LFT Interpretation
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Direct answer
Liver function tests divide into hepatocellular markers (alanine aminotransferase more liver-specific, aspartate aminotransferase more ubiquitous), cholestatic enzymes (alkaline phosphatase from canalicular and biliary epithelium, with GGT rising in parallel in liver disease), excretory markers (bilirubin in conjugated and unconjugated fractions) and synthetic markers (albumin and the prothrombin time or INR — the most sensitive, because factor VII's roughly six-hour half-life outruns albumin's twenty days). Jaundice classification follows the fractions: unconjugated predominance means haemolysis or a conjugation defect; conjugated predominance with high alkaline phosphatase and GGT means cholestasis; a mixed picture with transaminases in the thousands means hepatocellular necrosis. The hereditary set — Gilbert, Crigler–Najjar I and II, Dubin–Johnson and Rotor — is guaranteed FMGE territory.
What you must remember
- Unconjugated bilirubin travels bound to albumin, cannot filter at the glomerulus and is absent from urine (the indirect fraction); only the conjugated, water-soluble fraction appears in urine, so dark urine with pale stool means obstruction.
- Haemolytic pattern: predominantly unconjugated hyperbilirubinaemia, urine bilirubin negative, urine urobilinogen increased, normal enzymes, reticulocytosis and splenomegaly.
- Obstructive pattern: conjugated hyperbilirubinaemia, alkaline phosphatase and GGT several-fold raised, modest transaminases, pruritus from retained bile salts, and acholic stool lacking stercobilin.
- The De Ritis ratio: AST divided by ALT above 2, with levels usually below about 500 U/L, suggests alcoholic hepatitis through hepatic pyridoxal phosphate depletion.
- In viral hepatitis, transaminases peak early and bilirubin peaks later; falling transaminases with a still-rising bilirubin mark the recovery phase — and hepatitis E carries a high fulminant-failure risk in the third trimester of pregnancy, an Indian exam favourite.
- A prothrombin time that fails to correct with parenteral vitamin K points to hepatocellular failure rather than cholestasis, because the cholestatic coagulopathy is a vitamin K absorption problem and corrects.
- Hereditary set: Gilbert syndrome — mild unconjugated hyperbilirubinaemia unmasked by fasting or stress, reduced UDP-glucuronosyl transferase activity, benign; Crigler–Najjar I — absent enzyme, kernicterus, unresponsive to phenobarbitone; type II — partial deficiency that responds to phenobarbitone; Dubin–Johnson — conjugated, MRP2 canalicular transporter defect, black pigmented liver; Rotor syndrome — conjugated, normal-looking liver, both benign.
- Six-monthly alpha-fetoprotein with ultrasound is the surveillance standard for hepatocellular carcinoma in cirrhosis; a rising value with a nodule is near-diagnostic.
A worked case: painless jaundice at sixty-five
A 65-year-old presents with two months of painless deepening jaundice, six kilograms of weight loss and intractable pruritus. Bilirubin is 14 mg/dL with 11 direct, alkaline phosphatase 800 U/L, GGT 350, ALT 60, INR 1.4 which corrects with vitamin K. Reason the pattern: the direct fraction dominates, the parallel alkaline phosphatase and GGT declare cholestasis, and the small transaminase rise excludes a hepatitis. The INR correction with vitamin K confirms the coagulopathy is cholestatic malabsorption, not synthetic failure — the liver still makes factors when given its cofactor. Age, painlessness and weight loss point to pancreatic head carcinoma until imaging says otherwise; a palpable non-tender gallbladder (Courvoisier sign) completes the clinical picture. The pathway runs ultrasound first — dilated intrahepatic ducts separate extrahepatic from intrahepatic cholestasis — then contrast CT and endoscopic ultrasound with biopsy or MRCP for the map. The gallstone contrast: colicky right upper quadrant pain, fluctuating jaundice, younger patient, near-normal alkaline phosphatase between attacks.
Where students slip
An isolated alkaline phosphatase is chased as liver disease without a GGT, forgetting bone sources — adolescent growth spurt, Paget disease, osteoblastic metastases — in which GGT stays normal. Second, "direct" and "conjugated" are treated as different things; they are synonyms, as are "indirect" and "unconjugated". Third, urobilinogen logic is inverted: it disappears from urine in complete obstruction because no bilirubin reaches the gut, and increases in haemolysis. Fourth, Gilbert syndrome is over-investigated when the pattern — bilirubin of 2–3 mg/dL, unconjugated, normal enzymes, no haemolysis, worsened by fasting — asks only for reassurance. Fifth, ALT is called more sensitive than AST; ALT is more specific, while AST also rises in muscle, heart and haemolysis — which is why the ratio carries information. Finally, hepatitis E in pregnancy is underestimated; the exam expects the association with fulminant hepatic failure and high maternal mortality in the third trimester.
Frequently asked questions
Which liver function test is the most sensitive marker of synthetic function?
The prothrombin time or INR: factor VII has the shortest half-life, about six hours, outpacing albumin's twenty-day turnover.
Which hereditary jaundice produces a black liver?
Dubin–Johnson syndrome, from an MRP2 canalicular transporter defect causing conjugated hyperbilirubinaemia with otherwise normal enzymes.
Which unconjugated hyperbilirubinaemia responds to phenobarbitone?
Crigler–Najjar type II, which has partial UDP-glucuronosyl transferase activity; type I has none and needs phototherapy or transplantation.
What does an AST:ALT ratio above 2 suggest?
Alcoholic hepatitis, from pyridoxal phosphate depletion limiting both transaminases, with absolute values usually below 500 U/L.
Why is hepatitis E dangerous in pregnancy?
It risks fulminant hepatic failure and maternal death in the third trimester; early delivery is part of management.
Which test separates cholestatic from hepatocellular coagulopathy?
The response to parenteral vitamin K — correction favours cholestasis with malabsorption, and non-correction favours hepatocellular synthetic failure.