Living-related liver transplantation for siblings with progressive familial intrahepatic cholestasis 2, with novel genetic findings

Am J Transplant. 2011 Feb;11(2):394-8. doi: 10.1111/j.1600-6143.2010.03397.x. Epub 2011 Jan 10.

Abstract

Progressive familial intrahepatic cholestasis is a syndrome of severe cholestasis progressing to biliary cirrhosis and liver failure that develops in childhood. This report describes two siblings with PFIC-2 who underwent living-related liver transplantation from their genetically proven heterozygous parents. Both patients had normal gamma-glutamyl transpeptidase levels, but showed severe pruritus with sleep disturbance, cholestasis, jaundice and growth failure. Genetic testing of each patient revealed two missense mutations of the bile salt export pump, S901R and C1083Y, which have not previously been associated with PFIC-2. Usual medical treatment failed to improve their clinical symptoms, and the two siblings underwent living-related liver transplantation from their heterozygous parents. The transplants improved their clinical symptoms significantly, and the patients have since shown age-appropriate growth. Electron microscopic findings of the explanted liver of the younger sister revealed dense and amorphous bile, which is characteristic of PFIC-2. In the cases presented here, living-related liver transplantation from a heterozygous donor was associated with better quality of life and improvement of growth, and thus appears to be a feasible option for PFIC-2 patients. Mutation analysis is a useful tool to help decide the course of treatment of PFIC.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters / genetics
  • Adult
  • Child
  • Child Development
  • Child, Preschool
  • Cholestasis, Intrahepatic / genetics
  • Cholestasis, Intrahepatic / pathology
  • Cholestasis, Intrahepatic / surgery
  • Female
  • Heterozygote
  • Humans
  • Liver Transplantation / methods*
  • Living Donors
  • Male
  • Mutation, Missense
  • Parents
  • Quality of Life
  • Siblings

Substances

  • ABCB11 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters

Supplementary concepts

  • Cholestasis, progressive familial intrahepatic 2