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World J Gastroenterol. May 21, 2022; 28(19): 2088-2099
Published online May 21, 2022. doi: 10.3748/wjg.v28.i19.2088
Mechanisms of ductular reaction in non-alcoholic steatohepatitis
Yue Chen, Wen-Kang Gao, Yan-Yun Shu, Jin Ye
Yue Chen, Wen-Kang Gao, Yan-Yun Shu, Jin Ye, Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Author contributions: Chen Y searched the literature and drafted the manuscript; Gao WK checked the manuscript and provided assistance regarding illustrations; Shu YY assisted in designing and polishing the manuscript; Ye J revised the important intellectual content in this manuscript; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81770582; and the Graduates’ Innovation Fund, Huazhong University of Science and Technology, No. 2021yjsCXCY106.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jin Ye, MD, PhD, Chief Doctor, Professor, Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China. yejin8688@sina.com
Received: January 17, 2022
Peer-review started: January 17, 2022
First decision: February 7, 2022
Revised: February 18, 2022
Accepted: April 3, 2022
Article in press: April 3, 2022
Published online: May 21, 2022
Processing time: 119 Days and 22.9 Hours
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a disease spectrum caused in part by insulin resistance and genetic predisposition. This disease is primarily characterized by excessive lipid accumulation in hepatocytes in the absence of alcohol abuse and other causes of liver damage. Histologically, NAFLD is divided into several periods: simple steatosis, non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. With the increasing prevalence of obesity and hyperlipidemia, NAFLD has become the main cause of chronic liver disease worldwide. As a result, the pathogenesis of this disease is drawing increasing attention. Ductular reaction (DR) is a reactive bile duct hyperplasia caused by liver injury that involves hepatocytes, cholangiocytes, and hepatic progenitor cells. Recently, DR is shown to play a pivotal role in simple steatosis progression to NASH or liver fibrosis, providing new research and treatment options. This study reviews several DR signaling pathways, including Notch, Hippo/YAP-TAZ, Wnt/β-catenin, Hedgehog, HGF/c-Met, and TWEAK/Fn14, and their role in the occurrence and development of NASH.

Keywords: Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Ductular reaction; Mechanisms; Signaling pathways

Core Tip: With the increasing prevalence of obesity and hyperlipidemia, Non-alcoholic fatty liver disease (NAFLD) has become the primary cause of chronic liver disease worldwide. Thus, the pathogenesis of non-alcoholic steatohepatitis (NASH) is drawing increasing attention. Ductular reaction (DR) is a reactive bile duct hyperplasia involving hepatocytes, cholangiocytes, and hepatic progenitor cells, that plays an important role in NAFLD pathogenesis and promotes the occurrence and development of NASH and liver fibrosis. This minireview describes the characteristics of DR and summarizes its pivotal mechanisms. A role for DR during NASH is described that supplements current knowledge about the pathogenesis of this disease and informs potential prevention and treatment strategies.