“Hep C, where art thou”: What are the remaining (fundable) questions in hepatitis C virus research?

Hugo Ramón Rosen – 19 September 2016 – Hepatitis C virus (HCV) has dominated the field of hepatology for the past 25 years, and its cure in the majority of treated patients is one of the greatest achievements in all of medicine. However, the latter has led to the belief by some that HCV research should be shelved for other, more pressing areas. The mission for HCV eradication is far from accomplished.

Low‐grade endotoxemia and platelet activation in cirrhosis

Valeria Raparelli, Stefania Basili, Roberto Carnevale, Laura Napoleone, Maria Del Ben, Cristina Nocella, Simona Bartimoccia, Cristina Lucidi, Giovanni Talerico, Oliviero Riggio, Francesco Violi – 19 September 2016 – Patients with cirrhosis may display impaired or enhanced platelet activation, but the reasons for these equivocal findings are unclear. We investigated if bacterial lipopolysaccharide (LPS) is implicated in platelet activation.

Affinity maturation of a broadly neutralizing human monoclonal antibody that prevents acute hepatitis C virus infection in mice

Zhen‐Yong Keck, Yong Wang, Patrick Lau, Garry Lund, Sneha Rangarajan, Catherine Fauvelle, Grant C. Liao, Frederick W. Holtsberg, Kelly L. Warfield, M. Javad Aman, Brian G. Pierce, Thomas R. Fuerst, Justin R. Bailey, Thomas F. Baumert, Roy A. Mariuzza, Norman M. Kneteman, Steven K.H. Foung – 19 September 2016 – Direct‐acting antivirals (DAAs) have led to a high cure rate in treated patients with chronic hepatitis C virus (HCV) infection, but this still leaves a large number of treatment failures secondary to the emergence of resistance‐associated variants (RAVs).

CD14+ monocyte‐derived galectin‐9 induces natural killer cell cytotoxicity in chronic hepatitis C

Akira Nishio, Tomohide Tatsumi, Takatoshi Nawa, Takahiro Suda, Teppei Yoshioka, Yoshiki Onishi, Satoshi Aono, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Daisuke Okuzaki, Takasuke Fukuhara, Yoshiharu Matsuura, Naoki Hiramatsu, Tetsuo Takehara – 19 September 2016 – Natural killer (NK) cell activation is associated with both liver injury and persistent infection in chronic hepatitis C (CHC); however, the detailed mechanism of this activation has not yet been fully elucidated.

The dendritic cell–T helper 17–macrophage axis controls cholangiocyte injury and disease progression in murine and human biliary atresia

Celine S. Lages, Julia Simmons, Avery Maddox, Keaton Jones, Rebekah Karns, Rachel Sheridan, Shiva Kumar Shanmukhappa, Sujit Mohanty, Matthew Kofron, Pierre Russo, Yui‐Hsi Wang, Claire Chougnet, Alexander G. Miethke – 19 September 2016 – Biliary atresia (BA) is a fibroinflammatory obstruction of the extrahepatic biliary tree in neonates. While intrahepatic bile duct proliferation is universal at diagnosis, bile duct paucity develops later. We hypothesized that polarized T helper lymphocyte responses orchestrate progression of intrahepatic biliary injury in this disease.

Preferential association of hepatitis C virus with CD19+ B cells is mediated by complement system

Richard Y. Wang, Patricia Bare, Valeria De Giorgi, Kentaro Matsuura, Kazi Abdus Salam, Teresa Grandinetti, Cathy Schechterly, Harvey J. Alter – 19 September 2016 – Extrahepatic disease manifestations are common in chronic hepatitis C virus (HCV) infection. The mechanism of HCV‐related lymphoproliferative disorders is not fully understood. Recent studies have found that HCV in peripheral blood mononuclear cells from chronically infected patients is mainly associated with cluster of differentiation 19‐positive (CD19+) B cells.

Hepatic stellate cells induce hepatocellular carcinoma cell resistance to sorafenib through the laminin‐332/α3 integrin axis recovery of focal adhesion kinase ubiquitination

Amalia Azzariti, Serena Mancarella, Letizia Porcelli, Anna Elisa Quatrale, Alessandra Caligiuri, Luigi Lupo, Francesco Dituri, Gianluigi Giannelli – 17 September 2016 – In patients with hepatocellular carcinoma (HCC) receiving sorafenib, drug resistance is common. HCC develops in a microenvironment enriched with extracellular matrix proteins including laminin (Ln)‐332, produced by hepatic stellate cells (HSCs). Ln‐332 is the ligand of α3β1 and α6β4 integrins, differently expressed on the HCC cell surface, that deliver intracellular pathways.

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