title: HCV core gene polymorphisms correlate with liver fibrosis but not sustained virological response in patients with genotype 1 infection.
abstract: BACKGROUND
  Amino acid (aa) substitutions in genotype 1 HCV core region (HCV-CR) serve as a negative predictor of treatment responses in Japanese chronic hepatitis C (CHC) patients. Whether this phenomenon could be extrapolated to non-Japanese patients remains unclear. We evaluated the effect of aa substitutions in HCV-CR on clinicopathological features and treatment responses in Taiwanese patients.
  
  
  METHODS
  Clinical and serial virological data were collected from 147 consecutive Taiwanese HCV genotype 1 patients who received pegylated interferon plus ribavirin therapy. Quantification of HCV RNA and sequences of HCV-CR were determined by molecular methods.
  
  
  RESULTS
  Of 147 patients, 90 (61.2%) attained rapid virological response (RVR) and 97 (66.0%) attained sustained virological response (SVR). Patients without aa substitutions in HCV-CR (coreWW) had a higher SVR than those with both aa70 and aa91 substitutions (coreMM; 70.5% versus 45.0%; P=0.039). Moreover, coreMM was associated with a higher γ-glutamyl transpeptidase level (P=0.026) as well as more severe liver fibrosis (P=0.027) than coreWW, and patients with aa70 substitution (coreMW) were associated with more severe liver steatosis and fibrosis than those without (P=0.020 and P=0.002, respectively). In multivariate analyses, lower pretreatment body mass index, milder liver fibrosis, 48 weeks of treatment and RVR, but not aa substitutions in HCV-CR, predicted a higher SVR rate.
  
  
  CONCLUSIONS
  Although aa substitution in genotype 1 HCV-CR is associated with more severe liver fibrosis and might be a negative predictor of SVR in Taiwanese CHC patients with interferon-based therapy, RVR and other clinical factors outweigh its role in predicting SVR.
authors: Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin County, Taiwan.
authors: Shih-Jer
authors: SJ
authors: Hsu
authors: Ching-Sheng
authors: CS
authors: Hsu
authors: Chen-Hua
authors: CH
authors: Liu
authors: Chun-Jen
authors: CJ
authors: Liu
authors: Chi-Ling
authors: CL
authors: Chen
authors: Pei-Jer
authors: PJ
authors: Chen
authors: Ding-Shinn
authors: DS
authors: Chen
authors: Jia-Horng
authors: JH
authors: Kao
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000097:blood; D013624:Taiwan; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D014758:Viral Core Proteins