The BRUCE‐ATR Signaling Axis Is Required for Accurate DNA Replication and Suppression of Liver Cancer Development

Chunmin Ge, Chrystelle L. Vilfranc, Lixiao Che, Raj K. Pandita, Shashank Hambarde, Paul R. Andreassen, Liang Niu, Olugbenga Olowokure, Shimul Shah, Susan E. Waltz, Lee Zou, Jiang Wang, Tej K. Pandita, Chunying Du – 28 January 2019 – Replication fork stability during DNA replication is vital for maintenance of genomic stability and suppression of cancer development in mammals. ATR (ataxia‐telangiectasia mutated [ATM] and RAD3‐related) is a master regulatory kinase that activates the replication stress response to overcome replication barriers.

JNJ‐4178 (AL‐335, Odalasvir, and Simeprevir) for 6 or 8 Weeks in Hepatitis C Virus‐Infected Patients Without Cirrhosis: OMEGA‐1

Stefan Zeuzem, Stefan Bourgeois, Susan Greenbloom, Maria Buti, Alessio Aghemo, Pietro Lampertico, Ewa Janczewska, Seng Gee Lim, Christophe Moreno, Peter Buggisch, Edward Tam, Chris Corbett, Wouter Willems, Leen Vijgen, Bart Fevery, Sivi Ouwerkerk‐Mahadevan, Oliver Ackaert, Maria Beumont, Ronald Kalmeijer, Rekha Sinha, Michael Biermer, on behalf of the OMEGA‐1 study team – 28 January 2019 – The combination of three direct‐acting antiviral agents (AL‐335, odalasvir, and simeprevir: JNJ‐4178 regimen) for 6 or 8 weeks demonstrated good efficacy and safety in a phase IIa study in chronic hepatit

An Efficient Combination Immunotherapy for Primary Liver Cancer by Harmonized Activation of Innate and Adaptive Immunity in Mice

Liang Wen, Bing Xin, Panyisha Wu, Chia‐Hao Lin, Chuanhui Peng, Gaowei Wang, Jin Lee, Li‐Fan Lu, Gen‐Sheng Feng – 28 January 2019 – Immunotherapy with checkpoint inhibitors for liver cancer, while active in many clinical trials worldwide, may have uncertain outcomes due to the unique immunotolerant microenvironment of the liver. In previous experiments, we unexpectedly identified a robust liver tumor‐preventive effect of a synthetic double‐stranded RNA, polyinosinic‐polycytidylic acid (polyIC), in mice.

Low Risk of Variceal Bleeding in Patients With Cirrhosis After Variceal Screening Stratified by Liver/Spleen Stiffness

Grace Lai‐Hung Wong, Lilian Yan Liang, Raymond Kwok, Aric Josun Hui, Yee‐Kit Tse, Henry Lik‐Yuen Chan, Vincent Wai‐Sun Wong – 25 January 2019 – We previously demonstrated the possible noninferiority of a screening strategy for varices guided by liver and spleen stiffness measurement (LSSM) compared to universal endoscopic screening in detecting clinically significant varices in patients with cirrhosis. We now report the long‐term outcome of the patients recruited in this trial for incident variceal bleeding and other hepatic events.

Alpha‐1 Antitrypsin Deficiency Liver Disease, Mutational Homogeneity Modulated by Epigenetic Heterogeneity With Links to Obesity

Liguo Wang, George W. Marek, Ryan A. Hlady, Ryan T. Wagner, Xia Zhao, Virginia C. Clark, Alex Xiucheng Fan, Chen Liu, Mark Brantly, Keith D. Robertson – 25 January 2019 – Alpha‐1 antitrypsin deficiency (AATD) liver disease is characterized by marked heterogeneity in presentation and progression, despite a common underlying gene mutation, strongly suggesting the involvement of other genetic and/or epigenetic modifiers. Variation in clinical phenotype has added to the challenge of detection, diagnosis, and testing of new therapies in patients with AATD.

Adipocyte Death Preferentially Induces Liver Injury and Inflammation Through the Activation of Chemokine (C‐C Motif) Receptor 2‐Positive Macrophages and Lipolysis

Seung‐Jin Kim, Dechun Feng, Adrien Guillot, Shen Dai, Fengming Liu, Seonghwan Hwang, Richard Parker, Wonhyo Seo, Yong He, Grzegorz Godlewski, Won‐Il Jeong, Yuhong Lin, Xuebin Qin, George Kunos, Bin Gao – 25 January 2019 – Adipocyte death occurs under various physiopathological conditions, including obesity and alcohol drinking, and can trigger organ damage particularly in the liver, but the underlying mechanisms remain obscure.

Alpha‐1 Antitrypsin Deficiency Liver Disease, Mutational Homogeneity Modulated by Epigenetic Heterogeneity With Links to Obesity

Liguo Wang, George W. Marek, Ryan A. Hlady, Ryan T. Wagner, Xia Zhao, Virginia C. Clark, Alex Xiucheng Fan, Chen Liu, Mark Brantly, Keith D. Robertson – 25 January 2019 – Alpha‐1 antitrypsin deficiency (AATD) liver disease is characterized by marked heterogeneity in presentation and progression, despite a common underlying gene mutation, strongly suggesting the involvement of other genetic and/or epigenetic modifiers. Variation in clinical phenotype has added to the challenge of detection, diagnosis, and testing of new therapies in patients with AATD.

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