Background: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by pruritus and biochemical evidence of cholestasis, typically occurring in the third trimester. It is associated with adverse perinatal outcomes including preterm birth and fetal distress. Pregnancy following renal transplantation is considered high risk due to the need for continuous immunosuppressive therapy and its potential effects on graft function and fetal wellbeing. Azathioprine, a commonly used immunosuppressant, has been implicated in hepatotoxicity and cholestatic liver injury.

Case Presentation: We report a case of a 28-year-old primigravida with spontaneous conception who presented at 30 weeks of gestation with pruritus over the palms and soles, vomiting, fever, and jaundice. She was a renal transplant recipient for chronic interstitial nephritis and end-stage renal disease on tacrolimus, azathioprine, and steroids. Laboratory evaluation revealed markedly elevated bilirubin levels with deranged coagulation parameters. Following multidisciplinary consultation, azathioprine dose was reduced and supportive management including ursodeoxycholic acid was initiated. Coagulopathy was corrected with fresh frozen plasma and vitamin K prior to delivery. The patient underwent lower segment caesarean section after steroid cover for fetal lung maturity. Postoperatively, she showed gradual clinical and biochemical improvement.

Conclusion: This case highlights the diagnostic and therapeutic challenges of managing cholestatic liver dysfunction in pregnancy in renal transplant recipients. Early recognition, multidisciplinary care, and individualized adjustment of immunosuppressive therapy are essential for optimal maternal and fetal outcomes.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific hepatic disorder characterized by pruritus and elevated bile acid levels, most commonly presenting in the third trimester [1,2]. Although maternal prognosis is generally favorable, ICP is associated with adverse fetal outcomes such as preterm birth, fetal distress, and stillbirth [3,4].

With advances in transplantation medicine, pregnancy following renal transplantation has become increasingly common. However, these pregnancies remain high risk due to complications such as hypertension, pre-eclampsia, graft dysfunction, and infections [5-7]. Immuno-suppressive agents including azathioprine are widely used and are generally considered safe with respect to teratogenicity [8]. Nevertheless, azathioprine has been associated with hepatotoxicity and cholestatic liver injury in certain cases [9,10].

The coexistence of ICP or cholestatic liver dysfunction in pregnancy among renal transplant recipients receiving azathioprine is uncommon and poses diagnostic and therapeutic challenges. We present a case highlighting this complex clinical scenario and its successful multidisciplinary management.

A 28-year-old primigravida with spontaneous conception, married for one year, presented at 30 weeks of gestation with complaints of itching over the palms and soles for six days, along with vomiting, fever, and yellowish discoloration of the eyes for one day. She was a known case of renal transplantation for chronic interstitial nephritis and end-stage renal disease and was on maintenance immunosuppressive therapy with tacrolimus, azathioprine, and steroids. On examination, her vital parameters were stable, fetal heart rate was reassuring, and icterus was present.

Table 1: Results of laboratory investigations.

A nephrology consultation was obtained, and the dose of azathioprine was reduced. A hepatology consultation was also sought, and ultrasonography of the abdomen was performed. The patient was started on ursodeoxycholic acid (300 mg three times daily) and serial monitoring of liver function was done.

In view of coagulopathy, thromboelastography was performed and fresh frozen plasma transfusion was administered preoperatively. Vitamin K injection was also given.

After administration of steroids for fetal lung maturity, the patient underwent lower segment caesarean section (LSCS). Intraoperatively, one unit of packed red blood cells and fresh frozen plasma were transfused.

Postoperatively, the patient was closely monitored and demonstrated gradual decline in bilirubin levels with clinical improvement. 

Pregnancy following renal transplantation is increasingly feasible due to advances in immunosuppressive therapy and improved graft survival. However, these pregnancies remain high risk, with increased incidence of hypertension, pre-eclampsia, graft dysfunction, and infections [5-7]. Favourable outcomes can be achieved with careful monitoring and multidisciplinary care.

Intrahepatic cholestasis of pregnancy is a pregnancy-specific disorder typically presenting in the late second or third trimester with pruritus and biochemical cholestasis [11]. The incidence ranges from 0.7% to 1.5% globally [1]. Our patient’s presentation at 30 weeks with classical symptoms is consistent with established literature. ICP is associated with adverse fetal outcomes including preterm delivery and stillbirth [3,4].

The pathogenesis of ICP is multifactorial, involving hormonal, genetic, and environmental factors [12]. In transplant recipients, immunosuppressive therapy adds complexity. Azathioprine is generally considered safe in pregnancy [8]; however, it has been associated with cholestatic liver injury and hepatotoxicity [9,10].

Several reports have highlighted azathioprine-associated cholestasis in pregnancy. Ceruti et al. described improvement in liver function following dose reduction or discontinuation [9]. Similarly, other studies have suggested a temporal relationship between azathioprine exposure and cholestatic liver dysfunction [10,11].

This case highlights the complexity of managing cholestatic liver dysfunction in pregnancy in a renal transplant recipient receiving immunosuppressive therapy. Early recognition, prompt multidisciplinary evaluation, and individualized modification of therapy are essential to achieve favorable maternal and fetal outcomes.

The authors declare no conflict of interest.