On LFT interpretation, which combination indicates the most specific pattern for intrahepatic cholestasis as opposed to hepatocellular disease?

• A AST:ALT ratio >2 with elevated direct bilirubin
• B ALP and GGT proportionally elevated with minimally elevated transaminases ✓
• C Isolated ALT elevation with normal ALP and GGT
• D Elevated unconjugated bilirubin with normal GGT and ALP

Explanation

In cholestatic liver disease (intra- or extrahepatic), ALP and GGT rise disproportionately because bile acid–induced synthesis of these canalicular membrane enzymes is upregulated. Transaminases may be mildly elevated from secondary hepatocyte damage. An AST:ALT >2 suggests alcoholic hepatitis (hepatocellular). Isolated ALT elevation without ALP/GGT rise points to hepatocellular pathology. Isolated unconjugated hyperbilirubinaemia with normal enzymes indicates prehepatic or Gilbert syndrome, not cholestasis.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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