A matched case-controlled study of 48 and 72 weeks of peginterferon plus ribavirin combination therapy in patients infected with HCV genotype 1b in Japan: amino acid substitutions in HCV core region as predictor of sustained virological response.

Substitution of amino acid (aa) 70 and 91 in the core region of HCV genotype 1b is a useful pretreatment predictor of efficacy of 48-week peginterferon (PEG-IFN) plus ribavirin (RBV) therapy. Here, we determined the efficacy of 72-week PEG-IFN/RBV and the predictive factors to such therapy in a case-control study matched for sex, age, and periods from the start of treatment to initial point of HCV RNA-negative. We compared the treatment efficacy of 72-week regimen in 65 patients with that of 48-week in 130 patients, who were infected with HCV genotype 1b and treated with PEG-IFN/RBV. They consisted mainly of late virological responders (LVR) (HCV RNA-positive at 12 weeks and negative at 24 weeks after start of treatment). Sustained virological response (SVR) was achieved by 61.5% and 32.3% of patients of the 72- and 48-week groups, respectively, while non-virological response was noted in 9.2% and 29.2% of the respective groups. Multivariate analysis identified substitution of aa 70 and 91 (Arg70 and/or Leu91) and duration of treatment (72-week) as independent parameters that significantly influenced SVR. For Arg70 and/or Leu91 of core region, SVR rate was significantly higher in 72- (68.0%) than 48-week group (37.8%). For wild-type of ISDR, SVR rate was significantly higher in 72- (61.2%) than in 48-week group (29.3%). We conclude that 72-week PEG-IFN/RBV improves SVR rate for LVR, especially those with Arg70 and/or Leu91 of core region or wild-type of ISDR. Substitution of aa 70 and 91 is also a useful pretreatment predictor of response to 72-week PEG-IFN/RBV.