GGT

**Function:** GGT transfers the gamma-glutamyl group from glutathione and other peptides to amino acids/peptides. It plays a role in glutathione metabolism and amino acid transport across membranes. It is located on the cell membrane of bile canaliculi/biliary epithelium and hepatocytes, and is also found in kidney (highest tissue concentration), pancreas, and intestine, though serum GGT is primarily from the liver.

**Clinical significance:** - **Confirms hepatobiliary origin of elevated ALP.** GGT is NOT found in bone or placenta. Elevated ALP + normal GGT suggests bone disease (Paget disease, osteoblastic metastases, healing fracture, growing child) or pregnancy (placental ALP). Elevated ALP + elevated GGT suggests cholestasis. - **Cholestatic/obstructive patterns:** Marked elevation in biliary obstruction (choledocholithiasis, cholangitis), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and infiltrative disease (cholestatic pattern: ALP and GGT disproportionately elevated vs AST/ALT, with elevated conjugated bilirubin). - **Alcohol use:** GGT is induced by chronic alcohol consumption (microsomal enzyme induction), so it is elevated in alcohol use disorder. It is sensitive but not specific. Alcoholic hepatitis classically shows AST:ALT > 2:1 with elevated GGT. GGT also falls after abstinence (over weeks), so it can be used to monitor abstinence. - **Other causes of elevation:** Enzyme-inducing drugs (phenytoin, phenobarbital, carbamazepine, rifampin), NAFLD/MASLD, obesity, diabetes, congestive hepatopathy, pancreatitis, hyperthyroidism, and MI (minor). - **Low/normal GGT with cholestasis:** Seen in some inherited cholestatic syndromes, e.g., progressive familial intrahepatic cholestasis types 1 and 2 (PFIC1/2) and benign recurrent intrahepatic cholestasis, which are classic "low-GGT cholestasis" (PFIC3 has high GGT).

**Limitations:** Highly sensitive but poorly specific; it does not indicate the cause of liver disease alone. Interpret in context with AST, ALT, ALP, bilirubin, and clinical history.

**High-yield pearls:** - Elevated ALP: check GGT (or 5'-nucleotidase) to localize source (liver vs bone). - Isolated GGT elevation → think alcohol or enzyme-inducing medications. - Hepatocellular pattern = AST/ALT >> ALP/GGT; cholestatic pattern = ALP/GGT >> AST/ALT. - Not a typical marker of acute hepatocellular injury like ALT, which is more liver-specific.