Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Management of Recurrent Intrahepatic Cholestasis of Pregnancy: A Case Report

Authors
1 Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
2 Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Background: Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent hepatic disorder exclusive to pregnancy, associated with significant maternal morbidity and increased risk of adverse perinatal outcomes. Recurrence in subsequent pregnancies and comorbidities such as gestational diabetes and hypertensive disorders further complicate clinical management. This case presentation, an attempted to describe the diagnostic and therapeutic challenges in managing recurrent ICP, especially in the context of overlapping maternal comorbidities and limited diagnostic resources. Case Presentation: A case of a 32-year-old Iranian woman, gravida 3 para 2, with a history of one intrauterine fetal death and one neonatal death, was ultimately diagnosed with recurrent ICP. In her third pregnancy, elevated bile acid levels were confirmed by routine monitoring from 20 weeks’ gestation, peaking at 333 µmol/L by 32 weeks. Despite intensive medical therapy including ursodeoxycholic acid, hydroxychloroquine, corticosteroids, and low-molecular-weight heparin, her pruritus worsened and bile acid levels escalated, prompting preterm cesarean delivery. The neonate experienced complications, including respiratory distress, suspected Hirschsprung’s disease, sepsis, and hyperbilirubinemia. Management included continuous positive airway pressure (CPAP), broad-spectrum antibiotics, surgery, phototherapy, and parenteral nutrition. Multidisciplinary intervention enabled neonatal recovery, and maternal symptoms resolved postpartum. Conclusion: This case underscores the complexities of managing recurrent ICP, particularly in resource-limited settings. It highlights the critical need for early diagnosis, vigilant monitoring, and a multidisciplinary approach to mitigate the risk of stillbirth and improve perinatal outcomes. Additionally, it suggests that recurrent ICP may present earlier or with greater intensity in subsequent pregnancies, necessitating more comprehensive surveillance and tailored management strategies for affected mothers.
Keywords

  1. Goel A, Jamwal KD, Ramachandran A, Balasubramanian KA, Eapen CE. Pregnancy-related liver disorders. J Clin Exp Hepatol. 2014;4(2):151-62.
  2. Tang M, Xiong L, Cai J, Fu J, Liu H, Ye Y, et al. Intrahepatic cholestasis of pregnancy: insights into pathogenesis and advances in omics studies. Hepatol Int. 2024;18(1):50-62.
  3. Girling J, Knight CL, Chappell L. Intrahepatic cholestasis of pregnancy: green‐top guideline No. 43 June 2022. BJOG. 2022;129(13):e95-114.
  4. Beuers U, Wolters F, Oude Elferink RP. Mechanisms of pruritus in cholestasis: understanding and treating the itch. Nat Rev Gastroenterol Hepatol. 2023;20(1):26-36.
  5. Parsaei M, Dashtkoohi M, Haddadi M, Rashidian P, Mansouri Z, Hantoushzadeh S. The association of serum total bile acid levels with gestational diabetes mellitus: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2024;24(1):744.
  6. Arrese M, Macias RI, Briz O, Perez MJ, Marin JJ. Molecular pathogenesis of intrahepatic cholestasis of pregnancy. Expert Rev Mol Med. 2008;10:e9.
  7. Xiao J, Li Z, Song Y, Sun Y, Shi H, Chen D, et al. Molecular pathogenesis of intrahepatic cholestasis of pregnancy. Can J Gastroenterol Hepatol. 2021;2021:6679322.
  8. Jamshidi Kerachi A, Shahlaee MA, Habibi P, Dehdari Ebrahimi N, Ala M, Sadeghi A. Global and regional incidence of intrahepatic cholestasis of pregnancy: a systematic review and meta-analysis. BMC Med. 2025;23(1):129.
  9. Hobson SR, Cohen ER, Gandhi S, Jain V, Niles KM, Roy-Lacroix MÈ, et al. Guideline No. 452: diagnosis and management of intrahepatic cholesta-sis of pregnancy. J Obstet Gynaecol Can. 2024;46(8):102618.
  10. Odutola PO, Olorunyomi PO, Olatawura OO, Olorunyomi I, Madojutimi O, Fatunsin AO, et al. Intrahepatic cholestasis of pregnancy is associated with increased risk of hepatobiliary disease and adverse fetal outcomes: a systematic review and meta-analysis. ILIVER. 2023;2(4):219-26.
  11. Lyutakov I, Ursini F, Penchev P, Caio G, Carroccio A, Volta U, et al. Methods for diagnosing bile acid malabsorption: a systematic review. BMC Gastroenterol. 2019;19(1):185.
  12. Moar L, Simela C, Nanda S, Marnerides A, Al-Adnani M, Nelson-Piercy C, et al. Chronic histiocytic intervillositis (CHI): current treatments and perinatal outcomes, a systematic review and a meta-analysis. Front Endocrinol (Lausanne). 2022; 13:945543.
  13. Myszkowski S, Ayuk PT. Intra-hepatic cholestasis of pregnancy: management challenges. Case Rep Womens Health. 2024;41:e00576.
  14. Liu C, Gao J, Liu J, Wang X, He J, Sun J, et al. Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes and preeclampsia. Ann Transl Med. 2020;8(23):1574.
  15. Raz Y, Lavie A, Vered Y, Goldiner I, Skornick-Rapaport A, Landsberg Asher Y, et al. Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies. Am J Obstet Gynecol. 2015;213(3):395.e1-8.
  16. Sahni A, Jogdand SD. Effects of intrahepatic cholestasis on the foetus during pregnancy. Cureus. 2022;14(10):e30657.
  17. Glantz A, Marschall HU, Mattsson LÅ. Intrahepa-tic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology. 2004;40(2):467-74.
  18. Shah PA, Nishio A, Hasan S, Wu L, Chie L, Rehermann B, et al. A Rare case of recurrent intrahepatic cholestasis of pregnancy with prolonged postpartum hepatic inflammation despite normalization of bile acid levels. Gastro Hep Adv. 2022;2(1):46-8.
  19. Hämäläinen ST, Turunen K, Mattila KJ, Kosunen E, Sumanen M. Intrahepatic cholestasis of pregnancy and comorbidity: A 44-year follow-up study. Acta Obstet Gynecol Scand. 2019;98(12):1534-9.
  20. Sabahath S, Aldabbous F, Mohammed M, Al Alhendi A, Al Yaqoot N, Ali A,et al. Emerging Medical Treatments of Intrahepatic Cholestasis of Pregnancy. J Pharm Res Int. 2021;33(45A):243-8.
  21. Hague WM, Callaway L, Chambers J, Chappell L, Coat S, de Haan-Jebbink J, et al. A multicentre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset intrahepatic cholestasis of pregnancy: the TURRIFIC randomised trial. BMC Pregnancy Childbirth. 2021;21(1):51.
  22. Li C, Yang J, Wang Y, Qi Y, Yang W, Li Y. Farnesoid X receptor agonists as therapeutic target for cardiometabolic diseases. Front Pharmacol. 2020;11:1247.
  23. Wasmuth HE, Glantz A, Keppeler H, Simon E, Bartz C, Rath W, et al. Intrahepatic cholestasis of pregnancy: the severe form is associated with common variants of the hepatobiliary phospholipid transporter ABCB4 gene. Gut. 2007;56(2):265-70.
  24. Anzivino C, Odoardi MR, Meschiari E, Baldelli E, Facchinetti F, Neri I, et al. ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population. Dig Liver Dis. 2013;45(3): 226-32.
  25. Dixon PH, Sambrotta M, Chambers J, Taylor-Harris P, Syngelaki A, Nicolaides K, et al. An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahe-patic cholestasis of pregnancy. Sci Rep. 2017;7(1):11823.