Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2015; 21(25): 7814-7823
Published online Jul 7, 2015. doi: 10.3748/wjg.v21.i25.7814
miR-122 negatively correlates with liver fibrosis as detected by histology and FibroScan
Tünde Halász, Gábor Horváth, Gabriella Pár, Klára Werling, András Kiss, Zsuzsa Schaff, Gábor Lendvai
Tünde Halász, András Kiss, Zsuzsa Schaff, Gábor Lendvai, Second Department of Pathology, Semmelweis University, 1091 Budapest, Hungary
Tünde Halász, Department of Pathology, Military Hospital, 1134 Budapest, Hungary
Gábor Horváth, Hepatology Center of Buda, 1111 Budapest, Hungary
Gabriella Pár, First Department of Medicine, University of Pécs, 7624 Pécs, Hungary
Klára Werling, Second Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary
Zsuzsa Schaff, Gábor Lendvai, MTA-SE Tumor Progression Research Group, Semmelweis University, 1091 Budapest, Hungary
Author contributions: Halász T and Schaff Z designed the study; Halász T, Horváth G, Pár G, Werling K, Kiss A and Schaff Z chose, diagnosed, or examined the patients and the histologic samples; Lendvai G performed the data acquisition; Halász T, Kiss A, Schaff Z and Lendvai G analyzed and interpreted the data and drafted the paper; all authors critically reviewed and approved the manuscript.
Supported by Grant from the National Scientific Research Fund, OTKA K101435 and K108548.
Ethics approval: This study was reviewed and approved by the review board, Scientific Ethical Committee of the Health Care Scientific Council, Budapest, Hungary, permission number: 45727-2/2013/EKU(545/2013).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrolment.
Conflict-of-interest statement: The authors have nothing to declare.
Data sharing statement: No additional data are available.
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:
Correspondence to: Gábor Lendvai, PhD, Second Department of Pathology, Semmelweis University, Ulloi 93, 1091 Budapest, Hungary.
Telephone: +36-1-215-6921 Fax: +36-1-215-6921
Received: December 16, 2014
Peer-review started: December 17, 2014
First decision: January 22, 2015
Revised: March 2, 2015
Accepted: April 3, 2015
Article in press: April 3, 2015
Published online: July 7, 2015

AIM: To investigate whether expression of selected miRNAs obtained from fibrotic liver biopsies correlate with fibrosis stage.

METHODS: Altogether, 52 patients were enrolled in the study representing various etiologic backgrounds of fibrosis: 24 cases with chronic hepatitis infections (types B, C), 19 with autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, overlapping syndrome cases), and 9 of mixed etiology (alcoholic and nonalcoholic steatosis, cryptogenic cases). Severity of fibrosis was determined by both histologic staging using the METAVIR scoring system and noninvasive transient elastography. Following RNA isolation, expression levels of miR-21, miR-122, miR-214, miR-221, miR-222, and miR-224 were determined using TaqMan MicroRNA Assays applying miR-140 as the reference. Selection of miRNAs was based on their characteristic up- or downregulation observed in hepatocellular carcinoma. Relative expression of miRNAs was correlated with fibrosis stage and liver stiffness (LS) value measured by transient elastography, as well as with serum alanine aminotransferase (ALT) level.

RESULTS: The expression of individual miRNAs showed deregulated patterns in stages F1-F4 as compared with stage F0, but only the reduced level of miR-122 in stage F4 was statistically significant (P < 0.04). When analyzing miRNA expression in relation to fibrosis, levels of miR-122 and miR-221 showed negative correlations with fibrosis stage, and miR-122 was found to correlate negatively and miR-224 positively with LS values (all P < 0.05). ALT levels displayed a positive correlation with miR-21 (P < 0.04). Negative correlations were observed in the fibrosis samples of mixed etiology between miR-122 and fibrosis stage and LS values (P < 0.05), and in the samples of chronic viral hepatitis, between miR-221 and fibrosis stage (P < 0.01), whereas miR-21 showed positive correlation with ALT values in the samples of autoimmune liver diseases (P < 0.03). The results also revealed a strong correlation between fibrosis stage and LS values (P < 0.01) when etiology of fibrosis was not taken into account.

CONCLUSION: Reduced expression of miR-122 in advanced fibrosis and its correlation with fibrosis stage and LS values seem to be characteristic of hepatic fibrosis of various etiologies.

Keywords: Expression, FibroScan, Liver fibrosis, METAVIR, microRNA, miR-122

Core tip: In this study, the expression of selected miRNAs was determined in fibrotic liver tissues of various etiologic backgrounds and was correlated with fibrosis stage (METAVIR scores) and liver stiffness as measured by transient elastography. In advanced fibrosis, the level of miR-122 was reduced and showed negative correlations with fibrosis stage and liver stiffness values, indicating that it could be a useful molecule to assess severity of fibrosis regardless of etiology.