What is the recommended treatment for patients with MAFLD (Metabolic Associated Fatty Liver Disease) or NASH (Non-Alcoholic Steatohepatitis)?

Treatment Recommendations for MASLD/NASH

Lifestyle modifications should be the first-line treatment for all patients with MASLD/NASH, with a target weight loss of 7-10% to improve liver inflammation and >10% to improve fibrosis. 1, 2

Dietary Recommendations

• Caloric restriction: 500-1000 kcal daily deficit to achieve gradual weight loss (up to 1 kg/week) 1, 2
• Mediterranean diet pattern: Focus on vegetables, fruits, whole grains, lean proteins, and healthy fats 1, 2
• Avoid or limit:
  • Fructose-containing beverages and foods
  • Ultra-processed foods high in added sugars and saturated fats
  • Alcohol (complete abstinence recommended for patients with significant fibrosis) 1, 3

Physical Activity

• Aerobic exercise: 150-200 minutes/week of moderate-intensity activity in 3-5 sessions 1
• Resistance training: Incorporate to promote musculoskeletal fitness and improve metabolic risk factors 1
• Tailor exercise: Based on patient preferences to ensure long-term adherence 1, 2

Protein Intake

• Recommended intake: 1.2-1.5 g/kg body weight, focusing on branched-chain amino acids 2
• Both animal and plant protein diets can effectively reduce intrahepatic lipid content by 36-48% 1

Pharmacological Interventions

For patients with significant fibrosis (stage ≥2) or those who fail to achieve adequate response with lifestyle modifications:

1. Resmetirom: First choice for non-cirrhotic MASLD with significant liver fibrosis due to demonstrated histological efficacy on steatohepatitis and fibrosis 2

2. GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide):

   • Safe to use in MASLD, including compensated cirrhosis
   • Particularly beneficial for patients with concurrent type 2 diabetes and obesity 2

3. SGLT2 inhibitors (empagliflozin, dapagliflozin):

   • Safe in MASLD but should be used primarily for their indicated conditions (type 2 diabetes, heart failure, chronic kidney disease)
   • Insufficient evidence to recommend as MASLD-specific therapy 2

Surgical Interventions

• Bariatric surgery: Consider for non-cirrhotic MASLD patients with obesity who are unresponsive to lifestyle and medical interventions 2, 3
• Requires careful evaluation by a multidisciplinary team with bariatric surgery experience if patient has compensated cirrhosis 2

Special Considerations for Normal-Weight MASLD

• Diet and exercise interventions are still recommended to reduce liver fat in normal-weight patients 1
• Limited evidence regarding pharmacotherapy specifically for lean MASH patients 4
• Focus on reducing visceral adiposity even if overall weight is normal 4

Monitoring and Follow-up

• Liver enzymes: Monitor every 3 months 2
• Imaging: Repeat at 6-12 months 2
• HCC surveillance: Ultrasound examination every 6 months for patients with advanced fibrosis or cirrhosis 2

Treatment Algorithm

1. All patients: Implement lifestyle modifications (diet, exercise, alcohol limitation)
2. After 6 months, assess response:
   • If adequate response (weight loss achieved, liver enzymes improved): continue lifestyle modifications
   • If inadequate response and significant fibrosis present: add pharmacotherapy
3. For patients with obesity and inadequate response to lifestyle and pharmacotherapy: Consider bariatric surgery
4. For patients with cirrhosis: Implement HCC surveillance and manage portal hypertension complications

Remember that MASLD/NASH management requires addressing both liver-specific outcomes and associated metabolic comorbidities to improve overall morbidity and mortality.