The Management of Viral Hepatitis

Canadian Association for Study of the Liver

Proceedings of a consensus conference held in
Montreal, Quebec in March 1999

SUMMARY OF RECOMMENDATIONS

CHRONIC HEPATITIS B

• Although acute hepatitis B continues to be an important clinical problem in Canada the majority of acute cases will resolve and clear HBsAg spontaneously. Chronic HBV infection, established when HBsAg is detectable for longer than 6 months with or without continuing liver enzyme abnormalities accounts for the greatest burden of disease.

Who should be tested?

• Any patient with clinical or laboratory evidence for either acute or chronic liver disease should be considered as possibly infected with HBV.

HBV DNA Assays

• It is important for the clinician to understand the type of assay methodology used, and its limitations, and that a consistent methodology be used for all assays.

• HBV DNA testing should be limited to those patients being considered for treatment and to evaluate response to treatment. It is not indicated routinely in the evaluation of all HBsAg-positive patients. HBV DNA testing should be readily available to qualified practitioners regularly involved in the treatment of HBV.

Treatment of the Hepatitis B Carrier

• In the HBeAg-positive patient with abnormal ALT levels liver biopsy is Bly recommended, but not mandatory.

• Therapy may be with either interferon or lamivudine. Interferon is given at a dose of 27-35 mu weekly (5-6mu daily or 9-10 mu TIW) for 16 weeks. Lamivudine is given at a dose of 100 mg daily for 52 weeks.

• Lamivudine therapy for patients who are anti-HBe-positive and HBV DNA-positive is still considered experimental.

• The use of prednisone withdrawal prior to interferon therapy is contraindicated in the management of HBV-associated disease.

• There is insufficient information to recommend routine screening of immunosuppressed patients for HBV infection.

• There is also insufficient information to recommend lamivudine anti-viral prophylaxis for immunosuppressed patients who are known to be hepatitis B carriers.

Hepatitis D Virus

• Patients with active hepatitis D should be treated in expert centres.

Decompensated Hepatitis B Cirrhosis:

• Low dose interferon is not recommended in decompensated hepatitis B cirrhosis. Patients with decompensated chronic hepatitis B should be referred to a liver transplant center, and treatment with lamivudine coordinated with the transplant center.

Glomerulonephritis

• The indications for interferon therapy in patients with hepatitis B-induced membranproliferative glomerulonephritis are the same as for hepatitis B patients without glomerulonephritis. In membranous glomerulonephritis, the renal disease per se is an indication for interferon therapy. No recommendations for or against the use of lamivudine could be made.

Chronic Hepatitis B in Children

• Optimal treatment is between 3-6 Mu/m2 interferon thrice weekly for 6 months. The indications for treatment are similar to those in adults.

HEPATITIS C VIRUS

• Patients who are anti-HCV-positive who have spontaneously developed negative HCV RNA by PCR should continue to be monitored at intervals for the presence of liver disease.

• Factors that increase the risk of progression to cirrhosis include age over 40, consumption of even moderate amounts of alcohol, and increased age of acquisition of infection.

• The risk of progression to cirrhosis also appears related to the degree of liver inflammation and fibrosis seen at the time of a biopsy. Patients with persistently normal ALT have a lower likelihood of progression to cirrhosis.

Use of HCV RNA testing

• Qualitative HCV-RNA testing is not essential to make the diagnosis of hepatitis C in typical patients who are anti-HCV positive.

• Quantitative HCV RNA testing is not routinely required for all patients.

Sexual transmission of the hepatitis C virus

• HCV intra-spousal transmission appears to be rare in the absence of a parenteral risk in the partner.

• The infected person should inform sexual partners. Testing should be offered to the sexual partner. Patients should be advised to avoid sharing items of personal hygiene. In short-term sexual relationships condom use is advised. Unprotected sex during menstruation should be avoided. Couples should be given information about the risks of transmission, and about precautions which may reduce the risk of transmission in stable monogamous relationships. The committee neither recommends nor recommends against the use of condoms. The choice belongs to the couple.

Mother-to-Infant Transmission of Hepatitis C Virus

• Rates of transmission of hepatitis C from mother to newborn infant vary between 0 and 3% according to different reports.

• Breast feeding is considered safe and is not contraindicated

• Testing for hepatitis C infection within the first 18 months of life should be by PCR assays.

Therapy for Chronic Hepatitis C

• The prime indication for treatment in chronic hepatitis C is an ALT level more than 1.5 times the upper limit of normal on three consecutive occasions over more than three months.

• A liver biopsy is recommended for grading and staging of the liver disease.

• It is recommended that response to treatment be defined in virologic terms.

• Successful treatment is indicated by clearance of hepatitis C virus RNA from serum (by sensitive PCR-based assays) 24 weeks after the completion of therapy (sustained response).

Dose and Duration of Treatment

• The recommended treatment for chronic hepatitis C is with a combination of interferon alpha 2b and ribavirin. The dose of interferon is 3 mu TIW, and the dose of ribavirin is 1000 mg for patients weighing less that 75 kg, and 1200 mg daily for patients weighing more than 75 kg

• Patients who carry genotypes 2 or 3 may be treated for 24 weeks. Patients carrying any other genotype should be treated for 48 weeks.

• A positive HCV RNA assay after 24 weeks of therapy is an indication to stop treatment.

• Interferon monotherapy should now be reserved for patients who cannot tolerate ribavirin

Contraindications to therapy

• In assessing whether a patient is a good candidate for therapy with interferon and ribavirin, it is essential to consider the benefits and risks for that individual.

• Absolute contraindications to therapy with interferon and ribavirin are decompensated liver disease, active alcohol abuse, pregnancy or lack of appropriate contraception and expected non-compliance.

Treatment Failures

• Relapse after interferon monotherapy: - These patients should be offered treatment with interferon and ribavirin.

• Non-responder to interferon monotherapy: -There is insufficient information to make a recommendation on the effectiveness of any of the therapeutic options for patients who were non-responders to interferon monotherapy.

• Failure of combination therapy: - There are no proven treatment options for these patients at present

Hepatitis C Infection in Children

• Chronic hepatitis C in children should not be treated except in controlled trials.

Acute hepatitis C

• No recommendations can be made about the timing of therapy of acute hepatitis C

• Healthcare workers or others subjected to needle-stick injury or equivalent exposure should be tested by anti-HCV at the time of the injury at 12 weeks to detect infection. Treatment should be with standard combination therapy of interferon and ribavirin for the standard duration despite the lack of prospective studies proving efficacy. Given the urgent need to gather data on such cases it is strongly recommended that patients with acute hepatitis C be treated in the setting of a clinical trial or a registry.

COMBINED INFECTIONS

• In patients who are HBeAg-positive with detectable HBV DNA, undetectable HCV RNA and elevated aminotransferases, treatment is with interferon 27-36 mu weekly for 4 months.

• In patients who are HBeAg-positive with detectable HBV DNA, undetectable HCV RNA and elevated aminotransferases, treatment is with interferon 27-36 mu weekly for 4 months.

• Chronic hepatitis B in HIV-infected patients must not be treated with lamivudine monotherapy.

• There are no recommendations about therapy in patients co-infected with hepatitis C and HIV.

SCREENING FOR HEPATOCELLULAR CARCINOMA

• In the absence of documented benefit of mass screening, the committee makes no recommendations for or against screening for HCC in HBsAg-positive patients, nor for patients with chronic hepatitis C. Screening may be justified in high risk cases (presence of cirrhosis, long duration of infection, HBV/HCV co-infection, past curative resection for HCC, family history of HCC [HBV only]).

HEPATITIS B VACCINATION

• The vaccination strategy for Canada should be universal vaccination of all neonates, combined with screening of all pregnant women. Newborns of infected mothers should be given hepatitis B immunoglobulin in addition to the vaccine. A catch up program should be instituted for all children and young adults who have not yet been vaccinated. There should be a standardized national policy, so that vaccination is assured for all children when their families move between provinces.

• Serologic testing post-immunization is not routinely recommended.

HEPATITIS A VACCINATION

• Current recommendations by NACI with regard to populations in whom vaccination is appropriate remain pertinent.

HEPATITIS G VIRUS

• Routine screening of blood donors or wide spread testing for HGV is not recommended.

TRANSFUSION TRANSMITTED VIRUS

• No active attempt at diagnosing this infection is required.

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