Prothrombin Complex Concentrates for Coagulopathy in Liver Disease: Single‐Center, Clinical Experience in 105 Patients

Anja Drebes, Marie de Vos, Sunita Gill, Emma Fosbury, Sue Mallett, Andy Burroughs, Banwari Agarwal, David Patch, Pratima Chowdary – 5 February 2019 – Patients with liver disease frequently develop coagulopathy, and fresh frozen plasma is traditionally used for correction of coagulopathy to manage and prevent bleeding. Prothrombin complex concentrates (PCCs) offer an attractive alternative because they are more readily available and avoid large‐volume transfusion. This retrospective, single‐center study reviewed clinical use of PCC in patients with acute/chronic liver disease.

Exosomal Interferon‐Induced Transmembrane Protein 2 Transmitted to Dendritic Cells Inhibits Interferon Alpha Pathway Activation and Blocks Anti–Hepatitis B Virus Efficacy of Exogenous Interferon Alpha

Ying Shi, Lingyao Du, Duoduo Lv, Hong Li, Jin Shang, Jiajie Lu, Lingyun Zhou, Lang Bai, Hong Tang – 5 February 2019 – The negative regulators in the interferon (IFN) signaling pathway inhibit intrahepatic immune response, resulting in suboptimal therapeutic response to IFNα treatment in chronic hepatitis B (CHB) patients. Identifying the key negative factors and elucidating the regulating mechanism are essential for improving anti‐HBV (hepatitis B virus) efficacy of IFNα.

Prominin‐1 Promotes Biliary Fibrosis Associated With Biliary Atresia

Jessica A. Zagory, Michael Fenlon, William Dietz, Menghan Zhao, Marie V. Nguyen, Pavin Trinh, Maeva Adoumie, Alex Park, Jiabo Xu, Elaa Mahdi, Alison Glazier, Nicolas Malkoff, Nirmala Mavila, Kasper S. Wang, in conjunction with the Childhood Liver Disease Research Network – 5 February 2019 – In patients with biliary atresia (BA), the extent of intrahepatic biliary fibrosis negatively correlates with successful surgical bypass of the congenital cholangiopathy as well as subsequent transplant‐free survival.

Outcomes After Listing for Liver Transplant in Patients With Acute‐on‐Chronic Liver Failure: The Multicenter North American Consortium for the Study of End‐Stage Liver Disease Experience

Jacqueline G. O’Leary, Jasmohan S. Bajaj, Puneeta Tandon, Scott W. Biggins, Florence Wong, Patrick S. Kamath, Guadalupe Garcia‐Tsao, Benedict Maliakkal, Jennifer Lai, Michael Fallon, Hugo E. Vargas, Paul Thuluvath, Ram Subramanian, Leroy R. Thacker, K. Rajender Reddy – 5 February 2019 – Acute‐on‐chronic liver failure (ACLF) characterized with ≥2 extrahepatic organ failures in cirrhosis carries a high mortality. Outcomes of patients listed for liver transplantation (LT) after ACLF and after LT are largely unknown.

Tumor Microenvironment Regulation by the Endoplasmic Reticulum Stress Transmission Mediator Golgi Protein 73 in Mice

Congwen Wei, Xiaoli Yang, Ning Liu, Jin Geng, Yanhong Tai, Zhenyu Sun, Gangwu Mei, Pengyu Zhou, Yumeng Peng, Chenbin Wang, Xiaoli Zhang, Pingping Zhang, Yunqi Geng, Yujie Wang, Xiaotong Zhang, Xin Liu, Yanhong Zhang, Feixiang Wu, Xiang He, Hui Zhong – 5 February 2019 – The unfolded protein response (UPR) signal in tumor cells activates UPR signaling in neighboring macrophages, which leads to tumor‐promoting inflammation by up‐regulating UPR target genes and proinflammatory cytokines.

Amelioration of Ductular Reaction by Stem Cell Derived Extracellular Vesicles in MDR2 Knockout Mice via Lethal‐7 microRNA

Kelly McDaniel, Nan Wu, Tianhao Zhou, Li Huang, Keisaku Sato, Julie Venter, Ludovica Ceci, Demeng Chen, Sugeily Ramos‐Lorenzo, Pietro Invernizzi, Francesca Bernuzzi, Chaodong Wu, Heather Francis, Shannon Glaser, Gianfranco Alpini, Fanyin Meng – 5 February 2019 – Cholangiopathies are diseases that affect cholangiocytes, the cells lining the biliary tract. Liver stem cells (LSCs) are able to differentiate into all cells of the liver and possibly influence the surrounding liver tissue by secretion of signaling molecules.

Improved Graft Survival After Liver Transplantation for Recipients With Hepatitis C Virus in the Direct‐Acting Antiviral Era

Thomas G. Cotter, Sonali Paul, Burhaneddin Sandıkçı, Thomas Couri, Adam S. Bodzin, Ester C. Little, Vinay Sundaram, Michael Charlton – 4 February 2019 – Highly effective direct‐acting antiviral (DAA) therapy has transformed outcomes of liver transplantation in hepatitis C virus (HCV) patients. We examined longer‐term outcomes in HCV‐positive recipients in the DAA era and analyzed the Scientific Registry of Transplant Recipients for primary adult, single‐organ, nonfulminant liver transplant recipients in the United States from January 1, 2008 to June 30, 2018.

Glial Cell Line–Derived Neurotrophic Factor Enhances Autophagic Flux in Mouse and Rat Hepatocytes and Protects Against Palmitate Lipotoxicity

Simon Musyoka Mwangi, Ge Li, Lan Ye, Yunshan Liu, Francois Reichardt, Samantha M. Yeligar, C. Michael Hart, Mark J. Czaja, Shanthi Srinivasan – 4 February 2019 – Glial cell line–derived neurotrophic factor (GDNF) is a protein that is required for the development and survival of enteric, sympathetic, and catecholaminergic neurons. We previously reported that GDNF is protective against high fat diet (HFD)‐induced hepatic steatosis in mice through suppression of hepatic expression of peroxisome proliferator activated receptor‐γ and genes encoding enzymes involved in de novo lipogenesis.

Extracellular Vesicle‐Based Therapeutic Targeting of β‐Catenin to Modulate Anticancer Immune Responses in Hepatocellular Cancer

Akiko Matsuda, Kaori Ishiguro, Irene K. Yan, Tushar Patel – 4 February 2019 – Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related death worldwide. Although HCC can respond to immune checkpoint inhibitors, such as monoclonal antibodies against programmed death 1 (PD‐1), many patients fail to respond or develop secondary resistance. Activation of Wnt/β‐catenin signaling can contribute to immune evasion. Mutations in β‐catenin are among the most frequent mutations associated with HCC.

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