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

Autor: Hsi E; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Taiwan., Huang CF; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Taiwan., Dai CY; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan., Juo SH; Department of Medical Research, Kaohsiung Medical University Hospital, Taiwan; Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Chou WW; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan., Huang JF; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan., Yeh ML; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan., Lin ZY; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Chen SC; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Wang LY; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Chuang WL; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: waloch@kmu.edu.tw., Yu ML; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: fish6069@gmail.com.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2014 May; Vol. 105, pp. 135-42. Date of Electronic Publication: 2014 Mar 15.
DOI: 10.1016/j.antiviral.2014.03.003
Abstrakt: 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 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.
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.
(Copyright © 2014 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE