Treatment for Metabolic Associated Steatotic Disease (MASLD)
The cornerstone of MASLD treatment is lifestyle modification, including weight loss of 7-10%, Mediterranean diet, and regular exercise, with pharmacotherapy reserved for biopsy-proven MASH with significant fibrosis (stage ≥2). 1, 2
First-Line Treatment: Lifestyle Modifications
Weight Loss
- Target weight loss of 7-10% in overweight/obese patients with MASLD, as this significantly improves liver histology, reduces steatosis, inflammation, and can reverse MASH 2, 3
- Even modest weight loss (5-7%) can improve hepatic steatosis 2
- Aim for gradual weight loss of approximately 0.5-1 kg/week to avoid rapid weight reduction which may worsen liver disease 1
Dietary Recommendations
- Mediterranean diet is strongly recommended, characterized by: 2
- Reduced carbohydrate intake
- Increased monounsaturated and omega-3 fatty acid intake
- Rich in fruits, vegetables, whole grains, legumes, nuts, and olive oil
- Specific dietary modifications include: 1, 2
- Limit excess fructose consumption and avoid processed foods with added sugars
- Replace saturated fats with polyunsaturated and monounsaturated fats
- Avoid processed foods, fast food, and commercial bakery goods
- Discourage alcohol consumption 1
Physical Activity
- Both aerobic and resistance training effectively reduce liver fat in MASLD patients 2
- Vigorous exercise provides greater benefit than moderate exercise for MASH and fibrosis 2
- Any increase in physical activity over previous levels is beneficial compared to continued inactivity 2
Pharmacological Treatment
For Non-Cirrhotic MASH with Significant Fibrosis (Stage ≥2)
- Resmetirom should be considered if locally approved, as it has demonstrated histological effectiveness on steatohepatitis and fibrosis with acceptable safety profile 1
- Vitamin E (800 IU/day) is recommended for non-diabetic adults with biopsy-confirmed MASH, improving liver histology through antioxidant properties 2
- Note: Potential concerns about increased risk of all-cause mortality, hemorrhagic stroke, and prostate cancer with long-term use 2
- Pioglitazone (30 mg daily) is effective for patients with biopsy-proven MASH with or without diabetes 2
- Side effects include weight gain, bone fractures in women, and rarely congestive heart failure 2
For Diabetic Patients with MASLD
- Incretin-based therapies (e.g., semaglutide, tirzepatide) are recommended for management of comorbid type 2 diabetes or obesity 1
- Pioglitazone has the strongest evidence for MASH treatment in diabetic patients 2
- GLP-1 receptor agonists show promise for MASH treatment 2
For MASH-Related Cirrhosis
- No MASH-targeted pharmacotherapy is currently recommended for cirrhotic stage 1
- Management includes: 1
- Adaptations of metabolic drugs
- Nutritional counseling
- Surveillance for portal hypertension and hepatocellular carcinoma (HCC)
- Liver transplantation in decompensated cirrhosis
Bariatric Surgery
- Consider bariatric surgery as an option for individuals with MASLD and obesity 1
- Effective for sustained weight loss and improvement in MASLD/MASH 3
Treatment Algorithm Based on Disease Stage
For MASL (Simple Steatosis) or MASH with Minimal Fibrosis (F0-F1)
For MASH with Significant Fibrosis (F2-F3)
- Intensive lifestyle modifications 2
- Consider pharmacotherapy: 1, 2
- Resmetirom if locally approved
- Vitamin E for non-diabetic patients
- Pioglitazone for diabetic patients
- Incretin-based therapies for patients with diabetes or obesity
For MASH with Cirrhosis (F4)
- Lifestyle modifications with careful monitoring 2
- Limited evidence for pharmacotherapy 2
- HCC surveillance with ultrasound every 6 months 2
- Consider liver transplantation for decompensated cirrhosis 1