Kimura T, Tanaka N, Fujimori N, Sugiura A, Yamazaki T, Joshita S, Komatsu M, Umemura T, Matsumoto A, Tanaka E. Mild drinking habit is a risk factor for hepatocarcinogenesis in non-alcoholic fatty liver disease with advanced fibrosis. World J Gastroenterol 2018; 24(13): 1440-1450 [PMID: 29632425 DOI: 10.3748/wjg.v24.i13.1440]
Corresponding Author of This Article
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
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
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/
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 Processing time: 63 Days and 4.5 Hours
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.
