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Immunopathogenic mechanisms and immunoregulatory therapies in MASLD

Yong He1,2, Yingfen Chen3,4, Shengying Qian3,4

  • 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China. heyong@simm.ac.cn.

Cellular & Molecular Immunology
|June 10, 2025
PubMed

Insights

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 30% of the global population, yet treatments are limited. This review explores the immunological mechanisms driving MASLD and its progression to metabolic dysfunction-associated steatohepatitis (MASH).

Area of Science:

  • Hepatology
  • Immunology
  • Metabolic Diseases

Background:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly NAFLD, is the most common chronic liver disease globally, affecting ~30% of people.
  • MASLD pathogenesis involves overnutrition, genetic factors, hepatocyte damage, and liver inflammation, with inflammation driving progression to steatohepatitis and fibrosis.
  • Current MASH therapies target metabolic injury but not inflammation directly, highlighting a need for improved understanding and treatment strategies.

Purpose of the Study:

  • To review current data on the immunological mechanisms underlying MASLD.
  • To summarize the impact of existing and experimental therapies on immunoregulation in MASLD.

Main Methods:

  • Literature review of immunological mechanisms in MASLD.
  • Analysis of current and experimental therapeutic effects on immunoregulation.

Main Results:

  • Hepatic inflammation is a critical factor in MASLD progression from simple steatosis to steatohepatitis and fibrosis.
  • Existing MASH treatments like resmetirom and incretin mimetics primarily address metabolic aspects, not direct inflammation.
  • Emerging research focuses on understanding immune pathways to develop targeted anti-inflammatory therapies.

Conclusions:

  • A deeper understanding of MASLD's immunological drivers is crucial for developing effective treatments.
  • Targeting hepatic inflammation represents a promising therapeutic avenue for MASLD and MASH.
  • Future research should focus on immunomodulatory strategies to combat MASLD progression.
Keywords:
MASHMASLDinflammationpathogenesis.

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