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New guidelines define metabolic dysfunction and alcohol-associated liver disease (MetALD) as an overlap condition. Research is exploring therapeutics for MetALD, focusing on cessation strategies and promising drug classes for steatotic liver disease.

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Area of Science:

  • Hepatology
  • Pharmacology
  • Metabolic Diseases

Background:

  • New guidelines introduce metabolic dysfunction and alcohol-associated liver disease (MetALD) as an overlap of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD).
  • While numerous therapeutics are in development for MASLD, their efficacy and safety in patients with ongoing alcohol use remain largely unstudied.
  • Understanding the risks associated with MASLD and MetALD is crucial for developing effective treatments.

Purpose of the Study:

  • To review the current understanding of endogenous and exogenous risks for MASLD and MetALD.
  • To discuss rational therapeutic strategies for MetALD, including interventions for alcohol use and steatotic liver disease.
  • To identify promising therapeutic agents and highlight the need for further research in MetALD.

Main Methods:

  • Literature review of existing studies on MASLD and alcohol-associated liver disease.
  • Analysis of current and developing therapeutic strategies for steatotic liver diseases.
  • Discussion of risk factors and potential treatment interventions for MetALD.

Main Results:

  • Therapeutic interventions for MetALD should encompass biopsychosocial approaches, alcohol cessation strategies (including medications), and judicious use of steatotic liver disease treatments.
  • Promising therapeutic classes for MetALD include incretin-based therapies, FGF21 agonists, thyroid hormone receptor beta agonists, SGLT2 inhibitors, and agents targeting de novo lipogenesis.
  • Current research predominantly supports glucagon-like peptide 1 receptor agonists and PPAR-γ agonists for MASLD, with limited agents in trials for ALD. The optimal therapeutic approach for MetALD remains unclear.

Conclusions:

  • Effective management of MetALD requires a multifaceted approach combining lifestyle interventions, alcohol cessation, and targeted pharmacotherapy.
  • Further clinical trials are essential to evaluate the safety and efficacy of MASLD-associated therapies in the MetALD population.
  • Elucidating the specific therapeutic needs for MetALD is paramount for advancing treatment options and improving patient outcomes.