Effect of Ursodeoxycholic Acid Alone Versus Ursodeoxycholic Acid and Rifampicin in Obstetric Cholestasis

Authors

  • Ayesha Amjad Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.
  • Sadia Aftab Pakistan Institute of Medical Sciences ,Islamabad,Pakistan.
  • Tahreem Sehar Pakistan Institute of Medical Sciences ,Islamabad,Pakistan.
  • Samana Haider Pakistan Institute of Medical Sciences, Islamabad, Pakistan.
  • Tehmina Aziz Qureshi Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.
  • Kainaat Kanwal Pakistan Institute of Medical Sciences ,Islamabad,Pakistan.

DOI:

https://doi.org/10.36283/ziun-pjmd14-3/040

Keywords:

Ursodeoxycholic acid, Intrahepatic Cholestasis of Pregnancy, Rifampin, Pruritus, Liver Function Tests

Abstract

Background: Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder in pregnancy, associated with pruritus, elevated bile acids, and increased risk of adverse perinatal outcomes. While Ursodeoxycholic Acid (UDCA) is the first-line treatment, some patients respond inadequately. This study aimed to compare the effectiveness of UDCA alone versus UDCA combined with Rifampicin in reducing clinical symptoms and improving biochemical markers in women with ICP.

Methods: This quasi-experimental study was conducted at the Department of Obstetrics and Gynecology, Maternal and Child Health Hospital, Unit 1, PIMS Islamabad, from August 1, 2022, to January 31, 2023. A total of 122 pregnant women diagnosed with ICP were enrolled using non-probability consecutive sampling and divided into two groups. Group A received UDCA alone, and Group B received UDCA plus Rifampicin. Inclusion criteria were singleton pregnancy, gestational age 24–36 weeks, serum bile acids >10 µmol/L, and/or raised liver enzymes. Data were analyzed using SPSS version 21, with independent t-tests for continuous variables and chi-square tests for categorical data. A p-value < 0.05 was considered statistically significant.

Results: The combination therapy group showed significantly greater reductions in pruritus (p = 0.023), serum bile acids, liver enzymes, and bilirubin levels (p < 0.0001) at 2 and 4 weeks compared to UDCA alone.

Conclusion: Rifampicin combined with UDCA is more effective than UDCA monotherapy in improving both clinical and biochemical outcomes in ICP.

Author Biographies

  • Ayesha Amjad, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.

    Department of Obstetrics and Gynecology,

  • Sadia Aftab, Pakistan Institute of Medical Sciences ,Islamabad,Pakistan.

    Department of Obstetrics and Gynecology,

  • Tahreem Sehar, Pakistan Institute of Medical Sciences ,Islamabad,Pakistan.

    Department of Obstetrics and Gynecology,

  • Samana Haider, Pakistan Institute of Medical Sciences, Islamabad, Pakistan.

    Department of Obstetrics and Gynecology,

  • Tehmina Aziz Qureshi, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.

    Department of Obstetrics and Gynecology,

  • Kainaat Kanwal, Pakistan Institute of Medical Sciences ,Islamabad,Pakistan.

    Department of Obstetrics and Gynecology,

References

1. Hague WM, Callaway L, Chambers J, Chappell L, Coat S, de Haan‑Jebbink J, et al. A multi‑centre, open‑label, randomised, parallel‑group, superiority trial to compare the efficacy of ursodeoxycholic acid with rifampicin in management of severe early onset intrahepatic cholestasis of pregnancy: the TURRIFIC randomised trial. BMC Pregnancy Childbirth. Jan 2021;21(1):51. DOI: 10.1186/s12884-020-03481-y

2. Kulshrestha V, Narang S, Shalimar, Bhatla N. Rifampicin as an adjunct to ursodeoxycholic acid for treating severe refractory intrahepatic cholestasis of pregnancy in a patient with elevated bilirubin. J Obstet Gynecol India. Apr 2021;71(1):188‑90. DOI: 10.1007/s13224-020-01388-4

3. Akram A, Sadaf J, Aziz A, Ara S, Rafiq T, Malik AM. The frequency of feto‑maternal complications in patients with intrahepatic cholestasis of pregnancy. Prof Med J. 2022;29(2):212‑7. DOI: 10.29309/TPMJ/2022.29.02.6394

4. Batool H, Khan MD, Chughtai OR, Ashraf S, editors. Diagnostic significance of serum total bile acid levels in suspected cases of obstetric cholestasis. Proceedings. 2020. DOI: 10.21542/gcsp.2024.37

5. Ahmadi AR, Chicco M, van den Berge M. Rifampicin for treatment of cholestatic pruritus caused by drug‑induced acute liver injury as assessed by the RUCAM classification. Case Rep Hepatol. 2020;2020(1):1. DOI: 10.1155/2020/8872804

6. Chen R, Deng M, Rauf YM, Lin GZ, Qiu JW, Zhu SY, et al. Intrahepatic cholestasis of pregnancy as a clinical manifestation of sodium‑taurocholate cotransporting polypeptide deficiency. Tohoku J Exp Med. 2019;248(1):57‑61. DOI: 10.1620/tjem.248.57

7. Cui Y, Xu B, Zhang X, He Y, Shao Y, Ding M. Diagnostic and therapeutic profiles of serum bile acids in women with intrahepatic cholestasis of pregnancy—a pseudo‑targeted metabolomics study. Clin Chim Acta. 2018;483:135‑41. DOI: 10.1016/j.cca.2018.04.035

8. Estin ML, Campbell AI, Watkins VY, Dotters‑Katz SK, Brady CW, Federspiel JJ. Risk of stillbirth in United States patients with diagnosed intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol. Oct 2023;229(4):453.e1‑e8. DOI: 10.1016/j.ajog.2023.06.036

9. Wolf MF, Sloma R, Akria L, Rimon E, Wiener Y, Carmiel Haggai M, et al. Azathioprine and 6‑mercaptopurine‑induced intrahepatic cholestasis of pregnancy: case report and literature review. Taiwan J Obstet Gynecol. 2023;62(5):761‑4. DOI: 10.1016/j.tjog.2023.07.023

10. Gardiner FW, McCuaig R, Arthur C, Carins T, Morton A, Laurie J, et al. The prevalence and pregnancy outcomes of intrahepatic cholestasis of pregnancy: a retrospective clinical audit review. Obstet Med. 2019;12(3):123‑8. DOI: 10.1177/1753495X18797749

11. Gok K, Takmaz T, Kose O, Tuten N, Acikgoz AS, Bostanci MS, et al. Can first‑trimester aspartate aminotransferase/platelet ratio index score predict intrahepatic cholestasis of pregnancy? Hepatol Forum. 2023;4(1):30‑4. DOI: 10.14744/hf.2022.2022.0031

12. Grady J, Clifford C, Treadwell MC, Parikh ND, Satishchandran A. Use of fenofibrate for intrahepatic cholestasis of pregnancy. J Hepatol. 2023;79(2):e84‑e6. DOI: 10.1016/j.jhep.2023.04.014

13. Granese R, Calagna G, Alibrandi A, Martinelli C, Romeo P, Filomia R, et al. Maternal and neonatal outcomes in intrahepatic cholestasis of pregnancy. J Clin Med. Jul 2023;12(13):4344‑07. DOI: 10.3390/jcm12134407

14. Gruszczynska‑Losy M, Wender‑Ozegowska E, Wirstlein P, Szczepanska M. Assessment of selected parameters of placental microstructure in patients with intrahepatic cholestasis of pregnancy. Ginekol Pol. 2019;90(8):452‑7. DOI: 10.5603/GP.2019.0077

15. Guo J, Wang Y, Wang N, Bai Y, Shi D. Celastrol attenuates intrahepatic cholestasis of pregnancy by inhibiting matrix metalloproteinases‑2 and ‑9. Ann Hepatol. 2019;18(1):40‑7. DOI: 10.5604/01.3001.0012.7860

16. Karpale M, Hukkanen J, Hakkola J. Nuclear receptor PXR in drug‑induced hypercholesterolemia. Cells. Jan 18 2022;11(3):313. DOI: 10.3390/cells11030313

17. Li T, Chiang JY. Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7α‑hydroxylase gene transcription. Am J Physiol Gastrointest Liver Physiol. 2005;288(1):G74‑G84. DOI: 10.1152/ajpgi.00258.2004

18. Zhao Y, Zhang Q, Sheng Y, Zhang M, He G, Liu X. Preterm birth and stillbirth: total bile acid levels in intrahepatic cholestasis of pregnancy and outcomes of twin pregnancies: a retrospective cohort from 2014 to 2022. BMC Pregnancy Childbirth. Dec 2025;25(1):1‑7. DOI: 10.1186/s12884‑025‑07644‑7

19. Schattenberg JM, Pares A, Kowdley KV, Heneghan MA, Caldwell S, Pratt D, et al. A randomized placebo‑controlled trial of elafibranor in primary biliary cholangitis patients with incomplete response to UDCA. J Hepatol. Jun 1 2021;74(6):1344‑54. DOI: 10.1016/j.jhep.2021.01.013

20. Ding D, Guo G, Liu Y, Zheng L, Jia G, Deng J, et al. Efficacy and safety of fenofibrate add‑on therapy in cirrhotic primary biliary cholangitis patients with incomplete response to ursodeoxycholic acid. Hepatol Commun. Dec 2022;6(12):3487‑95. DOI: 10.1002/hep4.2103

21. Kulshrestha V, Narang S, Shalimar, Bhatla N. Rifampicin as adjunct to ursodeoxycholic acid for treating severe refractory intrahepatic cholestasis of pregnancy in patient with elevated bilirubin. J Obstet Gynecol India. Apr 2021;71(1):188‑90. DOI: 10.1007/s13224-020-01388-4

22. Perri A, Patti ML, Velardi M, Sbordone A, Prontera G, Fattore S, et al. Bile acids pneumonia: a respiratory distress syndrome in early‑term neonates. J Clin Med. Oct 17 2023;12(20):6565. DOI: 10.3390/jcm12206565

23. Zarkesh M, Mahdipour S, Aghili S, Jafari A, Nouri SA, Hassanzadeh Rad A, et al. Evaluation of therapeutic effect of oral ursodeoxycholic acid on indirect hyperbilirubinemia in term neonates undergoing phototherapy: a randomized controlled trial. PLoS One. Dec 12 2023;18(12):e0273516. DOI: 10.1371/journal.pone.0273516

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Published

2025-07-21

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How to Cite

1.
Amjad A, Aftab S, Sehar T, Haider S, Qureshi TA, Kanwal K. Effect of Ursodeoxycholic Acid Alone Versus Ursodeoxycholic Acid and Rifampicin in Obstetric Cholestasis. PJMD [Internet]. 2025 Jul. 21 [cited 2026 Jun. 5];14(3):258-63. Available from: https://ojs.zu.edu.pk/pjmd/article/view/3803

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