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Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2018; 24(25): 2661-2672
Published online Jul 7, 2018. doi: 10.3748/wjg.v24.i25.2661
Apoptosis and non-alcoholic fatty liver diseases
Tatsuo Kanda, Shunichi Matsuoka, Motomi Yamazaki, Toshikatsu Shibata, Kazushige Nirei, Hiroshi Takahashi, Tomohiro Kaneko, Mariko Fujisawa, Teruhisa Higuchi, Hitomi Nakamura, Naoki Matsumoto, Hiroaki Yamagami, Masahiro Ogawa, Hiroo Imazu, Kazumichi Kuroda, Mitsuhiko Moriyama
Tatsuo Kanda, Shunichi Matsuoka, Motomi Yamazaki, Toshikatsu Shibata, Kazushige Nirei, Hiroshi Takahashi, Tomohiro Kaneko, Mariko Fujisawa, Teruhisa Higuchi, Hitomi Nakamura, Naoki Matsumoto, Hiroaki Yamagami, Masahiro Ogawa, Hiroo Imazu, Kazumichi Kuroda, Mitsuhiko Moriyama, Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
Author contributions: Kanda T designed research, performed research, and analyzed data; Kanda T, Matsuoka S, Yamazaki M, Shibata T, Nirei K, Takahashi H, Kaneko T, Fujisawa M, Higuchi T, Nakamura H, Matsumoto N, Yamagami H, Ogawa M, Imazu H, Kuroda K, and Moriyama M wrote the paper.
Conflict-of-interest statement: Kanda T received research grants from AbbVie, MSD, Chugai Pharma, and Sysmex. These companies played no role in this study. Other authors declare no conflict of interests related to this publication.
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: Tatsuo Kanda, MD, PhD, Associate Professor, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan. kanda2t @yahoo.co.jp
Telephone: +81-3-39728111 Fax: +81-3-39568496
Received: April 3, 2018
Peer-review started: April 3, 2018
First decision: May 29, 2018
Revised: June 4, 2018
Accepted: June 22, 2018
Article in press: June 22, 2018
Published online: July 7, 2018
Processing time: 93 Days and 4.1 Hours
Abstract

The number of patients with nonalcoholic fatty liver diseases (NAFLD) including nonalcoholic steatohepatitis (NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma (HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice.

Keywords: Apoptosis; Autophagy; c-Jun N-terminal kinase; Nonalcoholic fatty liver diseases; Nonalcoholic steatohepatitis

Core tip: Nonalcoholic fatty liver diseases (NAFLD), including nonalcoholic steatohepatitis (NASH), are one of the most serious health issues. We searched articles written in English and listed on PubMed for the role of apoptosis in NASH. There are close association between apoptosis and NAFLD/NASH. Several inhibitors of apoptosis have been suggested as potential treatments for NASH, and some are now being tested in clinical trials. Therefore, we should focus on the role of apoptosis in the progression of NAFLD/NASH.