Treatment of chronic hepatitis C: impact of combination therapy

Interferon as a single agent results in normalization of the serum alanine aminotransferase (ALT) levels, loss of detectable serum hepatitis C virus RNA, and histologic improvement in approximately 40% of patients. However, regardless of the duration of initial therapy, most patients relapse within the first few months after the drug is stopped, and only a small proportion have a sustained response. Ribavirin is a nucleoside analogue that is known to have in vitro activity against a number of both RNA and DNA viruses. As a single agent, oral ribavirin treatment transiently lowers serum ALT values into the normal range in about 40% of cases of chronic hepatitis C, but it does not affect the level of viremia. However, when given in combination with interferon for 6 to 12 months, ribavirin results in a sustained normalization of serum ALT levels and loss of detectable hepatitis C virus RNA in 30% to 40% of previously untreated patients. Retreatment of interferon relapsers with the combination of interferon and oral ribavirin for 6 months results in a sustained viral-negative response in about half of patients. Thus far, there is little evidence that combination therapy is effective in patients in whom ALT fails to normalize and who have lost hepatitis C virus RNA during a previous treatment course (nonresponders). Studies are ongoing in this group.