First Report of Living Donor Liver Transplantation for NR1H4 Disease

Nuclear Receptor Subfamily 1, Group H, Member 4 (NR1H4) related cholestasis is a recently described entity, which can rapidly lead to liver failure in infancy. Outcomes of liver transplantation (LT) in NR1H4 disease, such as extrahepatic manifestations and catch-up in somatic growth, are poorly described. In this report, we describe the role of early LT in a 3-month-old infant genetically diagnosed to have NR1H4 disease, presenting to us with decompensated cirrhosis and intractable coagulopathy. A 2.5-month-old boy presented with decompensated liver disease. Homozygosity for a predictably pathogenic variant in NR1H4, encoding the farnesoid X receptor (FXR), was diagnosed by genomic sequencing. Due to rapidly evolving liver disease, he underwent a living donor liver transplantation (LDLT) with a left lateral segment from his father. Immunostaining of the explant demonstrated loss of expression of both bile salt export pump (BSEP) and multidrug resistance protein 3 (MDR3) along biliary canaliculi and of FXR in hepatocyte nuclei. The child is well at 14 months after LT and has had no medical or surgical complications. Graft function is preserved, and growth and development are age-appropriate. In our experience and that of others, infants with NR1H4 disease often die before LT can be offered, and in only a few instances have outcomes of LT been described. Early LT is recommended in NR1H4 disease of infancy, a disorder with high mortality. LDLT can permit survival with a favorable clinical outcome as seen in our patient.