Factors responsible for the discrepancy between IL28B polymorphism prediction and the viral response to peginterferon plus ribavirin therapy in Japanese chronic hepatitis C patients

Abstract

IL28B polymorphisms serve to predict response to pegylated interferon plus ribavirin therapy (PEG IFN/RBV) in Japanese patients with chronic hepatitis C (CHC) very reliably. However, the prediction by the IL28B polymorphism contradicted the virological response to PEG IFN/RBV in some patients. Here, we aimed to investigate the factors responsible for the discrepancy between the IL28B polymorphism prediction and virological responses. CHC patients with genotype 1b and high viral load were enrolled in this study. In a case-control study, clinical and virological factors were analyzed for 130 patients with rs8099917 TT genotype and 96 patients with rs8099917 TG or GG genotype who were matched according to sex, age, hemoglobin level and platelet count. Higher low-density lipoprotein (LDL) cholesterol, lower γ-glutamyltransferase and the percentage of wild-type phenotype at amino acids 70 and 91 were significantly associated with the rs8099917 TT genotype. Multivariate analysis showed that rs8099917 TG or GG genotype, older age and lower LDL cholesterol were independently associated with the non-virological responder (NVR) phenotype. In patients with rs8099917 TT genotype (predicted as virological responder [VR]), multivariate analysis showed that older age was independently associated with NVR. In patients with rs8099917 TG or GG genotype (predicted as NVR), multivariate analysis showed that younger age was independently associated with VR. Patient age gave rise to the discrepancy between the prediction by IL28B polymorphism and the virological responses, suggesting that patients should be treated at a younger age.