Ratziu hépatites nane vhg ttv du 2012

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  • ABOTT A partir du sérum des tamarins infectés deux agents inf furent clonés GB-A et GB-B. Synthese de primers communs aux GB-A et B et VHC. Utilisation de ces primers pour PCR dégénerée à partir de sérums de malades ayant ne hépatite inconnue. Ceci a permis le clonage d’n troisième virus GB-C GENELABS Ils ont cloné directement le génome d’un nouveau virus à partir de deux malades ayant une hépatite post-transfusionnelle. Le virus identifié a été appelé VHG VHG et GB-C ont 95% d’homologie. C’est le même virus. GB-A etGB-B ont 27% d’homologie et il s’agit donc de deux virus distincts.
  • antiE2 anticorps dirigés contre la glycoprotéine E2 d’enveloppe
  • the ratio liver / serum of viral RNAis > 100 IN HCV vs<1 in HGV
  • There is agreement that viral RNA in liver is higher than in serum (at least one log for HCV) this indicating that the virus is hepatotropic. There is evidence of interaction between hepatottropic viruses.
  • Ratziu hépatites nane vhg ttv du 2012

    1. 1. Hepatites Non A-E <ul><li>Virus G et TTV … </li></ul><ul><li>et autres considérations métaboliques </li></ul><ul><li>Vlad Ratziu, </li></ul><ul><li>DU Hépatites Virales 2012 </li></ul><ul><li>Hôpital Pitié Salpêtrière, </li></ul><ul><li>Paris, France </li></ul>
    2. 2. Evidence for Additional Hepatitis Agents <ul><li>Prospective transfusion-associated hepatitis studies : 12% </li></ul><ul><li>Acute cases of overt hepatitis : 20% </li></ul><ul><li>Fulminant hepatitis : 25% </li></ul><ul><li>Chronic liver disease : 20-30% </li></ul><ul><li>Hepatitis-associated aplastic anemia : most of them </li></ul>
    3. 3. VHG : GBV-C, 95 % homology VHG : HCV, 29 % homology
    4. 4. HGV Epidemiology and Diagnosis <ul><li>HGV transmission: parenteral +++; vertical </li></ul><ul><li>Risk groups: polytransfused, hemophiliacs, hemodialysis, patients infected with HIV, HCV, HBV </li></ul><ul><li>Diagnosis: </li></ul><ul><ul><li>ongoing infection : HGVRNA without anti-E2 </li></ul></ul><ul><ul><li>exposure with viral clearance : anti-E2 Ab </li></ul></ul>
    5. 5. HGV Epidemiology and Diagnosis <ul><li>HGV prevalence : </li></ul><ul><ul><li>blood donors 1.5-2.5% </li></ul></ul><ul><ul><li>chronic NA-NE hepatitis 10-13% </li></ul></ul><ul><ul><li>cryptogenic cirrhosis 20% </li></ul></ul><ul><ul><li>HCV infection 18-20% </li></ul></ul><ul><ul><li>HBV infection 8-10% </li></ul></ul>
    6. 6. Prevalence of Serum HGVRNA in Acute Hepatitis of Viral Origin <ul><li>non A-E 9 </li></ul><ul><li>HBV 32* </li></ul><ul><li>HAV 25 </li></ul><ul><li>HCV 20 </li></ul>% * : p<0.05 vs HAV and HCV Alter M, NEJM 1997
    7. 7. HGV : is it an Hepatotropic Virus ? Pessoa, Hepatology 1998
    8. 8. HGV : is it an Hepatotropic Virus ? <ul><li>low level of hepatic HGVRNA compared to HCVRNA </li></ul><ul><li>no interaction of hepatic HCVRNA and HGVRNA levels when patients with monoinfection are compared with those infected with both viruses </li></ul>Pessoa, Hepatology 1998
    9. 9. HGV has no Pathogenic Role on the Course of Acute Hepatitis <ul><li>No apparent effect on the clinical course of acute disease among the patients with hepatitis A, B or C </li></ul><ul><li>No effect on the frequency or severity with which chronic hepatitis C develops </li></ul><ul><li>Long-standing HGV viremia but no chronic hepatitis </li></ul>
    10. 10. HGV and Transfusion associated Hepatitis (TAH) <ul><li>HGV can be transmitted by transfusion +++ </li></ul><ul><li>Protracted viremia possible (years) but 90% are mild </li></ul><ul><li>Prevalence of HGV is not higher in non-A-C transfusion associated hepatitis than in HCV, minor ALT elevation or transfused patients with no hepatitis </li></ul><ul><li>HGV milder forms than HCV; HCV-HGV not more severe than HCV </li></ul>A CAUSAL RELATION BETWEEN HGV AND TAH IS NOT ESTABLISHED Alter H, NEJM 1997
    11. 11. HGV in End-Stage Liver Disease and Liver Transplantation <ul><li>HGV infection frequently present in end-stage liver disease (13% in HCV, 22-64% in cryptogenic cirrhosis) </li></ul><ul><li>HGV frequently present and/or acquired after liver transplantation </li></ul><ul><li>HGV does not influence the clinical outcome after liver transplantation. </li></ul>Fried, Hepatology 1997 Pessoa, Hepatology 1998
    12. 12. Does HGV Impact on the Course of other Viral Infections? <ul><li>HCV </li></ul><ul><li>HIV </li></ul>
    13. 13. No Histopathologic Impact of HGV on Chronic Hepatitis C <ul><li>Patients: </li></ul><ul><ul><li>Chronic HCV alone in 85 pts </li></ul></ul><ul><ul><li>Chronic HCV-HGV in 17 pts </li></ul></ul><ul><li>No difference in the necroinflammatory grade, fibrosis stage, proportion of cirrhosis, steatosis or bile duct lesions </li></ul>HGV INFECTION DOES NOT MODIFY THE COURSE OF CHRONIC HCV INFECTION CONTRIBUTION TO LIVER DISEASE LESS THAN OTHER HEPATOTROPIC VIRUSES Bralet, Gastroenterology 1997
    14. 14. Establishing Causality for New Viruses <ul><li>Pathogen present in most cases of the disease </li></ul><ul><li>Pathogen found preferentially in the target organ </li></ul><ul><li>Should not be significantly detectable in subjects without the disease </li></ul><ul><li>Copy number should decrease or become undetectable with resolution of the disease </li></ul><ul><li>Copy number should correlate with disease severity </li></ul>Alter, Postgraduate Course, AASLD 2000
    15. 15. Chronic Liver Disease - Beyond the Viruses ... <ul><li>Definition </li></ul><ul><li>Etiologies </li></ul>
    16. 16. Etiologie de la Cirrhose (n=78) Etude Dionysos (Hepatology 1994) HCV 28 % HBV 9 % HBV+ ALCOOL 3 % HEMO CHROMATOSE 1 % ALCOOL 26 % CBP 1 % HCV+ ALCOOL 3% CRYPTOGENIC 24 %
    17. 17. Factors Associated with ALT Levels <ul><li>SEX </li></ul><ul><li>BMI </li></ul><ul><li>Cholesterol </li></ul><ul><li>Triglycerides </li></ul><ul><li>Glycemia </li></ul><ul><li>Oral contraceptives </li></ul><ul><li>Smoking </li></ul><ul><li>Age </li></ul><ul><li>Physical exercise </li></ul><ul><li>Medications </li></ul>Piton, Hepatology 1998 Prati, Ann Intern Med 2002
    18. 18. What is a Normal ALT Value ? <ul><li>“ Normal” ALT ranges from </li></ul><ul><ul><li>26 UI/l (females, 95th percentile) to </li></ul></ul><ul><ul><li>66 UI/l (males BMI > 26 kg/m²) </li></ul></ul><ul><li>New definitions of normal ALT (no overweight, lipid, carbohydrate alterations) : </li></ul><ul><ul><li>30 UI/l for men </li></ul></ul><ul><ul><li>19 UI/l for women </li></ul></ul>Piton, Hepatology 1998 Prati, Ann Intern Med 2002
    19. 19. Clinical Implications of the Different Thresholds for Normal ALT <ul><li>Blood donors </li></ul><ul><ul><li>male donors : 4 - 20% </li></ul></ul><ul><ul><li>female donors : 1.5 - 16% </li></ul></ul><ul><li>HCV infection </li></ul><ul><ul><li>males : 13 - 22 % </li></ul></ul><ul><ul><li>females : 20 - 45 % </li></ul></ul>Piton, Hepatology 1998 abnormal ALT
    20. 20. Chronic Liver Disease - Beyond the Viruses ... <ul><li>Etiologies : </li></ul><ul><ul><li>Overweight, Diabetes +++ </li></ul></ul><ul><ul><li>Covert Alcohol </li></ul></ul><ul><ul><li>Drugs </li></ul></ul><ul><ul><li>Seronegative autoimmune liver diseases </li></ul></ul><ul><ul><li>Vascular liver diseases </li></ul></ul><ul><ul><li>Celiac disease </li></ul></ul><ul><ul><li>Occult HBV </li></ul></ul>
    21. 21. Impact of Overweight on Chronic Liver Disease <ul><li>< 25 32 0.3 (0.32-0.33) </li></ul><ul><li>25-27 25 1.16 (1.15-1.17) </li></ul><ul><li>> 27 45 1.83 (1.81-1.85) </li></ul>BMI (kg/m 2 ) % Relative Risk (CI 95%) Dionysos Study, n = 1211 (6917 total) (Bellentani Hepatology 1994)
    22. 22. Proportion of Patients With Cryptogenic Cirrhosis according to BMI - UNOS Database > 40 BMI 35 - 40 30 - 35 25 - 30 < 25 HCV Alcohol Cryptogenic N =19271 % (Nair, Hepatology 2002)
    23. 23. Obésité et Cirrhose Cryptogénétique Cirrhose X NASH Cirrhose C CBP N Age Obésité (%) Femmes (%) Diabète (%) 70 50 39 33 63 (+/- 11) 49(+/- 14 ) 60 (+/-7) 54 (+/-10) 70 56 36 100 47 64 3 15 53 42 25 15 Caldwell, Hepatology 1999
    24. 24. <ul><li>Normal : 10 % </li></ul><ul><li>Steatosis alone : 48 % </li></ul><ul><li>Steatohepatitis : 42 % </li></ul>Liver Histology in Overweight Patients n = 858 ; 9 studies, 1978 - 2002
    25. 25. Prevalence of NASH/NAFLD <ul><li>First (or second) cause of chronic liver disease in Western Countries </li></ul><ul><li>Prevalence among patients with abnormal LFTs of undetermined etiology (n=673, 5 studies) </li></ul><ul><li>steatosis alone : 30% </li></ul><ul><li>steatohepatitis : 26% </li></ul>
    26. 26. Hepatic Fibrosis in NASH <ul><li>None or mild 65 </li></ul><ul><li>Severe (cirrhosis excepted) 20 </li></ul><ul><li>Cirrhosis 15 </li></ul>% n= 572, 9 studies 1980 - 2001
    27. 27. Risk Factors for Severe Fibrosis in NASH <ul><li>Age > 45-50 yrs </li></ul><ul><li>Diabetes </li></ul><ul><li>ALT>2N </li></ul><ul><li>BMI > 27 kg/m² </li></ul><ul><li>HTA </li></ul><ul><li>HyperTG </li></ul><ul><li>AST/ALT > 1 </li></ul>Ratziu, Gastroenterology 2000 Angulo, Hepatology 1999 Dixon, Gastroenterology 2001
    28. 28. Abnormal Liver Function Tests <ul><li>A frequent problem in clinical hepatology </li></ul><ul><li>New viruses : less of a problem </li></ul><ul><li>NAFLD : more of a problem </li></ul><ul><li>Identifying patients at risk of liver disease - that is the problem ! </li></ul>

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