Primary sclerosing cholangitis: a review and update on therapeutic developments.
Primary sclerosing cholangitis (PSC) is a chronic, cholestatic, idiopathic liver disease characterized by fibro-obliterative inflammation of the hepatic bile ducts. In a clinically significant proportion of patients, PSC progresses to cirrhosis, end-stage liver disease, and in some cases, cholangiocarcinoma. Despite clinical trials of nearly 20 different pharmacotherapies over several decades, safe and effective medical therapy, albeit critically needed, remains to be established. PSC is pathogenically complex, with genetic, immune, enteric microbial, environmental and other factors being potentially involved and, thus, not surprisingly, it manifests as a clinically heterogeneous disease with a relatively unpredictable course. It is likely that this complexity and clinical heterogeneity are responsible for the negative results of clinical trials, but novel insights about and approaches to PSC may shift this trend. The authors herein provide a review of previously tested pharmacologic agents, discuss emerging fundamental concepts and present viewpoints regarding how identifying therapies for PSC may evolve over the next several years.
Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. tabibian.james@mayo.edu
James H
JH
Tabibian
Keith D
KD
Lindor
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015209:Cholangitis, Sclerosing / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000601:surgery; D004195:Disease Models, Animal; D016145:Endoscopy, Digestive System; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D020123:Sirolimus / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000627:therapeutic use; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D016201:Receptors, Lymphocyte Homing; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus