Dr Anna Kermond1, Dr Ann Maree Craven1, Dr Katherine Poulsen1, Dr Karin Lust1, Dr Fiona Britten1
1Royal Brisbane Women's Hospital, Brisbane, Australia
Biography:
Dr Anna Kermond is a final year rheumatology advanced trainee with a special interest in obstetric medicine. She is completing her training at Royal Brisbane Women's Hospital and plans to expand the obstetric medicine and rheumatology research space.
Abstract:
Background: This presentation investigates the occurrence of liver toxicity associated with Azathioprine and 6-Mercaptopurine (6-MP) metabolites during pregnancy. Azathioprine, an immunosuppressive medication, is commonly used to manage autoimmune conditions such as inflammatory bowel disease and systemic lupus erythematosus, and its use during pregnancy requires careful consideration. This retrospective case series aims to highlight the necessity for metabolite and liver function monitoring in pregnant individuals using 6-MP and Azathioprine.
Methods: This retrospective case series included 6 pregnant women all taking either azathioprine or 6-Mercaptopurine with newly deranged liver function, or liver function that had worsened from baseline in the setting of elevated 6 Methylmercaptopurine (6-MMP metabolite levels). Data includes patient demographics (age, gravidity, parity), other patient co-morbidities, gestation at the time of liver dysfunction, liver function trend and patterns, azathioprine dose, 6MMP metabolite levels, and other relevant foetal or maternal factors.
Results: Data analysis revealed a correlation between elevated 6-MMP (6 methylmercaptopurine) levels and new onset liver dysfunction, with demonstrated improvement through dose reduction or drug cessation. Notably, the predominant manifestation of liver dysfunction was transaminitis with variable cholestatic enzyme derangement. Metabolite levels failed to correlate with the severity of liver dysfunction.
Of the cases studied, five necessitated emergency caesarean sections, with two resulting in premature deliveries, while the rest were carried to term. Two infants were born at low birth weight. Notably the dosage was appropriate for TPMT (thiopurine methyltransferase) enzyme activity when performed, with normal liver function pre-pregnancy, indicating a change in drug pharmacodynamics in pregnancy.
Conclusion: This research underscores the importance of vigilant monitoring and consideration of potential liver toxicity in pregnant individuals undergoing Azathioprine or 6-MP treatment. Despite adherence to safe dosing practices, both medications exhibited liver dysfunction linked to metabolite elevation during pregnancy, highlighting the necessity for heightened awareness and proactive management strategies in such cases
References
Maya Frank Wolf, Ronen Sloma, Luiza Akria, Eli Rimon, Yifat Wiener, Michal Carmiel Haggai, Lior Lowenstein, Azathioprine and 6-mercaptopurine-induced intrahepatic cholestasis of pregnancy: Case report and review of the literature, Taiwanese Journal of Obstetrics and Gynecology, Volume 62, Issue 5, 2023, Pages 761-764, ISSN 1028-4559,
Maya Frank Wolf, Ronen Sloma, Luiza Akria, Eli Rimon, Yifat Wiener, Michal Carmiel Haggai, Lior Lowenstein, Azathioprine and 6-mercaptopurine-induced intrahepatic cholestasis of pregnancy: Case report and review of the literature, Taiwanese Journal of Obstetrics and Gynecology, Volume 62, Issue 5, 2023, Pages 761-764, ISSN 1028-4559
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