Adult Progressive Intrahepatic Cholestasis Associated with Genetic Variations in Atp8b1 and Abcb11
Resource
HEPATOLOGY RESEARCH v.39 n.6 pp.625-631
Journal
HEPATOLOGY RESEARCH
Journal Volume
v.39
Journal Issue
n.6
Pages
625-631
Date Issued
2009
Date
2009
Author(s)
HSU, YAO-CHUN
CHEN, HUEY-LING
WU, MU- ZON
LIU, YU-JUNG
LEE, PO-HUANG
SHEU, JIN-CHUAN
CHEN, CHIEN-HUNG
CHEN, CHIEN- HUNG
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.
Type
journal article