Introduction
Ductopenia is defined by loss of ≥50% intrahepatic bile ducts. For an accurate diagnosis on a liver biopsy, at least 11 portal tracts need to be evaluated1-2. Ductopenia is associated with a wide variety of liver pathologies including congenital and genetic diseases such as biliary atresia and cystic fibrosis, autoimmune diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), infections such as CMV and HIV, neoplasms such as Hodgkin lymphoma, ischemic insults, and injuries induced by a large array of drugs or toxins3. However, some cases have no identifiable etiology, a phenomenon previously recognized as idiopathic adulthood ductopenia but now better known as vanishing bile duct syndrome (VBDS)3-4. These conditions typically present with chronic cholestasis, although isolated transaminitis has been reported5-6.
Drug-induced liver injury (DILI) can be divided into hepatitic, cholestatic or mixed hepatitic and cholestatic patterns clinically. Microscopically, DILI varies from necroinflammatory injury, cholestatic injury, steatosis or steatohepatitis, fibrosis with cirrhosis, vascular lesions, neoplasia, to other rare patterns7. Drug-induced cholestatic liver injury also takes several forms. The mildest form is acute cholestasis or bland cholestasis, which shows intrahepatic cholestasis with minimal inflammation. When intrahepatic cholestasis is accompanied by necroinflammation and duct injury, it is cholestatic hepatitis8. Drug-induced cholestatic liver injury may also be chronic, and can be further divided into PSC-like, PBC-like, or VBDS pattern8-9. The VBDS pattern was initially recognized with chlorpromazine, but many other drugs were later found to be associated with ductopenia9-11. Ductopenia diagnosed on liver biopsy has been reported as early as three weeks after the onset of symptoms12. Some sources also distinguish between acute and chronic drug-induced VBDS, the latter characterized histologically by the presence of ductular reaction and copper accumulation7. In certain cases, jaundice and abnormal liver function tests may eventually resolve, and successful treatments have been reported13-15. However, VBDS may also progress to biliary cirrhosis and require liver transplantation (LT)12,16-18.
Cloxacillin, oxacillin, and flucloxacillin belong to a group of penicillinase-resistant isoxazolyl penicillins which are often used for methicillin-sensitive Staphylococcus species,Pneumococcus , and beta-hemolyticStreptococci19 . Flucloxacillin is a well-known cause of drug-induced cholestasis and particularly ductopenia12,20-23. In contrast, oxacillin and cloxacillin have only been reported in cases of acute intrahepatic cholestasis, with bile accumulation in hepatocytes or canaliculi without duct loss, or cholestatic hepatitis with associated inflammation24-26. We present the first case of cloxacillin-induced acute ductopenia and review the clinicopathologic features of reported cases of cloxacillin-related liver injury.