Interaction Between Schistosomiasis and HCV€¦ · hepatitis C virus in Egypt (Frank C et al.,...
Transcript of Interaction Between Schistosomiasis and HCV€¦ · hepatitis C virus in Egypt (Frank C et al.,...
Interaction Between Interaction Between SchistosomiasisSchistosomiasis and HCVand HCV
By:By:
Gamal EsmatGamal EsmatPROF.OF HEPATOLOGY&TROPICAL MEDICINEPROF.OF HEPATOLOGY&TROPICAL MEDICINE
CAIRO UNIVERSITYCAIRO UNIVERSITY--EGYPTEGYPT
PRESIDENT OF IASLPRESIDENT OF IASL(INTERN. ASSOC.FOR THE STUDY OF THE LIVER(INTERN. ASSOC.FOR THE STUDY OF THE LIVER))
Prof. Gamal Esmat
Prof. Gamal Esmat
EpidemiologyEpidemiology
Effect of Combined infection Effect of Combined infection
–– ImmunopathogenesisImmunopathogenesis
–– SeveritySeverity
–– SVRSVR
Prof. Gamal Esmat
Prof. Gamal Esmat
Prof. Gamal Esmat
♦Trematode parasitic infection
♦ Intermediate host: water snails
♦Debilitating disease, severity depends on “worm load”
Theodor Bilharz (1825-1862) first described the trematode working at Kasr El Ainy hospital in Cairo
in 1851
Schistosomiasis
Prof. Gamal Esmat
♦ Snail habitat: irrigation canals, lakes, ponds
♦ Humans get infected through skin contact with water
♦ Humans excrete schistosomal eggs in urine or stool into water, keep-up life cycle of parasites
Life cycle of schistosomiasis
Prof. Gamal Esmat
Prof. Gamal Esmat
Prof. Gamal Esmat
(El(El--MenezaMeneza et al., 1989).et al., 1989).
Hepatic fibrosis is the major Hepatic fibrosis is the major
clinical sequel of the infection with clinical sequel of the infection with
the the SchistosomaSchistosoma mansoni.mansoni.
Prof. Gamal Esmat
Hematemesis and Hematemesis and melenamelena are the most are the most common clinical presentation of hepatic common clinical presentation of hepatic SchistosomisisSchistosomisis..Abdominal pain is usually caused by Abdominal pain is usually caused by HepatosplenomegalyHepatosplenomegaly..JuandiceJuandice and manifestations of LCF are and manifestations of LCF are rare clinical presentation.rare clinical presentation.
Prof. Gamal Esmat
HpatitisHpatitis C Virus (HCV)C Virus (HCV)
Prof. Gamal Esmat
Prof. Gamal Esmat
The association of The association of hepatosplenichepatosplenicschistosomiasisschistosomiasis and hepatitis C is very and hepatitis C is very common especially in countries with high common especially in countries with high transmission of both infections e.g., Egypt, transmission of both infections e.g., Egypt, as well as in other endemic areas as as well as in other endemic areas as Brazil. Brazil.
Prof. Gamal Esmat
* age-adjusted prevalence, population between 10 and 50SUDAN
EGYPT
Upper Egypt19.4%
(95% CI: 17.2-21.6)
Middle Egypt26.5%
(95% CI: 23.7-29.4)
Alexandria 5.9% (95% CI: 4.2-7.7)
Lower Egypt28.4%
(95% CI: 27.1-29.2)
Cairo8.2% (95% CI: 6.7-9.8)
LIBYA Red
Sea
Geographic HCV Geographic HCV Prevalence* Prevalence*
Prof. Gamal Esmat
hepatitis C infection in Egypthepatitis C infection in Egypt
Approximately Approximately 90%90% of Egyptian of Egyptian isolates belong to a single isolates belong to a single subtype, subtype, 4a.4a. (Ray et al., 2000, (Ray et al., 2000, Kamal et al., 2000).Kamal et al., 2000).Furthermore, HCV is Furthermore, HCV is less less prevalent in countries prevalent in countries neighbouring Egyptneighbouring Egypt having having similar socio medical conditions similar socio medical conditions and similar strains (WHO 1997).and similar strains (WHO 1997).
One genotype
Higher prevalence than surroundings
Prof. Gamal Esmat
ParenteralParenteral antischistosomalantischistosomal treatment treatment (PAT) programs are believed to have (PAT) programs are believed to have infectedinfected a large proportion of the exposed a large proportion of the exposed population with HCV from 1950s until the population with HCV from 1950s until the early 1980s (early 1980s (NafehNafeh et al., 2000 & et al., 2000 & RaoRao et et al., 2002).al., 2002).
Large reservoir
Prof. Gamal Esmat
The role of parenteral The role of parenteral antischistosomalantischistosomal therapy in the spread of therapy in the spread of hepatitis C virus in Egypt hepatitis C virus in Egypt
(Frank C et al., 2000; Lancet)(Frank C et al., 2000; Lancet)
The risk factor for HCV transmission that The risk factor for HCV transmission that
specifically sets Egypt apart from other specifically sets Egypt apart from other
countries is a personal history of countries is a personal history of parenteral parenteral
antischistosomalantischistosomal therapy (PAT). therapy (PAT).
A review of the Egyptian PAT massA review of the Egyptian PAT mass--
treatment campaigns, discontinued only in treatment campaigns, discontinued only in
the 1980s, show a very high potential for the 1980s, show a very high potential for
transmission of bloodtransmission of blood--borne pathogens. borne pathogens. Prof. Gamal Esmat
This problem is not prominent in other This problem is not prominent in other countries endemic for countries endemic for schistosmiasisschistosmiasisprobably because control efforts were less probably because control efforts were less population intensive and geographically population intensive and geographically extensive.extensive.
Prof. Gamal Esmat
EpidemiologyEpidemiology
Effect of Combined infectionEffect of Combined infection
–– ImmunopathogenesisImmunopathogenesis
–– SeveritySeverity
–– SVRSVR
Prof. Gamal Esmat
ImmunopathogenesisImmunopathogenesis of of Combined InfectionCombined Infection
Dual infection of schistosomiasis and HCV Dual infection of schistosomiasis and HCV display display significant influence on host significant influence on host immune reactionsimmune reactions including cytokine shift including cytokine shift pattern alteration, pattern alteration, cytotoxiccytotoxic T lymphocytes T lymphocytes response and other impaired immunologic response and other impaired immunologic functions with diminished capacity to clear functions with diminished capacity to clear the virus (Elthe virus (El--KadyKady et al., 2004).et al., 2004).
Prof. Gamal Esmat
THoIL-2IFN-γIL-4IL-5IL-10
Th2IL-4IL-5IL-10
+++
Viral clearance
IL-2IFN-γ
Th1+
++
Immunopathogenesisof
Combined infectionProf. Gamal Esmat
ImmunopathogenesisImmunopathogenesis of of Combined InfectionCombined Infection
Schistosomiasis appears to Schistosomiasis appears to induce induce Th2 cytokineTh2 cytokine profile, with profile, with ↑↑ ILIL--4, IL4, IL--10. It 10. It downregulatedownregulate the stimulatory the stimulatory effect of HCV on effect of HCV on Th1 cytokinesTh1 cytokines and and this may lead to this may lead to chronicitychronicity of HCV of HCV infection in infection in coinfectedcoinfected patients (Elpatients (El--KadyKady et al., 2004& 2005).et al., 2004& 2005).
Prof. Gamal Esmat
EpidemiologyEpidemiology
Effect of Combined infection Effect of Combined infection
–– ImmunopathogenesisImmunopathogenesis
–– SeveritySeverity
–– SVRSVR
Prof. Gamal Esmat
Pathologically Pathologically schistoschisto--HCV coHCV co--infection has infection has possibly a synergistic effect especially on possibly a synergistic effect especially on hepatic fibrosis.hepatic fibrosis.
By serial liver biopsies ,progression of By serial liver biopsies ,progression of hepatic fibrosis was shown to be faster in hepatic fibrosis was shown to be faster in patients with copatients with co--infection than in those infection than in those with HCV (0.6 point/year with HCV (0.6 point/year vsvs 0.2point/year)0.2point/year)
This may refer to altered immune response This may refer to altered immune response or or fibrogenesisfibrogenesis signals.signals.
Prof. Gamal Esmat
Influence Of Combined Influence Of Combined Infection On Infection On The Clinical The Clinical Course Of Liver DiseaseCourse Of Liver Disease
HCV infection causes a HCV infection causes a more severemore severe and and irreversibleirreversible form of liver disease than infection form of liver disease than infection with with S. mansoni. S. mansoni. AngelicoAngelico et al., (1997) et al., (1997)
ComplicationsComplications of cirrhosis were of cirrhosis were more commonmore common in in patients with both diseases than in those with patients with both diseases than in those with either disease alone (either disease alone (KoshyKoshy et al., 1993 and et al., 1993 and Kamal et al., 2000 and Gad et al., 2001).Kamal et al., 2000 and Gad et al., 2001).
Prof. Gamal Esmat
CLDCLDDecompensated
CLD–– ↑↑ grade C Childgrade C Child--Pugh score, Pugh score, –– ↑↑ episodes of upper GI bleeding, episodes of upper GI bleeding, –– ↑↑ renal impairment renal impairment –– ↑↑ mortality rate mortality rate
(Kamal et al., 2000 and Gad et al., 2001). (Kamal et al., 2000 and Gad et al., 2001).
Prof. Gamal Esmat
What about the relation of What about the relation of
combined infection on combined infection on HCC HCC
prevalence ?prevalence ?
HCC is present only in coinfection or HBV HCC is present only in coinfection or HBV
& HCV infection and never observed in & HCV infection and never observed in S. S.
mansonimansoni infection alone (Ahmed et al., infection alone (Ahmed et al.,
(1998) and Kamal et al., 2000).(1998) and Kamal et al., 2000).
Prof. Gamal Esmat
EpidemiologyEpidemiology
Effect of Combined infection Effect of Combined infection
–– ImmunopathogenesisImmunopathogenesis
–– SeveritySeverity
–– Sustained Sustained VirologicalVirological Response (SVR)Response (SVR)
Prof. Gamal Esmat
Is schistosomal infection has Is schistosomal infection has an influence on an influence on
antianti--viral therapy?viral therapy?ELEL--ShazlyShazly et al., (1994); reported et al., (1994); reported low rate of low rate of responseresponse in combined infection than in HCV in combined infection than in HCV alone. alone.
The presence of associated schistosomiasis has The presence of associated schistosomiasis has determined the response of Egyptians with determined the response of Egyptians with chronic hepatitis C to therapy with interferon chronic hepatitis C to therapy with interferon ((AbdelAbdel Basset et al., 1994).Basset et al., 1994).
Prof. Gamal Esmat
Response to INF in subjects Response to INF in subjects with dead and living ova at 24 with dead and living ova at 24
weeks treatmentweeks treatment
5060
10
20
30
40
50
60
70
80
90
100
Living ova Dead ova
Living ova
Dead ova
%
Dead Ova, 22
Living Ova, 14
Living Ova
Dead Ova
Prof. Gamal Esmat
57 64
102030405060708090
100
Had SchistoTTT
Did not haveSchisto TTT
Had Schisto TTTDid not have Schisto TTT
Had Schisto TTT, 86
Did not have Schisto
TTT, 114
%
Response to INF according to Response to INF according to anti anti schistosomalschistosomal treatmnettreatmnet
at 24 weeks treatmentat 24 weeks treatment
Prof. Gamal Esmat
Those who did not receive Those who did not receive parentralparentralantischistosomalantischistosomal therapy( PAT )in the past therapy( PAT )in the past responded to treatment better than those responded to treatment better than those who did. who did. The SVR being 44% in those not The SVR being 44% in those not previously receiving (PAT) and only 30% previously receiving (PAT) and only 30% in those who had been given PAT (p=.07).in those who had been given PAT (p=.07).
EsmatEsmat et al 2003et al 2003
Prof. Gamal Esmat
ConclusionConclusion
Patients coinfected with HCV and schistosomiasis exhibit a unique clinical, virological and histological pattern
Virologially: by viral persistence with high HCV-RNA titres.
Pathologically: higher necroinflammatory and fibrosis scores in their liver biopsy samples.
Prof. Gamal Esmat
ConclusionConclusion
Dual infections of schistosomiasis and viral infections display significant influences on host immune reactions
cytotoxic T-lymphocyte response,Upregulation of Th2 response → Granulomaformation → fibrosisDownregulation of Th1 response→ chronicity of HCV infection
Prof. Gamal Esmat
ConclusionConclusion
The presence of associated The presence of associated schistosomiasis has determined the schistosomiasis has determined the response of Egyptians with chronic response of Egyptians with chronic hepatitis C to therapy with interferonhepatitis C to therapy with interferon
Prof. Gamal Esmat
Thank youThank you
Prof. Gamal Esmat