Interpreting Liver Function Tests
A stepwise approach to abnormal liver chemistries for Step 2 CK: assign the pattern — hepatocellular vs cholestatic (R factor) vs isolated hyperbilirubinemia (enzymes normal) — then use enzyme magnitude, the AST:ALT ratio, and bilirubin fractionation to reach the diagnosis and next best step.
Two questions, one panel
Liver chemistries answer two separate questions. Aminotransferases (AST, ALT) signal hepatocyte injury; alkaline phosphatase (ALP) with GGT signals cholestasis / biliary disease. Neither reflects true function — synthetic capacity is captured by albumin and PT/INR, and excretory/clearance capacity by bilirubin.
So the first move on any abnormal panel is to assign a pattern: hepatocellular (AST/ALT ↑↑), cholestatic (ALP ↑↑ ± direct bilirubin), or isolated hyperbilirubinemia (enzymes normal). The R factor = (ALT/ULN) ÷ (ALP/ULN) formalizes the enzyme patterns — R > 5 hepatocellular, R < 2 cholestatic, 2–5 mixed. Then read the magnitude and the AST:ALT ratio to build a differential, and check INR and albumin to grade severity. The boards reward this stepwise logic over pattern-matching a single value.
- AST:ALT > 2:1 (AST usually < 400) → alcoholic liver disease
- ALT > AST (ratio < 1) → viral hepatitis, NAFLD
- Transaminases > 1000 U/L → ischemic hepatitis (shock liver), acute viral, acetaminophen toxicity, autoimmune
- ALP ↑ → check GGT: GGT high = hepatobiliary source; GGT normal = bone, pregnancy/placenta, or childhood growth
- Assign the pattern with the R factor = (ALT/ULN) ÷ (ALP/ULN): > 5 hepatocellular, < 2 cholestatic, 2–5 mixed
- True liver function: synthetic = albumin + PT/INR, excretory = bilirubin — transaminases measure injury, not function
- Shock liver clue: transaminases spike then fall fast, LDH markedly ↑ (ALT:LDH < 1.5 favors ischemia over viral)
Pattern recognition
| Pattern | AST / ALT | ALP / GGT | Bilirubin | R factor | Classic causes |
|---|---|---|---|---|---|
| Hepatocellular | ↑↑ | normal–mild | variable | > 5 | viral, alcohol, NAFLD, ischemia, drugs, autoimmune, Wilson |
| Cholestatic | normal–mild | ↑↑ (GGT ↑) | ↑ direct | < 2 | stones, tumor, stricture, PBC, PSC, drugs |
| Isolated unconjugated | normal | normal | ↑ indirect | — | hemolysis, Gilbert, Crigler-Najjar |
| Isolated conjugated | normal | normal | ↑ direct | — | Dubin-Johnson, Rotor |
A 46-year-old man with heavy alcohol use presents with jaundice, low-grade fever, and tender hepatomegaly. AST 260, ALT 95 (ratio 2.7), total bilirubin 9 mg/dL, INR 1.9, ALP mildly elevated.
- Diagnosis: alcoholic hepatitis — note the AST:ALT > 2:1 and that AST rarely exceeds ~400. Higher AST suggests a second insult (e.g., acetaminophen, ischemia).
- Next step / severity: calculate the Maddrey discriminant function (uses PT and bilirubin). DF ≥ 32 — or hepatic encephalopathy / high MELD — defines severe disease → prednisolone (only if no active infection or GI bleed) plus abstinence and nutritional support.
- Pitfall: the disproportionately low ALT reflects pyridoxal-5'-phosphate (B6) depletion in alcoholics, which exaggerates the ratio.
A 60-year-old woman reports 3 weeks of painless jaundice, dark urine, pale stools, and pruritus. ALP 480, GGT 5× ULN, direct bilirubin 11 mg/dL, ALT 70 → R factor < 2 (cholestatic).
- Next best step: RUQ ultrasound to assess for ductal dilation.
- Dilated ducts → mechanical obstruction. Painless jaundice + weight loss + a palpable non-tender gallbladder (Courvoisier sign) suggests pancreatic head / periampullary malignancy → CT / MRCP.
- Stones cause painful obstruction; fever + RUQ pain + jaundice (Charcot triad) = ascending cholangitis → IV antibiotics + urgent ERCP (source control).
- Non-dilated ducts → intrahepatic cholestasis: PBC (anti-mitochondrial Ab, middle-aged woman), PSC (young man + IBD), or drugs.
"toAST" with alcohol
- AST : ALT ≥ 2 : 1 → alcoholic liver disease. You make a toAST (AST rises higher) when you drink; a concurrently high GGT supports the alcohol source.
ALT = Liver
- The L in aLt is the more Liver-specific enzyme. AST is also released from heart, skeletal muscle, and RBCs — so an unexplained isolated AST↑ warrants a CK to exclude a muscle source.
GGT confirms the ALP
- High ALP + high GGT localizes to the hepatobiliary tree; high ALP + normal GGT points to bone (or placenta in pregnancy).
- Unconjugated (indirect) ↑ → hemolysis (retic ↑, LDH ↑, haptoglobin ↓), Gilbert (mild, precipitated by fasting/stress/illness, otherwise normal LFTs — benign, no workup or treatment), Crigler-Najjar.
- Conjugated (direct) ↑ → hepatocellular or obstructive → RUQ ultrasound: dilated ducts = mechanical obstruction (→ MRCP/ERCP); non-dilated = intrahepatic (hepatitis, PBC/PSC, drugs).
- Dark urine (bilirubinuria) = conjugated only (water-soluble). Unconjugated bilirubin is albumin-bound and not renally filtered, so acholuric jaundice points to hemolysis or Gilbert.
- Grade severity by synthetic function: INR rises early (short-lived factor VII, t½ ~6 h) and tracks acute injury; albumin falls in chronic disease (t½ ~20 days).
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