REVIEW article
Front. Endocrinol.
Sec. Systems Endocrinology
Multiorgan Crosstalk in MASLD/MASH: From Hepatic Pathogenesis to Systemic Complications
Provisionally accepted
Wenhua Bai
Zheng Zhu*- Department of Diagnostic Radiology, Center for National Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Metabolic dysfunction-associated steatotic liver disease (MASLD) has evolved from a hepatic-centric condition to a systemic metabolic disorder, with multisystem complications driving clinical outcomes. This review comprehensively examines the pathogenesis and extrahepatic manifestations of MASLD, focusing on interorgan crosstalk. We first delineate the hepatic progression from steatosis to fibrotic metabolic dysfunction-associated steatohepatitis (MASH), emphasizing lipotoxicity, mitochondrial dysfunction, and inflammatory cascades. Subsequently, we analyze key extrahepatic axes: (1) the liver-brain axis, where neuroinflammation and cognitive impairment are linked to hepatic metabolic disturbances; (2) the gut-liver axis, highlighting roles of gut microbiota dysbiosis and intestinal permeability in disease progression; and (3) the liver-kidney axis, exploring shared fibrotic mechanisms and functional decline. Common pathways-including chronic inflammation, oxidative stress, and immune-metabolic dysregulation-underpin these systemic complications. Therapeutically, we advocate a shift from isolated liver-targeted approaches to integrated multisystem strategies. This review underscores the imperative to reconceptualize MASLD as a systemic disease, necessitating collaborative efforts to refine diagnostic frameworks and therapeutic paradigms for improving patient outcomes.
Keywords: MASLD, MASH, Liver-brain axis, Gut-liver axis, Liver-kidney axis, Multisystem complications, Metabolic inflammation, therapy
Received: 08 Oct 2025; Accepted: 30 Nov 2025.
Copyright: © 2025 Bai and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zheng Zhu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.