Interferons and liver disease

ABSTRACT

Interferons [INF] are naturally occurring peptides which have antiviral, antitumour and immunomodulatory properties. Interferons alpha, beta and Gamma constitute the main forms. INF alpha is administered by subcutaneous injection in doses ranging from 3 million units three times a week for 24 weeks in treatment of chronic hepatitis C to 5 million units daily for 16 weeks in treatment of chronic hepatitis B. However caution must be exercised before declaring IFN alpha a panacea for chronic viral hepatitis. For example, in chronic hepatitis C only 25% of cases demonstrate a biochemical improvement which is sustained through 6 months follow-up after completion of treatment. Some but not all biochemical responders will have an associated loss of hepatitis C virus. The presence of cirrhosis and/or high viral titres are poor prognostic indicators for biochemical response. It is unclear in HCV infection whether an absent or transient biochemical response would respond to higher doses or longer courses of INF or whether a sustained response is associated with reduced morbidity. Similary, in chronic HBV infection with evidence of active replication, INF may induce seroconversion [HBeAg converting to anti-HBe; loss of HBV DNA] in about 50% of cases and a sustained loss of HBsAg in 10-20% of cases during long-term follow-up. A large viral load, lack of inflammatory activity in the liver with near normal liver enzymes prior to treatment and positive anti-HIV are poor prognostic factors. It is unknown whether INF alpha alters mortality in chronic hepatitis B infection. The efficacy of INF alpha in chronic hepatitis due to mutant forms of HBV has not been studied adequately. INF alpha may be efficacious in some patients with HBV plus HDV infection. INF therapy may be limited by unwanted side effects including leucopenia, thrombocytopenia and malaise