High‐throughput T‐cell receptor sequencing across chronic liver diseases reveals distinct disease‐associated repertoires

Evaggelia Liaskou, Eva Kristine Klemsdal Henriksen, Kristian Holm, Fatemeh Kaveh, David Hamm, Janine Fear, Marte K. Viken, Johannes Roksund Hov, Espen Melum, Harlan Robins, Johanna Olweus, Tom H. Karlsen, Gideon M. Hirschfield – 7 August 2015 – Hepatic T‐cell infiltrates and a strong genetic human leukocyte antigen association represent characteristic features of various immune‐mediated liver diseases. Conceptually the presence of disease‐associated antigens is predicted to be reflected in T‐cell receptor (TCR) repertoires.

Sorafenib enriches epithelial cell adhesion molecule–positive tumor initiating cells and exacerbates a subtype of hepatocellular carcinoma through TSC2‐AKT cascade

Dong‐Xian Guan, Jie Shi, Yang Zhang, Jiang‐Sha Zhao, Ling‐Yun Long, Tian‐Wei Chen, Er‐Bin Zhang, Yuan‐Yuan Feng, Wen‐Dai Bao, Yue‐Zhen Deng, Lin Qiu, Xue‐Li Zhang, H. Phillip Koeffler, Shu‐qun Cheng, Jing‐Jing Li, Dong Xie – 7 August 2015 – Sorafenib is a specific adenosine triphosphate–competitive RAF inhibitor used as a first‐line treatment of advanced hepatocellular carcinoma (HCC). However, the responses are variable, reflecting heterogeneity of the disease, while the resistance mechanism remains poorly understood.

Antibodies to an interfering epitope in hepatitis C virus E2 can mask vaccine‐induced neutralizing activity

Alla Kachko, Sharon E. Frey, Lev Sirota, Ranjit Ray, Frances Wells, Iryna Zubkova, Pei Zhang, Marian E. Major – 6 August 2015 – Hepatitis C virus (HCV) neutralization occurring at the E2 region 412‐426 (EP‐I) could be enhanced when antibodies directed specifically to the E2 region 434‐446 (EP‐II) were removed from serum samples of persistently infected patients and vaccinated chimpanzees, a phenomenon of so‐called antibody interference. Here, we show that this type of interference can be observed in individuals after immunization with recombinant E1E2 proteins.

A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance

Hui Wang, Souhayla El Maadidi, Janett Fischer, Elena Grabski, Sabine Dickhöfer, Sascha Klimosch, Sinead M. Flannery, Angela Filomena, Olaf‐Oliver Wolz, Nicole Schneiderhan‐Marra, Markus W. Löffler, Manfred Wiese, Tica Pichulik, Beat Müllhaupt, David Semela, Jean‐François Dufour, Pierre‐Yves Bochud, Andrew G. Bowie, Ulrich Kalinke, Thomas Berg, Alexander N.R.

Validation of hepatitis B virus–related hepatocellular carcinoma prediction models in the era of antiviral therapy

Kyu Sik Jung, Seung Up Kim, Kijun Song, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Beom Kyung Kim, Kwang‐Hyub Han – 6 August 2015 – Several risk prediction models have been created to predict hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) occurrence, with promising results. However, their prognostic performances need to be validated in the era of antiviral therapy. From 2006 to 2011, patients with chronic HBV infection were recruited and those with a history of HCC or hepatic decompensation were excluded.

Flunarizine prevents hepatitis C virus membrane fusion in a genotype‐dependent manner by targeting the potential fusion peptide within E1

Paula M. Perin, Sibylle Haid, Richard J.P. Brown, Juliane Doerrbecker, Kai Schulze, Carsten Zeilinger, Markus von Schaewen, Brigitte Heller, Koen Vercauteren, Eva Luxenburger, Yasmine M. Baktash, Florian W.R. Vondran, Sietkse Speerstra, Abdullah Awadh, Furkat Mukhtarov, Luis M. Schang, Andreas Kirschning, Rolf Müller, Carlos A. Guzman, Lars Kaderali, Glenn Randall, Philip Meuleman, Alexander Ploss, Thomas Pietschmann – 6 August 2015 – To explore mechanisms of hepatitis C viral (HCV) replication we screened a compound library including licensed drugs.

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