Future Medical Treatment of PSC

AbstractPurpose of ReviewPrimary 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 FindingsWhile 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).SummaryOngoing 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 ...
Source: Current Hepatitis Reports - Category: Infectious Diseases Source Type: research