Hepatitis C Virus Eradication with New Interferon‐Free Treatment Improves Metabolic Profile in Hepatitis C Virus‐Related Liver Transplant Recipients

Junaid Beig, David Orr, Barry Harrison, Edward Gane – 25 March 2018 – Interferon (IFN)‐free, direct‐acting antiviral (DAA) therapy agents provide a safe and efficacious treatment for liver transplant recipients with recurrent hepatitis C virus (HCV) infection. The aim of this study is to evaluate the impact of HCV eradication on the metabolic factors in liver transplant recipients. We completed a retrospective single‐center study on HCV‐related liver transplant recipients treated with IFN‐free DAAs including both treatment‐naive and treatment‐experienced patients.

Patient Selection by Tumor Markers in Liver Transplantation for Advanced Hepatocellular Carcinoma

Hae Won Lee, Gi‐Won Song, Sung‐Gyu Lee, Jong Man Kim, Jae‐Won Joh, Dai Hoon Han, Soon Il Kim, Seong Hoon Kim, Dong‐Sik Kim, Jai Young Cho, Kyung‐Suk Suh – 25 March 2018 – Although far advanced hepatocellular carcinoma (HCC) is generally considered a contraindication for liver transplantation (LT), biologically favorable tumors among them could show acceptable results. However, it is still unclear which tumors can be treated with LT. Data were collected on adult patients who underwent LT for HCC beyond the Milan criteria in 8 Korean LT centers between January 2000 and June 2013.

Na+‐taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice

Davor Slijepcevic, Reinout L.P. Roscam Abbing, Claudia D. Fuchs, Lizette C.M. Haazen, Ulrich Beuers, Michael Trauner, Ronald P.J. Oude Elferink, Stan F.J. van de Graaf – 24 March 2018 – Accumulation of bile salts (BSs) during cholestasis leads to hepatic and biliary injury, driving inflammatory and fibrotic processes. The Na+‐Taurocholate Cotransporting Polypeptide (NTCP) is the major hepatic uptake transporter of BSs, and can be specifically inhibited by myrcludex B. We hypothesized that inhibition of NTCP dampens cholestatic liver injury.

Nicotinamide adenine dinucleotide phosphate (reduced) oxidase 2 modulates inflammatory vigor during nonalcoholic fatty liver disease progression in mice

Rajib Mukherjee, Maria E. Moreno‐Fernandez, Daniel A. Giles, Monica Cappelletti, Traci E. Stankiewicz, Calvin C. Chan, Senad Divanovic – 24 March 2018 – Nonalcoholic fatty liver disease (NAFLD) represents a disease spectrum ranging from benign steatosis to life‐threatening cirrhosis and hepatocellular carcinoma. Elevated levels of reactive oxygen species (ROS) and exacerbated inflammatory responses have been implicated in NAFLD progression.

Argininosuccinate synthase 1 and periportal gene expression in sonic hedgehog hepatocellular adenomas

Jean‐Charles Nault, Gabrielle Couchy, Stefano Caruso, Léa Meunier, Laure Caruana, Eric Letouzé, Sandra Rebouissou, Valérie Paradis, Julien Calderaro, Jessica Zucman‐Rossi – 24 March 2018 – Genetic alterations define different molecular subclasses of hepatocellular adenoma (HCA) linked with risk factors, histology and clinical behavior. Recently, Argininosuccinate Synthase 1 (ASS1), a major periportal protein, was proposed as a marker of HCA with a high risk of hemorrhage. We aimed to assess the significance of ASS1 expression through the scope of the HCA molecular classification.

PRDM8 exhibits antitumor activities toward hepatocellular carcinoma by targeting NAP1L1

Zhiqiang Chen, Wen Gao, Liyong Pu, Long Zhang, Guoyong Han, Xueliang Zuo, Yao Zhang, Xiangcheng Li, Hongbing Shen, Jindao Wu, Xuehao Wang – 23 March 2018 – Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. PRDI‐BF1 and RIZ homology domain containing 8 (PRDM8) is a key regulator in neural development and testis steroidogenesis; however, its role in liver carcinogenesis remains to be investigated. In this study, PRDM8 was found to be down‐regulated in HCC, which was linked with shorter recurrence‐free survival.

Sphingosine kinase 1 promotes liver fibrosis by preventing miR‐19b‐3p‐mediated inhibition of CCR2

Tian Lan, Changzheng Li, Guizhi Yang, Yue Sun, Lihang Zhuang, Yitao Ou, Hui Li, Genshu Wang, Tatiana Kisseleva, David Brenner, Jiao Guo – 23 March 2018 – Chronic liver disease mediated by activation of hepatic stellate cells (HSCs) and Kupffer cells (KCs) leads to liver fibrosis. Here, we aimed to investigate the molecular mechanism and define the cell type involved in mediating the sphingosine kinase (SphK)1‐dependent effect on liver fibrosis. The levels of expression and activity of SphK1 were significantly increased in fibrotic livers compared with the normal livers in human.

Liver‐enriched transcription factor expression relates to chronic hepatic failure in humans

Jorge Guzman‐Lepe, Eduardo Cervantes‐Alvarez, Alexandra Collin de l'Hortet, Yang Wang, Wendy M. Mars, Yoshinao Oda, Yuki Bekki, Masahiro Shimokawa, Huanlin Wang, Tomoharu Yoshizumi, Yoshihiko Maehara, Aaron Bell, Ira J. Fox, Kazuki Takeishi, Alejandro Soto‐Gutierrez – 23 March 2018 – The mechanisms by which the liver fails in end‐stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects.

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