TRAIL but not FasL and TNFα, regulates IL‐33 expression in murine hepatocytes during acute hepatitis

Muhammad Imran Arshad, Claire Piquet‐Pellorce, Annie L'Helgoualc'h, Michel Rauch, Solène Patrat‐Delon, Frédéric Ezan, Catherine Lucas‐Clerc, Sabrina Nabti, Agnès Lehuen, Francisco Javier Cubero, Jean‐Philippe Girard, Christian Trautwein, Michel Samson – 10 September 2012 – Interleukin (IL)‐33, a member of the IL‐1 cytokine family, positively correlates with acute hepatitis and chronic liver failure in mice and humans. IL‐33 is expressed in hepatocytes and is regulated by natural killer T (NKT) cells during concanavalin A (ConA)‐induced acute liver injury.

Impairment of CD4+ cytotoxic T cells predicts poor survival and high recurrence rates in patients with hepatocellular carcinoma

Junliang Fu, Zheng Zhang, Lin Zhou, Zhaorui Qi, Shaojun Xing, Jiyun Lv, Jianfei Shi, Baoyun Fu, Zhenwen Liu, Ji‐Yuan Zhang, Lei Jin, Yulai Zhao, George K.K. Lau, Jingmin Zhao, Fu‐Sheng Wang – 7 September 2012 – The role of CD4+ cytotoxic T cells (CTLs) in hepatocellular carcinoma (HCC) remains obscure. This study characterized CD4+ CTLs in HCC patients and further elucidated the associations between CD4+ CTLs and HCC disease progression. In all, 547 HCC patients, 44 chronic hepatitis B (CHB) patients, 86 liver cirrhosis (LC) patients, and 88 healthy individuals were enrolled in the study.

A novel murine model to deplete hepatic stellate cells uncovers their role in amplifying liver damage in mice

Juan E. Puche, Youngmin A. Lee, Jingjing Jiao, Costica Aloman, Maria I. Fiel, Ursula Muñoz, Thomas Kraus, Tingfang Lee, Hal F. Yee, Scott L. Friedman – 7 September 2012 – We have developed a novel model for depleting mouse hepatic stellate cells (HSCs) that has allowed us to clarify their contributions to hepatic injury and fibrosis. Transgenic (Tg) mice expressing the herpes simplex virus thymidine kinase gene (HSV‐Tk) driven by the mouse GFAP promoter were used to render proliferating HSCs susceptible to killing in response to ganciclovir (GCV).

Disruption of the histidine triad nucleotide‐binding hint2 gene in mice affects glycemic control and mitochondrial function

Juliette Martin, Olivier Maurhofer, Nadège Bellance, Giovanni Benard, Franziska Graber, Dagmar Hahn, Anne Galinier, Caroline Hora, Anirudh Gupta, Gisèle Ferrand, Hans Hoppeler, Rodrigue Rossignol, Jean‐François Dufour, Marie V. St‐Pierre – 7 September 2012 – The histidine triad nucleotide‐binding (HINT2) protein is a mitochondrial adenosine phosphoramidase expressed in the liver and pancreas. Its physiological function is unknown. To elucidate the role of HINT2 in liver physiology, the mouse Hint2 gene was deleted.

Quantifying the fraction of cirrhosis attributable to alcohol among chronic hepatitis C virus patients: Implications for treatment cost‐effectiveness

Hamish A. Innes, Sharon J. Hutchinson, Stephen Barclay, Elaine Cadzow, John F. Dillon, Andrew Fraser, David J. Goldberg, Peter R. Mills, Scott A. McDonald, Judith Morris, Adrian Stanley, Peter Hayes, on behalf of the Hepatitis C Clinical Database Monitoring Committee – 7 September 2012 – A substantial baseline risk of liver cirrhosis exists for patients with chronic hepatitis C virus (HCV) infection. However, the extent to which this could be driven by heavy alcohol use is unclear.

Single determination of C‐reactive protein at the time of diagnosis predicts long‐term outcome of patients with hepatocellular carcinoma

Wolfgang Sieghart, Matthias Pinter, Florian Hucke, Ivo Graziadei, Maximilian Schöniger‐Hekele, Christian Müller, Wolfgang Vogel, Michael Trauner, Markus Peck‐Radosavljevic – 7 September 2012 – We investigated the prognostic value of C‐reactive protein (CRP) in patients with hepatocellular carcinoma (HCC) not amenable to surgery. A total of 615 patients diagnosed with HCC not amenable to surgery between April 1999 and December 2009 at the Department of Gastroenterology of the Medical Universities of Vienna and Innsbruck were included.

Hepatic and Abdominal Carbon Dioxide Measurements Detect and Distinguish Hepatic Artery Occlusion and Portal Vein Occlusion in Pigs

Soeren Erik Pischke, Christian Tronstad, Lars Holhjem, Pål Dag Line, Håkon Haugaa, Tor Inge Tønnessen – 7 September 2012 – Hepatic artery (HA) occlusion and portal vein (PV) occlusion are the most common vascular complications after liver transplantation with an impact on mortality and retransplantation rates. The detection of severe hypoperfusion may be delayed with currently available diagnostic tools. Hypoperfusion and anaerobically produced lactic acid lead to increases in tissue carbon dioxide.

Reduced hepatic stellate cell expression of kruppel‐like factor 6 tumor suppressor isoforms amplifies fibrosis during acute and chronic rodent liver injury

Zahra Ghiassi‐Nejad, Virginia Hernandez‐Gea, Christopher Woodrell, Ursula E. Lang, Katja Dumic, Allison Kwong, Scott L. Friedman – 7 September 2012 – Kruppel‐like factor 6 (KLF6), a zinc finger transcription factor and tumor suppressor, is induced as an immediate‐early gene during hepatic stellate cell (HSC) activation. The paradoxical induction of a tumor suppressor in HSCs during proliferation led us to explore the biology of wildtype KLF6 (KLF6WT) and its antagonistic, alternatively spliced isoform KLF6SV1 in cultured HSCs and animal models.

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