期刊
JOURNAL OF MEDICAL VIROLOGY
卷 78, 期 1, 页码 83-90出版社
WILEY-LISS
DOI: 10.1002/jmv.20507
关键词
HCV; core region; hepatocyte steatosis; interferon; ribavirin; virological non-response; case-control study
类别
Patients with high viral load (>= 1.0 X 10(5) IU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve high sustained virological response rates to interferon (IFN)/ribavirin combination therapy. Previous studies suggested that pretreatment amino acid (aa) substitution patterns in the HCV core region could affect virological non-response especially in patients who could not achieve HCV-RNA negativity during treatment. The present study evaluated 167 consecutive Japanese adults with high HCV genotype 1b viral load who received combination therapy for >= 24 weeks. A case-control study matched for age, sex, genotype, and viral load was conducted to investigate the predictive factors for virological non-response, especially absolute virological non-response (patients who could not achieve > 2 log decline of HCV RNA from baseline during the initial 24 weeks of therapy). Virological non-response was identified in 26.3% of patients, and 45.5% of these were absolute virological non-responders. Multivariate analysis identified ribavirin dose < 11.0 mg/ kg, moderate-to-severe hepatocyte steatosis, and substitutions of aa 70 and/or 91 in the core region as significant independent factors associated with virological non-response. The majority of absolute virological non-responders had such substitutions in the core region (95.0%), as well as substitution of glutamine at aa 70 and/or methionine at aa 91 (90.0%). In the present work, such substitutions significantly affected the viral kinetics in virological non-responders. The results suggest that viral, host, and treatment-related factors determine the response to IFN/ ribavirin combination therapy in patients with high HCV genotype1b viral load, and that amino acid substitution patterns in the core region is potentially useful pretreatment predictor of virological non-response.
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