Suresh Lakshmi, Menon Jagadeesh, Shanmugam Naresh, Vij Mukul, Rammohan Ashwin, Rela Mohamed
The Institute of Liver Disease & Transplantation, Dr Rela Institute & Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India.
Pediatr Transplant. 2025 Nov;29(7):e70175. doi: 10.1111/petr.70175.
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.
核受体亚家族1、H组、成员4（NR1H4）相关胆汁淤积是一种最近描述的疾病实体，可在婴儿期迅速导致肝衰竭。关于NR1H4疾病肝移植（LT）的结果，如肝外表现和身体生长追赶情况，描述甚少。
在本报告中，我们描述了早期LT在一名3个月大的经基因诊断患有NR1H4疾病的婴儿中的作用，该婴儿因失代偿性肝硬化和难治性凝血病前来就诊。
一名2.5个月大的男孩出现失代偿性肝病。通过基因组测序诊断出NR1H4中一个可预测的致病变异的纯合子，该基因编码法尼醇X受体（FXR）。由于肝病迅速进展，他接受了来自其父亲左外侧叶的活体供肝移植（LDLT）。移植肝的免疫染色显示胆小管沿线的胆汁盐输出泵（BSEP）和多药耐药蛋白3（MDR3）以及肝细胞核中的FXR表达缺失。该患儿在LT后14个月情况良好，未出现医疗或手术并发症。移植肝功能得以保留，生长发育与年龄相符。根据我们及他人的经验，患有NR1H4疾病的婴儿常在能够进行LT之前死亡，仅有少数LT结果被描述过。
对于婴儿期NR1H4疾病这种死亡率高的疾病，建议早期进行LT。如我们的患者所示，LDLT可使患者存活并获得良好的临床结果。
