Metabolic steatotic liver disease (MASLD, MASH)
- Lesion
Fat builds up in the liver of people with obesity or diabetes; in some it inflames the liver and slowly scars it.
What it is
Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) is fat in the liver of a person with at least one cardiometabolic risk factor and little or no alcohol intake. Its inflammatory form, MASH (formerly NASH), shows hepatocyte injury and can progress to cirrhosis and hepatocellular carcinoma. It is now the most common chronic liver disease worldwide, driven by obesity and type 2 diabetes, and is common in Colombia.
Structure
- Gross: enlarged, yellow, greasy liver; shrunken nodular liver in late stages.
- Micro: macrovesicular steatosis, lobular inflammation, ballooned hepatocytes; pericellular fibrosis in zone 3 seen on trichrome.
Step by step
- Obesity and insulin resistance increase lipolysis in fat tissue; free fatty acids flood the liver.
- Hyperinsulinemia drives de novo lipogenesis; triglycerides accumulate in hepatocytes.
- Lipotoxic lipids (free fatty acids, ceramides, free cholesterol) cause ER stress and mitochondrial injury.
- Damaged hepatocytes balloon and release signals that activate Kupffer cells.
- Gut microbiome products and adipokines add inflammation; stellate cells activate.
- Fibrosis starts around zone 3 sinusoids and can end in cirrhosis; PNPLA3 and TM6SF2 variants raise the risk.
Alcohol-associated vs metabolic steatohepatitis
| Feature | Alcohol-associated | Metabolic (MASH) |
|---|---|---|
| Main driver | Ethanol metabolism (NADH, acetaldehyde, CYP2E1) | Insulin resistance and lipotoxicity |
| Steatosis | Macrovesicular, zone 3 | Macrovesicular, zone 3 (zone 1 in some children) |
| Ballooning and Mallory-Denk bodies | Prominent | Present, often fewer |
| Neutrophils | Often many | Usually few |
| Typical labs | AST higher than ALT; high GGT | ALT often higher than AST until advanced fibrosis |
| Associations | Pancreatitis, cardiomyopathy, neuropathy | Obesity, type 2 diabetes, dyslipidemia, hypertension |
Clinical notes
- Usually silent; found by raised ALT or a bright liver on ultrasound.
- Weight loss and control of diabetes and lipids reduce fat and can improve inflammation.
Test yourself
Think of the answer, then tap the question to see it.
What defines MASLD under the current nomenclature?
Hepatic steatosis plus at least one cardiometabolic risk factor in a person with little or no alcohol intake and no other cause.
What histologic features separate MASH from simple steatosis?
Hepatocyte ballooning and lobular inflammation (with or without fibrosis) in addition to fat.
What is the most common cause of death in people with MASLD?
Cardiovascular disease.
Why may a cirrhotic liver from long-standing MASH show no fat?
Steatosis often disappears in advanced cirrhosis (burnt-out MASH), so many such cases are labelled cryptogenic.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Nonalcoholic fatty liver disease: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.