Clinical use of interferon in hepatitis B and C

Abstract

The concept of antiviral therapy with interferon for chronic hepatitis B emerged in the middle of the seventies and was supported by the suppressive effect of human interferon on HBV-DNA polymerase levels in 3 patients. This effect of leukocyte interferon was confirmed in a small controlled study of patients with HBeAg-positive chronic hepatitis B; however, no effect was found on other indices of hepatitis B. More than 10 years elapsed before one large RCT demonstrated clinically relevant virological responses in 35% vs. < 10% in placebo and led to registration of interferon for hepatitis B. Responses in HBeAg-negative chronic hepatitis B were very high during treatment but high relapse rates eliminated most of the long-time treatment effect. Interferon has now to compete with highly effective nucleoside analog therapy, but still has a prominent place as a limited duration therapy leading to sustained and sometimes complete responses. In the middle of the eighties, interferon was tested in 10 patients with non-A, non-B chronic hepatitis and ALT normalization was observed in the majority. After the discovery of the hepatitis C virus and the introduction of the HCVRNA PCR test it became clear that interferon therapy can cure hepatitis C infections. Widespread therapy was introduced after a co-drug ribavirin was found to reduce relapse rates and two pivotal trials with recombinant interferon showed sustained virological responses in about 50% of patients, with much higher positive outcomes in genotype 2 and 3. Therapy-induced sustained virological remission has been shown to reduce liver-related death, liver failure and to a lesser extent hepatocellular carcinoma. Interferon has become the key drug for hepatitis C.