Peripheral Blood Mononuclear Cells MicroRNA Predicts Treatment Outcome of Hepatitis C Virus genotype 1 infection.

Abstract Backgrounds Chronic hepatitis C virus (HCV) infection has been associated with induction of microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMC). We aimed to evaluate the role of PBMC–miRNAs in the treatment outcome to antiviral therapy for HCV genotype 1 (HCV-1) patients. Methods Treatment-naive chronic HCV-1 patients, including 13 in screening phase and 48 in validation phase, were treated with 48 weeks of peginterferon/ribavirin. The primary end-point was the achievement of a sustained virological response (SVR, HCV RNA undetectable during 24 weeks post-treatment follow-up). Expression profiling of PBMC–miRNAs was performed by quantitative PCR-based array in typical responders and null-responders. Then candidate PBMC–miRNAs were validated by quantitative PCR in an independent validation set. Results PBMC–miR-125b was significantly predictive of an SVR, with expression levels of 5.28-fold lower in sustained responders versus null-responders ( p  = 0.0163). In multivariate analysis, PBMC–miR-125b was significantly associated with the achievement of SVR (per 2-fold decrease, odds ratio/95% confidence interval (OR/CI): 2.07/1.14-6.31) independent of sex, age and interleukin-28B genotype. In patients who did not achieve a rapid virological response (RVR, undetectable HCV RNA at treatment week 4), PBMC–miR-125b was the only predictive factor of an SVR (per 2-fold decrease, OR/CI: 2.07/1.14-6.31). However, the circulating and hepatic miR-125b did not show significant difference between responders and non-responders. Conclusions PBMC–miR-125b expression levels were inversely related to the achievement of an SVR in HCV-1 patients, independent of interleukin-28B genotype, and was the single predictor of SVR in non-RVR patients.