A practical guide to the use of interferons in the management of hepatitis virus infections.

The recommended interferon dosage for patients with chronic hepatitis and typical hepatitis B virus (HBV) infection is 10 MU 3 times weekly for 4 to 6 months; with such a regimen sustained alanine aminotransferase (ALT) normalisation, liver histology improvement, clearance of HBV DNA and seroconversion from hepatitis B e antigen (HBeAg) to anti-HBe are obtained in about 40% of treated patients. Patients with elevated disease activity (high ALT values, active chronic hepatitis, low HBV DNA levels) tend to respond better to therapy; Oriental patients and immunocompromised patients are not ideal candidates for interferon. Patients with chronic hepatitis B and the HBeAg-negative variant should be given intermediate dosages (6 to 9 MU thrice weekly) of interferon for prolonged periods (12 months); however, even with this approach, the relapse rate is high (> 60%) during the follow-up. In chronic hepatitis D virus (HDV) infection, therapy with 9 to 10 MU of interferon 3 times weekly for 12 months induces a transient remission in disease (ALT normalisation, HDV RNA clearance) in more than 50% of treated patients, but a sustained response is found in less than 20% of patients. In such disease, baseline predictive factors of long term response are still unknown. In chronic hepatitis C, treatment with 3 to 5 MU of interferon given 3 times weekly for 6 to 12 months induces a sustained remission in no more than 30% of treated patients. Probable predictive factors of long term response are: low viraemia, genotype other than 1, absence of cirrhosis, low intrahepatic iron content, low nucleotide diversity of the envelope 2 gene of the hepatitis C virus. Prolonged (> 12 months) therapeutic courses seem to enhance the sustained response rate; in nonresponders/relapsers, combined therapy (interferon plus indomethacin, interferon plus ketoprofen, interferon plus ribavirin) is promising but randomised controlled trials are needed in order to establish the real efficacy and safety of such therapeutic regimens.