Dr Lyra Meehan1, Dr Daniel Saitta2, Dr Natasha Frawley1, Dr Sajith Kattiparambil2, Dr David Langsford2,3
1Women’s and Children’s, Grampians Health, Ballarat , Australia, 2Internal Medicine, Grampians Health, Ballarat, Australia, 3University of Melbourne, Melbourne, Australia
Biography:
A Doctor at Grampians Health Ballarat currently enrolled in Diploma of O&G. She completed her MD at the University of Notre Dame, Sydney, and BSc(Hons) at the University of Melbourne. She has previously worked as research assistant at the MCRI and RCH and been a member of the ASMR.
Abstract:
Introduction: Very severe intrahepatic cholestasis of pregnancy (ICP) characterised by total serum bile acid (TSBA) > 100umol/L is associated with an increased stillbirth risk of 3.4%. Patients exposed to thiopurines may be at increased risk of ICP.
Case: A 34 year old primigravida presented at 27+3/40 with a 7 week history of pruritus and jaundice was diagnosed with very severe ICP (TSBA = 117umol/L). She has Crohns, controlled on azathioprine 200mg daily. Her bilirubin was 162umol/L, AST 65U/L, ALT 54U/L, GGT 24U/L. Coagulation, viral, autoimmune, urine and liver and foetal ultrasound studies were normal. Simultaneously, she was diagnosed with GDM.
Ursodeoxycholic acid was inefficacious. Thiopurine metabolites ratio (6MMP:TGN) was 34 at 12/40 and 21 at 27/40. Cessation of azathioprine precipitated a TSBA fall to 31umol/L within 7 days. Recommencement of azathioprine at 29/40 50mg BD led to an increase in TSBA to 89umol/L. Azathioprine was ceased at 30/40 and TSBA, bilirubin and symptoms normalised. Crohns remained in remission. A multidisciplinary plan was made in conjunction with the patient for delivery between 35 and 36 weeks.
Discussion: Azathioprine induced ICP has been reported in IBD and post-transplant patients. The SOMANZ 2023 ICP guidelines references a cohort (n= 8 pregnancies) of azathioprine treated IBD complicated by ICP, 5 with TBSA > 100. A retrospective UK cohort (n = 386 pregnancies) demonstrated an increased incidence of ICP (3.9%) in patients with IBD accounted for by thiopurine exposure. An Australian prospective cohort of IBD patients (n= 131 pregnancies) demonstrated increased metabolite shunting (6MMP:TGN > 11) contributes to ICP.
Conclusion: Thiopurines may contribute to ICP with TSBA > 40umol/L, however their use for patients with autoimmune conditions or post-transplantation is common in pregnancy. Prospective research is warranted to understand how best to maintain maternal and foetal when use of thiopurines in pregnancy is indicated.
Keywords
Intrahepatic cholestasis of pregnancy, azathioprine
References
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