Patterns of hepatocyte injury
- Lesion
A sick liver cell swells, fills with fat or bile, or dies; where in the lobule it dies points to the cause.
What it is
The liver has only a few ways to show damage, whatever the cause: hepatocytes swell (ballooning), store fat or bile, die one by one by apoptosis, or die in groups by necrosis. Reading these changes, and where they sit in the acinus, is the first step of every liver biopsy. Zone 3 (around the central vein) has the least oxygen and the most cytochrome P450, so ischemia and many toxins hit it first.
Structure
- Ballooning: a swollen, pale hepatocyte with wispy cleared cytoplasm, often with a Mallory-Denk body (ropy pink inclusion).
- Steatosis: one large fat vacuole pushing the nucleus aside (macrovesicular) or many tiny droplets with a central nucleus (microvesicular).
- Cholestasis: brown-green bile in canaliculi and hepatocytes, with feathery degeneration of bile-soaked cells.
- Apoptosis: a shrunken, deeply eosinophilic round body, with or without a dense nuclear fragment.
- Necrosis: swollen cells that rupture; macrophages cluster where they were (lytic necrosis).
- Confluent necrosis: zonal loss of contiguous hepatocytes, around central veins, across the acinus (panacinar) or bridging vessels.
Step by step
- An insult (virus, toxin, low oxygen, immune attack, fat, bile) reaches the hepatocyte.
- Reversible changes come first: swelling, ballooning, fat or bile accumulation.
- If injury continues, the cell dies by apoptosis (single cells) or necrosis (swelling and rupture).
- Dying cells release danger signals; macrophages and lymphocytes gather at the site.
- Widespread death becomes confluent necrosis; reticulin collapses and portal and central areas are bridged.
- Survivors regenerate; if injury persists, stellate cells lay down scar.
Injury patterns of the hepatocyte and what they suggest
| Pattern | What the pathologist sees | Typical settings |
|---|---|---|
| Ballooning with Mallory-Denk bodies | Swollen clear hepatocytes with ropy pink keratin inclusions | Alcoholic and metabolic steatohepatitis; also Wilson disease and chronic cholestasis |
| Macrovesicular steatosis | One big fat droplet per cell | Alcohol, obesity and insulin resistance, corticosteroids |
| Microvesicular steatosis | Foamy cells full of tiny droplets, nucleus central | Acute fatty liver of pregnancy, Reye syndrome, tetracycline or valproate toxicity |
| Acidophil bodies | Scattered shrunken eosinophilic hepatocytes | Acute and chronic viral hepatitis, autoimmune and drug injury, yellow fever |
| Zone 3 necrosis | Dead hepatocytes around the central vein | Shock, heart failure, acetaminophen, carbon tetrachloride |
| Zone 1 necrosis | Dead hepatocytes at the portal edge | Some toxins (white phosphorus); eclampsia (periportal fibrin and hemorrhage) |
| Bridging or massive necrosis | Bands or sheets of lost parenchyma, collapsed reticulin | Severe viral, autoimmune or toxic hepatitis; acute liver failure |
Markers
- Trichrome (collagen)
- Reticulin (framework collapse)
- Keratin 8/18 and ubiquitin (Mallory-Denk bodies)
- PAS with diastase (globules, macrophages)
Clinical notes
- Hepatocyte death raises serum ALT and AST; bile-duct injury raises alkaline phosphatase and GGT.
- The liver's large reserve hides mild injury: symptoms appear when most function is lost or bile flow is blocked.
Test yourself
Think of the answer, then tap the question to see it.
Why does shock injure the pericentral hepatocytes first?
Zone 3 receives blood last and has the lowest oxygen tension, so it is the most sensitive to low flow.
What is a Mallory-Denk body made of?
Clumped intermediate filaments, mainly keratins 8 and 18, bound to ubiquitin, inside ballooned hepatocytes.
Which disorders typically cause microvesicular steatosis?
Mitochondrial injury states: acute fatty liver of pregnancy, Reye syndrome, and toxicity of drugs such as valproate or tetracycline.
What is bridging necrosis?
Confluent necrosis that links portal tracts to central veins (or portal to portal), a marker of severe injury that favours fibrosis.
Elsewhere in DurgiPedia
- Liver: lobule, acinus, hepatocytes, sinusoids, Kupffer cells
- Functions of the liver
- Aminotransferases (ALT and AST) as lab tests
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: Liver biopsy: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Liver disease: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.