Advances and controversies in the pathogenesis and management of primary sclerosing cholangitis.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a chronic immune-mediated liver disease that results in end-stage liver disease requiring liver transplantation. PSC is closely associated with inflammatory bowel disease (IBD) with 70% of patients with PSC also suffering from IBD.

SOURCES OF DATA: Data for this review were obtained from PubMed.

AREAS OF AGREEMENT: Historical and genome-wide association studies have established a strong human leukocyte antigen (HLA) linkage to PSC and defined specific haplotypes associated with enhanced PSC risk. Fifteen non-HLA loci have been defined in PSC.

AREAS OF CONTROVERSY: The biological role of risk loci in PSC and their place in PSC pathogenesis remain speculative but suggest significant interactions with the host microbiome and therapeutic opportunities.

GROWING POINTS: Genetics provides a platform to systematically target emerging therapies in PSC.

AREAS TIMELY FOR DEVELOPING RESEARCH: Linking PSC genotypes with biology and disease phenotypes paves the way for a personalized medicine approach to manage PSC.