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The many pathways driving liver inflammation in MASH
Herbert Tilg1, Timon E Adolph1, Stefano Romeo2
1Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
Cell Metabolism
|March 24, 2026
Summary
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of the global population. New therapies targeting its complex inflammatory pathways show promise for improved clinical management.
Area of Science:
- Hepatology and metabolic disease research
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health concern, impacting one-third of the world's population.
- A significant portion of MASLD patients progress to metabolic dysfunction-associated steatohepatitis (MASH), increasing the risk of cirrhosis and liver cancer.
Purpose of the Study:
- To review the complex, multifactorial inflammatory mechanisms driving MASH development.
- To analyze the pleiotropic metabolic and anti-inflammatory effects of emerging MASH therapies.
Main Methods:
- Review of current scientific literature on MASLD and MASH pathogenesis.
- Analysis of polygenetic and multiomic risk scores for patient stratification.
- Evaluation of the pharmacological properties of novel MASH drug candidates.
Main Results:
- MASH pathogenesis involves parallel inflammatory hits, including hepatic lipotoxicity, gut dysbiosis, and diet-induced immune responses.
- Obesity-driven adipose tissue inflammation exacerbates MASH.
- Emerging MASH therapies demonstrate broad metabolic and anti-inflammatory actions.
Conclusions:
- Understanding the intricate inflammatory pathways in MASH is crucial for effective treatment.
- Current and upcoming MASH therapies possess multifaceted properties that are expected to significantly alter clinical practice.
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