Optimizing Treatment with Pegylated Interferon-Ribavirin of Genotype 3 Chronic Hepatitis C: More Questions than Answers

Hepatitis C virus (HCV) is the foremost cause of parenterally transmitted non-A, non-B hepatitis. Effective treatment with Interferon (IFN) based regimens has been shown to reduce morbidity and mortality, improve health-related quality of life, and avoid the huge costs associated with end stage liver disease. HCV-3 has been associated in Europe and the USA to illicit drug abuse in the 70's, while recent epidemiological reports have shown that HCV-3 prevalence is on the rise in both Western Europe and in Middle East. The standard of care for patients with HCV-3 is a 24 week therapy regimen with a combination of Pegylated Interferon (Peg-IFN) and Ribavirin (RBV). Despite the cumulative high rates of sustained virological response (SVR) obtained with this schedule of treatment, it is now clear that a subgroup of patients exists in which lower rates of SVR are achieved. Bridging fibrosis/cirrhosis, high baseline viremia and lack of rapid virological response (RVR) have been identified as predictors of treatment failure in many studies. Recently, "allocation" and randomization trials based on HCV-RNA negativity at week 4 (RVR) have evaluated the chance of abbreviating the treatment schedule to 12-16 weeks, since RVR emerged as a strong predictor of SVR. In this review article we will discuss the current therapeutic strategies in HCV-3 to understand in which subset of patients further treatment customization is possible.