Flucloxacillin induced liver disease: histopathological findings at biopsy and autopsy

The histological appearances of liver biopsies of 13 patients who developed cholestasis following courses of flucloxacillin are presented. In most of the cases jaundice and pruritus were protracted and in nearly all cases liver function tests are yet to return to normal after mean follow-up of 18 mths. One patient died after 7 mths of jaundice and another shows clinical evidence of secondary biliary cirrhosis. Biopsies typically showed hepatocellular and canalicular bile stasis with minimal or no hepatitis. Mild portal fibrosis and a patchy portal lymphocytic infiltrate were usually present. In 4 cases bile ducts were reduced in number and in 6 cases reduced in size. Bile duct epithelium showed degenerative changes but only occasional infiltration by inflammatory cells. Ductular proliferation was quite variable and in some cases--most noticeably the fatal case--was inconspicuous despite depletion of bile ducts. The appearances suggested damage not only of hepatocytes but also of bile ducts and proliferating ductules. This may explain the prolonged and occasionally irreversible hepatic disease associated with the use of flucloxacillin. Flucloxacillin should be included amongst the causes of vanishing bile duct syndrome.