MASLD development: From molecular pathogenesis toward therapeutic strategies

Area of Science:

• Hepatology and metabolic disorders
• Molecular pathogenesis of liver disease
• Gut-liver axis research

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a range of liver conditions, from steatosis to cirrhosis.
• Key liver cell types, including hepatocytes, LSECs, Kupffer cells, immune cells, and HSCs, are implicated in MASLD.
• The interplay between liver cells, aberrant metabolism, and gut dysbiosis is central to MASLD development.

Purpose of the Study:

• To systematically review advances in understanding the molecular pathogenesis of MASLD.
• To identify and evaluate emerging therapeutic targets for MASLD.
• To summarize ongoing translational clinical trials for MASLD treatment.

Main Methods:

• Systematic literature review of MASLD pathogenesis.
• Analysis of cell-specific regulatory mechanisms in the liver and gut-liver axis.
• Evaluation of preclinical and clinical data for therapeutic targets and trials.

Main Results:

• Detailed delineation of molecular mechanisms involving diverse liver cells in MASLD.
• Identification of key pathways and cell-specific insights into MASLD progression.
• Summary of promising therapeutic targets and current clinical trial landscape.

Conclusions:

• Cell-specific pathogenic insights are crucial for precision medicine in MASLD.
• Understanding the gut-liver axis and cellular crosstalk advances MASLD treatment strategies.
• This review provides a comprehensive update to guide novel pharmacotherapy development for MASLD.