Recent Advances in Pegylated Interferon Antiviral Therapy of Chronic Hepatitis C

Effective hepatitis C antiviral treatment is important given the significant global morbidity and mortality from liver-related complications. Therapy for hepatitis C has advanced remarkably in the past two decades starting with interferon- alpha (IFN) monotherapy, followed by genetically engineered recombinant interferons (consensus IFN alpha) and subsequently IFN alpha in combination with the nucleoside analog ribavirin. The current gold standard is a combination of long-acting pegylated interferon (PEG-IFN) with ribavirin achieving a sustained virological response (SVR) with acceptable safety profiles in 54-66% of patients. These therapies have significantly contributed to our armamentarium against hepatitis C virus infection. Despite this success some subgroups have lower response rates (i.e. previous IFN nonresponders, patients with genotype 1 or cirrhosis). Moreover, the question of a “true SVR ” has been raised. Recent studies confirming detection of residual HCV RNA using ultra-sensitive polymerase chain reaction (PCR) based assays in patients many years after complete clinical resolution of chronic hepatitis C raise concerns whether these patients have actually been cured. In this paper we review the natural history, epidemiology and basic virology of hepatitis C. Current treatments and long-term benefits of achieving a SVR, including the antiviral and anti-inflammatory effects of IFN are also explored. Finally, we review the current understanding of persistent occult viremia in patients apparently cleared of HCV after achieving SVR with antiviral treatment.