06). No differences were observed in frequency of fatigue, ursodeoxycholic acid (UDCA) dose, presence of advanced fibrosis on biopsy, or duration of follow-up between Hispanics and non-Hispanics. Liver biochemis- tries were overall more abnormal in Hispanic subjects: AST (median 62 vs. 30 IU/L, p= 0.004), ALT (50 vs. 30 IU/L, p=0.004), ALP (242 vs. 97 IU/L, p=0.0008), bilirubin (0.85 vs. 0.5, p=0.03) and albumin (3.95 vs. 4.2 g/dL, p=0.02). Among patients treated with UDCA for .1 year (n=181), the serum ALP at last follow-up was higher in Hispanics (median 179 [26-1276] vs. 144 [54-746], p=0.0025), and more often ≥1.67 XULN (42% vs. 15%, p=0.0002). At the end of follow-up (median 3.5 years [0-26]) there were no differences in the rates of esophageal varices, GI bleeding, ascites or hepatic encephalopathy between the 2 groups. Only 2 patients underwent liver transplantation, both Hispanic (p= 0.5). No deaths occurred. Conclusion: OS is more prevalent among Hispanics. After at least 1 year of UDCA therapy they have higher levels of serum ALP, a marker of poor prognosis in PBC. Hispanic patients should be carefully evaluated and treated for OS to prevent worse outcomes. Tu1006 Validation of the Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Hispanic Patients Blanca Norero, Carlos Agüero, Juan Pablo Ortega, Rodrigo Wolff, Luis A. Diaz, Cristian Hernández-Rocha, Ignacio Duarte, Carlos Benítez, Rosa Pérez-Ayuso, Alejandro Soza, Marco A. Arrese, Roberto A. Candia INTRODUCTION: In 2008 the International Autoimmune Hepatitis (AIH) Group proposed a simplified diagnostic criteria for this disease. The original cohort study was performed in 11 international centers around the world, but validation studies are scarce in Hispanic American patients. The aim of this study is validate these criteria in Chilean patients. METHODS: We selected a retrospective cohort of adult patients with percutaneous liver biopsy performed between January 2007 and January 2012 with at least 6 months of clinical follow up in a Chilean university hospital. We excluded patients with incomplete laboratory data, cirrhosis, previous immunosuppressive therapy and liver transplant recipients. Sensitiv- ity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the ROC curve (AUROC) of the AIH simplified score were calculated. The definite AASLD Abstracts
Transcript of Tu1004 Ursodeoxycholic Acid Therapy Improves Survival of Non-Caucasian Patients With Primary Biliary...
serum alkaline phosphatase (ALP) .1.5x ULN who received fenofibrate 160mg/day for 6months. Wilcoxon Signed-Rank Test was used to compare changes in serial liver chemistriesfrom baseline to the end of 6 months of therapy. Liver biochemistries were again measuredat 9 weeks after drug discontinuation. Results: Eight patients (7 male, 1 female, median age41) with established PSC received fenofibrate 160mg/d for 6 months. Four (50%) hadassociated inflammatory bowel disease, one of whom also had psoriasis. Median serumalkaline phosphatase (ALP) at baseline was 290 IU/dL (range 216-850) and decreased to165.5 IU/dL (104-273) at month 6, p=0.008. The median drop in ALP was of 47% (range21-70%). Serum alanine aminotransferase (ALT) also decreased significantly (108 [40-205]vs. 75 [34-119], p= 0.04). There were no significant changes in serum bilirubin, alanineaminotransferase, albumin or prothrombin time. Mayo risk score did not change betweenbaseline and 6 months: median -0.41 (-0.71 to 1.4) vs. -0.46 (-0.96 to 1.8), p=0.46. Tofurther demonstrate the effect of fenofibrate, liver biochemistries were measured again at 9weeks after drug discontinuation. Median serum ALP was 165 (104-273) at month 6 onthe drug and increased to 340 (264-670) after drug discontinuation, p= 0.02, demonstratinga clear rebound in ALP levels. Serum ALT increased from 75 (34-119) to 123 (45-191),but this was not statistically significant (p=0.11). The only adverse event was worsening ofpsoriasis in one study participant which did not require drug discontinuation. Conclusion:Use of fenofibrate 160 mg/d in patients with PSC appears safe and efficacious in reducingserum levels of ALP and ALT. Further studies are warranted.
Tu1003
Primary Non-Response to Ursodeoxycholic Acid Is Associated With LowerVitamin D Levels in Patients With Primary Biliary CirrhosisKate D. Williamson, Said Al Mamari, Roger W. Chapman
Background and aims Ursodeoxycholic acid (UDCA) is the only licensed proven effectivetreatment in PBC. 20-40% of patients do not have a "good biochemical response" to UDCAwhich is associated with a worse clinical outcome. A lower vitamin D level has been shownto be a poor prognostic indicator in various liver diseases. Additionally, the vitamin Dreceptor has been shown to be upregulated in the biliary epithelium in patients with PBCon UDCA, and postulated to play a role in the therapeutic effect of UDCA. The aim of thisstudy was to determine if low Vitamin D levels was associated with primary non-responseto UDCA in PBC. Methods A retrospective audit was performed of patients with PBC whohad been treated with UDCA (13-15mg/kg/day). Patients who discontinued UDCA due tointolerance, or who did not have an available vitamin D level were excluded. The earliestvitamin D level on record was used and biochemical and demographic features were collected.Patients were defined as responders according to Barcelona criteria (ALP drop by 40% ornormalisation at one year of UDCA). The median Vitamin D level was compared betweenresponders and non-responders. Results 42 patients with PBC who were treated with UDCAhad an available vitamin D level, of whom 9 were excluded due to intolerance to UDCA orno response data available. 33 patients were included in the analysis, with 30 patients (91%)being female, median age at diagnosis 53.0y (31.1-75.5y), and median ALP at diagnosis633U/L (2.1xULN) (305-2528U/L). 11/33 patients (33%) were non-responders. The medianVit D level was lower in non-responders (33.2nmol/L, IQR 36.7-84.9) compared withresponders (56.3nmol/L, IQR 36.7-84.9, p=0.020). However, using stepwise logistic regres-sion analysis, vitamin D was not a significant predictor of response. Additionally, there wasa trend towards lower age and AMA-negativity in the non-responder group as comparedwith responders (55.5y (IQR 47.7-67.1y) vs 46.9y (IQR 35.0- 55.9), p=0.070), as well asa trend for AMA-negativity (27.3% vs 4.5%, p=0.097). Conclusions Patients with PBC whohad a primary non-response to UDCA had lower vitamin D levels compared with thosewho responded. The fact that vitamin D was not identified as an independent predictor ofresponse may be due to small numbers in the study, however, this study is ongoing. Thesedata provide the basis for future research into the impact of Vitamin D on response totherapy with UDCA.
Tu1004
Ursodeoxycholic Acid Therapy Improves Survival of Non-Caucasian PatientsWith Primary Biliary Cirrhosis With Limited Liver TransplantationAvailabilityYazmin K. Melchor-Mendoza, Segundo Moran, Aline Mina Hawat, Gustavo Rodriguez-Leal, Aldo Torre, Misael Uribe
Introduction: The natural history of primary biliary cirrhosis (PBC) has greatly improvedin the last 25 years, do to the introduction of ursodeoxycholic acid (UDCA) treatment; thesurvival further improved once the liver transplantation became an option for rescue thosePBC patients who deteriorate; however, survival improvement in those studies were per-formed in developed countries mainly in Caucasian population and in less degree in Japanesepatients. Survival information of PBC patients is limited in non-Caucasian population particu-larly in Latin American countries where the number of liver transplants performed remainsscarce in patients with advanced liver disease who fulfill criteria for liver transplantation,we therefore decided to review our single center experience. Aim: To compare the survivalof non-Caucasian patients with PBC using UDCA vs. the survival of patients who receivedany other treatment prescribed before UDCA era. Patients and Methods: A retrospectivestudy was performed including 93 patients [Female n=(85): Male (n=8)] with PBC, whowere diagnosed with clinical, histological and immunological (antimitochondrial/Antibody)criteria. Patients were followed at least for 5 years after the initial diagnosis and death relatedto liver disease was recorded during this time. Patients were divided into two groups: GroupI (n=55) received treatment with UDCA (15 mg/kg/per day); Group II (n=38) received othertreatment (Colchicine, Cholestyramine, Penicillamine, Azathioprine, or Prednisolone) beforeintroduction of UDCA in Mexico. Statistical analysis: Results are expressed as means ±standard deviation and median (minimum-maximum values). For survival analysis, KaplanMeier method was used for survival curves, log-rank test for univariate comparisons, andCox proportional hazard model for multivariate analysis. Results: The mean age in GroupI was 45.0±12.6 yr and 48.4±10.5 yr in Group II. Eighteen percent of Group I had cirrhosisat the moment of diagnosis and thirteen percent of the Group II. No differences werefound at baseline in cholestatic clinical and biochemical characteristics. After one month of
S-1029 AASLD Abstracts
treatment, the Group I show response at the very early period of treatment, having asignificant decrease of the levels of bilirubin and AST; while in both groups the concentrationsof ALT diminish. (Table 1) After 5 years of follow-up, the survival probability was 82.6%in patients treated with UDCA while was only 42.5% in patients who received any othertreatment (p=0.0001) (Figure 1). Treatment different to UDCA was a predictive variable formortality in the patients with PBC (HR 4.339, 95% CI: 1.89-9.9; p= 0.0001) Conclusions:The study suggests that the use of UDCA improves survival in patients with PBC in Latinpopulation even though transplantation is not generally available in Latin America.
Tu1005
Hispanics With Primary Biliary Cirrhosis Have More Overlap Syndrome WithAutoimmune HepatitisChristin Giordano, Jahnavi Naik, Amar Mandalia, Paul Martin, Cynthia Levy
Background and aims: An Overlap Syndrome (OS) of primary biliary cirrhosis (PBC) withautoimmune hepatitis (AIH) is recognized in 2-20% of patients with PBC and is implicatedin worse clinical outcomes. We aimed to evaluate the impact of Hispanic ethnicity on theprevalence, presentation, and outcomes of OS. Methods: Retrospective study utilizing adatabase of patients with PBC seen between 01/01/2001 and 8/31/2011. Patients with PBCwho scored ≥6 in the simplified AIH criteria or who met the Poupon criteria were designatedas having OS. A comparison was made between patients with and without Hispanic ethnicity.Results: Of 204 patients with PBC, 70 (34%) were of Hispanic origin. While Hispanicsubjects were more likely to be male (13% vs. 5%, p=0.06), no differences were seen inage at diagnosis, race, BMI or AMA positivity. Prevalence of OS was significantly higher inHispanics (22/70, 31% vs. 17/134, 12.8%, p=0.002). Among patients with OS, Hispanicswere more likely to have pruritus (47% vs. 12.5%, p=0.06). No differences were observedin frequency of fatigue, ursodeoxycholic acid (UDCA) dose, presence of advanced fibrosison biopsy, or duration of follow-up between Hispanics and non-Hispanics. Liver biochemis-tries were overall more abnormal in Hispanic subjects: AST (median 62 vs. 30 IU/L, p=0.004), ALT (50 vs. 30 IU/L, p=0.004), ALP (242 vs. 97 IU/L, p=0.0008), bilirubin (0.85vs. 0.5, p=0.03) and albumin (3.95 vs. 4.2 g/dL, p=0.02). Among patients treated withUDCA for .1 year (n=181), the serum ALP at last follow-up was higher in Hispanics(median 179 [26-1276] vs. 144 [54-746], p=0.0025), and more often ≥1.67 XULN (42%vs. 15%, p=0.0002). At the end of follow-up (median 3.5 years [0-26]) there were nodifferences in the rates of esophageal varices, GI bleeding, ascites or hepatic encephalopathybetween the 2 groups. Only 2 patients underwent liver transplantation, both Hispanic (p=0.5). No deaths occurred. Conclusion: OS is more prevalent among Hispanics. After at least1 year of UDCA therapy they have higher levels of serum ALP, a marker of poor prognosisin PBC. Hispanic patients should be carefully evaluated and treated for OS to preventworse outcomes.
Tu1006
Validation of the Simplified Criteria for the Diagnosis of AutoimmuneHepatitis in Hispanic PatientsBlanca Norero, Carlos Agüero, Juan Pablo Ortega, Rodrigo Wolff, Luis A. Diaz, CristianHernández-Rocha, Ignacio Duarte, Carlos Benítez, Rosa Pérez-Ayuso, Alejandro Soza,Marco A. Arrese, Roberto A. Candia
INTRODUCTION: In 2008 the International Autoimmune Hepatitis (AIH) Group proposeda simplified diagnostic criteria for this disease. The original cohort study was performed in11 international centers around the world, but validation studies are scarce in HispanicAmerican patients. The aim of this study is validate these criteria in Chilean patients.METHODS: We selected a retrospective cohort of adult patients with percutaneous liverbiopsy performed between January 2007 and January 2012 with at least 6 months of clinicalfollow up in a Chilean university hospital. We excluded patients with incomplete laboratorydata, cirrhosis, previous immunosuppressive therapy and liver transplant recipients. Sensitiv-ity, specificity, positive predictive value (PPV), negative predictive value (NPV) and areaunder the ROC curve (AUROC) of the AIH simplified score were calculated. The definite
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