Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load

This study explores pretreatment predictive factors for ultimate virological responses to pegylated interferon-alpha (1.5 mu g/kg/week) and ribavirin (600-1000 mg/day) (PEG-IFN/RBV) combination therapy for patients infected with hepatitis C virus (HCV)-1b and a high viral load. A total of 75 patients underwent PEG-IFN/RBV combination therapy for 48 weeks. HCV amino acid (aa) substitutions in non-structural protein 5a, including those in the IFN/RBV resistance-determining region (IRRDR) and the IFN sensitivity-determining region and the core regions, as well as the genetic variation (rs8099917) near the interleukin 28B (IL28B) gene (genotype TT) were analyzed. Of the 75 patients, 49 % (37/75) achieved a sustained virological response (SVR), 27 % (20/75) showed relapse, and 24 % (18/75) showed null virological response (NVR). Multivariate logistic regression analysis identified IRRDR with 6 or more mutations (IRRDR a parts per thousand yen6) [odds ratio (OR) 11.906, p < 0.0001] and age < 60 years (OR 0.228, p = 0.015) as significant determiners of SVR and IL28B minor (OR 14.618, p = 0.0019) and platelets < 15 x 10(4)/mm(3) (OR 0.113, p = 0.0096) as significant determiners of NVR. A combination of IRRDR a parts per thousand yen6 and age < 60 years improved SVR predictability (93.3 %), and that of IRRDR a parts per thousand currency sign5 and age a parts per thousand yen60 years improved non-SVR predictability (84.0 %). Similarly, a combination of IL28B minor and platelets < 15 x 10(4)/mm(3) improved NVR predictability (85.7 %), and that of IL28B major and platelets a parts per thousand yen15 x 10(4)/mm(3) improved non-NVR (response) (97.1 %) predictability. IRRDR a parts per thousand yen6 and age < 60 years were significantly associated with SVR. IL28B minor and platelets < 15 x 10(4)/mm(3) were significantly associated with NVR. Certain combinations of these factors improved SVR and NVR predictability and could, therefore, be used to design therapeutic strategies.