THERAPY OF HEPATITIS-C - OVERVIEW

Based on the first decade of research on alpha interferon in viral hep atitis, one can conclude that up to 40% of patients with compensated c hronic hepatitis C and elevated alanine aminotransferase (ALT) levels will respond at least transiently to interferon, Four forms of alpha i nterferon have been evaluated in large numbers of patients with chroni c hepatitis C: alfa-2b, alfa-2a, alfa-n1, and consensus interferon (CI FN). Responses are defined on the basis of biochemical (ALT) or virolo gical (hepatitis C virus [HCV] RNA. testing by polymerase chain reacti on [PCR]) end points, and as end-of-treatment response (ETR) or sustai ned response (SR). Biochemical ETR rates to 6 months of therapy range from 35% to 50%, and SR rates 6 months after treatment from 8% to 21%. Although 6-month treatment courses are associated with a significant rate of relapse, 12 months of initial treatment and re-treatment regim ens markedly improve the SR rate. Long-term follow-up evaluation in pa tients with an SR to interferon consistently show long-lasting and sig nificant clinical, virological, and histological improvement. Finally, baseline factors that have been shown to be associated with SR to 6 m onths of treatment are not accurate enough to predict response. Theref ore, the best treatment strategy is a therapeutic trial. Further studi es of interferon therapy of hepatitis C are needed to define better vi rological end points useful in stopping therapy, to understand and bet ter manage significant side effects of interferon, and to evaluate the histological effects of interferon in biochemical nonresponders. Also needed is a better understanding of the causes of resistance to inter feron. Finally, newer therapeutic regimens such as the use of inductio n therapy and combination therapies with ribavirin, other antiviral ag ents, cytokines, and cytokine modifiers are of primary importance in e ventually developing safe and effective means of treatment of hepatiti s C.