An update on genetic analysis of cholestatic liver diseases: digging deeper

Investigations into the molecular mechanisms of cholestasis have revealed intricate and intriguing details of bile salt metabolism as well as its regulatory mechanisms in health and disease. Extensive studies on genotype-phenotype correlations in monogenic diseases, such as progressive familial and benign recurrent intrahepatic cholestasis, facilitate diagnostics and improve the risk assessment of hepatobiliary transporter gene variants in bile transport pathophysiology. While the comparatively easy targets in monogenic cholestasis have been identified for some time now, progress in complex liver disease is rather laborious but steady. Genome-wide association scans are the next step in gathering information about common contributors towards polygenic (multifactorial) cholestatic diseases. New determinants of bile salt metabolism affecting feedback loops within the liver or the enterohepatic circulation are presently under investigation for their contribution towards complex cholestatic syndromes.