title: New Therapeutic Strategies for Primary Sclerosing Cholangitis.
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.
authors: Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom.
authors: Kate D
authors: KD
authors: Williamson
authors: Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom.
authors: Roger W
authors: RW
authors: Chapman
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000009:adverse effects / Q000627:therapeutic use*; D015209:Cholangitis, Sclerosing / Q000209:etiology / Q000378:metabolism / Q000382:microbiology / Q000628:therapy*; D016099:Endoscopy, Gastrointestinal / Q000009:adverse effects; D000069467:Fecal Microbiota Transplantation / Q000009:adverse effects; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000209:etiology / Q000378:metabolism / Q000628:therapy; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics