The role of genomic and antigenomic HCV-RNA strands as predictive factors of response to pegylated interferon plus ribavirin therapy

Background: Hepatitis C virus replicates by the synthesis of an antigenomic HCV-RNA. As the end point of anti-viral therapy is to decrease viral replication, the amount of antigenomic HCV-RNA could influence the response. Aim: To study if amounts of genomic and antigenomic HCV-RNA in the baseline liver biopsy are predictive factors of response to anti-viral therapy. Methods: Eighty-eight patients with chronic HCV infection (anti-HIV-negative) treated with pegyltaed-interferon-α2b plus ribavirin for 12 months were included. Intrahepatic genomic and antigenomic HCV-RNA concentrations were determined by real-time polymerase chain reaction and percentage of infected hepatocytes by in situ hybridization. Results: Of the 88 patients, 31% were responders while 69% were not. Median of antigenomic HCV-RNA in liver of responders and non-responders was 120 000 copies/μg RNA (range: 10 000-775 000) vs. 150 000 copies/μg RNA (range: 100-3 200 000; P = 0.38). Median of genomic HCV-RNA in liver of responders was 1 250 000 copies/μg RNA (range: 5000-9 000 000) and in non-responders 3 180 000 copies/μg RNA (range: 4600-18 000 000; P = 0.0191). Predictive factors of response in the logistic regression were: intrahepatic amount of genomic HCV-RNA, percentage of infected hepatocytes and previous therapy. Conclusion: Response to 12 months of therapy with pegylated interferon-α2b plus ribavirin depends on the amount of genomic HCV-RNA in the pre-treatment liver biopsy. © 2007 The Authors.