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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.