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Semin Liver Dis 2016; 36(01): 005-014
DOI: 10.1055/s-0035-1571274
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

New Therapeutic Strategies for Primary Sclerosing Cholangitis

Kate D. Williamson
1   Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom
2   Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
,
Roger W. Chapman
1   Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom
2   Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
12 February 2016 (online)

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Abstract

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, which in the majority of patients progresses to liver transplantation or death. To date, no medical treatment has been proven to be of benefit, although ursodeoxycholic acid is widely used. The etiopathogenesis of PSC is unclear, although it is associated with inflammatory bowel disease. Various hypotheses have been suggested, which have led to different therapeutic strategies. Recent studies have suggested that the microbiome may play a role in PSC, raising the possibility of efficacy of antibiotics and fecal microbiota transplantation. Gut-homing T cells may be important in the pathogenesis of PSC, and several agents are in development, targeting various receptors, integrins, and ligands on this pathway, including VAP-1, MAdCAM-1, α4β7, and CCR9. Nuclear receptor agonists such as obeticholic acid and fibrates hold promise, as do other therapies that alter bile acid composition such as norUDCA. Antifibrotic agents such as Loxl2 inhibitors are also being assessed. In conclusion, it is likely that an effective drug therapy for PSC will become available over the next decade.

Keywords

primary sclerosing cholangitis - inflammatory bowel disease - ulcerative colitis - Crohn's disease - cholangiocarcinoma
 

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