Predicting the therapeutic response in patients with chronic hepatitis C: the role of viral kinetic studies

A substantial proportion of patients infected with hepatitis C virus (HCV) genotype 1 still does not respond to pegylated interferon-alfa/ribavirin (IFN/RBV) therapy. Factors which identify potential non-responders are needed to limit exposure to drugs in patients unlikely to benefit from treatment and to save health care resources. Host predictive factors have a low negative predictive value. In contrast, viral factors have a high precision in predicting outcome of therapy. Viral kinetics are the basis for the study of response of therapy. The decrease in viral load within 24 h after administration of a single test dose of conventional IFN reflects the IFN-sensitivity of the virus strain and predicts the outcome of conventional IFN/RBV therapy even before treatment with a specificity of 100% and a sensitivity of 83%. In contrast to conventional IFN, the two available PEG-IFN preparations differ considerably in how they suppress viral replication, and cut-off values have to be prospectively established separately for each drug. Patients without an early virological response (HCV-RNA either undetectable or decrease by >or=2 log10 after 12 weeks) (EVR), do not achieve a sustained virological response (SVR; negative predictive value: 97-98%). Thus, in the absence of an EVR, treatment should be stopped. The outcome of PEG-IFN alfa-2a/RBV combination therapy is dependent on the rapidity of the virological response. Patients who become HCV-RNA negative after 4 weeks have the best chance of achieving an SVR. The rapidity of viral elimination may be a useful guide to tailoring the length of treatment in patients with an EVR.