Hepatitis C virus double‐stranded RNA is the predominant form in human liver and in interferon‐treated cells

Arielle Klepper, Francis J. Eng, Erin H. Doyle, Ahmed El‐Shamy, Adeeb H. Rahman, M. Isabel Fiel, Gonzalo Carrasco Avino, Moonju Lee, Fei Ye, Sasan Roayaie, Meena B. Bansal, Margaret R. MacDonald, Thomas D. Schiano, Andrea D. Branch – 19 September 2016 – Hepatitis C virus (HCV) is unique among RNA viruses in its ability to establish chronic infection in the majority of exposed adults. HCV persists in the liver despite interferon (IFN)‐stimulated gene (ISG) induction; robust induction actually predicts treatment failure and viral persistence.

Pivotal role of glutamine synthetase in ammonia detoxification

Theodorus B.M. Hakvoort, Youji He, Wim Kulik, Jacqueline L.M. Vermeulen, Suzanne Duijst, Jan M. Ruijter, Jurgen H. Runge, Nicolaas E.P. Deutz, S. Eleonore Koehler, Wouter H. Lamers – 19 September 2016 – Glutamine synthetase (GS) catalyzes condensation of ammonia with glutamate to glutamine. Glutamine serves, with alanine, as a major nontoxic interorgan ammonia carrier. Elimination of hepatic GS expression in mice causes only mild hyperammonemia and hypoglutaminemia but a pronounced decrease in the whole‐body muscle‐to‐fat ratio with increased myostatin expression in muscle.

Liver serine palmitoyltransferase activity deficiency in early life impairs adherens junctions and promotes tumorigenesis

Zhiqiang Li, Inamul Kabir, Hui Jiang, Hongwen Zhou, Jenny Libien, Jianying Zeng, Albert Stanek, Peiqi Ou, Kailyn R. Li, Shane Zhang, Hai H. Bui, Ming‐Shang Kuo, Tae‐Sik Park, Benjamin Kim, Tilla S. Worgall, Chongmin Huan, Xian‐Cheng Jiang – 19 September 2016 – Serine palmitoyltransferase is the key enzyme in sphingolipid biosynthesis. Mice lacking serine palmitoyltransferase are embryonic lethal.

“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.

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