 It has been found that mothers of patients with this disease have a higher incidence of ICP, suggesting that heterozygote carriers of these mutations are also predisposed to ICP.In addition to genetic changes to bile salt transport molecules, high levels of estrogen glucuronides have been shown to inhibit the bile salt export pump (BSEP) ABCB11, and high levels of progesterone to inhibit the ABCB4 (MDR3) phospholipid transporter.Consequently, both genetic mutations in hepatocyte proteins involved in bile secretion together with inhibition of those proteins by high levels of hormone metabolites in pregnancy may have roles in the pathogenesis of ICP.