Pathogenesis

Pathogenesis of intrahepatic cholestasis of pregnancy is unclear

• multiple factors probably interact with a genetic predisposition to alter the membrane composition of bile ducts and hepatocytes and increase their sensitivity to sex steroids
• a family history (autosomal dominant and possibly X linked) is commonly associated with haplotypes HLA-B8 and HLA-Bw16
• hormonal factors are implicated because intrahepatic cholestasis worsens with multiple pregnancies and can recur with menstruation and oestrogen treatment
• occurs more commonly in mothers of patients with rare, inborn cholestatic syndromes such as progressive familial intrahepatic cholestasis type 3 or recurrent familial intrahepatic cholestasis, both related to dysfunction of biliary transporters

Reference:

1. Walker KF et al. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. Cochrane Database of Systematic Reviews 2020, Issue 7. Art. No.: CD000493. DOI: 10.1002/14651858.CD000493.pub3.
2. Royal College of Obstetricians and Gynaecologists. Intrahepatic cholestasis of pregnancy (Green-top Guideline No. 43). Published August 2022