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13.02.2019 | Autoimmune, Cholestatic, and Biliary Diseases (S Gordon and C Bowlus, Section Editors) | Ausgabe 1/2019 Open Access

Current Hepatology Reports 1/2019

Future Medical Treatment of PSC

Zeitschrift:
Current Hepatology Reports > Ausgabe 1/2019
Autoren:
Elisabeth Krones, Hanns-Ulrich Marschall, Peter Fickert
Wichtige Hinweise
This article is part of the Topical Collection on Autoimmune, Cholestatic, and Biliary Diseases

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abstract

Purpose of Review

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder characterized by inflammation of intrahepatic and/or extrahepatic bile ducts leading to stricturing, biliary fibrosis, cirrhosis, and liver failure. PSC is highly associated with inflammatory bowel diseases (IBD) and bears significant risk for cholangiocellular and colorectal cancer. To date, no medical treatment has been proven in randomized controlled trials to improve transplant-free and overall patient survival. However, numerous innovative therapeutic concepts are currently tested in phase 2 to phase 3 clinical trials. Based on currently suggested pathogenetic mechanisms of PSC, such drugs target its immunopathogenesis and nuclear and membrane receptors regulating bile acid transport and metabolism, gut microbiota, and liver fibrosis. The purpose of this review is to discuss recent advances in targeted medical treatment options for PSC.

Recent Findings

While a large carefully designed phase 2b trial targeting fibrosis development in PSC failed (simtuzumab), another compound was promoted from phase 2a to phase 3 trial based on significant improvements of alkaline phosphatase (AP) and excellent safety profile (norursodeoxycholic acid, norUDCA).

Summary

Ongoing trials evaluate numerous different targets considered to be involved in PSC pathogenesis, with so far, no clear advantage of either compound. This must be attributed to the still unknown cause of PSC. It may turn out that only combination therapy may reach a breakthrough. The fact that numerous studies isochronally test the same drug or therapeutic concept like in the case of vancomycin or faecal microbiota transplantation (FMT) demands improved and coordinated international strategies for study design to develop more effective drug pipelines, which is one major target of the International PSC Study Group (IPSCSG).

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Literatur
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