What are the primary treatment steps in a MASH (Mobile Army Surgical Hospital) scenario?

MASH Treatment

For patients with metabolic dysfunction-associated steatohepatitis (MASH), prioritize lifestyle modification through weight loss of 7-10% via caloric restriction and increased physical activity, with resmetirom as the only FDA-approved pharmacological option for noncirrhotic MASH with stage 2-3 fibrosis. 1

Primary Treatment Strategy

Lifestyle Modification (First-Line for All Patients)

• Weight loss of 7-10% through caloric restriction and increased physical activity is the cornerstone of MASH treatment, as it can induce histological improvement in steatohepatitis and fibrosis 1
• Dietary modifications should emphasize reduction of simple carbohydrates, saturated fats, and processed foods while increasing fiber intake 1
• Physical activity should target at least 150 minutes of moderate-intensity aerobic exercise per week, combined with resistance training 1
• For patients with MASH cirrhosis, dietary recommendations must be adapted to severity of liver disease, nutritional status, and presence of sarcopenia/sarcopenic obesity 1

Pharmacological Treatment

Resmetirom (FDA-Approved)

• Resmetirom is currently the only FDA-approved medication specifically for MASH treatment in adults with noncirrhotic MASH and stage 2-3 fibrosis 1
• Data on sustainability of histological benefits, individual prediction of response, liver-related outcomes, and long-term safety are currently not available 1

GLP-1 Receptor Agonists

• GLP-1RAs cannot currently be recommended as MASH-targeted therapies due to absence of formal demonstration of histological improvement in large phase III trials 1
• However, GLP-1RAs are safe to use in MASH (including compensated cirrhosis) and should be used for their respective indications—type 2 diabetes and obesity—as their use improves cardiometabolic outcomes 1
• In cases of substantial weight loss induced by GLP-1RAs, hepatic histological benefit could be expected, although this has not been extensively documented 1

Vitamin E

• Vitamin E cannot be recommended as a MASH-targeted therapy despite some evidence of benefit, due to lack of robust demonstration of histological efficacy from large phase III trials and potential long-term risks 1

Pioglitazone

• Pioglitazone is safe to use in adults with non-cirrhotic MASH but cannot be recommended as a MASH-targeted therapy due to lack of robust demonstration of histological efficacy on steatohepatitis and liver fibrosis in large phase III trials 1

Other Glucose-Lowering Agents

• SGLT2 inhibitors and metformin have insufficient evidence as MASH-targeted therapies, but are safe to use in MASLD for their respective indications (type 2 diabetes, heart failure, chronic kidney disease) 1
• Non-incretin-based weight-loss agents are not recommended as MASH-targeted therapies 1

Surgical and Endoscopic Interventions

Bariatric Surgery

• In adults with non-cirrhotic MASLD who have an approved indication, bariatric surgery should be considered because it can induce long-term beneficial effects on the liver and is associated with remission of type 2 diabetes and improvement of cardiometabolic risk factors 1
• For patients with MASLD-related compensated advanced chronic liver disease/compensated cirrhosis, bariatric surgery can be considered but requires careful evaluation (indication, type of surgery, presence of clinically significant portal hypertension) by a multidisciplinary team with experience in this population 1
• Metabolic/bariatric endoscopic procedures require further validation and cannot currently be recommended 1

Management of Advanced Disease

Compensated Cirrhosis

• High-protein diet should be provided along with a late-evening snack for patients with sarcopenia, sarcopenic obesity, or decompensated cirrhosis 1
• Moderate weight reduction can be suggested in adults with compensated cirrhosis and obesity, with emphasis on high protein intake and physical activity to maintain muscle mass and reduce sarcopenia risk 1
• Metformin can be used in adults with compensated cirrhosis and preserved renal function but should not be used in decompensated cirrhosis, especially with concomitant renal impairment, due to lactic acidosis risk 1
• Sulfonylureas should be avoided in adults with hepatic decompensation 1

Critical Pitfalls to Avoid

• Do not delay lifestyle modification while waiting for pharmacological options—weight loss through diet and exercise remains the most effective intervention with proven histological benefit 1
• Do not use vitamin E or pioglitazone as primary MASH-targeted therapies despite their availability, as they lack robust phase III trial evidence for histological efficacy 1
• Do not withhold GLP-1RAs or SGLT2 inhibitors from patients with MASH who have appropriate indications (diabetes, obesity, heart failure, chronic kidney disease), as they improve cardiometabolic outcomes even if not proven as MASH-specific therapies 1
• Do not recommend bariatric surgery in patients with decompensated cirrhosis or clinically significant portal hypertension without careful multidisciplinary evaluation 1
• Do not use metformin in decompensated cirrhosis or with renal impairment due to lactic acidosis risk 1

Monitoring and Follow-Up

• Regular assessment of weight, metabolic parameters, and liver function tests should guide treatment response 2
• Noninvasive tests (NITs) should be used to identify "at-risk MASH" patients and monitor disease progression 2
• For patients on resmetirom, close monitoring is required given limited long-term safety data 1