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  Intrahepatic Cholestasis of Pregnancy                           
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Intrahepatic cholestasis of pregnancy (IHCP) is characterized by intense generalized pruritus (itching) during pregnancy without a primary skin lesion. The condition is caused by maternal liver dysfunction and may occur as early as the 10th week of pregnancy [8], but most often presents during late pregnancy. The pruritus is worse on the palms and the soles of the feet, and disappears within days following delivery. Approximately 10% of patients suffering from IHCP experience jaundice. [2] IHCP is associated with an increased risk of fetal death, prematurity, and postpartum hemorrhage [9].

“The prevalence of IHCP in pregnant women in Chile, Bolivia, Scandinavian, Mediterranean countries, Portugal, Poland, Australia, Canada, and China is approximately 1% to 4%. In the United States, Switzerland, and France the prevalence of reported IHCP is low (below 0.5% of pregnancies).” In high-prevalence regions, a family history of IHCP is present in up to 50% of the patients [3]. Other groups at risk are twin gestations [4] and women with hepatitis C infection [5].

For more on the inheritance of cholestasis of pregnancy see OMIM

The differential for generalized itching without a primary skin lesion source includes [6,7]

  • Xerosis (dry skin)

  • Almost any drug

  • Numerous systemic diseases including:

    • Uremia
    • Iron deficiency
    • Leukemia
    • Polycythemia
    • Lymphoma
    • Thyroid disorders
    • Diabetes
    • Visceral malignancies
    • Multiple sclerosis
  • HIV

The diagnosis of IHCP is made when there is pruritus in the absence of other pathology with an abnormality in gamma-glutamyl transpeptidase (GTT), alanine amino-transferase (ALT), aspartate amino-transferase (AST), or fasting serum total bile acids [1]. The fasting serum total bile acid concentration is the most specific test for the diagnosis of IHCP [2].

The risk of postpartum hemorrhage is increased because of poor vitamin K absorption [9,15]. Prothrombin time should, therefore, be checked periodically and treated as necessary with parenteral vitamin K [16].

Pruritus may be treated with ursodeoxycholic acid (15 mg per kg per day). Ursodeoxycholic acid also appears to normalize liver function [13] and may improve fetal outcome [14, 18,19]. Pruritus may also be treated with cholestyramine. However, it may worsen malabsorption of vitamin K and does not alter liver function or fetal prognosis [12].

Although adverse perinatal outcome is not consistently predicted by conventional fetal surveillance [10] active management comprised of twice weekly non-stress test and AFI, with delivery at 37 weeks or earlier in the presence of non-reassuring fetal testing, meconium, or severe maternal symptoms unresponsive to therapy with mature fetal lungs has been shown to significantly reduce the incidence of fetal death [11]. In the absence of active management perinatal mortality is 2.5 to 11 % [9,10]

Patients should be advised that cholestasis of pregnancy recurs in up to 70 percent of subsequent pregnancies [17].

Management
Initial studies:

  • CBC with differential
  • Chem 7
  • Gamma-glutamyl transpeptidase (GGT)
  • Alanine amino-transferase (ALT)
  • Aspartate amino-transferase(AST)
  • Total bile acids
  • Alkaline phosphatase

Other studies as clinically indicated : Hepatitis C , total bilirubin , TSH, fasting blood glucose, HIV, CXR, and skin biopsy.

Treatment

  • Cholestyramine: 4 g PO 1-6 times qd (cartons of 60 pkts,1pkt=4gm)
  • Ursodeoxycholic acid (Actigall, Urso): 300 mg PO QID with food. (300 mg caps) may also be offered.
  • Parenteral vitamin K (phytonadione; AquaMephyton) 5 to 10 mg/d IM QD in patients with an abnormal PT.

Surveillance

  • Twice weekly antenatal testing (NST and AFI) commencing at diagnosis.
  • Monitor prothrombin time especially if taking cholestyramine.

Delivery

  • Amniocentesis prior to 36 weeks in severe cases.
  • Deliver after 37 weeks or earlier in the presence of fetal lung maturity.
  • Deliver by 38 weeks in all cases.

 

More information on cholestasis of pregnancy

 

REFERENCES
1. Kenyon AP, Piercy CN, Girling J, Williamson C, Tribe RM, Shennan AH. Obstetric cholestasis, outcome with active management: a series of 70 cases. BJOG. 2002 ;109:282-8. PMID: 11950183

2. Rioseco A., et al Intrahepatic cholestasis of pregnancy: a retrospective case-control study of perinatal outcome. Am J Obstet Gynecol. 1994;170:890-5. PMID: 8141222
3. Fagan EA. Intrahepatic cholestasis of pregnancy. Clin Liver Dis. 1999 ;3:603-32. PMID: 11291241
4. Gonzales MC, Reyes H, Arrese M, et al: Intrahepatic cholestasis of pregnancy in twin pregnancies. J Hepatol 9:84, 1989
5. Paternoster DM, Fabris F, Palu G, Santarossa C, Bracciante R, Snijders D, Floreani A. Intra-hepatic cholestasis of pregnancy in hepatitis C virus infection. Acta Obstet Gynecol Scand. 2002;81:99-103. PMID: 11942897
6. Parker F. Structure and Function of the Skin In :Goldman ed Cecil Textbook of Medicine, 21st ed., W. B. Saunders Company p 2266
7. Uthayakumar S, Nandwani R, Drinkwater T, et al. The prevalence of skin disease in HIV infection and its relationship to the degree of immunosuppression. Br J Dermatol. 1997;137:595-8.PMID: 9390338
8. Brites D,et al. Unusual case of severe cholestasis of pregnancy with early onset, improved by ursodeoxycholic acid administration. Eur J Obstet Gynecol Reprod Biol. 1998 ;76:165-8. PMID: 9481568
9. Reid R, Ivey KJ, Rencoret RH, Storey B. Fetal complications of obstetric cholestasis. Br Med J 1976;1:870-2
10. Alsulyman OM, Ouzounian JG, Ames-Castro M, Goodwin TM Intrahepatic cholestasis of pregnancy: perinatal outcome associated with expectant management. Am J Obstet Gynecol. 1996;175:957-60. PMID: 8885754
11 Roncaglia N, Arreghini A, Locatelli A, Bellini P, Andreotti C, Ghidini A.Obstetric cholestasis: outcome with active management. Eur J Obstet Gynecol Reprod Biol. 2002;100(2):167-70. PMID: 11750958)
12. Reyes H, Simon FR. Intrahepatic cholestasis of pregnancy: an estrogen-related disease. Semin Liver Dis 1993;13:289-301.
13. Palma J, Reyes H, Ribalta J, Iglesias J, Gonzalez MC, Hernandez I, et al. Effects of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy. Hepatology 1992;15:1043-7.
14. Palma J, Reyes H, Ribalta J, Hernandez I, et al. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo. J Hepatol. 1997;27:1022-8. PMID: 9453428
15. Lammert F, Marschall HU, Glantz A, Matern S. Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J Hepatol. 2000;33:1012-21. PMID: 11131439
16. McDonald JA. Cholestasis of pregnancy. J Gastroenterol Hepatol. 1999 ;14:515-8.PMID: 10385057
17. Samuels P, Cohen AW. Pregnancies complicated by liver disease and liver dysfunction. Obstet Gynecol Clin North Am 1992;19:745-63.
18.Kondrackiene J,et al. Efficacy and safety of ursodeoxycholic acid versus cholestyramine in intrahepatic cholestasis of pregnancy.Gastroenterology.2005;129(3):894-901.PMID: 16143129
19.Zapata R, et al. Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy. A 12-year experience.Liver Int.2005 Jun;25(3):548-54.PMID: 15910492

Created: 4/1/2003
Update: 4/1/2003
Update: 10/17/2005

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