Adult progressive intrahepatic cholestasis associated with genetic variations in ATP8B1 and ABCB11

Severe intrahepatic cholestasis with low serum γ‐glutamyltranspeptidase (γ‐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 γ‐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 γ‐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.

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