Peripheral blood mononuclear cells microRNA predicts treatment outcome of hepatitis C virus genotype 1 infection Edward Hsi a,b , Chung-Feng Huang c,d , Chia-Yen Dai a,c , Suh-Hang Hank Juo b,e , Wen-Wen Chou c , Jee-Fu Huang f,g , Ming-Lun Yeh c , Zu-Yau Lin c,f , Shinn-Cherng Chen c,f , Liang-Yen Wang c,f , Wan-Long Chuang c,f,1,⇑ , Ming-Lung Yu c,f,1,⇑ a Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan b Department of Medical Research, Kaohsiung Medical University Hospital, Taiwan c Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan d Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Taiwan e Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan f Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan g Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan article info Article history: Received 9 December 2013 Revised 10 February 2014 Accepted 7 March 2014 Available online 15 March 2014 Keywords: HCV PBMC MicroRNA SVR IL28B miR-125b 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 achieve- ment 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 typ- ical 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. Ó 2014 Elsevier B.V. All rights reserved. 1. Introduction Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma in Taiwan (Yang et al., 2011), as well as worldwide (Ghany et al., 2009). The standard treatment for chronic hepatitis C (CHC) is peginterferon-a/ribavirin at 48 weeks for HCV genotype 1 or 4 (HCV-1/4) and 24 weeks for HCV-2/3 (EASL, 2011; Ghany et al., 2009; Omata et al., 2012). The goal of treatment for CHC is to achieve a sustained virological response (SVR), which is highly durable during long-term follow-up (Yu et al., 2013). With the rec- ommended regimen of peginterferon/ribavirin, the SVR rate is approximately 50––79% and 75–94% for HCV-1/4 and HCV-2/3, respectively, in both Western and Eastern countries (Ghany et al., 2009; Yu and Chuang, 2009). Recently, two newly approved http://dx.doi.org/10.1016/j.antiviral.2014.03.003 0166-3542/Ó 2014 Elsevier B.V. All rights reserved. ⇑ Corresponding authors at: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan. Tel.: +886 7 312 1101x7475; fax: +886 7 323 4553. E-mail addresses: waloch@kmu.edu.tw (W.-L. Chuang), fish6069@gmail.com (M.-L. Yu). 1 Equal contribution. Antiviral Research 105 (2014) 135–142 Contents lists available at ScienceDirect Antiviral Research journal homepage: www.elsevier.com/locate/antiviral