Significance of a reduction in HCV RNA levels at 4 and 12 weeks in patients infected with HCV genotype 1b for the prediction of the outcome of combination therapy with peginterferon and ribavirin

BACKGROUND: The importance of the reduction in hepatitis C virus (HCV) RNA levels 4 and 12 weeks after starting peginterferon (PEG-IFN) and ribavirin combination therapy has been reported to predict a sustained virologic response (SVR) in patients infected with HCV genotype 1. We conducted a multicenter study to validate this importance along with baseline predictive factors in this patient subpopulation. METHODS: A total of 516 patients with HCV genotype 1 and pretreatment HCV RNA levels ≥5.0 log(10) IU/mL who completed response-guided therapy according to the AASLD guidelines were enrolled. The reduction in serum HCV RNA levels 4 and 12 weeks after starting therapy was measured using real-time PCR, and its value in predicting the likelihood of SVR was evaluated. RESULTS: The area under the receiver operating characteristics (ROC) curve was 0.852 for 4-week reduction and 0.826 for 12-week reduction of HCV RNA levels, respectively. When the cut-off is fixed at a 2.8-log(10) reduction at 4 weeks and a 4.9-log(10) reduction at 12 weeks on the basis of ROC analysis, the sensitivity and specificity for SVR were 80.9% and 77.9% at 4 weeks and were 89.0% and 67.2% at 12 weeks, respectively. These variables were independent factors associated with SVR in multivariate analysis. Among 99 patients who showed a delayed virologic response and completed 72-week extended regimen, the area under ROC curve was low: 0.516 for 4-week reduction and 0.482 for 12-week reduction of HCV RNA levels, respectively. CONCLUSIONS: The reduction in HCV RNA levels 4 and 12 weeks after starting combination therapy is a strong independent predictor for SVR overall. These variables were not useful for predicting SVR in patients who showed a slow virologic response and experienced 72-week extended regimen.