Long-term Outcomes of Living-donor Liver Transplantation for Progressive Familial Intrahepatic Cholestasis Type 1

Objectives: Progressive familial intrahepatic cholestasis type 1 (PFIC-1), an autosomal recessive disorder, is characterized by cholestasis, jaundice, and refractory pruritus. In some patients with PFIC-1, liver cirrhosis and end-stage liver disease develop and lead to liver transplantation (LT). In this observational study, we sought to clarify the long-term outcomes of LT for PFIC-1 and predictors of favorable outcomes.

Methods: The study cohort constituted 12 patients with PFIC-1 who had undergone living donor liver transplantation (LDLT) during the previous 3 decades (1990-2019). We compared the clinical manifestations and type of ATP8B1 mutations between patients in whom LDLT had been successful and those in whom it had been unsuccessful.

Results: LDLT failed in 5 of the 12 patients and the 25-year survival rate was 58%. Comparison of physical growth after LDLT revealed significant retardation of stature in patients in whom LDLT had been unsuccessful; these patients developed severe and persistent diarrhea. ATP8B1 genotypic analysis revealed that frameshifting, splicing, and large deletion mutations occurred more commonly in successful cases, whereas missense mutations occurred more frequently in unsuccessful cases. No mutations were identical in the 2 groups.

Conclusions: These results suggest an association between post-LT outcomes and extrahepatic manifestations, especially intestinal function. Further investigation of correlations between ATP8B1 genotypes and intestinal function could help to identify patients with PFIC-1 who will achieve favorable post-LT outcomes.