Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review and results from an International PSC Study Group consensus process

Cyriel Y. Ponsioen, Roger W. Chapman, Olivier Chazouillères, Gideon M. Hirschfield, Tom H. Karlsen, Ansgar W. Lohse, Massimo Pinzani, Erik Schrumpf, Michael Trauner, Gregory J. Gores – 29 September 2015 – Primary sclerosing cholangitis (PSC) is a rare, but serious, cholestatic disease for which, to date, no effective therapy exists to halt disease progression toward end‐stage liver disease. Clinical trial design to study drugs that improve prognosis is hampered by the relatively low event rate of clinically relevant endpoints.

Interferon lambda 4 genotypes and resistance‐associated variants in patients infected with hepatitis C virus genotypes 1 and 3

Kai‐Henrik Peiffer, Lisa Sommer, Simone Susser, Johannes Vermehren, Eva Herrmann, Matthias Döring, Julia Dietz, Dany Perner, Caterina Berkowski, Stefan Zeuzem, Christoph Sarrazin – 25 September 2015 – Single‐nucleotide polymorphisms (SNPs) in the interferon lambda 4 (IFNL4) gene are predictors for treatment success in patients with hepatitis C virus (HCV) infection. For direct‐acting antiviral combinations only weak association with IFNL4 SNPs was observed. Little is known about potential selections of resistance‐associated variants (RAVs) by the IFNL4 genotype.

Mixed lineage kinase 3 mediates release of C‐X‐C motif ligand 10–bearing chemotactic extracellular vesicles from lipotoxic hepatocytes

Samar H. Ibrahim, Petra Hirsova, Kyoko Tomita, Steven F. Bronk, Nathan W. Werneburg, Stephen A. Harrison, Val S. Goodfellow, Harmeet Malhi, Gregory J. Gores – 25 September 2015 – Mixed lineage kinase 3 (MLK3) deficiency reduces macrophage‐associated inflammation in a murine model of nonalcoholic steatohepatitis (NASH). However, the mechanistic links between MLK3 activation in hepatocytes and macrophage‐driven inflammation in NASH are uncharted.

Long‐term clinical outcomes after fatty liver screening in patients undergoing coronary angiogram: A prospective cohort study

Vincent Wai‐Sun Wong, Grace Lai‐Hung Wong, Judy Ching‐Lam Yeung, Chloe Yuk‐Kiu Fung, Jasmine Ka‐Lei Chan, Zoe Hoi‐Yi Chang, Chelsia Tsz‐Yan Kwan, Hiu‐Wan Lam, Jenny Limquiaco, Angel Mei‐Ling Chim, Cheuk‐Man Yu, Henry Lik‐Yuen Chan – 25 September 2015 – There is ongoing debate on whether screening for nonalcoholic fatty liver disease (NAFLD) is worthwhile in high‐risk groups. Because of shared risk factors, NAFLD is highly prevalent in patients with coronary artery disease.

Differing impact of the deletion of hemochromatosis‐associated molecules HFE and transferrin receptor‐2 on the iron phenotype of mice lacking bone morphogenetic protein 6 or hemojuvelin

Chloé Latour, Céline Besson‐Fournier, Delphine Meynard, Laura Silvestri, Ophélie Gourbeyre, Patricia Aguilar‐Martinez, Paul J. Schmidt, Mark D. Fleming, Marie‐Paule Roth, Hélène Coppin – 25 September 2015 – Hereditary hemochromatosis, which is characterized by inappropriately low levels of hepcidin, increased dietary iron uptake, and systemic iron accumulation, has been associated with mutations in the HFE, transferrin receptor‐2 (TfR2), and hemojuvelin (HJV) genes.

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