Pegylated interferon with ribavirin therapy for chronic infection with the hepatitis C virus

Chronic infection with the hepatitis C virus is common. In the past, therapy involved a combination of thrice-weekly interferon (IFN) injections combined with oral ribavirin. This therapy was expensive, poorly tolerated and poorly effective, only curing approximately 40% of treated patients. Long-acting IFNs have recently been developed by linking IFN to polyethylene glycol and these 'pegylated' IFNs are now the standard of care for patients with chronic hepatitis C (CHC). Two pegylated (PEG) IFNs are available; 40 kDa PEG-IFNalpha(2a) (Pegasys, Hoffmann-La Roche) and the 12 kDa PEG-IFN-alpha(2b) (Peg-Intron, Schering-Plough). They have different physicochemical, pharmacokinetic and pharmacodynamic properties. The 40 kDa PEG-IFN-alpha(2a) is dispensed as a solution and used at a fixed dose whereas the 12 kDa PEG-IFN-alpha(2b) is a dry powder, which is reconstituted prior to administration, and the dose is dependent upon body weight. Both PEG-IFNs are given by a once-weekly injection and as monotherapy, they are more effective than standard IFN-alpha. The 40 kDa PEGIFN-alpha(2a) cures 36 - 39% of patients and the 12 kDa pegylated-IFN-alpha(2b) cures 23 - 25%. When combined with ribavirin, the two PEG-IFNs have acceptable safety profiles and cure > 50% of treated patients (56 and 54% for the 40 kDa PEG-IFN-alpha(2a) and 12 kDa PEG-IFN-alpha(2b), respectively). For the 40 kDa PEG-IFN-alpha(2a) it is possible to predict the outcome of therapy after 12 weeks of treatment. The new PEG-IFNs are a significant advance in the therapy of CHC infection. Their ease of administration, coupled with their improved efficacy, is likely to lead to an increase in the proportion of infected patients who wish to receive treatment.