Observational Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2016; 22(44): 9844-9852
Published online Nov 28, 2016. doi: 10.3748/wjg.v22.i44.9844
Disease-specific miR-34a as diagnostic marker of non-alcoholic steatohepatitis in a Chinese population
Xiao-Lin Liu, Qin Pan, Rui-Nan Zhang, Feng Shen, Shi-Yan Yan, Chao Sun, Zheng-Jie Xu, Yuan-Wen Chen, Jian-Gao Fan
Xiao-Lin Liu, Qin Pan, Rui-Nan Zhang, Feng Shen, Shi-Yan Yan, Chao Sun, Zheng-Jie Xu, Yuan-Wen Chen, Jian-Gao Fan, Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Author contributions: Pan Q, Zhang RN and Fan JG designed the research; Yan SY, Sun C, Xu ZJ and Chen YW collected material and clinical data from the patients; Liu XL, Zhang RN and Shen F performed the assays; Liu XL analyzed the data; Liu XL and Fan JG wrote the manuscript.
Supported by grants from the State Key Development Program for Basic Research of China, No. 2012CB517501; National Natural Science Foundation of China, No. 81270491 and No. 81470840; Hundred Talents Program of the Shanghai Board of Health, No. XBR2011007; and Program of the Shanghai Committee of Science and Technology, No. 10411956300.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Xin Hua Hospital Affiliated to Shanghai Jiaotong University School of Medicine.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jian-Gao Fan, Professor, Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China. fattyliver2004@126.com
Telephone: +86-21-25077340
Received: July 21, 2016
Peer-review started: July 22, 2016
First decision: August 22, 2016
Revised: August 29, 2016
Accepted: September 14, 2016
Article in press: September 14, 2016
Published online: November 28, 2016
Abstract
AIM

To assess disease-specific circulating microRNAs (miRNAs) in non-alcoholic steatohepatitis (NASH) patients.

METHODS

A total of 111 biopsy-proven non-alcoholic fatty liver disease (NAFLD) or chronic hepatitis B (CHB) patients and healthy controls from mainland China were enrolled to measure their serum levels of miR-122, -125b, -146b, -16, -21, -192, -27b and -34a. The correlations between serum miRNAs and histological features of NAFLD were determined. The diagnostic value of miRNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI), respectively.

RESULTS

Circulating miR-122, -16, -192 and -34a showed differential expression levels between NAFLD and CHB patients, and miR-34a had an approximately 2-fold increase in NAFLD samples compared with that of CHB samples (P < 0.01). Serum miR-122, -192 and -34a levels were correlated with steatosis (R = 0.302, 0.323 and 0.470, respectively, P < 0.05) and inflammatory activity (R = 0.445, 0.447 and 0.517, respectively, P < 0.01); only serum miR-16 levels were associated with fibrosis (R = 0.350, P < 0.05) in patients with NAFLD. The diagnostic value of miR-34a for NASH (area under the receiver operating characteristic, 0.811, 95%CI: 0.670-0.953) was superior to that of alanine aminotransferase, CK-18, FIB-4 and APRI in NAFLD, but miR-16 showed a limited performance in the diagnosis of significant fibrosis in NASH.

CONCLUSION

Circulating miR-34a may serve as a disease-specific noninvasive biomarker for the diagnosis of NASH.

Keywords: MicroRNA, Non-alcoholic steatohepatitis, Hepatic fibrosis, Biomarker, Chronic hepatitis B

Core tip: Circulating miR-122, -192, -34a and -16 showed differential expression levels between non-alcoholic fatty liver disease and chronic hepatitis B patients, and serum miR-122, -192 and -34a could also differentiate non-alcoholic steatohepatitis (NASH) from non-alcoholic fatty liver. The latter were correlated with steatosis and inflammatory activity, and only serum miR-16 was associated with hepatic fibrosis. The diagnostic value of miR-34a for NASH was superior to that of alanine aminotransferase and cytokeratin-18, but miR-16 showed a slightly poorer performance than that of fibrosis-4 and aspartate aminotransferase to platelet ratio index in the diagnosis of significant fibrosis in NASH.