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MASH Treatment and Monitoring
MASH Matters: A Multidisciplinary Approach to Treatment and Monitoring

Released: March 26, 2025

Expiration: March 25, 2026

Mazen Noureddin
Mazen Noureddin, MD, MHSc
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Key Takeaways
  • Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive liver disease with strong associations with metabolic syndrome, obesity, and diabetes.
  • Resmetirom is the first FDA-approved therapy for patients with MASH and moderate to severe liver fibrosis, with GLP-1 RAs and other agents showing promising results in current research.
  • A multidisciplinary approach that includes primary care, endocrinology, hepatology, nutrition, and metabolic medicine is essential for optimizing patient outcomes. 

Metabolic dysfunction–associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (or NASH), is a critical public health concern that affects millions worldwide. With its strong association with obesity, diabetes, and metabolic syndrome, MASH is more than just a liver disease—it is a systemic condition with far-reaching implications, including cardiovascular disease, cirrhosis, and hepatocellular carcinoma. 

Despite its prevalence, MASH remains underdiagnosed and undertreated, often due to a lack of awareness and the complexity of its management. A multidisciplinary approach that integrates hepatology, endocrinology, primary care, nutrition, and metabolic medicine is essential to optimize patient care. As our understanding of the disease deepens and new pharmacologic therapies emerge, healthcare professionals must adopt a proactive, team-based strategy to identify at-risk patients, initiate early treatment, and monitor progression effectively.

The Evolution of MASH and Its Relationship With Metabolic Syndrome
MASH exists within the broader category of metabolic dysfunction–associated steatotic liver disease (MASLD), a term reflecting its close ties to metabolic disorders. The disease progresses through stages, starting with simple steatosis (fat accumulation in the liver) and advancing to inflammation, fibrosis, and ultimately cirrhosis. The key risk factors for MASH include obesity, type 2 diabetes (T2D), hypertension, and dyslipidemia—a cluster of conditions commonly seen in primary care and endocrinology settings.

The pathogenic link between insulin resistance, chronic inflammation, and liver fibrosis is central to MASH progression. Patients with T2D have a significantly higher risk of developing advanced liver fibrosis, making routine screening and early intervention crucial. Noninvasive tests, such as fibrosis-4 (FIB-4), vibration controlled-transient elastography (FibroScan), and magnetic resonance elastography, offer effective ways to identify those at risk before irreversible liver damage occurs.

A New Era in MASH Treatment: The Role of Emerging Therapies
Historically, the management of MASH has relied heavily on lifestyle modification, particularly weight loss through diet and exercise. Studies have shown that losing 10% or more of body weight can significantly reduce liver fat, improve inflammation, and even reverse fibrosis. However, achieving and maintaining such weight loss remains a challenge for many patients, highlighting the need for pharmacologic interventions. 

In 2024, the FDA approved resmetirom, the first medication specifically indicated for MASH with fibrosis (F2-F3). Resmetirom is a thyroid hormone receptor-β agonist that reduces liver fat and fibrosis by enhancing hepatic metabolism. Clinical trials have demonstrated significant histologic improvement, making it a landmark advancement in MASH treatment

Other emerging therapies target key metabolic and inflammatory pathways involved in MASH. GLP-1 receptor agonists such as semaglutide have gained attention for their dual benefits in diabetes and liver disease. Data from the ESSENCE trial show that semaglutide led to significant steatohepatitis resolution without worsening fibrosis, making it a promising option for patients with MASH, obesity, and diabetes.

In addition, PPAR agonists (lanifibranor), FGF21 analogs (pegozafermin, efruxifermin), tirzepatide (a dual GLP-1/GIP receptor agonist), and survodutide (a dual glucagon/GIP receptor agonist) are undergoing phase II/III trials and show potential in reducing liver fat and fibrosis in patients with MASH. Although no single agent is a cure-all, the expanding therapeutic landscape offers personalized options based on individual patient profiles.

The Importance of a Multidisciplinary Approach
MASH management requires collaboration across multiple specialties. The involvement of primary care providers, endocrinologists, hepatologists, and dietitians or nutritionists ensures a comprehensive treatment strategy that addresses both liver disease and its associated metabolic comorbidities.

Screening and Early Diagnosis in Primary Care
Primary care providers play a pivotal role in early identification of MASH, particularly in patients with obesity, T2D, or metabolic syndrome. Simple screening tools like the FIB-4 index (which incorporates age, alanine aminotransferase, aspartate aminotransferase, and platelet count) can help stratify low-, intermediate-, and high-risk patients for further evaluation. Patients with elevated liver function tests, persistent metabolic risk factors, or suspected fibrosis should undergo noninvasive liver fibrosis assessment. Those at high risk should be referred to hepatology for further evaluation and consideration of advanced therapies.

Endocrinologists and Metabolic Specialists: Addressing the Root Causes
Given the strong association between MASH and insulin resistance, endocrinologists play a crucial role in disease management. Optimizing diabetes control, weight management, and cardiometabolic risk factors through lifestyle interventions and medications like GLP-1 receptor agonists or SGLT2 inhibitors can help prevent disease progression.

Endocrinologists should also collaborate closely with hepatologists when selecting antidiabetic medications for patients with coexisting MASH and T2D, ensuring that treatment aligns with both glycemic control and liver health.

Hepatologists: Guiding Advanced Care and Therapeutics
Hepatologists are responsible for confirming MASH diagnoses, assessing fibrosis severity, and initiating advanced pharmacologic treatments. With the approval of resmetirom and the expansion of clinical trials for new agents, liver specialists must tailor treatments based on the latest evidence while also considering liver function, fibrosis stage, and patient-specific factors.

In addition, hepatologists should provide long-term monitoring for patients with advanced fibrosis or cirrhosis, coordinating care with other specialists to prevent progression to end-stage liver disease.

Lifestyle Medicine and Nutrition: The Role of Dietitians and Obesity Specialists
Weight loss remains a cornerstone of MASH management, making dietitians or nutritionists and obesity medicine specialists essential members of the care team. Tailored nutritional counseling, physical activity recommendations, and behavioral interventions can reinforce pharmacologic strategies, improving long-term patient outcomes.

For patients with severe obesity and progressive MASH, bariatric surgery may be a viable option, with studies showing histologic improvement and reduced fibrosis progression following significant weight loss.

Looking Ahead: Future Directions in MASH Care
The landscape of MASH diagnosis and treatment is evolving rapidly, with ongoing research paving the way for novel combination therapies, improved biomarkers, and individualized treatment approaches. As noninvasive diagnostic tools become more sophisticated, reliance on liver biopsies may decrease, allowing for earlier and more accessible disease detection.

In addition, combination therapy approaches—such as pairing resmetirom with GLP-1 receptor agonists—could offer synergistic benefits, targeting both hepatic fat accumulation and metabolic dysfunction. The future of MASH treatment is likely to involve tailored regimens that integrate lifestyle changes, pharmacologic agents, and multidisciplinary support.

Your Thoughts?
How is your practice adapting to the new treatment landscape for MASH? What strategies have been most effective in collaborative care for patients with metabolic liver disease? Share your insights below.

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