title: Adult progressive intrahepatic cholestasis associated with genetic variations in ATP8B1 and ABCB11.
abstract: Severe intrahepatic cholestasis with low serum gamma-glutamyltranspeptidase (gamma-GT) activity is exceptionally rare in adult patients, and its association with multi-genetic alterations of bile salt transporters has not been reported. We investigated a 25-year-old man presenting with a four-year history of jaundice. Laboratory and radiographic examinations revealed clinical pictures of progressive intrahepatic cholestasis with low gamma-GT. Serial liver histopathology demonstrated cirrhosis resulting from progressive persistent cholestatic injury. Genetic sequencing studies for the entire coding exons of ATP8B1 and ABCB11 uncovered a heterozygous missense mutation 1798 C->T (R600W) in ATP8B1, and a homozygous nucleotide substitution 1331 T->C (V444A) in ABCB11. In conclusion, this is a rare case of adult onset progressive intrahepatic cholestasis with low gamma-GT associated with heterozygous ATP8B1 mutation and homozygous ABCB11 polymorphism. Further studies are necessary to investigate the impact of heterozygous R600W mutation and whether other cholestatic disorders are multi-genetic.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Lo-Tung Pohai Hospital, I-Lan.
authors.forename: Yao-Chun
authors.initials: YC
authors.lastname: Hsu
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Chen
authors.forename: Mu-Zon
authors.initials: MZ
authors.lastname: Wu
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Liu
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.forename: Jin-Chuan
authors.initials: JC
authors.lastname: Sheu
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen