Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2018; 24(13): 1440-1450
Published online Apr 7, 2018. doi: 10.3748/wjg.v24.i13.1440
Mild drinking habit is a risk factor for hepatocarcinogenesis in non-alcoholic fatty liver disease with advanced fibrosis
Takefumi Kimura, Naoki Tanaka, Naoyuki Fujimori, Ayumi Sugiura, Tomoo Yamazaki, Satoru Joshita, Michiharu Komatsu, Takeji Umemura, Akihiro Matsumoto, Eiji Tanaka
Takefumi Kimura, Naoyuki Fujimori, Ayumi Sugiura, Tomoo Yamazaki, Satoru Joshita, Michiharu Komatsu, Takeji Umemura, Akihiro Matsumoto, Eiji Tanaka, Department of Internal Medicine, Division of Gastroenterology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Naoki Tanaka, Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan
Naoki Tanaka, Research Center for Agricultural Food Industry, Shinshu University, Matsumoto 390-8621, Japan
Author contributions: Kimura T and Tanaka N designed the research; Fujimori N, Sugiura A, Yamazaki T, Joshita S, Komatsu M, Umemura T, and Matsumoto A treated the patients and collected materials and clinical data; Kimura T analyzed the data; Kimura T and Tanaka N wrote the paper; Tanaka E supervised the research.
Institutional review board statement: The study was reviewed and approved by the Committee for Medical Ethics of Shinshu University School of Medicine Institutional Review Board.
Informed consent statement: Informed written consent was obtained from all patients.
Conflict-of-interest statement: The authors declare that no conflict of interest exists.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Naoki Tanaka, MD, PhD, Associate Professor, Doctor, Department of Metabolic Regulation, Shinshu University Graduate School of Medicine and Research Center for Agricultural Food Industry, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan. naopi@shinshu-u.ac.jp
Telephone: +81-263-372634 Fax: +81-263-329412
Received: January 31, 2018
Peer-review started: January 31, 2018
First decision: February 26, 2015
Revised: March 3, 2015
Accepted: March 10, 2018
Article in press: March 10, 2018
Published online: April 7, 2018
ARTICLE HIGHLIGHTS
Research background

The prevalence rate of non-alcoholic fatty liver disease (NAFLD) has doubled during the last 20 years.

Research motivation

The impact of mild drinking habit (less than 20 g/d of ethanol) on the clinical course of NAFLD has not been determined. We examined the influence of a mild drinking habit on liver carcinogenesis from NAFLD.

Research objectives

A total of 301 patients who had been diagnosed as having NAFLD by liver biopsy between 2003 and 2016 (median age: 56 years, 45% male, 56% with non-alcoholic steatohepatitis, 26% with advanced fibrosis (F3-4) were divided into the mild drinking group with ethanol consumption of less than 20 g/d (mild drinking group, n = 93) and the non-drinking group (n = 208).

Research methods

Clinicopathological features at the time of liver biopsy and factors related to hepatocellular carcinoma (HCC) occurrence were compared between the groups.

Research results

We observed significant differences in male prevalence (P = 0.01), platelet count (P = 0.04), and gamma-glutamyl transpeptidase (P = 0.02) between the test groups. Over 6 years of observation, the HCC appearance rate was significantly higher in the mild drinking group (6.5% vs 1.4%, P = 0.02). Multivariate survival analysis using Cox’s regression model revealed that hepatic advanced fibrosis (F3-4) (P < 0.01, risk ratio: 11.60), diabetes mellitus (P < 0.01, risk ratio: 89.50), and serum triglyceride (P = 0.04, risk ratio: 0.98) were factors significantly related to HCC in all NAFLD patients, while the effect of a drinking habit was marginal (P = 0.07, risk ratio: 4.43). In patients with advanced fibrosis (F3-4), however, a drinking habit (P = 0.04, risk ratio: 4.83), alpha-fetoprotein (P = 0.01, risk ratio: 1.23), and diabetes mellitus (P = 0.03, risk ratio: 12.00) were identified as significant contributors to HCC occurrence.

Research conclusions

A mild drinking habit appears to be a risk factor for hepatocarcinogenesis in NAFLD patients, especially those with advanced fibrosis.

Research perspectives

Prospective studies investigating the effect of ethanol cession in NAFLD patients with a mild drinking habit are also required to confirm the impact of mild drinking on the clinical course of NAFLD.