Peripheral blood mononuclear cells microRNA predicts treatment outcome of hepatitis C virus genotype 1 infection

• Published in: Antiviral research 2014-05, Vol.105, p.135-142
• Main Authors: Hsi, Edward, Huang, Chung-Feng, Dai, Chia-Yen, Juo, Suh-Hang Hank, Chou, Wen-Wen, Huang, Jee-Fu, Yeh, Ming-Lun, Lin, Zu-Yau, Chen, Shinn-Cherng, Wang, Liang-Yen, Chuang, Wan-Long, Yu, Ming-Lung
• Format: Article
• Language: English
• Subjects: Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - therapeutic use; Biological and medical sciences; Biomarkers; Female; Gene Expression Profiling; Genotype; HCV; Hepacivirus - classification; Hepacivirus - genetics; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - pathology; Human viral diseases; Humans; IL28B; Infectious diseases; Interferon-alpha - therapeutic use; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - virology; Male; Medical sciences; MicroRNA; MicroRNAs - analysis; MicroRNAs - genetics; Middle Aged; miR-125b; PBMC; Pharmacology. Drug treatments; Prospective Studies; Real-Time Polymerase Chain Reaction; Ribavirin - therapeutic use; SVR; Treatment Outcome; Viral diseases; Viral hepatitis
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2014.03.003

•PBMC–miR125b is inversely associated with treatment outcome in HCV-1 patients.•PBMC–miR125b is independent to the most important baseline factor IL28B genotype.•PBMC–miR125b is the only factor associated with treatment success in nonRVR patients. 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. Treatment-naive chronic HCV-1 patients, including 13 in screening phase and 48 in validation phase, were treated with 48weeks of peginterferon/ribavirin. The primary end-point was the achievement of a sustained virological response (SVR, HCV RNA undetectable during 24weeks 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. 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. 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.