Falk Gastro Info 11/2016

Video report

Treating PBC and PSC

Summary

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 in the bile ducts. 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.

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.

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Latest research in brief:

Bowel

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Papamichael K et al. J Crohns Colitis. 2016;10(9):1015–23

Outcome of ulcerative colitis patients with primary non-response to infliximab About half of patients will undergo colectomy within 3 years.

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Shah SC et al. Clin Gastroenterol Hepatol. 2016;14(9):1245–55.e8

Outcome measures in ulcerative colitis: Early mucosal healing correlates with long-term clinical remission, avoidance of colectomy and steroid-free remission.

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Fischer M et al. Am J Gastroenterol. 2016;111(7):1024–31

Fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) Severe and complicated disease, inpatient status during FMT and the number of previous CDI-related hospitalizations are strongly associated with early failure of FMT.

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Liver Biliary Tracts

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ANRS Collaborative Study Group on Hepatocellular Carcinoma, J Hepatol. 2016;65(4):734–40

Hepatitis C In contrast to recent reports, analysis of 3 large prospective studies did not show an unexpected high recurrence rate of hepatocellular carcinoma (HCC) in patients that had received curative procedures for HCC followed by treatment with direct-acting antivirals (DAA).

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Sun J et al, J Hepatol. 2016;65(4):674–82

Hepatitis B: A first randomized trial on response-guided therapy of HBeAg-positive chronic hepatitis B with pegylated interferon demonstrates that patients with early response (HBsAg < 1500 IU/ml or HBV DNA < 10⁵ copies/ml at week 24) may benefit from a 48-week course of therapy on the long term (HBeAg seroconversion with HBV-DNA < 2000 IU/ml at end of follow-up approximately 38%).

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Hartl J et al, J Hepatol. 2016;65(4):769–75

Autoimmune hepatitis: Before and during early immunosuppressive treatment, transient elastography has limited diagnostic accuracy. After 6 months of immunosuppressive therapy, transient elastography has an excellent diagnostic accuracy for separating severe and non-severe fibrosis.

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Oesophagus Stomach Duodenum

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Peterson K et al. Am J Gastroenterol. 2016;111(7):926–32

Eosinophilic esophagitis: Patients with EoE have an increased risk to develop autoimmune diseases including systemic sclerosis and multiple sclerosis or ulcerative colitis.

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Faleck DM et al. Am J Gastroenterol. 2016 [Epub ahead of print]

Proton pump inhibitors (PPIs) and the risk for Clostridium difficile infection (CDI): PPIs do not increase risk for CDI in the intensive care unit.

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Connolly SJ et al. N Engl J Med. 2016;375(12):1131–41

Reversal of factor Xa inhibition for acute major bleeding: The decoy protein andexanet alfa substantially reduces anti-factor Xa activity and results in effective hemostasis in 79% of patients.

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Pancreas

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Harinck F et al. Gut. 2016;65(9):1505–13

Screening of pancreatic cancer: Endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) are complementary rather than interchangeable. EUS is particularly sensitive for detection of solid lesions while MRI is more sensitive for detecting cystic lesions.

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