Intrahepatic cholestasis of pregnancy associated with azathioprine: A case series

J Gynecol Obstet Hum Reprod. 2021 Apr;50(4):102083. doi: 10.1016/j.jogoh.2021.102083. Epub 2021 Feb 15.

Abstract

Background: Intrahepatic cholestasis of pregnancy (ICP) is characterised by otherwise unexplained maternal pruritus, increased serum bile acid concentration over 10 μmol/L and spontaneous relief of symptoms and liver abnormalities after delivery. It occurs most frequently during the third trimester and is usually not induced by medication. Besides, azathioprine is recommended as first-line immunosuppressant in patients with steroid-dependent inflammatory bowel disease and is allowed during pregnancy, in order to stabilize maternal disease.

Methods: We reviewed all cases of ICP between 2010 and 2018 in two French perinatal centers.

Results: We encountered eight pregnancies complicated by atypical ICP among patients treated with azathioprine. ICP associated with azathioprine appears to be biologically more severe and to occur earlier than "standard" ICP. Furthermore, clinical and biochemical abnormalities related to ICP disappear when azathioprine is discontinued. Azathioprine safety should be reconsidered and practitioners advised to discuss discontinuing this drug as soon as ICP diagnosis is established.

Keywords: Azathioprine; Bile acids; Colitis; Crohn’s disease; Inflammatory bowel disease; Intrahepatic cholestasis of pregnancy.

Publication types

  • Case Reports
  • Multicenter Study

MeSH terms

  • Adult
  • Azathioprine / adverse effects*
  • Bile Acids and Salts / blood
  • Cholagogues and Choleretics / therapeutic use
  • Cholestasis, Intrahepatic / blood
  • Cholestasis, Intrahepatic / chemically induced*
  • Colitis, Ulcerative / drug therapy
  • Crohn Disease / drug therapy
  • Drug Substitution
  • Female
  • France
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Mesalamine / therapeutic use
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / chemically induced*
  • Pregnancy Complications / drug therapy
  • Pruritus / chemically induced*
  • Remission, Spontaneous
  • Retrospective Studies
  • Ursodeoxycholic Acid / therapeutic use
  • Withholding Treatment

Substances

  • Bile Acids and Salts
  • Cholagogues and Choleretics
  • Immunosuppressive Agents
  • Mesalamine
  • Ursodeoxycholic Acid
  • Azathioprine

Supplementary concepts

  • Intrahepatic Cholestasis of Pregnancy