• Cholestatic hepatosis of pregnant women: issues of etiopathogenesis, diagnosis, management
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Cholestatic hepatosis of pregnant women: issues of etiopathogenesis, diagnosis, management

HEALTH OF WOMAN. 2020.7(153): 8-13; doi 10.15574/HW.2020.153.8
Beniuk S. V. , Kovaliuk T. V.
Bogomolets National Medical University, Kiev

Cholestatic hepatosis of pregnant women complicates approximately 0.2% to 2% of pregnancies and may increase the risk of pregnancy and fetal pathology.
The article provides information on diagnosis, treatment methods and possible risks to pregnant women and the fetus associated with cholestatic hepatosis of pregnancy.
The diagnosis of cholestatic hepatosis of pregnant women is usually based on clinical (itching) and laboratory (elevated bile acid levels) signs. Other markers that reflect liver function, such as alanine aminotransferase and aspartate aminotransferase, are also often elevated, and this requires a differential diagnosis with other pathological conditions leading to liver dysfunction.
Cholestatic hepatosis of pregnant women causes an increased risk of premature birth, fetal distress, respiratory distress syndrome of the newborn and stillbirth. There is evidence that with increasing levels of bile acids increases the risk of adverse effects for newborns. Ursodeoxycholic acid therapy reduces maternal symptoms, but this therapy has not been shown to reduce risks to the fetus. Women diagnosed with cholestatic hepatosis in pregnant women have a high risk of recurrence during subsequent pregnancies and hepatobiliary disease later in life.
Keywords: cholestatic hepatosis of pregnant women, intrahepatic cholestasis of pregnant women, obstetric cholestasis.

REFERENCES

1. South Australian Perinatal practice guidelines «Obstetric cholestasis». 2016.

2. Royal College of Obstetricians and Gynaecologists. 2011, April. Obstetric Cholestasis. Green top Guidelines Guideline 43. RCOG: London.

3. Wood AM, Livingston EG, Hughes BL, Kuller JA. 2018. Intrahepatic Cholestasis of Pregnancy:A Review of Diagnosis and Management. Obs. and gyn. survey. 73(2):103-109. https://doi.org/10.1097/OGX.0000000000000524; PMid:29480924

4. Germain AM, Carvajal JA, Glasinovic JC et al. 2002. Intrahepatic cholestasis of pregnancy: an intriguing pregnancyspecific disorder. J. Soc. Gynecol. Investig. 9:10-14. https://doi.org/10.1177/107155760200900103; PMid:11839502

5. Pusl Т, Beuers U. 2007. Intrahepatic cholestasis of pregnancy. Orphan et J. Rare Dis. 2:26. https://doi.org/10.1186/1750-1172-2-26; PMid:17535422 PMCid:PMC1891276

6. Zecca E. 2006. Intrahepatic cholestasis of pregnancy and neonatal respiratory distress syndrome. Pediatrics 117:1669-1672. https://doi.org/10.1542/peds.2005-1801; PMid:16651322

7. Bicocca MJ et al. 2018. Intrahepatic cholestasis of pregnancy: Review of six national and regional guidelines. European Journal of Obstetrics & Gynecology and Reproductive Biology 231:180-187. https://doi.org/10.1016/j.ejogrb.2018.10.041; PMid:30396107

8. PauliMagnus C, Meier PJ, Stieger B. 2010. Genetic determinants of drug induced cholestasis and intrahepatic cholestasis of pregnancy. Semin. Liver Dis. 30;2:147-159. https://doi.org/10.1055/s-0030-1253224; PMid:20422497

9. Palmer DG, Eads J. 2000. Obstetric cholestasis of pregnancy: A critical review. J Perinat Neonat Nurs 14:39-52. https://doi.org/10.1097/00005237-200006000-00004; PMid:11249293

10. Williamson C, Girling J. 2011. Obstetric cholestasis. In: James DK, Steer PJ, Weiner CP, Gonik B, Crowther C, Robson SC editors. High risk pregnancy. Fourth ed. Philadelphia: Elsevier: 843-846.

11. Geenes V, Williamson C. 2009. Intrahepatic cholestasis of pregnancy. World J Gastroenterol 15:2049-66. https://doi.org/10.3748/wjg.15.2049; PMid:19418576 PMCid:PMC2678574

12. Williamson C, Hems LM, Goulis DG, Walker I, Chambers J et al. 2004. Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group. BJOG 111:676-81. https://doi.org/10.1111/j.1471-0528.2004.00167.x; PMid:15198757

13. Martineau M, Raker C, Powrie R, Williamson C. 2014. Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes. Eur J Obstet Gynecol Reprod Biol 176:80-85. https://doi.org/10.1016/j.ejogrb.2013.12.037; PMid:24462052

14. Wikström Shemer C, Marschall HU, Ludvigssun JF, Stephansson O. 2013. Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: a 12-year population-based cohort study. BJOG 120:717-23. https://doi.org/10.1111/1471-0528.12174; PMid:23418899

15. Paternoster DM, Fabris F, Palù G, Santarossa C, Bracciante R et al. 2002. Intrahepatic cholestasis of pregnancy in hepatitis C virus infection. Acta Obs Gyn Scan 81:99-103. https://doi.org/10.1034/j.1600-0412.2002.810202.x; PMid:11942897

16. Lammert F, Marschall HU, Glantz A, Matern S. 2000. Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J. Hepatol. 33:1012-1021. https://doi.org/10.1016/S0168-8278(00)80139-7

17. Reyes H, Sjovall J. 2003. Bile acids and progesterone metabolites in intrahepatic cholestasis of pregnancy. Ann. Med. 32;2:94-106. https://doi.org/10.3109/07853890009011758; PMid:10766400

18. Reyes H. 2008. Sex hormones and bile acids in intrahepatic cholestasis of pregnancy. Hepatology 47:376-79. https://doi.org/10.1002/hep.22139; PMid:18220280

19. Geenes V, Chappell LC, Seed PT, Knight M, Williamson C. 2014. Association of severe intrahepatic cholestasis of pregnancy with adverse outcomes: a prospective population-based case-control study Hepatology vol/is/59/4(1482-91). https://doi.org/10.1002/hep.26617; PMid:23857305 PMCid:PMC4296226

20. Walker IAL, Nelson-Piercy C, Williamson C. 2002. Role of bile acid measurement in pregnancy. Anals Clin Biochem. 39:105-14. https://doi.org/10.1258/0004563021901856; PMid:11928758

21. Nichols AA. 2005. Cholestasis of pregnancy: a review of the evidence. J. Perinat. Neonatal. Nurs. 19:217-225. https://doi.org/10.1097/00005237-200507000-00007; PMid:16106229

22. Fagan EA. 2002. Intrahepatic cholestasis of pregnancy. Clin Liver Dis. 3:603-632. https://doi.org/10.1016/S1089-3261(05)70087-8

23. Ovadia C, Seed P et al. 2019, April. Association of adverse perinatal outcome on intrahepatic cholestasis of pregnancy with biochemical markers. The Lancet, 393, 10174, 899-909. Last accessed at https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31877-4/fulltext.

24. Huy A Tran. 2006. Biochemical tests in pregnancy Australian Prescriber Volume 20;4.

25. Egan N, Bartels A et al. 2012. Reference standard for serum bile acids in pregnancy BJOG 119:493-498. https://doi.org/10.1111/j.1471-0528.2011.03245.x; PMid:22251417

26. Juusela AL, Cordero L, Gimovsky M, Nazir M. 2019, Nov 23. Correlation of bile acids and aspartate-aminotransferase with outcomes in cholestasis of pregnancy. J Neonatal Perinatal Med. https://doi.org/10.3233/NPM-190276; PMid:31796691

27. Geenes V, Chappell LC, Seed PT, Steer PJ, Knight M, Williamson C. 2014. Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: A prospective population-based case-control study. Hepatology 59:1482-91. https://doi.org/10.1002/hep.26617; PMid:23857305 PMCid:PMC4296226

28. Lee RH, Kwok KM, Ingles S, Wilson ML, Mullin P, Incerpi M et al. 2008. Pregnancy outcomes during an era of aggressive management for intrahepatic cholestasis of pregnancy. Am J Perinatol. 25:341-5. https://doi.org/10.1055/s-2008-1078756; PMid:18509787

29. Saleh MM, Abdo KR. 2007. Consensus on the management of obstetric cholestasis:National UK survey. BJOG 114:99-103. https://doi.org/10.1111/j.1471-0528.2006.01102.x; PMid:17081185

30. Glantz A, Marschall H-U, Lammert F, Matteson L-A. 2005. Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid. Hepatology 42:1399-1405. https://doi.org/10.1002/hep.20952; PMid:16317669

31. Egan A. K.D. B. C. J. J. O., Bartels A, O'Donoghue K. 2012. Reference standard for serum bile acids in pregnancy. BJOG 119:493-8. https://doi.org/10.1111/j.1471-0528.2011.03245.x; PMid:22251417

32. Chappell LC, Gurung V, Seed PT, Chambers J, Williamson C, Thornton JG, on behalf of the PITCH study consortium. 2012. Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semi factorial randomised clinical trial. BMJ 344:e3799. https://doi.org/10.1136/bmj.e3799; PMid:22695903 PMCid:PMC3420230

33. Nicastri PL, Diaferia A, Tartagni M, Loizzi P Fanelli M. 1998. A randomised placebo controlled trial of ursodeoxycholic acid and S-adenosylmethionine in the treatment of intrahepatic cholestasis of pregnancy. Br J Obst Gynaecol 105:1205-07. https://doi.org/10.1111/j.1471-0528.1998.tb09976.x; PMid:9853771

34. Jenkins JK, Boothby LA. 2002. Treatment of itching associated with intrahepatic cholestasis of pregnancy. Ann Pharmacother. 36:1462-5. https://doi.org/10.1345/aph.1A479; PMid:12196068

35. Geenes V, Chambers J, Khurana R, Wikström Shemer E, Sia W, Mandair D et al. 2015. Rifampicin in the treatment of severe intrahepatic cholestasis of pregnancy. Eur J Obstet Gynecol Reprod Biol. 189:59-63. https://doi.org/10.1016/j.ejogrb.2015.03.020; PMid:25864112

36.Gurung V, Stokes M, Middleton P, Milan SJ, Hague W, Thornton JG. 2013. Interventions for treating cholestasis in pregnancy. Cochrane Database of Systematic Reviews 6;CD000493. DOI: 10.1002/14651858.CD000493.pub2. Available from URL: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000493.pub2/pdf/standard

37. British Medical Association, Pharmaceutical Society of Great Britain. 2010. Vitamin K. British National Formulary. London: British Medical Association, Pharmaceutical Society of Great Britain.

38. Arrese M, Reyes H. 2005. Intrahepatic cholestasis of pregnancy: A past and present riddle. Annals of Hepatol 5:202-5. https://doi.org/10.1016/S1665-2681(19)32012-5