Contraceptive vaginal ring-induced cholestasis in a patient with a history of intrahepatic cholestasis of pregnancy

• Published in: Clinics and research in hepatology and gastroenterology 2021-07, Vol.45 (4), p.101475, Article 101475
• Main Authors: Perrault, Florence, Echelard, Philippe, Viens, Daniel, Borduas, Martin
• Format: Article
• Language: English
• Subjects: ABCB11; ABCB4; ATP Binding Cassette Transporter, Subfamily B; Cholestasis - chemically induced; Cholestasis, Intrahepatic - chemically induced; Contraceptive Agents; Contraceptive Devices, Female; Contraceptive vaginal ring; Contraceptive-induced cholestasis; Drug-induced cholestasis; Estrogens; Female; Humans; Intrahepatic cholestasis of pregnancy; Pharmaceutical Preparations; Pregnancy; Pregnancy Complications
• ISSN: 2210-7401; 2210-741X
• DOI: 10.1016/j.clinre.2020.06.002

•Patients with a history of intrahepatic cholestasis of pregnancy are at risk of developing contraceptive-induced cholestasis, especially if they harbor a biliary transporter mutation.•Contraceptive-induced cholestasis is a diagnosis of exclusion.•Recent studies suggest a lower risk of cholestasis associated with low-dose oestrogen pills (20–35 mcg compared to the original 50 mcg).•Contraceptive vaginal rings (15 mcg) can trigger drug-induced cholestasis in a patient susceptible to the cholestatic effect of oestrogen. Intrahepatic cholestasis of pregnancy (ICP) is a heterogeneous group of liver disorders with a high recurrence rate. Patients with a history of ICP are at risk of developing contraceptive-induced cholestasis, especially if they harbour a biliary transporter mutation. We report the first case of drug-induced cholestasis associated with a contraceptive vaginal ring (CVR) in a patient with a prior history of ICP. Our patient was a women with a history of multiple pregnancies and spontaneous abortions and early and severe ICP. Two to four weeks after initiation of CVR, she developed signs and symptoms of cholestasis, which resolved after discontinuation of the CVR. A thorough investigation to exclude other plausible causes of cholestasis was performed, including a liver biopsy. Genetic testing revealed pathogenic mutations in both the ABCB11 and ABCB4 genes. Although a history of ICP used to be an absolute contraindication for oral contraceptive pills (OCP), recent studies suggest a lower risk of cholestasis associated with low-dose oestrogen pills (20–35 mcg compared to the original 50 mcg). No previous case report could confirm the theoretical risk associated with the use of a CVR, which delivers a very low estrogen dose (15 mcg). The two biliary transporter mutations identified in our case could potentially explain the patient's susceptibility to the cholestatic effect of oestrogen. This case illustrates that CVR can trigger drug-induced cholestasis in a susceptible patient. While such cases should not discourage the trial of low-dose hormonal contraception in women with prior ICP, an appropriate follow-up is necessary to ensure early detection and treatment of drug-induced cholestasis.