Living‐Related Liver Transplantation for Siblings with Progressive Familial Intrahepatic Cholestasis 2, with Novel Genetic Findings

• Published in: American journal of transplantation Vol. 11; no. 2; pp. 394 - 398
• Main Authors: Shimizu, H., Migita, O., Kosaki, R., Kasahara, M., Fukuda, A., Sakamoto, S., Shigeta, T., Uemoto, S., Nakazawa, A., Kakiuchi, T., Arai, K.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.02.2011; Wiley
• Subjects: Adult; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters - genetics; Biological and medical sciences; Child; Child Development; Child, Preschool; Cholestasis, Intrahepatic - genetics; Cholestasis, Intrahepatic - pathology; Cholestasis, Intrahepatic - surgery; Female; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Heterozygote; Humans; Liver Transplantation - methods; Liver, biliary tract, pancreas, portal circulation, spleen; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Living Donors; Male; Medical sciences; Mutation analysis; Mutation, Missense; novel mutations of the bile salt export pump; Other diseases. Semiology; Parents; pediatric living‐related liver transplantation; progressive familial intrahepatic cholestasis type 2; Quality of Life; Siblings; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Pediatrics; novel mutations of the bile salt export pump; pediatric living-related liver transplantation; Liver; Hepatic disease; Biliary tract disease; Homotransplantation; Intrahepatic cholostasis; Surgery; Graft; Export; Genetics; Child; Human; Digestive system; Family study; Bile salt; Living donor; Related donor; Pump; Progressive; Type; Treatment; Analysis; Digestive diseases; progressive familial intrahepatic cholestasis type 2; Mutation analysis; Mutation; Liver transplantation
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2010.03397.x

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. The authors report two siblings with progressive familial intrahepatic cholestasis type 2 who have a novel mutation in the ABCB11 gene and have been successfully treated with living related liver transplantation.