Hepatology Highlights

Hirsh D. Trivedi, Daryl T.Y. Lau, Tasha B. Kulai, Harmeet Malhi, Robert E. Schwartz, Joseph F. Pisa, Robert S. Brown, Nicholas Russo, Kavitha M. Nair, Giorgio Roccaro, Petra Hirsova, Vikas Gupta, Xu Xu, Tibor Krisko, Enis Kostallari – 12 April 2019

Causes of hOCT1‐Dependent Cholangiocarcinoma Resistance to Sorafenib and Sensitization by Tumor‐Selective Gene Therapy

Elisa Lozano, Rocio I.R. Macias, Maria J. Monte, Maitane Asensio, Sofia Carmen, Laura Sanchez‐Vicente, Marta Alonso‐Peña, Ruba Al‐Abdulla, Patricia Munoz‐Garrido, Letizia Satriano, Colm J. O'Rourke, Jesus M. Banales, Matias A. Avila, Maria L. Martinez‐Chantar, Jesper B. Andersen, Oscar Briz, Jose J.G. Marin – 10 April 2019 – Although the multi‐tyrosine kinase inhibitor sorafenib is useful in the treatment of several cancers, cholangiocarcinoma (CCA) is refractory to this drug.

Hyperglycemia‐Triggered Sphingosine‐1‐Phosphate and Sphingosine‐1‐Phosphate Receptor 3 Signaling Worsens Liver Ischemia/Reperfusion Injury by Regulating M1/M2 Polarization

Yuanchang Hu, Chao Yang, Gefengqiang Shen, Shikun Yang, Xuyu Cheng, Feng Cheng, Jianhua Rao, Xuehao Wang – 10 April 2019 – Hyperglycemia aggravates hepatic ischemia/reperfusion injury (IRI), but the underlying mechanism for the aggravation remains elusive. Sphingosine‐1‐phosphate (S1P) and sphingosine‐1‐phosphate receptors (S1PRs) have been implicated in metabolic and inflammatory diseases. Here, we discuss whether and how S1P/S1PRs are involved in hyperglycemia‐related liver IRI.

Physicians’ Perspectives on Palliative Care for Patients With End‐Stage Liver Disease: A National Survey Study

Nneka N. Ufere, John Donlan, Lauren Waldman, Arpan Patel, Jules L. Dienstag, Lawrence S. Friedman, Kathleen E. Corey, Nikroo Hashemi, Peter Carolan, Alan C. Mullen, Michael Thiim, Irun Bhan, Ryan Nipp, Joseph Greer, Jennifer Temel, Raymond T. Chung, Areej El‐Jawahri – 9 April 2019 – Specialty palliative care (PC) is underused for patients with end‐stage liver disease (ESLD). We sought to examine attitudes of hepatologists and gastroenterologists about PC for patients with ESLD. We conducted a cross‐sectional survey of these specialists who provide care to patients with ESLD.

A Frizzled‐Like Cysteine‐Rich Domain in Glypican‐3 Mediates Wnt Binding and Regulates Hepatocellular Carcinoma Tumor Growth in Mice

Na Li, Liwen Wei, Xiaoyu Liu, Hongjun Bai, Yvonne Ye, Dan Li, Nan Li, Ulrich Baxa, Qun Wang, Ling Lv, Yun Chen, Mingqian Feng, Byungkook Lee, Wei Gao, Mitchell Ho – 9 April 2019 – Wnt signaling is one of the key regulators of hepatocellular carcinoma (HCC) tumor progression. In addition to the classical receptor frizzled (FZD), various coreceptors including heparan sulfate proteoglycans (HSPGs) are involved in Wnt activation. Glypican‐3 (GPC3) is an HSPG that is overexpressed in HCC and functions as a Wnt coreceptor that modulates HCC cell proliferation.

MicroRNA‐223 Ameliorates Nonalcoholic Steatohepatitis and Cancer by Targeting Multiple Inflammatory and Oncogenic Genes in Hepatocytes

Yong He, Seonghwan Hwang, Yan Cai, Seung‐Jin Kim, Mingjiang Xu, Dingcheng Yang, Adrien Guillot, Dechun Feng, Wonhyo Seo, Xin Hou, Bin Gao – 9 April 2019 – Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to more severe forms of liver injury including nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC). In humans, only 20%‐40% of patients with fatty liver progress to NASH, and mice fed a high‐fat diet (HFD) develop fatty liver but are resistant to NASH development.

Evolutionary Pathways to Persistence of Highly Fit and Resistant Hepatitis C Virus Protease Inhibitor Escape Variants

Sanne Brun Jensen, Ulrik Fahnøe, Long V. Pham, Stéphanie Brigitte Nelly Serre, Qi Tang, Lubna Ghanem, Martin Schou Pedersen, Santseharay Ramirez, Daryl Humes, Anne Finne Pihl, Jonathan Filskov, Christina Søhoel Sølund, Julia Dietz, Slim Fourati, Jean‐Michel Pawlotsky, Christoph Sarrazin, Nina Weis, Kristian Schønning, Henrik Krarup, Jens Bukh, Judith Margarete Gottwein – 9 April 2019 – Protease inhibitors (PIs) are important components of treatment regimens for patients with chronic hepatitis C virus (HCV) infection.

Bone Morphogenetic Protein 9 Is a Paracrine Factor Controlling Liver Sinusoidal Endothelial Cell Fenestration and Protecting Against Hepatic Fibrosis

Agnès Desroches‐Castan, Emmanuelle Tillet, Nicolas Ricard, Marie Ouarné, Christine Mallet, Lucid Belmudes, Yohann Couté, Olivier Boillot, Jean‐Yves Scoazec, Sabine Bailly, Jean‐Jacques Feige – 9 April 2019 – Bone morphogenetic protein 9 (BMP9) is a circulating factor produced by hepatic stellate cells that plays a critical role in vascular quiescence through its endothelial receptor activin receptor‐like kinase 1 (ALK1). Mutations in the gene encoding ALK1 cause hereditary hemorrhagic telangiectasia type 2, a rare genetic disease presenting hepatic vessel malformations.

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