What is MASH (Mobile Army Surgical Hospital)?

MASH: Metabolic Dysfunction-Associated Steatohepatitis

MASH (Metabolic Dysfunction-Associated Steatohepatitis) is the progressive inflammatory subtype of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), characterized by liver inflammation and fibrosis that can lead to cirrhosis and liver failure if left untreated. This term represents the updated nomenclature that has replaced the previous term NASH (Non-Alcoholic Steatohepatitis) to better reflect the metabolic nature of the disease 1.

Disease Definition and Classification

MASH is defined by:

• Presence of hepatic steatosis (fatty liver)
• Liver inflammation and hepatocyte ballooning
• Fibrosis progression that correlates with adverse hepatic outcomes
• Association with metabolic risk factors

The disease spectrum includes:

• Simple steatosis without inflammation (MASL)
• MASH with early fibrosis (F0-F1)
• MASH with significant fibrosis (F2-F3) - considered "at-risk MASH"
• MASH cirrhosis (F4)

Clinical Significance

MASH represents a major and growing health concern:

• Estimated prevalence of 14% in middle-aged US population 2
• Significant upward trend in prevalence
• Major economic burden on healthcare systems
• Progressive disease that can lead to cirrhosis, liver failure, and hepatocellular carcinoma

Diagnostic Approach

Diagnosis of MASH involves:

1. Establishing MASLD diagnosis by confirming hepatic steatosis
2. Excluding other causes of liver disease
3. Identifying metabolic risk factors
4. Assessing for steatohepatitis and fibrosis

Assessment methods include:

• Liver biopsy (gold standard)
• Non-invasive tests:
  • Vibration Controlled Transient Elastography (VCTE/FibroScan)
  • Enhanced Liver Fibrosis (ELF) score
  • Magnetic Resonance Elastography (MRE)
  • Fibrosis-4 (FIB-4) index

Treatment Options

First FDA-Approved Therapy

On March 14,2024, the FDA granted conditional approval to resmetirom for the treatment of fibrotic (stage 2 or 3) MASH 2. This represents a landmark achievement after more than two decades of research.

Treatment Approaches

1. Lifestyle modifications (cornerstone for all patients):

   • Weight loss (7-10% of body weight)
   • Mediterranean diet pattern
   • Regular physical activity
   • Complete alcohol abstinence

2. Pharmacologic therapy:

   • Resmetirom: FDA-approved for adults with noncirrhotic MASH with moderate to advanced liver fibrosis (F2-F3)
   • GLP-1 receptor agonists: Not currently recommended specifically as MASH-targeted therapies but safe to use for their approved indications (type 2 diabetes, obesity) 2
   • Vitamin E: Cannot be recommended as a MASH-targeted therapy due to insufficient evidence 2

3. Surgical options:

   • Bariatric surgery: Should be considered for patients with approved indications as it can induce long-term beneficial effects on the liver 2

Monitoring and Surveillance

Patients with MASH require:

• Regular monitoring of liver enzymes every 3-6 months
• Repeat non-invasive fibrosis assessment every 1-2 years
• HCC surveillance every 6 months for those with advanced fibrosis or cirrhosis
• Monitoring of metabolic parameters (glucose, lipids, blood pressure)

Current Challenges in MASH Management

Several challenges exist in MASH management:

• Liver histology is recognized as one of the main hurdles in MASH drug development due to its invasive nature, associated cost, and high inter- and intra-reader variability 2
• Need for development of reliable non-invasive biomarkers as surrogate endpoints for drug approval 2
• Limited long-term data on sustainability of histological benefits and liver-related outcomes with current therapies 2

Future Directions

The field is moving toward:

• Development and validation of non-invasive biomarkers
• Use of AI-based technologies for quantitative assessment of liver fibrosis 2
• Expansion of therapeutic options with several drug candidates in phase III development 2

MASH represents a significant health concern with evolving diagnostic and therapeutic approaches. The recent FDA approval of resmetirom marks an important milestone in MASH management, though continued research is needed to optimize patient outcomes.