Review
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2017; 23(14): 2459-2469
Published online Apr 14, 2017. doi: 10.3748/wjg.v23.i14.2459
Pathogenesis and clinical spectrum of primary sclerosing cholangitis
Neelam G Gidwaney, Swati Pawa, Kiron M Das
Neelam G Gidwaney, Swati Pawa, Kiron M Das, Division of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, United States
Author contributions: Gidwaney NG, Pawa S and Das KM collaborated equally in performing the literature search and writing the review article.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kiron M Das, MD, PhD, FACP, FRCP, AGAF, FACG, Chief, Professor of Medicine, Division of Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, Medical Education Building 478B, New Brunswick, NJ 08903, United States. daskm@rwjms.rutgers.edu
Telephone: +1-732-2356994 Fax: +1-732-2355537
Received: October 24, 2016
Peer-review started: October 28, 2016
First decision: December 19, 2016
Revised: January 21, 2017
Accepted: March 20, 2017
Article in press: March 20, 2017
Published online: April 14, 2017
Processing time: 171 Days and 19.3 Hours
Abstract

Primary sclerosing cholangitis (PSC) is a disease of the biliary tract, which has been documented in the literature since 1867. This disease has a strong predilection for affecting men and can be seen in individuals as young as 2 years of age. PSC has a strong associated with inflammatory bowel disease, more commonly with ulcerative colitis, and is also part of the clinical spectrum of IgG4-related diseases. Small-duct PSC, a variant of PSC, also has an association with inflammatory bowel disease. The exact pathogenesis of PSC is not well understood at present, however, is likely a combination of a genetic predisposition with alteration of the molecular structure of the gut. Abnormal serum liver chemistry and presence of certain autoimmune markers are usually the first indicators leading to a diagnosis of PCS, however, these may often be normal in early stages of this disease. The diagnosis is made by cholangiography, which is now considered the gold standard. PSC is a known pre-malignant condition. Such patients have an increased risk of developing cholangiocarcinoma, gallbladder neoplasia, and colon cancer. Many new treatment modalities have emerged in the recent past, including anti-tumor necrosis factor- α and anti-integrins; however, liver transplantation is the only known cure for PSC. Despite past and present research, PSC remains an enigmatic biliary disease with few viable treatment options.

Keywords: Primary sclerosing cholangitis; Cholestasis; Inflammatory bowel disease; Autoimmune; Gallbladder neoplasia; Cholangiocarcinoma; IgG4 related disease; Colon cancer; Liver transplant

Core tip: Primary sclerosing cholangitis (PSC) is a fascinating disease with numerous and overlapping theorized pathogenetic models. An autoimmune etiology is in part due to its association with inflammatory bowel disease and autoimmune hepatitis, and inclusion within the IgG4 spectrum of diseases. Though PSC has been documented in the literature for more than a century, only sparse details exist regarding its true pathogenetics and even less about successful medical therapy. More rigorous research is needed to truly understand and treat this disease entity.