Sheptulina AF, Golubeva JA, Kiselev AR, Drapkina OM. Clinical significance and pathogenic mechanisms of fatigue in metabolic dysfunction-associated steatotic liver disease. World J Hepatol 2025; 17(10): 110848 [PMID: 41179723 DOI: 10.4254/wjh.v17.i10.110848]
Corresponding Author of This Article
Anton R Kiselev, Professor, Coordinating Center for Fundamental Research, National Medical Research Center for Therapy and Preventive Medicine, Petroverigsky Lane, 10, Building 3, Moscow 101990, Russia. antonkis@list.ru
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
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/
World J Hepatol. Oct 27, 2025; 17(10): 110848 Published online Oct 27, 2025. doi: 10.4254/wjh.v17.i10.110848
Clinical significance and pathogenic mechanisms of fatigue in metabolic dysfunction-associated steatotic liver disease
Anna F Sheptulina, Julia A Golubeva, Anton R Kiselev, Oxana M Drapkina
Anna F Sheptulina, Julia A Golubeva, Laboratory of Experimental and Preventive Gastroenterology, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia
Anton R Kiselev, Coordinating Center for Fundamental Research, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia
Oxana M Drapkina, Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia
Author contributions: Sheptulina AF and Golubeva JA draft the manuscript; Sheptulina AF contributed to performing critical revisions related to important intellectual content; Kiselev AR contributed to data analysis and interpretation; Drapkina OM contributed to study conception and design; all authors provided final approval of the version to be published.
Supported by Russian Science Foundation, No. 23-45-10030.
Conflict-of-interest statement: All the 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Anton R Kiselev, Professor, Coordinating Center for Fundamental Research, National Medical Research Center for Therapy and Preventive Medicine, Petroverigsky Lane, 10, Building 3, Moscow 101990, Russia. antonkis@list.ru
Received: June 18, 2025 Revised: July 23, 2025 Accepted: September 24, 2025 Published online: October 27, 2025 Processing time: 132 Days and 22.3 Hours
Abstract
Fatigue is among the most common, albeit underestimated, symptoms in patients with metabolic dysfunction-associated steatotic liver disease. It affects quality of life and reduces the effectiveness of non-pharmacological interventions, thereby negatively affecting the prognosis. This review discusses the clinical problems associated with increased fatigue, explores diagnostic methods, considers key pathogenetic mechanisms of this symptom development (including neuroinflammation, hyperammonemia, mitochondrial and muscle dysfunction, sleep disorders, changes in the composition of gut microbiota), and describes the role of interorgan communication (the liver-brain and gut-brain axes) in the formation of the central link of fatigue. The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue, which would include not only the impact on metabolic disorders, but also on neurophysiological and behavioral factors. Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention (which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy) and improve the prognosis of patients with this chronic liver disease.
Core Tip: Fatigue is a frequent but underrecognized symptom in metabolic dysfunction-associated steatotic liver disease (MASLD). This review presents an integrative perspective on fatigue as a systemic manifestation of MASLD, distinct from but overlapping with depression. Central (e.g., neuroinflammation, brain-liver axis dysfunction) and peripheral (e.g., sarcopenia, mitochondrial dysfunction) mechanisms are discussed. Current evidence on exercise, pharmacologic, and behavioral interventions is summarized. Recognizing fatigue as an active factor influencing lifestyle and outcomes may guide new therapeutic strategies and clinical trial designs in MASLD.
