Liver chemistry tests
Hepatocellular: ALT/AST. Cholestatic: ALP/GGT/bili. Mixed is common. ALP from bone vs liver: GGT or fractionation.
Name the pattern before you name the disease
ULN is lower than many lab printouts: ALT 33 IU/L in men, 25 in women; ALP 115 men, 100 women (ACG: ). R factor = (ALT/ULN) / (ALP/ULN). Integrate travel, meds, supplements, alcohol, , and autoimmunity — do not worship a ratio (; ).
R >5
Hepatocellular
↑↑ ALT/AST released from hepatocyte cytosol (ALT) and cytosol + mitochondria (AST). Extreme (>15× or >1000): ischemia, acetaminophen. Moderate (5–15×): add acute HAV/HBV/HCV/HEV. Mild (<5×): meds, alcohol, MASLD, chronic viral, AIH, iron, Wilson, A1AT, mixed biliary.
R <2
Cholestatic
↑↑ ALP + GGT ± bilirubin from canalicular / duct injury. Extrahepatic obstruction (stone, PSC, malignancy, AIDS cholangiopathy) vs intrahepatic (PBC, infiltration, drugs). ALP >4× ULN: cholestasis, infiltration (cancer, amyloid), high bone turnover.
R 2–5
Mixed
Both hepatocellular and cholestatic markers up. Common in DILI, choledocholithiasis, infiltrative disease, and alcohol. Work both sides of the fork.
Bili only
Isolated bilirubin
Unconjugated (indirect): hemolysis, hematoma, fasting, ineffective erythropoiesis, Gilbert (usually <3 mg/dL). Conjugated (direct): hepatocellular injury, impaired excretion, obstruction, Rotor, Dubin-Johnson. Only conjugated bilirubin appears in urine.
an isolated ALP is hepatic with GGT, 5′-nucleotidase, or fractionation. Skip that step if bilirubin or transaminases are already up. ALP 1–1.5× is common after age 60 (bone). Pregnancy ALP can be placental.
AST:ALT and non-hepatic traps
- Usually ALT > AST (AST half-life 16 h vs ALT 35 h). The ratio swings wildly in acute injury (Cell Rep Med 2024;5:101828).
- Mild elevation with AST:ALT ~2:1 suggests alcohol-associated injury, especially with high GGT and macrocytosis.
- Hepatocyte AST:ALT is ~2.5:1 — a ratio >2.5:1, think muscle, hemolysis, or other extrahepatic AST (Clin Biochem Rev 2013;34:117).
- Ischemic / toxin: ALT often >1000, AST > ALT, LDH very high, rise and fall over days, often with AKI.
Function, not just injury — and the DILI list
Transaminases measure leak. Transplant decisions use function: INR, bilirubin, albumin, glucose, and encephalopathy.
- Albumin falls in cirrhosis but also in inflammation, nephrosis, malnutrition, protein-losing enteropathy, and tense ascites (dilution).
- INR rises when vitamin K–dependent factors fall. Give vitamin K 10 mg IV/PO × 3 days: if INR drops on day 1, deficiency (diet, fat malabsorption) is in the mix. Vitamin K does not fix parenchymal liver disease. First exclude DIC, consumption, and warfarin.
- Thrombocytopenia: ↓ thrombopoietin, splenic sequestration from portal hypertension, and increased destruction.
Hepatocellular DILI — common culprits
Acetaminophen, amoxicillin-clavulanate, INH, nitrofurantoin, NSAIDs, methotrexate, amiodarone, allopurinol, AEDs (phenytoin, carbamazepine, valproate), azoles, fluoxetine, hydralazine, labetalol, lisinopril, losartan, statins, sulfa, checkpoint inhibitors, niacin, heparin, aspirin, glyburide, clindamycin, trazodone. Supplements: kava, black cohosh, green-tea extract, chaparral, ephedra, germander, weight-loss blends. Illicit: anabolic steroids, cocaine, ecstasy, PCP. Environmental: Amanita. Full list: livertox.nih.gov.