Huo YJ, Liang ZX, Bian JX, Zhang JT, Cha L, Yang QY, Zhao CJ, Li JY, Feng DP, Gao L. Bile acid metabolic disorders and their role in hepatic encephalopathy of cirrhosis. World J Gastroenterol 2026; 32(47): 122954 [DOI: 10.3748/wjg.122954]
Corresponding Author of This Article
Long Gao, PhD, Associate Chief Physician, Department of Oncological and Vascular Intervention, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Yingze District, Taiyuan 030001, Shanxi Province, China. gaolong@sxmu.edu.cn
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Gastroenterology & Hepatology
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review-article
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Huo YJ, Liang ZX, Bian JX, Zhang JT, Cha L, Yang QY, Zhao CJ, Li JY, Feng DP, Gao L. Bile acid metabolic disorders and their role in hepatic encephalopathy of cirrhosis. World J Gastroenterol 2026; 32(47): 122954 [DOI: 10.3748/wjg.122954]
World J Gastroenterol. Dec 21, 2026; 32(47): 122954 Published online Dec 21, 2026. doi: 10.3748/wjg.122954
Bile acid metabolic disorders and their role in hepatic encephalopathy of cirrhosis
Yu-Jie Huo, Zi-Xin Liang, Jing-Xuan Bian, Jing-Tian Zhang, Li Cha, Qi-Yue Yang, Chun-Juan Zhao, Jin-Yu Li, Dui-Ping Feng, Long Gao
Yu-Jie Huo, Qi-Yue Yang, Chun-Juan Zhao, Jin-Yu Li, Dui-Ping Feng, Long Gao, Department of Oncological and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Yu-Jie Huo, Zi-Xin Liang, Jing-Xuan Bian, Jing-Tian Zhang, Li Cha, Department of Medical Imaging, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Co-first authors: Yu-Jie Huo and Zi-Xin Liang.
Co-corresponding authors: Long Gao and Dui-Ping Feng.
Author contributions: Huo YJ and Liang ZX contributed equally to this work, conceptualized and designed the study, conducted the investigation, visualised the data, and drafted the original manuscript as co-first authors; Bian JX, Zhang JT, Cha L, and Yang QY critically reviewed and revised the manuscript; Zhao CJ and Li JY provided critical feedback and manuscript revisions; Feng DP and Gao L supervised the study and made critical revisions as co-corresponding authors; all authors approved the final version and publication of the manuscript.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Supported by the Shanxi Provincial Clinical Research Center for Interventional Medicine, No. 202204010501004; and the Central Government Guiding Local Science and Technology Development Funds, No. YDZJSX20231B010.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Long Gao, PhD, Associate Chief Physician, Department of Oncological and Vascular Intervention, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Yingze District, Taiyuan 030001, Shanxi Province, China. gaolong@sxmu.edu.cn
Received: May 12, 2026 Revised: July 12, 2026 Accepted: July 28, 2026 Published online: December 21, 2026 Processing time: 177 Days and 16.9 Hours
Abstract
Liver cirrhosis is a progressive chronic liver disease characterized by metabolic disorders. Among these, bile acid (BA) metabolic disturbance serves as a key pathological link in disease progression and as a core factor driving development of hepatic encephalopathy (HE). Dysbiosis of the gut microbiota and BA metabolic disturbance mutually reinforce each other, forming a vicious cycle. Abnormally accumulated toxic hydrophobic BAs can directly damage the integrity of the intestinal mucosal barrier, activate local intestinal inflammatory signaling pathways, and induce systemic inflammation. These abnormal BAs can disrupt the structure and function of the blood-brain barrier through multiple BA-receptor-mediated signaling pathways, induce neuroinflammation in the central nervous system, and synergize with hyperammonemia to promote accumulation of neurotoxins in the central nervous system, ultimately triggering HE. BA metabolic profiles of liver cirrhosis caused by different causes show characteristic changes, which are expected to provide potential biomarkers for etiological identification and individualized intervention. Targeted therapeutic strategies aimed at the BA metabolic pathway have shown promising application, offering new targets and directions for prevention and treatment of HE. This review summarizes the core pathological mechanisms of BA metabolic disturbance in the context of liver cirrhosis and its role in the development and progression of HE.
Core Tip: Cirrhosis disrupts bile acid (BA) homeostasis, creating a vicious cycle with gut dysbiosis and barrier injury. Accumulated toxic BAs cross the blood-brain barrier and modulate neuroinflammation via farnesoid X receptor, Takeda G protein-coupled receptor 5, and Sphingosine-1-phosphate receptor 2 signaling, synergizing with hyperammonemia to drive hepatic encephalopathy. BA profiles vary by cirrhosis etiology, offering diagnostic and prognostic potential. Targeting BA pathways represents a promising therapeutic strategy for hepatic encephalopathy.
