Hepatitis C Viral Kinetics as a Determinant of Stopping Pegylated Interferon and Ribavirin in Genotype 1 Infection

Despite a substantial progress in the management of hepatitis C virus (HCV) infection for the last decade, the probability of achieving sustained virologic response (SVR) in genotype 1 infection just ranges from 40% to 55% with pegylated interferon (PEG-IFN) and ribavirin (RBV) for 48 weeks which has been the standard-of-care. Furthermore, a variety of adverse events associated with PEG-IFN and RBV are major obstacles to complete the antiviral therapy, particularly in cirrhotic or elderly patients. The baseline predictors of achieving SVR in genotype 1 patients were extensively studied and include IL28B single nucleotide polymorphism, viral loads, body mass index, and so on. Currently, there are two stopping rules in genotype 1 HCV infected patients who receive PEG-IFN and RBV therapy. Failure to achieve early virologic response (EVR) defined by HCV RNA ≥2 logIU/mL at week 12 has been a strong indicator of stopping antiviral therapy with PEG-IFN and RBV. A high negative predictive value (97%) of EVR justifies universal assessment of viral loads at week 12 of PEG-IFN/RBV treatment in genotype 1 infection. Discontinuation of PEG-IFN and RBV is also recommended in patients who show detectable HCV RNA at week 24 if they achieve partial EVR (HCV RNA decrease ≥2 logIU/mL, but still detected). The clinical significance of rapid virologic response (RVR) defined by undetectable HCV RNA at week 4 is that the patient has a favorable response to interferon and it would be possible to shorten the treatment duration from 48 to 24 weeks. During antiviral therapy with PEG-IFN and RBV, early identification of patients with genotype 1 infection who are going to fail to achieve SVR has clinical implications that appropriate discontinuation could prevent wasting of medical resources and