Therapy of hepatitis C: overview

Based on the first decade of research on alpha interferon in viral hepatitis, one can conclude that up to 40% of patients with compensated chronic hepatitis C and elevated alanine aminotransferase (ALT) levels will respond at least transiently to interferon. Four forms of alpha interferon have been evaluated in large numbers of patients with chronic hepatitis C: alfa-2b, alfa-2a, alfa-n1, and consensus interferon (CIFN). Responses are defined on the basis of biochemical (ALT) or virological (hepatitis C virus [HCV] RNA testing by polymerase chain reaction [PCR]) end points, and as end-of-treatment response (ETR) or sustained 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 regimens markedly improve the SR rate. Long-term follow-up evaluation in patients with an SR to interferon consistently show long-lasting and significant clinical, virological, and histological improvement. Finally, baseline factors that have been shown to be associated with SR to 6 months of treatment are not accurate enough to predict response. Therefore, the best treatment strategy is a therapeutic trial. Further studies of interferon therapy of hepatitis C are needed to define better virological end points useful in stopping therapy, to understand and better 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 interferon. Finally, newer therapeutic regimens such as the use of induction therapy and combination therapies with ribavirin, other antiviral agents, cytokines, and cytokine modifiers are of primary importance in eventually developing safe and effective means of treatment of hepatitis C.