Open Access Research article

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

Hidenori Toyoda1, Takashi Kumada1*, Noritomo Shimada2, Koichi Takaguchi3, Tatsuya Ide4, Michio Sata4, Hiroyuki Ginba5, Kazuhiro Matsuyama5 and Namiki Izumi6

Author Affiliations

1 Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan

2 Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Japan

3 Department of Internal Medicine, Kagawa Prefectural Central Hospital, Takamatsu, Japan

4 Department of Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan

5 Department of Life Cycle Management, Roche Diagnostics Japan K.K, Tokyo, Japan

6 Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan

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BMC Infectious Diseases 2012, 12:324  doi:10.1186/1471-2334-12-324

Published: 27 November 2012

Abstract

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 log10 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-log10 reduction at 4 weeks and a 4.9-log10 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.

Keywords:
Chronic hepatitis C; Peginterferon; Ribavirin; Reduction in HCV RNA levels; Four and twelve weeks; Baseline factors; Response-guided therapy; Extended treatment