Assessment of efficacy of treatment in HCV: Infection and disease

The hepatitis C virus (HCV) lifecycle appears to be confined to the cytoplasm of hepatocytes. This has translated into the ability to produce sustained virological responses (SVRs) in a substantial proportion of HCV-infected people. Lower treatment responses and higher relapse rates in co-infection may be a consequence of HCV more frequently infecting difficult-to-access reservoirs such as peripheral blood mononuclear cells. However, the durability of sustained response appears to be minimally altered in co-infection. In light of these modest SVRs, and accelerated hepatic fibrosis progression among co-infected people, strategies to slow disease progression take on greater importance. In this context, histological response becomes an important endpoint in co-infection. Multicentre randomized trials of PEG-IFN and ribavirin demonstrate that assessment of histological responses either at the conclusion of therapy or 24 weeks after completion of therapy identify a number of patients who experience improvements in histological activity index in the absence of virological clearance. The prognostic value of serum markers of fibrosis in co-infection has not been validated, but this represents a particularly important area for development in co-infection in light of the probable need for more intensive histological sampling. Eventually, it is anticipated that genotype–phenotype correlations will permit selection of optimized antiviral regimens once virus specific enzymatic inhibitors have been approved.