Cefadroxil-associated cholestatic liver injury presenting as vanishing bile duct syndrome: a case report

Vanishing bile duct syndrome (VBDS) is an uncommon but clinically important form of cholestatic liver injury, defined by progressive loss of intrahepatic bile ducts and persistent cholestasis. Drug-induced liver injury is one of its recognized causes, and antibiotics are among the most frequently implicated agents. Cephalosporin-associated VBDS remains rare, and cefadroxil has been only exceptionally considered in this context.

A 72-year-old man developed jaundice and pruritus after completing a 21-day course of cefadroxil for a mild skin infection. Initial liver tests showed a predominantly cholestatic pattern, with marked elevation of gamma-glutamyl transferase and conjugated hyperbilirubinaemia. Viral, autoimmune, and IgG4-related causes were excluded, and magnetic resonance imaging showed no biliary obstruction. As cholestasis persisted despite withdrawal of the suspected drug, liver biopsy was performed and showed intrahepatic cholestasis with bile duct injury and ductopenic features, consistent with VBDS. The patient was treated with ursodeoxycholic acid, with gradual biochemical recovery and subsequent normalization of liver tests.

This case illustrates a rare but relevant presentation of antibiotic-associated VBDS after cefadroxil exposure. Although cephalosporins are widely used and generally safe, they can exceptionally be associated with clinically significant cholestatic drug-induced liver injury. The diagnosis of VBDS requires careful exclusion of mechanical obstruction, viral hepatitis, autoimmune cholangiopathies, and other systemic causes, and liver biopsy remains central when cholestasis is prolonged or unexplained. Treatment is mainly supportive, centered on withdrawal of the suspected agent and management of cholestasis; ursodeoxycholic acid is frequently used, although responses are variable across reported cases.

Cefadroxil-associated VBDS appears to be a rare manifestation of cholestatic drug-induced liver injury. Clinicians should consider this diagnosis in patients who develop persistent jaundice and pruritus after antibiotic exposure, particularly when imaging is normal and competing causes have been excluded. Early recognition, drug withdrawal, close biochemical follow-up, and timely biopsy in persistent cases are essential to avoid delayed diagnosis of this potentially severe condition.