STEPTRACKERGASTROINTESTINAL | PATHOLOGY + PHARMACOLOGY | HIGH-YIELD REVIEW

Liver Injury Patterns

Read the liver tests, place the injury in its zone, and name the drug or toxin behind it.

FOCUS ON

Hepatocellular injury → ALT/AST ↑ out of proportion to ALP; cholestatic → ALP, GGT, bilirubin ↑. Function = albumin and PT/INR. AST:ALT > 2 → alcohol. Aminotransferases in the thousands → acetaminophen, ischemia, acute viral. Zone 3 (centrilobular) takes ischemia and toxic metabolites.

TOPIC

MECHANISM

FINDINGS

CLUE

Hepatocellular pattern

Hepatocyte necrosis releases ALT (more liver-specific) and AST

ALT/AST ↑↑; ALP mildly ↑

Viral, toxins, ischemia, autoimmune

Cholestatic pattern

Impaired bile flow induces ALP and GGT

ALP + GGT ↑ (GGT confirms liver source), conjugated bilirubin ↑

Obstruction, PBC, PSC, drugs

Synthetic failure

↓ production of albumin and clotting factors (II, VII, IX, X)

↓ albumin (weeks), ↑ PT/INR (hours–days)

INR not corrected by vitamin K → liver failure

Acetaminophen toxicity

Excess drug → CYP2E1 → NAPQI; glutathione depleted → zone 3 necrosis

Nausea, then quiet phase, then ALT in the thousands, liver failure at 3–5 days

N-acetylcysteine · alcohol and fasting ↑ risk

Ischemic hepatitis (shock liver)

Hypotension, heart failure → zone 3 hypoxia

Very high ALT/AST and LDH that fall quickly

After cardiac arrest, sepsis

Drug-induced hepatitis

Idiosyncratic or metabolic

Isoniazid, halothane, statins, ketoconazole, nitrofurantoin, methyldopa

Halothane: fever, eosinophilia, massive necrosis

Drug-induced steatosis & fibrosis

Mitochondrial β-oxidation injury → microvesicular fat

Valproate, tetracyclines, aspirin (Reye) · amiodarone (steatohepatitis) · methotrexate (fibrosis)

Microvesicular = mitochondrial

Drug-induced cholestasis

Inhibited bile transport

OCPs, anabolic steroids, amoxicillin-clavulanate, chlorpromazine, erythromycin

Steroids also → hepatic adenoma, peliosis hepatis

Autoimmune hepatitis

T-cell attack on hepatocytes; plasma cells, interface hepatitis

Young women; ↑ ALT, ↑ IgG; ANA, anti-smooth muscle (type 1), anti-LKM1 (type 2, children)

Responds to steroids, azathioprine

Acute liver failure

Massive necrosis without prior liver disease

Encephalopathy + INR ≥ 1.5 within weeks; asterixis; hypoglycemia; cerebral edema

Acetaminophen (most in US), viral, drugs · transplant

Hepatic encephalopathy

↑ ammonia (shunting, ↓ urea cycle); triggers: GI bleed, infection, constipation, ↑ protein, hypokalemia, sedatives

Confusion, asterixis, coma

Lactulose (traps NH₄⁺) + rifaximin

Picture it — zones of the liver lobule

ZonesZone 1 around portal triads (teal) gets the most oxygen; zone 3 around the central vein gets the least.

Zone 3 necrosisAcetaminophen (most CYP2E1) and shock liver (least O₂).

Interface hepatitisPeriportal inflammation eating into the limiting plate — autoimmune, chronic viral.

SteatosisLarge fat droplets push nuclei aside — alcohol, obesity, drugs.

CholestasisBile plugs in canaliculi — drugs, obstruction.

Schematic diagrams, not to scale. Red = abnormal.

Mechanism — acetaminophen overdose

Normal doseGlucuronidation, sulfation

→

OverdosePathways saturate

→

CYP2E1NAPQI (toxic)

→

Glutathione used up

→

Zone 3 necrosisLiver failure

N-acetylcysteine regenerates glutathione — most effective within 8 hours; chronic alcohol use induces CYP2E1 and depletes glutathione.

Zones of the liver acinus

ZONE

LOCATION

INJURED BY

Zone 1

Periportal (most O₂)

Viral hepatitis, ingested toxins (cocaine)

Zone 2

Intermediate

Yellow fever

Zone 3

Centrilobular (least O₂, most CYP450)

Ischemia, acetaminophen, alcohol, CCl₄, halothane

AST:ALT clues

> 2:1 → alcohol (AST in mitochondria, pyridoxine-poor) · ALT > AST → viral, NAFLD · > 1000 → acetaminophen, ischemia, acute viral, autoimmune.

How it's tested

COMMON CONFUSIONAlbumin falls over weeks (long half-life); PT/INR rises within a day. In acute liver failure the INR is the early marker of synthetic loss.

THE TRAPA patient feels better on day 2 after an acetaminophen overdose. That's the quiet phase — liver failure comes on days 3–5. Treat by level and timing, not symptoms.

YOUR APPROACHPattern (hepatocellular vs cholestatic) → magnitude (thousands?) → zone → exposure (drug, alcohol, shock) → serology for viral/autoimmune.

If you see… think…

ALT 4000 two days after an overdose → acetaminophen — NAC

ALT/AST in the thousands after cardiac arrest, falling fast → ischemic hepatitis

AST 240, ALT 100 → alcoholic liver disease

↑ ALP with ↑ GGT → cholestasis

↑ ALP with normal GGT → bone source

Fever, eosinophilia and hepatitis after anesthesia → halothane hepatitis

Child on valproate with microvesicular steatosis → mitochondrial toxicity

Young woman, ↑ ALT, ↑ IgG, anti-smooth muscle antibody → autoimmune hepatitis

Cirrhotic with GI bleed, now confused with asterixis → hepatic encephalopathy — lactulose

Cholestatic jaundice on amoxicillin-clavulanate → drug-induced cholestasis