CD4+Foxp3+ T cells promote aberrant immunoglobulin G production and maintain CD8+ T‐cell suppression during chronic liver disease

Dana Tedesco, Manoj Thapa, Sanjeev Gumber, Elizabeth J. Elrod, Khalidur Rahman, Chris C. Ibegbu, Joseph F. Magliocca, Andrew B. Adams, Frank Anania, Arash Grakoui – 24 October 2016 – Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to nonfunctional intrahepatic CD8+ T‐cell responses. In light of dampened CD8+ T‐cell responses, liver disease often manifests systemically as immunoglobulin (Ig)‐related syndromes due to aberrant B‐cell functions.

METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N6‐methyladenosine‐dependent primary MicroRNA processing

Jin‐zhao Ma, Fu Yang, Chuan‐chuan Zhou, Feng Liu, Ji‐hang Yuan, Fang Wang, Tian‐tian Wang, Qing‐guo Xu, Wei‐ping Zhou, Shu‐han Sun – 24 October 2016 – N6‐Methyladenosine (m6A) modification has been implicated in many biological processes. However, its role in cancer has not been well studied. Here, we demonstrate that m6A modifications are decreased in hepatocellular carcinoma, especially in metastatic hepatocellular carcinoma, and that methyltransferase‐like 14 (METTL14) is the main factor involved in aberrant m6A modification.

Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups

Pavel Sumazin, Yidong Chen, Lisa R. Treviño, Stephen F. Sarabia, Oliver A. Hampton, Kayuri Patel, Toni‐Ann Mistretta, Barry Zorman, Patrick Thompson, Andras Heczey, Sarah Comerford, David A. Wheeler, Murali Chintagumpala, Rebecka Meyers, Dinesh Rakheja, Milton J. Finegold, Gail Tomlinson, D. Williams Parsons, Dolores López‐Terrada – 24 October 2016 – Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm.

Hyperoxidized albumin modulates neutrophils to induce oxidative stress and inflammation in severe alcoholic hepatitis

Sukanta Das, Jaswinder Singh Maras, Md. Shabir Hussain, Shvetank Sharma, Paul David, Sukriti Sukriti, Saggere Muralikrishna Shasthry, Rakhi Maiwall, Nirupama Trehanpati, Tej P. Singh, Shiv Kumar Sarin – 24 October 2016 – Albumin is a potent scavenger of reactive oxygen species (ROS). However, modifications in albumin structure may reduce its antioxidant properties and modulate its immune‐regulatory functions.

Metabolic profiling of fatty liver in young and middle‐aged adults: Cross‐sectional and prospective analyses of the Young Finns Study

Jari E. Kaikkonen, Peter Würtz, Emmi Suomela, Miia Lehtovirta, Antti J. Kangas, Antti Jula, Vera Mikkilä, Jorma S.A. Viikari, Markus Juonala, Tapani Rönnemaa, Nina Hutri‐Kähönen, Mika Kähönen, Terho Lehtimäki, Pasi Soininen, Mika Ala‐Korpela, Olli T. Raitakari – 24 October 2016 – Nonalcoholic fatty liver is associated with obesity‐related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease.

The association between race/ethnicity and the effectiveness of direct antiviral agents for hepatitis C virus infection

Feng Su, Pamela K. Green, Kristin Berry, George N. Ioannou – 24 October 2016 – Black race and Hispanic ethnicity were associated with lower rates of sustained virologic response (SVR) to interferon‐based treatments for chronic hepatitis C virus infection, whereas Asian race was associated with higher SVR rates compared to white patients. We aimed to describe the association between race/ethnicity and effectiveness of new direct‐acting antiviral regimens in the Veterans Affairs health care system nationally.

Bile acid excess induces cardiomyopathy and metabolic dysfunctions in the heart

Moreshwar S. Desai, Bhoomika Mathur, Zeena Eblimit, Hernan Vasquez, Heinrich Taegtmeyer, Saul J. Karpen, Daniel J. Penny, David D. Moore, Sayeepriyadarshini Anakk – 24 October 2016 – Cardiac dysfunction in patients with liver cirrhosis is strongly associated with increased serum bile acid concentrations. Here we show that excess bile acids decrease fatty acid oxidation in cardiomyocytes and can cause heart dysfunction, a cardiac syndrome that we term cholecardia.

Retracted: Redox‐dependent regulation of hepatocyte absent in melanoma 2 inflammasome activation in sterile liver injury in mice

Qian Sun, Patricia Loughran, Richard Shapiro, Indira H. Shrivastava, Daniel J. Antoine, Tunliang Li, Zhengzheng Yan, Jie Fan, Timothy R. Billiar, Melanie J. Scott – 24 October 2016 – Sterile liver inflammation, such as liver ischemia‐reperfusion, hemorrhagic shock after trauma, and drug‐induced liver injury, is initiated and regulated by endogenous mediators including DNA and reactive oxygen species.

Erythrocytosis in hepatocellular carcinoma portends poor prognosis by respiratory dysfunction secondary to mitochondrial DNA mutations

Shizhong Ke, Shuzhen Chen, Zihui Dong, Christopher S. Hong, Qi Zhang, Liang Tang, Pinghua Yang, Jian Zhai, Hexin Yan, Feng Shen, Zhengping Zhuang, Wen Wen, Hongyang Wang – 24 October 2016 – Erythrocytosis is a common paraneoplastic syndrome associated with hepatocellular carcinoma. Although increased erythropoietin (EPO) is found in these patients, the clinical significance and molecular mechanisms underlying this observation are unclear.

Polymorphisms in the IL‐1 gene cluster influence systemic inflammation in patients at risk for acute‐on‐chronic liver failure

José Alcaraz‐Quiles, Esther Titos, Mireia Casulleras, Marco Pavesi, Cristina López‐Vicario, Bibiana Rius, Aritz Lopategi, Andrea Gottardi, Ivo Graziadei, Henning Gronbaek, Pere Ginès, Mauro Bernardi, Vicente Arroyo, Joan Clària – 24 October 2016 – Acute‐on‐chronic liver failure (ACLF) in cirrhosis is an increasingly recognized syndrome characterized by acute decompensation, organ failure(s) and high short‐term mortality. Recent findings suggest that an overexuberant systemic inflammation plays a primary role in ACLF progression.

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