Treatment Options for Metabolic Dysfunction Associated with Steatohepatitis (MASH/NASH)
Lifestyle modification is the cornerstone of treatment for MASH/NASH, with weight loss of 7-10% being the most effective intervention for improving liver histology and reducing disease progression. 1, 2
First-Line Treatment: Lifestyle Modifications
Weight Loss Targets
- Weight loss goals:
Dietary Recommendations
- Mediterranean diet with caloric restriction of 500-1000 kcal/day 2, 3
- Reduce carbohydrates, especially refined carbohydrates and fructose 1, 2
- Avoid sugar-sweetened beverages 1, 2
- Limit saturated fat intake 1
- Increase fiber consumption through vegetables, fruits, and whole grains 2
Physical Activity
- 150-300 minutes/week of moderate-intensity exercise OR
- 75-150 minutes/week of vigorous-intensity exercise 2, 3
- Include muscle-strengthening activities twice weekly 1, 2
- Both aerobic and resistance training are beneficial 2
Alcohol Consumption
- Heavy alcohol consumption should be avoided 1
- No guidelines recommend light-moderate alcohol consumption as therapy 1
Pharmacological Options for MASH
For Non-Cirrhotic MASH with Significant Fibrosis (Stage ≥2)
- Resmetirom is recommended as the first MASH-targeted treatment with demonstrated histological effectiveness on steatohepatitis and fibrosis 1, 5
For MASH with Comorbid Metabolic Conditions
- GLP-1 receptor agonists (e.g., semaglutide, tirzepatide) are recommended for patients with MASH who have T2D or obesity 1, 6
- These medications have shown significant benefits for weight loss and metabolic improvement 6
Other Pharmacological Options
Vitamin E (800 IU daily) may be considered in non-diabetic patients with biopsy-confirmed MASH without cirrhosis 1, 2
- Caution: potential increased risk of all-cause mortality, hemorrhagic stroke, and prostate cancer 1
Pioglitazone (30 mg daily) may be considered in patients with biopsy-confirmed MASH without cirrhosis 1
- Caution: associated with weight gain, peripheral edema, heart failure, and fractures 1
Surgical Options
- Bariatric surgery should be considered for patients with obesity and MASH/NASH 1, 2, 7
- Particularly beneficial for those unable to achieve weight loss goals through lifestyle modifications alone 7
Monitoring and Follow-up
- Monitor liver enzymes every 3-6 months 2
- Repeat fibrosis assessment every 1-2 years using non-invasive tests (FIB-4 score, transient elastography) 2
- For patients with cirrhosis, surveillance for hepatocellular carcinoma with ultrasound ± AFP every 6 months 1
Treatment Algorithm
- Initial approach: Intensive lifestyle modification for all patients
- If inadequate response after 6 months:
- For patients with T2D or obesity: Add GLP-1 receptor agonists
- For non-diabetic patients with biopsy-proven MASH: Consider vitamin E
- For patients with significant fibrosis (stage ≥2): Consider resmetirom
- For patients with obesity unable to achieve weight loss goals: Consider bariatric surgery
- For patients with cirrhosis: No MASH-targeted pharmacotherapy is currently recommended; focus on complications management and transplant evaluation if decompensated 1
Common Pitfalls to Avoid
- Underestimating the importance of weight loss (most effective intervention)
- Prescribing pharmacotherapy without histological confirmation of MASH
- Using vitamin E in patients with diabetes or cirrhosis
- Failing to address all components of metabolic syndrome
- Neglecting regular monitoring for disease progression and complications
The treatment landscape for MASH/NASH continues to evolve, with resmetirom emerging as the first targeted therapy showing histological effectiveness for non-cirrhotic MASH with significant fibrosis 1, 5.