What are the best treatments for Non-Alcoholic Fatty Liver Disease (NAFLD) or Metabolic Associated Fatty Liver Disease (MAFLD)?

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Last updated: April 29, 2025View editorial policy

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From the Guidelines

The most effective treatment for metabolic associated liver disease (MASLD) is a combination of lifestyle modifications, including weight loss, dietary changes, and physical exercise, along with optimal management of comorbidities, as recommended by the EASL-EASD-EASO clinical practice guidelines 1. The primary approach to managing MASLD involves lifestyle modifications, with a focus on weight loss of 7-10% of body weight, which can reduce liver fat, inflammation, and even reverse fibrosis 1. A Mediterranean diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats is recommended, while limiting processed foods, added sugars, and saturated fats. Regular physical activity of at least 150 minutes per week of moderate-intensity exercise should be incorporated. Some key points to consider in the management of MASLD include:

  • Weight loss through caloric restriction and regular exercise is beneficial for all patients with MASLD 1
  • A Mediterranean diet is recommended, with a focus on minimizing saturated fatty acid intake and limiting or eliminating consumption of commercially produced fructose 1
  • Regular physical activity should be considered, with a target of 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity aerobic exercise per week 1
  • Management of comorbidities like hypertension, dyslipidemia, and obesity is crucial, as these conditions contribute to liver disease progression 1
  • Alcohol consumption should be restricted or eliminated from the diets of adults with MASLD 1
  • Incretin-based therapies, such as semaglutide or tirzepatide, may be considered for patients with type 2 diabetes or obesity, as they have shown liver benefits beyond glucose control 1
  • Resmetirom may be considered for adults with non-cirrhotic MASH and significant liver fibrosis, as it has demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile 1

From the Research

Treatment Options for Metabolic Associated Liver Disease

  • Insulin sensitizers such as biguanides, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase 4 inhibitors have been studied as therapeutic approaches for non-alcoholic fatty liver disease (NAFLD) 2
  • Metformin improves insulin sensitivity and serum alanine transaminase and aspartate transaminase (ALT/AST) levels, but has no significant effect on liver histology 2
  • TZDs improve insulin sensitivity, serum ALT/AST levels, and histology in some cases, but there are concerns about the safety of long-term therapy 2
  • A holistic approach to metabolic syndrome and related chronic liver disease, including lifestyle modification, is recommended for early detection and intervention 3

Pharmacological Treatments

  • No pharmacotherapy has been established for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD), but several trials of different drugs have been conducted 4
  • Resmetirom, a thyroid hormone receptor-β agonist, has been approved for treating MASLD with fibrosis 5
  • Other agents, such as peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 analogs, and fibroblast growth factor 21 analogs, are awaiting approval 5
  • Saroglitazar, a dual peroxisome proliferator-activated receptor alpha and gamma agonist, has demonstrated promising efficacy in managing MASLD, but its clinical adoption is hindered by several challenges 6

Lifestyle Modifications

  • Early detection of metabolic syndrome and MASLD is a top priority, allowing for timely interventions, primarily through lifestyle modification 3
  • A global and multidimensional approach to both conditions, metabolic syndrome and related chronic liver disease, should be applied to improve overall health and longevity 3

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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