What is the best management of Multiple System Atrophy with Autonomic Dysfunction (MASLD)?

Management of MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)

The cornerstone of MASLD management is structured weight loss through Mediterranean diet and exercise, targeting ≥7-10% weight reduction to improve inflammation and fibrosis, with resmetirom as first-line pharmacotherapy for non-cirrhotic MASH with significant fibrosis (stage ≥2). 1, 2

Lifestyle Modification: First-Line Therapy

Weight Loss Targets

• Achieve ≥5% sustained weight reduction to reduce liver steatosis 1, 2
• Target 7-10% weight loss to improve liver inflammation and resolve steatohepatitis 1, 2
• Aim for ≥10% weight reduction to achieve fibrosis regression 1, 2

Dietary Interventions

• Implement Mediterranean dietary pattern as the primary approach: high intake of vegetables, fruits, low-fat dairy, nuts, olive oil, legumes, unprocessed fish and poultry 1, 2
• Eliminate sugar-sweetened beverages completely 1, 3
• Minimize processed meat and ultra-processed foods rich in sugars and saturated fats 1, 3

Exercise Prescription

• Prescribe >150 minutes/week of moderate-intensity physical activity OR 75 minutes/week of vigorous-intensity activity 1, 2
• Tailor exercise programs to individual preference and ability to maximize adherence 1, 2

Pharmacological Management

MASH-Targeted Therapy

• Consider resmetirom (thyroid hormone receptor β-selective agonist) as first-line therapy for adults with non-cirrhotic MASH and significant fibrosis (stage ≥2) 2, 3
• Resmetirom has demonstrated histological efficacy on steatohepatitis and fibrosis with acceptable safety profile 3

Weight Loss Medications

• Consider GLP-1 receptor agonists (semaglutide) or dual GLP-1/GIP agonists (tirzepatide) for patients with coexisting type 2 diabetes or obesity requiring pharmacological intervention 2, 3
• These incretin-based therapies provide dual benefits for metabolic control and liver outcomes 2, 3

Bariatric Surgery

• Consider bariatric surgery for patients with MASLD and class II-III obesity (BMI ≥35 kg/m²) when lifestyle modification and pharmacotherapy are insufficient 2, 3
• For patients with compensated cirrhosis without clinically significant portal hypertension, sleeve gastrectomy may be considered as alternative to dietary or pharmacological weight loss 1
• Bariatric surgery is contraindicated in decompensated cirrhosis 1

Multidisciplinary Care Approach

A multidisciplinary team is mandatory to address both liver-related and extrahepatic outcomes, including hepatology/gastroenterology, endocrinology, cardiology, nutrition/dietetics, and behavioral therapy. 1, 2

Key Components

• Coordinate care across specialties to manage cardiometabolic comorbidities 1, 2
• Implement behavioral therapy including self-monitoring, goal-setting, and barrier identification 1
• Conduct regular multidisciplinary evaluations during healthcare visits 1

Monitoring Disease Progression

Non-Invasive Assessment

• Use liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) ≤15 kPa plus platelet count ≥150×10⁹/l to rule out clinically significant portal hypertension 1
• Perform upper gastrointestinal endoscopy to screen for varices if LSM ≥20 kPa and/or platelet count <150×10⁹/l 1
• Repeatedly use non-invasive tests to assess fibrosis progression in tailored fashion, though they provide limited information about treatment response 1, 3

Liver Biopsy

• Reserve liver biopsy for individual cases and clinical trials to monitor disease progression or treatment response, not for routine monitoring 1, 3

Management of Advanced Disease

Portal Hypertension

• Initiate non-selective beta-blockers if clinically significant portal hypertension is present, unless contraindicated 1

Pre-Transplant Optimization

• For patients with obesity and end-stage MASLD listed for transplantation, implement dietary modification and supervised physical exercise as first-line approach to reduce BMI <40 kg/m² (ideally <35 kg/m²) 1
• Conduct comprehensive cardiovascular screening using stepwise risk-adjusted cardiac work-up algorithm before transplantation 1
• Evaluate patients by multidisciplinary team to mitigate risk of major cardiovascular events in pre-, peri-, and post-transplant phases 1

Post-Transplant Care

• Continue therapeutic interventions to control obesity and cardiometabolic complications after transplantation to prevent MASLD recurrence 1
• Maintain optimal control of cardiometabolic risk factors to reduce risk of severe, fibrotic steatohepatitis recurrence 1

Common Pitfalls to Avoid

• Do not use nutraceuticals as there is insufficient evidence for their efficacy 1
• Do not rely solely on LSM ≥25 kPa threshold to rule in clinically significant portal hypertension in obese patients (BMI ≥30 kg/m²), as obesity confounds measurements 1
• Do not perform bariatric surgery in decompensated cirrhosis 1
• Do not use liver biopsy for routine monitoring due to invasiveness and procedure-related limitations 1, 3