Management of Viral Hepatitis: Clinical and Public Health Perspectives

1. 2 / 98 1 Management of Viral Hepatitis:Clinical and Public Health Perspectives This set of educational slides is made possible by The Hepatitis Information Network Schering-Plough of Canada (www.HepNet.com)

2. 2 / 98 2 Management of Viral Hepatitis:Clinical and Public Health PerspectivesDerived from...A Consensus Statement The CASL Hepatitis Consensus Group Published August 1997

3. 2 / 98 3 Participants Dr. Paul Adams Dr. Vince Bain Dr. William Depew Dr. Victor Feinman Dr. Cameron Ghent Dr. Jenny Heathcote Dr. Mang Ma Dr. Sam Lee Dr. Pierre Pare Dr. Eve Roberts Dr. Richard Schreiber Dr. Averell Sherker Dr. Morris Sherman Dr. Urs Steinbrecher Dr.Bernard Willems Dr. CN Williams Dr. Paul Gully: LCDC Dr. B. Larke: Red Cross Mr. R. McClory: CLF Ms. B. Potkonjak: CLF Dr. P. Chan: Krever Comm.

4. 2 / 98 4 Therapy for Hepatitis B Interferon alpha is the only licensed drug Standard indications and contraindications have not changed since last consensus Recommendation: HBeAg+ hepatitis B carriers who have ALT levels >2X ULN for >4 months should be treated with IFN-alpha with 27-35 MU weekly for 4 months. Can be given in divided doses three times/week or daily.

5. 2 / 98 5 Therapy Options for Hepatitis B Relapsers patients who relapse usually respond to second course of treatment Recommendation: HBeAg+ HBV carriers who relapse after treatment can be retreated. Non-responders patients who fail to normalize ALT or lose HBeAg Recommendation: Retreatment of non-responders not recommended. Refer to expert centers.

6. 2 / 98 6 Therapy Options for Hepatitis B Prednisone Pretreatment small benefit with added risk of death due to flare Recommendation: Pretreatment with Prednisone should be avoided. Hepatic Decompensation patients with lesser degree of hepatic decompensation may be treated with low dose of IFN-alpha (Child�s A and B), however, Child�s C should not be treated Recommendation: Carriers with hepatic decompensation should be referred to expert centers for assessment and possible treatment. Liver treatment may be required.

7. 2 / 98 7 Therapy Options for Hepatitis B Anti-HBe+ HBV carrier with replicating virus may be more aggressive with rapid progression to cirrhosis and liver failure good initial response to interferon, but relapse rate high (about 90%) Recommendation: Anti-HBe+ HBV carrier with >ALT and HBV-DNA+ should be treated only in trial settings.

8. 2 / 98 8 Therapy Options for Hepatitis B Chronic hepatitis B in children ALTs often normal if HBeAg+ with >ALT for 4-6 months can be considered for treatment response rates in randomized controlled trials ranged from 20-50% interferon not currently licensed for children Recommendation: Refer to expert centers.

9. 2 / 98 9 Coinfection with Hepatitis B Hepatitis B and HIV HIV+ patients do not respond well to interferon treatment with Lamivudine for HIV may clear HBV-DNA in some patients Hepatitis B and Hepatitis C dominant infection should be treated Recommendation: Refer to expert centers.

10. 2 / 98 10 Therapy Options for Hepatitis B Nucleoside Analogs Lamivudine analog of cytidine not licensed for hepatitis B <HBV replication and often clears HBV-DNA virological and clinical relapse frequent after treatment ends Famciclovir analog of guanine not licensed for hepatitis B <HBV replication and often clears HBV-DNA virological and clinical relapse frequent after treatment ends Recommendation: Nucleoside Analogs remain experimental and should be used only in a trial setting or in expert centers with select cases.

11. 2 / 98 11 HBV-DNA Testing Not widely available Almost all HBeAg+, >ALTs will be HBV-DNA+ and therefore testing not necessary In treatment responders (normal ALT, HBeAg-, HBV-DNA will likely be negative) Recommendation: HBV-DNA is advisable, but not essential. It is essential in some some subgroups (anti-HBeAg+, Normal Alts and some post transplant settings).

12. 2 / 98 12 Interferon Treatment for Hepatitis C Dose remains 3 MU three times/week Duration 12 months due to higher sustained response rates (previous consensus was 6 months) Response Rate expected in about 30% of patients Recommendation: If the ALT has not fallen to normal range at 8-12 weeks, treatment should be stopped.

13. 2 / 98 13 Patient Selection ALTs patients with ALTs 1.5X ULN (was 2X in 1994 Consensus) should be treated subjects with normal ALTs often fail to clear HCV-RNA Recommendation: Patients with chronic hepatitis C and normal ALTs should not be treated. HCV-RNA response to IFN inversely proportional to HCV-RNA Recommendation: HCV-RNA testing is not essential before undertaking treatment in patents with the standard indications.

14. 2 / 98 14 Patient Selection Genotypes 6 different genotypes now identified type 1 is more aggressive and responds less well Recommendation: HCV genotyping is not required for usual clinical practice.

15. 2 / 98 15 Patient Selection Cirrhosis response is lower than non-cirrhotics insufficient on it�s own to exclude patients from treatment Recommendation: Treatment should not be denied on the basis of cirrhosis alone, but careful consideration should be given to the likelihood of benefit. Patients with decompensation should not be treated with interferon.

16. 2 / 98 16 Sexual Transmission of Hepatitis C Although it occurs, it is NOT considered to be a sexually transmitted disease prevalence estimated at 0 to 4% in heterosexuals prevalence estimated at 1 to 3% in homosexuals Recommendations: inform sexual partners and offer testing pre-test counseling should be given patients and partners should know the risks of sexual transmission condoms recommended in short term relationships

17. 2 / 98 17 Interferon Treatment for Acute Hepatitis C Diagnosed following transfusion or needlestick Usually asymptomatic in community exposure Recommendation: Treat with interferon at a dose of at least 3 MU TIW for 3-6 months. Test healthcare workers with needlestick exposure from HCV source with PCR assays Tests could be positive 2 weeks after infection anti-HCV takes much longer to confirm Recommendation: Use most sensitive available test and treat at the first diagnosis of infection.

18. 2 / 98 18 Hepatitis C Infection in Children High prevalence in those who received multiple transfusions prior to hep C testing Perinatal infection from HCV+ mother approximately 5% Not licensed for use in children under 18 Young children treated with interferon may result in: anorexia, weight loss, and growth retardation Recommendation: Chronic hepatitis C in childhood should not be treated except in the setting of clinical trials.

19. 2 / 98 19 Population Screening for Hepatitis Both B and C common with significant mortality and morbidity Hepatitis B benefits: opportunity to offer vaccination to family and sexual contacts identification of patients suitable for treatment treatment decreases incidence of cirrhosis and HCC treatment increases survival screening should be offered to all members of high risk groups and programs developed for screening other 50% Hepatitis C widespread screening not recommended in the absence of identified risk factors, or liver disease

20. 2 / 98 20 Screening for Hepatocellular Carcinoma Risk highest in those with HBV in childhood in Canada, mostly immigrant population Screening is being widely carried out but benefits vary risk of HCC in non-cirrhotic patients with chronic hep C is very low Recommendation: In the absence of benefit from screening� no recommendation could be made for or against screening.

21. 2 / 98 21 Hepatitis G Structurally similar to hepatitis C virus Exists in blood and transmitted by transfusion Can cause elevation in ALTs and persist for months to years Evidence that it causes chronic liver disease is inconclusive Assays currently unsuitable for screening Recommendation: Widespread screening is not currently recommended.

22. 2 / 98 22 Role of Public Health Authorities Responsibility of prevention and control contact tracing of patients arranging and ensuring vaccination (hep B) chronic carriers should be informed about possible treatment Recommendation: standardized approach to monitoring is needed should include full follow-up and contact tracing for acute and chronic hepatitis B and hepatitis C patients should be given complete and accurate information about their infection should be standardized for all public health units data should be collected in a standard way for hepatitis B and C

23. 2 / 98 23 Summary Hepatitis B Therapy for hepatitis B remains the same Hepatitis B patients who relapse should be retreated, non-responders should not Refer the following to expert centres decompensated patients children with chronic hepatitis B hepatitis B and HIV coinfection hepatitis B and HCV coinfection Treat only in trial settings anti-HBe+ HBV carrier with replicating virus use of Nucleoside Analogs

24. 2 / 98 24 Summary for Hepatitis C Treatment length/dose: 3 MU TIW for 12 months Patients with ALTs 1.5 X ULN should be treated Response determined at 8-12 weeks by ALT Patients normalizing ALT will continue treatment to end of 12 month period After needle-stick exposure, test and treat at a dose of at least 3 TIW for 3-6 months. Children should not be treated except in clinical trials

25. 2 / 98 25 Summary for Hepatitis C Patients and partners should know the risks of sexual transmission HCV-RNA testing is not essential before undertaking treatment in patients with the standard indications. Normal ALT patients should not be treated at this time Patients should not be denied treatment due to cirrhosis, genotype, etc.

26. 2 / 98 26 Canadian Hepatitis Consensus Statement 1997Hepatitis B HBeAg+ patients with ALTs 2x ULN for more than 4 months should be treated (was 6 months in 1994 Consensus) Patients who respond and relapse can now be retreated Some patients should be referred to expert centres for treatment hepatitis B and HIV coinfection hepatitis B and HCV coinfection decompensated patients children with chronic hepatitis B

27. 2 / 98 27 Canadian Hepatitis Consensus Statement 1997Hepatitis C Patients with ALTs 1.5X ULN (was 2X in 1994 Consensus) should be treated for 12 months (was 6 months in 1994 Consensus) if ALTs normalize at 8 -12 weeks if HCV-RNA is negative at 8 -12 weeks HCV-RNA is not needed before treatment begins Increasing IFN dose for non-responders is not recommended Normal ALT patients should not be treated not enough clinical data available Patients should not be denied treatment due to: cirrhosis, genotype, older age, or duration of infection Chronic patients should be informed about possible treatment treatment decreases incidence of cirrhosis and HCC treatment increases survival

28. 2 / 98 28 Canadian Hepatitis Consensus Statement 1997General Information Sexual Transmission (hep C) short-term relationships should use condoms, long-term relationships - no recommendations for or against condom use (sexual transmission can occur, but hep C is not considered a sexually transmitted disease) Breast Feeding (hep C) virus can be found in breast milk - no recommendations for or against Hepatocellular Carcinoma no recommendations for or against Public Health recommends full follow-up and contact tracing for acute and chronic patients