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.

A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis

Marlyn J. Mayo, Paul J. Pockros, David Jones, Christopher L. Bowlus, Cynthia Levy, Imran Patanwala, Bruce Bacon, Velimir Luketic, Raj Vuppalanchi, Sharon Medendorp, Alejandro Dorenbaum, Ciara Kennedy, Patricia Novak, Joan Gu, George Apostol, Gideon M. Hirschfield – 1 February 2019 – Primary biliary cholangitis (PBC) is typically associated with elevated serum bile acid levels and pruritus, but pruritus is often refractory to treatment with existing therapies.

Liver Expression of a MiniATP7B Gene Results in Long‐Term Restoration of Copper Homeostasis in a Wilson Disease Model in Mice

Oihana Murillo, Daniel Moreno, Cristina Gazquez, Miren Barberia, Itziar Cenzano, Iñigo Navarro, Iker Uriarte, Victor Sebastian, Manuel Arruebo, Veronica Ferrer, Bernard Bénichou, Jean Philippe Combal, Jesus Prieto, Ruben Hernandez‐Alcoceba, Gloria Gonzalez Aseguinolaza – 1 February 2019 – Gene therapy with an adeno‐associated vector (AAV) serotype 8 encoding the human ATPase copper‐transporting beta polypeptide (ATP7B) complementary DNA (cDNA; AAV8‐ATP7B) is able to provide long‐term copper metabolism correction in 6‐week‐old male Wilson disease (WD) mice.

F‐box/WD Repeat‐Containing Protein 5 Mediates the Ubiquitination of Apoptosis Signal‐Regulating Kinase 1 and Exacerbates Nonalcoholic Steatohepatitis in Mice

Lan Bai, Ming‐Ming Chen, Ze‐Dong Chen, Peng Zhang, Song Tian, Yan Zhang, Xue‐Yong Zhu, Ye Liu, Zhi‐Gang She, Yan‐Xiao Ji, Hongliang Li – 31 January 2019 – Inhibition of apoptosis signal‐regulating kinase 1 (ASK1) activation has emerged as a promising target for the treatment of nonalcoholic steatohepatitis (NASH). Multiple forms of posttranslational modifications determine the activity of ASK1. In addition to phosphorylation, recent studies revealed that ubiquitination is essential for ASK1 activation.

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