Treating PBC and PSC
Video report presented by Professor Dr. Ulrich Beuers, University of Amsterdam, The Netherlands at the Symposium 201 „Gut-Liver Interactions: From IBD to NASH“, March 11 – 12, 2016 in Innsbruck.
© Falk Foundation e.V., Freiburg. All rights reserved.
”Gut-Liver Interactions: From IBD to NASH” – this was the title of an international symposium in March 2016, organized by the Falk Foundation. One of the main topics of focus was chronic liver diseases.
Professor Dr. Ulrich Beuers from Amsterdam spoke on the current and future treatment options for the cholestatic liver diseases primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
Ursodeoxycholic acid (UDCA) is the standard treatment for PBC and is also approved for other cholestatic liver diseases in some countries. This bile acid stimulates hepatocellular and cholangiocellular secretion. The UDCA-induced secretion of bicarbonate stabilizes a protective bicarbonate umbrella. UDCA has also antiapoptotic effects and reduces the toxicity of the bile acid pool.
Two out of three patients with PBC under UDCA treatment have meanwhile a normal life expectancy. The effects of UDCA on PSC are more distinct: Serum liver tests often markedly improve, but effects on long-term prognosis at therapeutic doses are unclear. Long-term studies in PSC with therapeutic doses of UDCA, an adequate patient cohort size, and an adequate treatment duration are lacking. (UDCA may not be approved for the treatment of PSC in your country). There is currently reason to hope that PSC can be treated using nor-ursodeoxycholic acid, a derivative of the traditional UDCA with a shortened side chain in the molecule. This chemical modification is associated with a pronounced stimulation of bicarbonate secretion, which potentially also causes an anticholestatic effect.
Clear anticholestatic, antifibrotic and anti-inflammatory effects have been demonstrated in animal testing. NorUDCA has already been tested in a large, multicenter phase 2 trial of 164 patients with PSC. The data look promising and were presented at the EASL Congress 2016 in Barcelona. Preparations for a phase 3 trial are underway.
UDCA is currently the standard treatment for PBC. The effect on PSC is less distinct. NorUDCA, a further development of UDCA, has displayed positive effects on PSC in recent trials.