What is metabolic dysfunction‑associated steatohepatitis (MASH)?

What is MASH?

MASH (metabolic dysfunction-associated steatohepatitis) is the inflammatory and progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by fat accumulation in the liver combined with inflammation and hepatocyte injury (ballooning), which can progress to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. 1

Understanding the Disease Spectrum

MASH represents the more severe end of the MASLD spectrum. While simple steatosis (isolated fat accumulation) may remain stable, MASH involves active liver inflammation and cellular damage that drives disease progression 1, 2. This distinction is critical because:

• MASH significantly increases mortality risk from liver-related complications, cardiovascular disease, and certain extrahepatic cancers (particularly gastrointestinal, breast, and gynecologic) 2
• Cardiovascular disease remains the leading cause of death in MASH patients, followed by extrahepatic cancers and then liver-related complications 2
• The presence of significant fibrosis (stage ≥2) is the strongest predictor of adverse liver-related outcomes 1

Terminology Update

MASH is the updated term for what was previously called NASH (non-alcoholic steatohepatitis). This nomenclature change reflects a shift toward defining the disease by what it is (metabolic dysfunction-driven) rather than what it isn't (non-alcoholic) 1.

Epidemiology and Risk Factors

The disease burden is substantial:

• MASLD affects 30-40% of the general adult population globally, with MASH representing the progressive subset 2
• Prevalence increases dramatically to 60-70% in patients with type 2 diabetes and 70-80% in those with obesity 2
• Key risk factors include older age (≥50 years), male sex (approximately 2:1 male-to-female ratio), obesity, type 2 diabetes, hypertension, and dyslipidemia 2

Diagnostic Criteria

MASH is diagnosed when hepatic steatosis occurs with:

1. At least one cardiometabolic risk factor (abdominal obesity, prediabetes/type 2 diabetes, hypertension, elevated triglycerides, low HDL cholesterol) 1
2. Absence of harmful alcohol intake (<140 g/week for women, <210 g/week for men) 1
3. Histological evidence of inflammation and hepatocyte ballooning on liver biopsy, or clinical/imaging evidence of progressive disease 1

Common pitfall: Don't overlook moderate alcohol consumption (20-50 g/day in women, 30-60 g/day in men), which creates a hybrid condition called MetALD (MASLD with increased alcohol consumption) that requires different management considerations 1.

Clinical Significance

MASH is now a leading indication for liver transplantation due to its association with end-stage liver disease 3. The disease creates a self-perpetuating cycle where metabolic dysfunction drives immune dysregulation, which in turn worsens metabolic stress—making MASH fundamentally an immunometabolic disorder 4, 5.