What does an AST:ALT ratio >2:1 suggest?

An AST:ALT ratio greater than 2:1 (and especially >3:1) strongly suggests alcoholic liver disease. In alcoholic hepatitis, AST is typically 2-10× elevated while ALT is lower than expected. Both values are rarely above 300-400 IU/L in alcoholic hepatitis, even in severe disease. This contrasts with viral or ischemic hepatitis, where ALT often exceeds AST and both may be >1000 IU/L. The AST:ALT ratio is called the De Ritis ratio.

What is Gilbert's syndrome and when does jaundice appear?

Gilbert's syndrome is a benign hereditary condition (UGT1A1 promoter mutation) causing mild unconjugated hyperbilirubinemia. Bilirubin typically 1-3 mg/dL with transient worsening during fasting, stress, illness, or alcohol. All other LFTs are normal. It affects ~5-10% of the population and requires no treatment. It is distinguished from hemolysis by: normal CBC/reticulocyte count, no splenomegaly, and a predictable trigger (fasting/illness) rather than hemolytic crisis.

Liver Function Tests — Hepatocellular vs Cholestatic Pattern

Hepatocellular Pattern

Hepatocellular injury: AST and ALT elevated (aminotransferases leak from damaged hepatocytes). Typically ALT > AST (ALT is more liver-specific). Marked elevation (>10× normal — 'acute hepatitis range'): viral hepatitis (HAV, HBV, HCV), ischemic hepatitis ('shock liver' — AST/ALT >1000 IU/L, rapidly improves if perfusion restored), acetaminophen toxicity (AST/ALT often >3000-10,000), autoimmune hepatitis. Moderate elevation (3-10× normal): NASH, alcoholic hepatitis, drug-induced liver injury (DILI), Wilson's disease. AST:ALT ratio >2:1 (especially >3:1): strongly suggests alcoholic liver disease ('De Ritis ratio'). Alcoholic hepatitis: AST usually <300-400 IU/L despite severe disease; ALT characteristically lower than AST. Mnemonic: 'AST = Alcohol, Scotch & Tequila (> ALT).'

Cholestatic Pattern

Cholestatic (obstructive) injury: Alkaline phosphatase (ALP) and GGT predominantly elevated, with lesser aminotransferase elevation. ALP elevation sources: liver (bile duct disease), bone (Paget's, metastases, fractures), placenta, intestine. Distinguish hepatic vs bone ALP: GGT is liver-specific — if GGT elevated + ALP elevated → hepatic source; if GGT normal + ALP elevated → bone source. Causes of cholestatic pattern: (1) Intrahepatic cholestasis — primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), drug-induced (estrogen, anabolic steroids, chlorpromazine), cholestasis of pregnancy, viral hepatitis with cholestatic variant. (2) Extrahepatic obstruction — choledocholithiasis, cholangiocarcinoma, pancreatic head cancer (Courvoisier's law: palpable non-tender GB + painless jaundice = malignant obstruction), pancreatic head mass, bile duct stricture.

Bilirubin Patterns

Bilirubin metabolism: unconjugated (indirect) bilirubin → liver conjugation (glucuronic acid) → conjugated (direct) bilirubin → secreted into bile. Total bilirubin = direct + indirect. Elevated indirect bilirubin (unconjugated hyperbilirubinemia): hemolysis (increased RBC breakdown → more unconjugated bilirubin produced faster than liver conjugates), ineffective erythropoiesis, Gilbert's syndrome. Gilbert's syndrome: most common hereditary hyperbilirubinemia; mild unconjugated hyperbilirubinemia with stress/fasting/illness; benign; no treatment needed; UGT1A1 promoter mutation. Elevated direct bilirubin (conjugated): hepatocellular disease (conjugated but cannot be secreted), intrahepatic cholestasis, extrahepatic obstruction, Dubin-Johnson syndrome (AR, benign, black liver pigment), Rotor syndrome.

Synthetic Function Markers

LFTs include markers of hepatic SYNTHETIC function (reflect true liver function): Prothrombin time (PT/INR): liver produces factors II, VII, IX, X (vitamin K-dependent) + V, fibrinogen. PT elevation = hepatic failure or vitamin K deficiency. Factor VII has shortest half-life → PT first to rise in acute liver failure. Albumin: made exclusively by hepatocytes; long half-life (20 days) → better marker of chronic hepatic function (cirrhosis) than acute injury. Low albumin: chronic liver disease, malnutrition, nephrotic syndrome (urinary losses), protein-losing enteropathy. MELD score: Model for End-stage Liver Disease = creatinine + bilirubin + INR → used for liver transplant waitlist prioritization.

Liver Function Tests Explained: Interpreting LFTs for USMLE and NCLEX

Hepatocellular Pattern

Cholestatic Pattern

Bilirubin Patterns

Synthetic Function Markers

Frequently asked questions

Lock this into long-term memory