Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2015; 21(21): 6665-6674
Published online Jun 7, 2015. doi: 10.3748/wjg.v21.i21.6665
Proportions of acetyl-histone-positive hepatocytes indicate the functional status and prognosis of cirrhotic patients
Ping Zhou, Jie Xia, Yong-Jie Zhou, Jun Wan, Li Li, Ji Bao, Yu-Jun Shi, Hong Bu
Ping Zhou, Jie Xia, Yong-Jie Zhou, Jun Wan, Li Li, Ji Bao, Yu-Jun Shi, Hong Bu, Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Ping Zhou, Hong Bu, Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Ping Zhou, Department of Pathology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Author contributions: Zhou P, Shi YJ and Bu H designed the project; Zhou P, Xia J, Zhou YJ and Wan J collected the clinical and pathologic data; Zhou P, Li L and Bao J performed the tissue microarray and pathologic staining; Zhou P and Shi YJ contributed to the interpretation of the data and wrote the manuscript; all the authors approved the version to be published.
Supported by Natural Science Foundation of China, No. 81170424.
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: Yu-Jun Shi, MD, PhD, Laboratory of Pathology, West China Hospital, Sichuan University, No. 37 Guoxue Road, Chengdu 610041, Sichuan Province, China. shiyujun@scu.edu.cn
Telephone: +86-28-85164030 Fax: +86-28-85164034
Received: October 20, 2014
Peer-review started: October 20, 2014
First decision: December 26, 2014
Revised: January 5, 2015
Accepted: February 13, 2015
Article in press: February 13, 2015
Published online: June 7, 2015
Processing time: 234 Days and 6.1 Hours
Abstract

AIM: To investigate whether the proportions of acetyl-histone-positive hepatocytes could be used as markers of deteriorating liver function.

METHODS: In total, 611 cirrhotic cases from 3701 patients who were diagnosed during the past 15 years were screened, and 152 follow-up cases were selected. Paraffin tissue microarray was prepared for immunohistochemistry to examine acetyl-histone expression. The proportions of positive hepatocytes were recorded, and their correlations to clinical and laboratory indicators were analyzed statistically.

RESULTS: The proportions of H2AK5ac+, H3K9/K14ac+ and H3K27ac+ hepatocytes gradually increased with deteriorating liver function and with increasing levels of serum markers of liver injury. In the follow-up cases, patients with > 70% H2AK5ac+, H3K9/K14ac+ or H3K27ac+ hepatocytes had statistically lower survival rates (P < 0.05). Furthermore, > 70% H2AK5ac+ or H3K27ac+ hepatocytes were strong independent predictors of overall survival (P < 0.05).

CONCLUSION: The proportions of acetyl-histone-positive hepatocytes are closely associated with the liver function and prognosis of cirrhotic patients.

Keywords: Histone acetylation; Cirrhosis; Liver function; Prognosis

Core tip: We previously divided hepatocytes into transcriptionally active and inactive cells based on their immunoreactivity to acetyl-histones. In the present study, we evaluated the expression of acetyl-histone markers in livers with progressive cirrhosis to investigate whether inactive hepatocytes can be activated for functional compensation and act as markers of liver function. We found that the proportions of acetyl-histone-positive hepatocytes were associated with liver function, which revealed a regeneration-independent compensatory mechanism of chronically damaged liver. In addition, assaying the proportions of acetyl-histone-positive hepatocytes may offer a novel strategy for evaluating patient liver function and prognosis.