Drug-induced bile duct injury

Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt B):1498-1506. doi: 10.1016/j.bbadis.2017.08.033. Epub 2017 Sep 4.

Abstract

Drug-induced liver injury includes a spectrum of pathologies, some related to the mode of injury, some to the cell type primarily damaged. Among these, drug-induced bile duct injury is characterized by the destruction of the biliary epithelium following exposure to a drug. Most of the drugs associated with bile duct injury cause immune-mediated lesions to the epithelium of interlobular ducts. These share common histopathological features with primary biliary cholangitis, such as inflammation and necrosis at the expense of cholangiocytes and, if the insult persists, bile duct loss and biliary cirrhosis. Some drugs selectively target larger ducts. Such injury is often dose-dependent and thought to be the result of intrinsic drug toxicity. The histological changes resemble those seen in primary sclerosing cholangitis. This overview focuses on the clinical and pathological features of bile duct injury associated with drug treatment and on the immunological and biochemical effects that drugs exert on the biliary epithelium. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Keywords: Bile duct; Cholangiocyte; Cholangiopathy; Drug-induced liver injury; Idiosyncrasy; Vanishing bile duct syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amoxicillin-Potassium Clavulanate Combination / pharmacokinetics
  • Amoxicillin-Potassium Clavulanate Combination / toxicity
  • Bile Acids and Salts / toxicity
  • Bile Ducts / cytology
  • Bile Ducts / drug effects
  • Bile Ducts / metabolism
  • Bile Ducts / pathology*
  • Biomarkers / analysis
  • Biotransformation
  • Carbamazepine / pharmacokinetics
  • Carbamazepine / toxicity
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / pathology*
  • Cholagogues and Choleretics / therapeutic use
  • Cholangitis, Sclerosing / chemically induced*
  • Cholangitis, Sclerosing / diagnosis
  • Cholangitis, Sclerosing / drug therapy
  • Cholangitis, Sclerosing / pathology
  • Cholestasis / chemically induced*
  • Cholestasis / diagnosis
  • Cholestasis / drug therapy
  • Cholestasis / pathology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology

Substances

  • Bile Acids and Salts
  • Biomarkers
  • Cholagogues and Choleretics
  • Carbamazepine
  • Amoxicillin-Potassium Clavulanate Combination