Long-term liver transplant outcomes for progressive familial intrahepatic cholestasis type 1: The Pittsburgh experience

Pediatr Transplant. 2021 Dec;25(8):e14108. doi: 10.1111/petr.14108. Epub 2021 Aug 2.


Background: Progressive familial intrahepatic cholestasis type 1 (PFIC1) arises from biallelic variants in the ATP8B1 gene that annul FIC1 activity, resulting in progressive liver disease. Liver transplant (LT) is indicated in refractory disease; however, post-LT complications including worsening diarrhea and steatohepatitis progressing to fibrosis with graft loss have been reported. We aim to describe long-term outcomes of PFIC1 LT recipients at our center, focusing on the histological changes of the allografts.

Methods: We assessed 7 PFIC1 patients post-LT at the Children's Hospital of Pittsburgh (CHP). All pre-transplant, explant, and sequential post-transplant pathology samples were reviewed. Continuous data are presented as the mean ± SD. We compared the pre- and post-transplant height and weight z-scores using Wilcoxon signed-rank test.

Results: Seven (29% male) patients with PFIC1 received a LT (n = 6) or had post-LT care (n = 1) at CHP. Six had confirmed or suspected identical genetic. At a mean follow-up of 10.9 years, both patient survival and graft survival were 100%. Diarrhea persisted (n = 3) or newly developed (n = 4) in all patients after LT contributing to ongoing growth failure, with mean z-scores -2.63 (weight) and -2.98 (height) at follow-up. Histologically, allograft steatosis was common but was not accompanied by significant inflammation, ballooning, or fibrosis.

Conclusion: We show that extrahepatic disease persists and near-universal allograft steatosis occurs. However, at a mean follow-up period of over 10 years, no patients developed steatohepatitis or significant fibrosis, and both patient survival and graft survival are excellent.

Keywords: ATP8B1; PFIC1; biliary diversion; byler disease; neonatal cholestasis; progressive familial intrahepatic cholestasis; transplant.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cholestasis, Intrahepatic / surgery*
  • Female
  • Humans
  • Infant
  • Liver Transplantation*
  • Male
  • Pennsylvania

Supplementary concepts

  • Cholestasis, progressive familial intrahepatic 1