Gamma-glutamyl transferase (GGT) is elevated in a patient with no clinical features of liver disease but who is on enzyme-inducing antiepileptics. This elevation is best explained by:

• A Hepatocellular necrosis caused by phenytoin hepatotoxicity
• B Inhibition of hepatic alkaline phosphatase releasing GGT into plasma
• C Transcriptional induction of GGT by nuclear receptor (CAR/PXR) activation ✓
• D Increased biliary pressure from drug-induced cholestasis

Explanation

Enzyme-inducing anticonvulsants (phenytoin, phenobarbital, carbamazepine) activate the constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in hepatocytes, which transcriptionally upregulate CYP450 enzymes and co-induces GGT synthesis. This causes isolated GGT elevation without hepatocellular necrosis or true cholestasis. The rise is an adaptive, non-pathological induction response. Alkaline phosphatase inhibition is not involved, and biliary pressure elevation would raise bilirubin as well.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.