TABLE 2.

CLINICAL SYNDROMES OF DRUG INDUCED CHOLESTASIS

	PATHOLOGY	CLINICAL FEATURES	BIOCHEMICAL FEATURES
INTRAHEPATIC
ACUTE
Cholestasis without hepatitis	Dilated canaliculi filled with few bile casts, especially in centrilobular area (acinar zone 3), Minimal or no inflammation or necrosis	Influenza like prodrome (nausea, anorexia, malaise)	Hyperbilirubinemia, < 3 times elevation of AP#, 1-8 times elevation of AST/ALT€
Cholestasis with hepatitis	Early portal inflammation-with or without eosinophils, Hepatocyte necrosis,	Influenza like prodrome, hypersensitivity symptoms, RUQ£ pain (can mimic acute cholangitis or cholecystitis)	Hyperbilirubinemia, > 3 times elevation of AP, 2-10 times elevation of AST/ALT
Cholestasis with bile duct injury	Biliary ductules filled with numerous bile casts, scattered steatosis and minimal or no hepatocellular damage	Eosinophilia, renal failure, Stevens-Johnson syndrome, Prolonged Jaundice ( > 6 months), may progress to VBDS	Hyperbilirubinemia, > 3 times elevation of AP, Elevated GGT*, 2-10 times elevation of AST/ALT
CHRONIC
Mils non-specific bile duct injury	Minimal bile duct epithelial disarray phosphatase Occasinal inflammatory cells in or Around biliry epithelia in portal triad	asymptomatic;	Mild elevation in alkaline Or GGT
Vanishing bile duct Syndrome (VBDS)	Loss of interlobular or septal bile ducts in ≥ 50 % of portal tracts or complete disappearance, portal tract inflammation, fibrosis, Hepatocellular necrosis, marked ductal destruction	Hepatosplenomegaly, hyperlipidemia, malabsorption, xanthelasmas, xanthomas, leads to cirrhosis	Hyperbilirubinemia, Antimitochondrial antibody absent, > 3 times elevation of AP, 2-10 times elevation of AST/ALT, initial elevation of GGT, Hypercholestrolemia
Primry Sclerosing Cholangitis -like	Non specific findings which may resemble PSC, marked ductal destruction, Hepatocellular necrosis	Jaundice develops within 3-6 months of the drug administration,	Hyperbilirubinemia, > 3 times elevation of AP, 2-10 times elevation of AST/ALT Hypercholestrolemia
EXTRAHEPATIC
Cholelithiasis		Biliary colic, gallstone pancreatitis, common bile duct dilatation	Hyperbilirubinemia, Elevated AP
Primary Sclerosing Cholangitis-like	PSC like pathology of extra hepatic ducts	Jaundice develops within 3-6 months of the drug administration,	Hyperbilirubinemia, > 3 times elevation of AP, 2-10 times elevation of

^#Alkaline phosphatase

^€Aspartate aminotransferases/ Alanine aminotransferase

^£Right upper quadrant

^*Gamma glutamyl transpeptidase