Severe hepatocellular dysfunction in obstetric cholestasis related to combined genetic variation in hepatobiliary transporters.

Obstetric cholestasis (OC) is a cholestatic disorder with a prominent genetic background including variation in diverse hepatobiliary lipid transporters, such as ABCB4 (phospholipids) and ABCB11 (bile salts). Given a marked hepatocellular dysfunction in an OC patient indicated by > 40-fold rise in alanine aminotransferase activity and minor gamma-glutamyl transpeptidase increases, we performed genotyping of candidate gene variants associated with adult cholestatic phenotypes. Genetic analysis revealed the heterozygous ABCB4 mutation p.R590Q, the ABCB11 variant p.V444A and the lithogenic ABCG8 variant p.D19H. Aggregation of multiple hepatobiliary transporter variants is rare in OC, and may cooperate to negatively modulate hepatobiliary transport capacities.