Peginterferon-A_2B plus ribavirin is more effective than peginterferon-A_2A plus ribavirin in menopausal women with chronic hepatitis C

. Under-enrolment of women to randomized clinical trials, including chronic hepatitis C, has long been recognized. The aim of this study was to identify factors predictive of sustained virological response (SVR) to PEG IFN/Ribavirin antiviral therapy in relation to gender and reproductive status of female patients involved. Seven hundred and forty-six treatment-naive patients (431 men, 315 women) treated with Peg-IFN alpha-2a (180 mu g/week) or Peg-IFN alpha-2b (1.5 mu g/kg/week) plus ribavirin (800-1400 mg/day) for 24 or 48 weeks were studied between 2006 and 2010. Differences in SVR rate, overall and by gender were assessed after adjustment and propensity score matching. SVR was obtained in 44.2% of Peg-IFN alpha-2a-treated patients and in 51.2% of Peg-IFN alpha-2b-treated patients (intention-to-treat; P = 0.139). Age, fibrosis stage and genotype 2 and 3 were independently associated with SVR by multivariate analysis. Analysing by gender, the difference in SVR between PEG-IFNa types was not significant in men but highly significant in women (Peg-IFN alpha-2a:39.1%vs Peg-IFN alpha-2b:54.4%, P = 0.007). This was attributable to a higher SVR rate with Peg-IFN alpha-2b in the difficult postmenopausal population (26.9% Peg-IFN alpha-2a vs 46.0% Peg-IFN alpha-2b, P = 0.040). In women, absence of menopause, genotype 2 hepatitis C virus infection and use of Peg-IFN alpha-2b were independently associated with SVR. In conclusion, predictive factors for SVR are different in men and women. Factors differing between genders are menopause, severe steatosis and peg-interferon used. The higher SVR rate with Peg-IFN alpha-2b in menopausal women is likely attributable to more favourable pharmacokinetics that allows Peg-IFN alpha-2b to reach visceral fat and oppose the increased cytokine production and enhanced inflammatory status in menopause.