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Donor transmitted mutation of the ABCB11 gene and ensuing intra-hepatic cholestasis of pregnancy in a liver transplant recipient.
Abstract
In liver transplant (LT) recipients, the cause of graft dysfunction in pregnancy is often difficult to ascertain. Moreover, a liver biopsy in late pregnancy is often avoided as a consequence of patient and physician factors. Management of graft dysfunction can be difficult in this setting. We report a 30-year-old female LT recipient who developed acutely deranged liver biochemistry during the third trimester of her first pregnancy. At 29 weeks gestation, her liver function test (LFT) became abnormal; AST peaked at 978 IU/L (normal range 10-50), GGT 25 IU/L (normal range 1-55), bilirubin 1.5 mg/dL (normal range 0.3-1) and serum bile acids 52 µmol/L (normal range <14). Immunosuppression levels were low or undetectable. The patient received empirical high dose methylprednisolone for three days and was induced at 36 weeks gestation. A liver biopsy performed 3 days after delivery was non-diagnostic other than for the presence of mild cholestatic rosetting. Previously elevated liver enzymes rapidly improved after delivery and were normal within 2 weeks. Next generation sequencing for a panel of genes known to cause genetic cholestasis revealed that the donor carried mutations in the ABCB11 gene; heterozygous for a missense mutation p.Arg698His and homozygous for the ABCB11 modifier variant p.Val444Ala. Whilst not constituting classical bile salt export pump (BSEP) deficiency, these mutations cause reduced canalicular transport of bile products leading to an increased risk of drug-induced cholestasis, gallstones and cholestasis of pregnancy. This case demonstrates the rare finding of donor-transmitted risk of intrahepatic cholestasis of pregnancy. This article is protected by copyright. All rights reserved.