The Basic Panel: What Each Test Reflects
The standard liver function panel includes markers of hepatocyte injury, cholestasis, synthetic function, and bilirubin metabolism. Understanding what each measures clarifies what an abnormality means:
Transaminases (Hepatocellular Injury Markers)
- ALT (Alanine Aminotransferase): More liver-specific than AST. The primary marker of hepatocyte injury. Elevated in most forms of liver disease.
- AST (Aspartate Aminotransferase): Also found in cardiac muscle, skeletal muscle, kidney, and brain. Less specific for the liver. Important in the AST:ALT ratio.
Cholestatic Markers
- ALP (Alkaline Phosphatase): Elevated in biliary obstruction, infiltrative disease, and bone disease. Also elevated in pregnancy (placental isoform). Check GGT to confirm hepatic origin.
- GGT (Gamma-Glutamyl Transferase): Highly sensitive for hepatic origin of ALP elevation. Also elevated with alcohol use, fatty liver, and many medications. Poor specificity in isolation.
Bilirubin
- Total bilirubin: Sum of conjugated (direct) and unconjugated (indirect) fractions.
- Direct (conjugated) bilirubin elevation → hepatic or post-hepatic cause
- Indirect (unconjugated) bilirubin elevation → pre-hepatic (hemolysis) or Gilbert syndrome
Synthetic Function Markers
- Albumin: Synthesized exclusively by the liver. Low albumin reflects reduced hepatic synthetic capacity (half-life ~20 days — chronic marker).
- PT/INR: Reflects clotting factors made by the liver. Prolonged INR in liver disease indicates synthetic dysfunction (acute marker, half-life hours to days).
Pattern Recognition
The ratio and magnitude of abnormalities is more informative than any individual value:
Hepatocellular Pattern
Predominant elevation of AST and ALT (disproportionate to ALP). Common causes:
- Viral hepatitis (ALT often > AST in chronic hepatitis)
- MASLD / MASH (usually mild; ALT > AST early, AST > ALT suggests advanced fibrosis)
- Alcohol-related hepatitis: AST:ALT ratio >2:1 is classic (rarely >8×ULN in either)
- Drug-induced liver injury (wide variation in pattern)
- Ischemic hepatitis ("shock liver"): dramatic transaminase elevation, often >1000 IU/L
- Autoimmune hepatitis
Cholestatic Pattern
Predominant ALP elevation with relatively preserved transaminases. Common causes:
- Biliary obstruction (choledocholithiasis, cholangiocarcinoma, pancreatic head mass)
- Primary biliary cholangitis (PBC): ALP elevated, AMA positive
- Primary sclerosing cholangitis (PSC): associated with IBD
- Intrahepatic cholestasis of pregnancy
- Medications (e.g., amoxicillin-clavulanate, estrogens)
Mixed Pattern
Both hepatocellular and cholestatic markers elevated. Consider DILI, viral hepatitis with cholestatic features, or sepsis.
Magnitude Matters
- <3× ULN: Mildly elevated — often MASLD, medication effect, or hemolysis. Reassess after lifestyle modification or medication removal.
- 3–10× ULN: Significant elevation — requires active investigation and likely specialist referral.
- >10× ULN: Severe — consider acute hepatitis, ischemic hepatitis, or DILI. Urgent evaluation.
- >1000 IU/L: Dramatic — ischemic hepatitis, acute viral hepatitis, acute biliary obstruction, acetaminophen toxicity.
When to Repeat vs. When to Refer
A single mildly elevated ALT does not require immediate specialist referral. The approach:
- Remove potential offending agents (medications, supplements, alcohol) and recheck in 4–6 weeks
- If persistently elevated >6 months → hepatology referral
- If elevated >3× ULN on repeat, or any concern for synthetic dysfunction (elevated INR, low albumin, elevated bilirubin) → expedite referral
- If clinical jaundice, encephalopathy, or coagulopathy → urgent/emergency evaluation