Intrahepatic cholestasis of pregnancy is a reversible form of cholestasis that occurs most often in the third trimester of pregnancy and recurs in 45 to 70% of subsequent pregnancies. Symptoms include pruritus, jaundice, increased serum bile salts, and ... Intrahepatic cholestasis of pregnancy is a reversible form of cholestasis that occurs most often in the third trimester of pregnancy and recurs in 45 to 70% of subsequent pregnancies. Symptoms include pruritus, jaundice, increased serum bile salts, and abnormal liver enzymes, all of which resolve rapidly after delivery. However, the condition is associated with fetal complications, including placental insufficiency, premature labor, fetal distress, and intrauterine death. Women with ICP are also susceptible to oral contraceptive-induced cholestasis (OCIC). Ursodeoxycholic acid (UDCA) is an effective treatment for conditions caused by ABCB4 mutations (summary by Pasmant et al., 2012). Mutation in the ABCB4 gene accounts for about 15% of ICP cases (summary by Ziol et al., 2008). For a discussion of genetic heterogeneity of ICP, see ICP1 (147480).
De Vree et al. (1998) reported a woman of North African descent who developed recurrent episodes of intrahepatic cholestasis of pregnancy. Her son had severe PFIC3 necessitating liver transplant.
Jacquemin et al. (1999) reported a family ... De Vree et al. (1998) reported a woman of North African descent who developed recurrent episodes of intrahepatic cholestasis of pregnancy. Her son had severe PFIC3 necessitating liver transplant. Jacquemin et al. (1999) reported a family in which 6 women had ICP characterized by pruritus and abnormal liver function tests with a cholestatic pattern in the third trimester. Fetal death occurred in 3 cases. Cholestasis disappeared spontaneously and progressively after delivery. Rosmorduc et al. (2001) reported a 23-year-old woman who developed cholestasis and biliary pain during pregnancy and delivered a premature infant. She later underwent cholecystectomy, but had recurrence of cholestasis and biliary pain during her second pregnancy and lost the fetus. She had intrahepatic gallstones and bile analysis showed cholesterol crystals. The patient's son developed acute cholangitis with intra- and extrahepatic cholesterol gallstones in his twenties, consistent with GBD1 (600803). The proband's father and aunt had biliary pain associated with cholesterol biliary gallstones. Rosmorduc et al. (2001) reported a 22-year-old woman who presented with cholestatic liver disease after she started taking oral contraceptives. She had multiple small gallstones in the intrahepatic bile ducts. After discontinuation of the oral contraceptives, her symptoms resolved rapidly, but liver enzymes remained elevated. She underwent cholecystectomy, but later developed ICP and gave birth to a premature baby. Liver biopsy showed portal inflammation, fibrosis, ductal proliferation, and cholestasis. Treatment with UDCA resulted in normalization of liver enzymes, but pruritus and increased liver enzymes were observed 15 days after discontinuation of UDCA. Pasmant et al. (2012) reported a 26-year-old woman who presented with biliary pain, jaundice, and elevated liver enzymes associated with taking oral contraceptives. Liver biopsy showed ductular proliferation. She was free of symptoms in the absence of oral contraception ingestion and later had a normal pregnancy and delivery under UDCA treatment.
In a woman of North African descent with ICP3, de Vree et al. (1998) identified a heterozygous mutation in the ABCB4 gene (R957X; 171060.0002). Her son, who had progressive familial intrahepatic cholestasis (PFIC3; 602347), was homozygous for the ... In a woman of North African descent with ICP3, de Vree et al. (1998) identified a heterozygous mutation in the ABCB4 gene (R957X; 171060.0002). Her son, who had progressive familial intrahepatic cholestasis (PFIC3; 602347), was homozygous for the mutation. In 4 affected women from a family with ICP3, Jacquemin et al. (1999) identified a heterozygous mutation in the ABCB4 gene (1712delT; 171060.0003). One family member who was homozygous for the mutation had severe PFIC3 requiring liver transplant at age 6 years. In 1 of 8 unrelated patients with ICP, Dixon et al. (2000) identified a heterozygous mutation in the ABCB4 gene (A546D; 171060.0004). In a woman with ICP and her son with GBD1, Rosmorduc et al. (2001) identified a heterozygous mutation in the ABCB4 gene (1327insA; 171060.0008). Another woman with OCIC and ICP carried a homozygous mutation in the ABCB4 gene (S320F; 171060.0005). Ziol et al. (2008) identified ABCB4 mutations (see, e g., R590Q, 171060.0012) in a woman with ICP and in 2 women with OCIC. Bacq et al. (2009) identified homozygous or heterozygous mutations in the ABCB4 gene (see, e.g., S320P, 171060.0005; R144X, 171060.0011; and R590Q) in 8 (16%) of 50 French Caucasian women with ICP. There was no phenotypic difference between patients with or without ABCB4 mutations. Pasmant et al. (2012) identified ABCB4 mutations in 16 (27%) of 59 patients with ICP or OCIC. One (2%) of the 59 patients carried a 5-Mb deletion of chromosome 7q including the ABCB4 gene. Pasmant et al. (2012) emphasized the importance of ABCB4 gene dosage studies in patients with adult-onset liver disease, particularly because treatment with UDCA had been proven effective.