The causes of<unk>  are still not fully understood, but are thought to be caused through a combination of genetics, hormones and environment. Hormones, environmental and genetic factors are all thought to contribute to the condition. *<unk>  commonly occurs in the third trimester at the time when hormone levels are at their highest. * Twin and triplet<unk> es, which are associated with higher hormone levels, show a higher incidence of<unk> . *<unk>  resolves quickly after delivery, when placental hormone production ceases. * Older high-dose estrogen oral contraceptive pills could cause features of<unk> . Estrogens Estrogens, and particularly glucuronides such as estradiol-17β-D-glucuronide, have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes. Progesterone Treatment with progesterone in the third trimester of<unk>  has been shown to be associated with the development of<unk> , and levels of metabolites of progesterone, particularly sulfated progesterone, are higher in patients with<unk>  than unaffected women, suggesting that progesterone may have a bigger role than estrogen in<unk> . Genetic factors Clustering of cases of<unk>  in families, geographic variation in rates of<unk> , and recurrence of<unk>  in 45-70% of subsequent<unk> es all suggest a genetic component to the disease. Genetic mutations in the hepatocellular transport protein ABCB4 (MDR3), which controls secretion of phosphatidylcholine into bile, have been found in cases of<unk> . Genetic mutations affecting hepatic bile salt transport molecules have also been found in patients with progressive familial intrahepatic cholestasis. It has been found that mothers of patients with this disease have a higher incidence of<unk> , suggesting that heterozygote carriers of these mutations are also predisposed to<unk> . 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<unk>  may have roles in the pathogenesis of<unk> . Environmental factors A number of features of<unk>  suggest that environmental factors also have a role in the disease: * It has been reported that the incidence of<unk>  is higher in winter than summer. * The incidence of<unk>  in Chile has dropped from 14% of<unk> es before 1975 to 4% in 2016. *<unk>  recurs in between 60% and 90% of subsequent<unk> es. * Low serum selenium levels have been linked to<unk> , although the role of selenium in bile secretion is not known.
Intrahepatic cholestasis of pregnancy
Neonatal cholestasis
Congenital hepatic fibrosis
Progressive familial intrahepatic cholestasis
Alcoholic hepatitis
Autoimmune hepatitis
Polycystic liver disease
Ischemic hepatitis