What is the disorder labeled MASH (Multiple system disorder)?

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. 1

Definition and Nomenclature

MASH represents a recent terminology update in liver disease classification:

• MASH was previously known as NASH (Non-Alcoholic Steatohepatitis)
• It is part of the MASLD spectrum (previously called NAFLD)
• The nomenclature change reflects the metabolic nature of the disease, with 99% overlap between old and new terminology 1

Disease Spectrum

The MASLD/MASH disease spectrum includes:

1. MASL - Simple steatosis without inflammation
2. MASH with early fibrosis (F0-F1) - Steatohepatitis with minimal fibrosis
3. MASH with significant fibrosis (F2-F3) - Also called "at-risk MASH"
4. MASH cirrhosis (F4) - Advanced fibrosis with cirrhotic changes

Clinical Significance

MASH is clinically significant because:

• It affects patients with metabolic risk factors (obesity, diabetes, dyslipidemia)
• Fibrosis progression correlates with adverse hepatic outcomes 1
• Patients with stage F2-F3 fibrosis are at increased risk of liver-related morbidity and mortality
• It can progress to complications including hepatic decompensation, hepatocellular carcinoma, and need for liver transplantation 1

Diagnostic Approach

Diagnosis of MASH involves:

1. Establishing MASLD diagnosis by:

   • Confirming hepatic steatosis (via imaging or biopsy)
   • Excluding other causes of liver disease (alcohol, viral hepatitis, autoimmune disease)
   • Identifying metabolic risk factors

2. Assessing for steatohepatitis and fibrosis using:

   • Liver biopsy (gold standard but invasive)
   • Non-invasive tests (NITs):
     • Vibration Controlled Transient Elastography (VCTE/FibroScan): 10-15 kPa suggests F2-F3
     • Enhanced Liver Fibrosis (ELF) score: 9.2-10.4 suggests F2-F3
     • Magnetic Resonance Elastography (MRE): 3.0-4.3 kPa suggests F2-F3 1

Treatment Options

Treatment for MASH includes:

1. Lifestyle modifications (cornerstone for all patients):

   • Weight loss (7-10% of body weight improves liver histology) 2
   • Mediterranean diet pattern
   • Regular physical activity (150+ minutes/week)
   • Complete alcohol abstinence 2

2. Pharmacologic therapy:

   • Resmetirom - First FDA-approved medication specifically for non-cirrhotic MASH with F2-F3 fibrosis 1, 2
   • GLP-1 receptor agonists (semaglutide, tirzepatide) - Beneficial for MASH patients with diabetes 1, 2
   • Vitamin E (800 IU/day) - May be considered for non-diabetic NASH patients 2

3. Bariatric surgery - May be considered for patients with obesity and hepatic steatosis 2

Clinical Monitoring

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 2
• Monitoring of metabolic parameters (glucose, lipids, blood pressure)

Key Distinctions

It's important to note that MASH is not related to:

• Multiple System Atrophy (MSA), a neurodegenerative disorder 3, 4, 5, 6
• Mast Cell Activation Syndrome (MCAS), an immunological disorder 7

The term MASH specifically refers to Metabolic Dysfunction-Associated Steatohepatitis in the context of liver disease.