Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2022; 28(28): 3555-3572
Published online Jul 28, 2022. doi: 10.3748/wjg.v28.i28.3555
Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions
Yao-Guang Li, Zu-Jiang Yu, Ang Li, Zhi-Gang Ren
Yao-Guang Li, Zu-Jiang Yu, Zhi-Gang Ren, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Yao-Guang Li, Zu-Jiang Yu, Ang Li, Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Zhi-Gang Ren, Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, Shandong Province, China
Author contributions: Ren ZG and Li A designed the study; Li YG, Yu ZJ, Li A and Ren ZG collected data and summary viewpoints; Li YG wrote the manuscript; Ren ZG and Li A revised the manuscript; and All authors reviewed and approved the manuscript.
Supported by National Key Research and Development Program of China, No. 2018YFC2000500; Research Project of Jinan Microecological Biomedicine Shandong Laboratory, No. JNL-2022001A; and National Natural Science Foundation of China, No. U2004121, No. 82070643 and No. U1904164.
Conflict-of-interest statement: All authors report no relevant conflicts 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:
Corresponding author: Zhi-Gang Ren, MD, PhD, Assistant Professor, Doctor, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Province, China.
Received: April 4, 2022
Peer-review started: April 4, 2022
First decision: May 9, 2022
Revised: June 6, 2022
Accepted: June 24, 2022
Article in press: June 24, 2022
Published online: July 28, 2022

Hepatitis B virus (HBV) has posed a threat to public health, mainly resulting in liver damage. With long-term accumulation of extracellular matrix, patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma. The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality. With deeper understanding of the bidirectional interaction between the liver and the gut (gut-liver axis), there is a growing consensus that the human health closely relates to the gut microbiota. Supported by animal and human studies, the gut microbiota alters as the HBV-related liver fibrosis initials and progresses, characterized as the decrease of the ratio between “good” and “potentially pathogenic” microbes. When the primary disease is controlled via antiviral treatment, the gut microbiota dysfunction tends to be improved. Conversely, the recovery of gut microbiota can promote the regression of liver fibrosis. Therapeutic strategies targeted on gut microbiota (rifaximin, probiotics, engineered probiotics and fecal microbiota transplantation) have been applied to animal models and patients, obtaining satisfactory results.

Keywords: Hepatitis B virus, Gut microbiota, Liver fibrosis, Liver cirrhosis, Hepatic encephalopathy, Fecal microbiota transplantation

Core Tip: Intimate connection between the gut microbiota alteration and hepatitis B virus (HBV)-related fibrosis and complications has been supported by animal and human studies. Researchers and clinicians are making effort to control and reverse fibrosis by rebuilding a healthy gut microbiota. We herein discuss the gut microbiota alteration in HBV-related fibrosis and therapies targeted on reconstruction of gut microbiota homeostasis.