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.

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.

Murine Liver Organoids as a Genetically Flexible System to Study Liver Cancer InVivo and In Vitro

Anna Saborowski, Katharina Wolff, Steffi Spielberg, Benedikt Beer, Björn Hartleben, Zulrahman Erlangga, Diana Becker, Lukas E. Dow, Silke Marhenke, Norman Woller, Kristian Unger, Peter Schirmacher, Michael P. Manns, Jens U. Marquardt, Arndt Vogel, Michael Saborowski – 5 February 2019 – The rising incidence of cholangiocarcinoma (CCA) coupled with a low 5‐year survival rate that remains below 10% delineates the urgent need for more effective treatment strategies.

Aberrant Super‐Enhancer Landscape in Human Hepatocellular Carcinoma

Felice Ho‐Ching Tsang, Cheuk‐Ting Law, Tsz‐Ching Chloe Tang, Carol Lai‐Hung Cheng, Don Wai‐Ching Chin, Wing‐Sum Vincy Tam, Lai Wei, Carmen Chak‐Lui Wong, Irene Oi‐Lin Ng, Chun‐Ming Wong – 5 February 2019 – Hepatocellular carcinoma (HCC) cells exploit an aberrant transcriptional program to sustain their infinite growth and progression. Emerging evidence indicates that the continuous and robust transcription of oncogenes in cancer cells is often driven by super‐enhancers (SEs).

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.

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.

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.

Surgical Aspects of Liver Transplantation and Domino Liver Transplantation in Maple Syrup Urine Disease: Analysis of 15 Donor‐Recipient Pairs

Uta Herden, Enke Grabhorn, René Santer, Jun Li, Silvio Nadalin, Xavier Rogiers, Marcus N. Scherer, Felix Braun, Jan Beime, Henning Lenhartz, Ania C. Muntau, Lutz Fischer – 3 February 2019 – Liver transplantation (LT) has been shown to be a feasible treatment in patients with severe forms of maple syrup urine disease (MSUD). Because of a sufficient extrahepatic enzyme activity in non‐MSUD individuals, the organ of MSUD patients can be used as a domino graft.

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