A Positive Feedback Loop Between Cancer Stem‐Like Cells and Tumor‐Associated Neutrophils Controls Hepatocellular Carcinoma Progression

Shao‐Lai Zhou, Dan Yin, Zhi‐Qiang Hu, Chu‐Bin Luo, Zheng‐Jun Zhou, Hao‐Yang Xin, Xin‐Rong Yang, Ying‐Hong Shi, Zheng Wang, Xiao‐Wu Huang, Ya Cao, Jia Fan, Jian Zhou – 1 April 2019 – Tumor‐associated neutrophils (TANs) play a crucial role in tumor development and progression in the cancer microenvironment. Despite increased understanding of TAN contributions to hepatocellular carcinoma (HCC) progression and prognosis, the direct interaction between TANs and HCC cells is not fully understood.

Cholesterol Crystals in Hepatocyte Lipid Droplets Are Strongly Associated With Human Nonalcoholic Steatohepatitis

George N. Ioannou, Charles S. Landis, Ga‐Young Jin, W. Geoffrey Haigh, Geoffrey C. Farrell, Rahul Kuver, Sum P. Lee, Christopher Savard – 1 April 2019 – It is unclear what drives the development of fibrosing nonalcoholic steatohepatitis (NASH). We aimed to determine whether cholesterol crystallization within hepatocyte lipid droplets (LDs) distinguishes patients with fibrosing NASH from patients with isolated hepatic steatosis and to study pathways leading to cholesterol accumulation in hepatocyte LDs.

Gallbladder Dyskinesia Is Associated With an Impaired Postprandial Fibroblast Growth Factor 19 Response in Critically Ill Patients

Kiran V.K. Koelfat, Mark P. Plummer, Frank G. Schaap, Martin Lenicek, Peter L.M. Jansen, Adam M. Deane, Steven W.M. Olde Damink – 1 April 2019 – Critical illness is associated with a disturbed regulation of gastrointestinal hormones resulting in functional and metabolic anomalies. Fibroblast growth factor 19 (FGF19) is an ileum‐derived metabolic hormone induced by bile salts upon gallbladder emptying after enteral nutrient stimulation. Our aim was to study the nutrient‐stimulated FGF19 response in 24 patients admitted to the intensive care unit (ICU) compared with 12 healthy controls.

Hepatocyte Nuclear Factor 4‐Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver

Avinash Thakur, Jasper C.H. Wong, Evan Y. Wang, Jeremy Lotto, Donghwan Kim, Jung‐Chien Cheng, Matthew Mingay, Rebecca Cullum, Vaishali Moudgil, Nafeel Ahmed, Shu‐Huei Tsai, Wei Wei, Colum P. Walsh, Tabea Stephan, Misha Bilenky, Bettina M. Fuglerud, Mohammad M. Karimi, Frank J. Gonzalez, Martin Hirst, Pamela A. Hoodless – 1 April 2019 – Cell‐fate determination is influenced by interactions between master transcription factors (TFs) and cis‐regulatory elements.

Expanding the Donor Pool With the Use of Extended Criteria Donation After Circulatory Death Livers

Plamen Mihaylov, Richard Mangus, Burcin Ekser, Arianna Cabrales, Lava Timsina, Jonathan Fridell, Marco Lacerda, Marwan Ghabril, Lauren Nephew, Naga Chalasani, Chandrashekhar A. Kubal – 31 March 2019 – Use of donation after circulatory death (DCD) donor livers for transplantation has remained cautious in the United States. The aim of this study was to demonstrate the expansion of a DCD liver transplantation (LT) program with the use of extended criteria donor (ECD) DCD livers. After institutional review board approval, 135 consecutive DCD LTs were retrospectively studied.

Adjuvant Treatment of Hepatocellular Carcinoma: Prospect of Immunotherapy

Zachary J. Brown, Tim F. Greten, Bernd Heinrich – 30 March 2019 – Although patients undergo procedures with curative intent for early‐stage hepatocellular carcinoma (HCC), up to 70% of patients may have disease recurrence in the liver at 5 years. Thus far, no therapy has proven to be effective in the adjuvant setting. Here, we discuss the application of immune‐based therapies in the adjuvant setting for HCC, focusing on the underlying rationale for immunotherapies, which patients may benefit from an immune‐based therapy, and what type of immune therapy should be implemented.

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