The protein kinase IKKε can inhibit HCV expression independently of IFN and its own expression is downregulated in HCV‐infected livers

Myriam Vilasco, Esther Larrea, Damien Vitour, Stephanie Dabo, Adrien Breiman, Béatrice Regnault, Jose‐Ignacio Riezu, Pierre Eid, Jesus Prieto, Eliane F. Meurs – 28 November 2006 – During a viral infection, binding of viral double‐stranded RNAs (dsRNAs) to the cytosolic RNA helicase RIG‐1 leads to recruitment of the mitochondria‐associated Cardif protein, involved in activation of the IRF3‐phosphorylating IKKε/TBK1 kinases, interferon (IFN) induction, and development of the innate immune response.

Oxidative‐stress and IL‐6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells

Natalia Nieto – 28 November 2006 – The impact of Kupffer cells (KCs) on the hepatic stellate cell (HSC) fibrogenic response was examined in an in vitro coculture model of primary KCs and HSCs. Coculture with KCs induced a more activated phenotype and greater proliferation compared to HSC cultured alone. Similar results were obtained on Matrigel which maintains HSCs quiescent.

Role of neutrophils in a mouse model of halothane‐induced liver injury

Qiang You, Linling Cheng, Timothy P. Reilly, Dale Wegmann, Cynthia Ju – 28 November 2006 – Drug‐induced liver injury (DILI) is a major safety concern in drug development. Its prediction and prevention have been hindered by limited knowledge of the underlying mechanisms, in part the result of a lack of animal models. We developed a mouse model of halothane‐induced liver injury and characterized the mechanisms accounting for tissue damage. Female and male Balb/c, DBA/1, and C57BL/6J mice were injected intraperitoneally with halothane.

Impact of disease severity on outcome of antiviral therapy for chronic hepatitis C: Lessons from the HALT‐C trial

Gregory T. Everson, John C. Hoefs, Leonard B. Seeff, Herbert L. Bonkovsky, Deepa Naishadham, Mitchell L. Shiffman, Jeffrey A. Kahn, Anna S. F. Lok, Adrian M. Di Bisceglie, William M. Lee, Jules L. Dienstag, Marc G. Ghany, Chihiro Morishima, HALT‐C Trial Group – 28 November 2006 – In patients with chronic hepatitis C, advanced fibrosis and cirrhosis are associated with lower rates of sustained virologic response (SVR) to interferon (IFN)‐based therapy.

IP‐10 predicts viral response and therapeutic outcome in difficult‐to‐treat patients with HCV genotype 1 infection

Martin Lagging, Ana I. Romero, Johan Westin, Gunnar Norkrans, Amar P. Dhillon, Jean‐Michel Pawlotsky, Stefan Zeuzem, Michael von Wagner, Francesco Negro, Solko W. Schalm, Bart L. Haagmans, Carlo Ferrari, Gabriele Missale, Avidan U. Neumann, Elke Verheij‐Hart, Kristoffer Hellstrand, DITTO‐HCV Study Group – 28 November 2006 – Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP‐10 levels prior to treatment with pegylated interferon‐α‐2a and ribavirin.

In vivo expansion of two distinct dendritic cells in mouse livers and its impact on liver immune regulation

Yalan Wang, Ning Zheng, Zhengbin Lu, Wenhan Wu, Lianfu Wang, Atsunori Nakao, Michael T. Lotze, Carrie E. Langer, John J. Fung, Shiguang Qian, Lina Lu – 28 November 2006 – Liver transplant tolerance in pigs, rats, and mice has been disclosed for decades, but the underlying mechanisms are not completely understood. Accumulating data indicate that residing dendritic cells (DC) are important in determining direction of immune responses in the liver. However, our knowledge remains very limited due to the difficulties in obtaining sufficient liver DC.

Relative adrenal insufficiency manifested with multiple organ dysfunction in a liver transplant patient

Takeshi Iwasaki, Masahiro Tominaga, Takumi Fukumoto, Nobuya Kusunoki, Takemi Sugimoto, Masahiro Kido, Satoshi Ogata, Atsushi Takebe, Motofumi Tanaka, Yonson Ku – 28 November 2006 – Relative adrenal insufficiency is now a well‐known clinical condition that occurs in critically ill patients particularly with septic complication. However, this pathology has long been unrecognized until recently in liver transplantation patients, for whom postoperative immunosuppressive therapies almost always comprise corticosteroids.

Conversion to sirolimus: A useful strategy for recalcitrant cutaneous viral warts in liver transplant recipient

Sébastien Dharancy, Benoît Catteau, Laurent Mortier, Emmanuel Boleslawski, Nicole Declerck, Valérie Canva, Frédéric Piette, Philippe Mathurin, François René Pruvot – 28 November 2006 – Dermatological complications following transplantation are very common and the majority of immunosuppressed transplant recipients develop some to many warts due to human papillomavirus (HPV) infection. In the setting of immunosuppression, therapeutic management may be disappointing because of the extent of the lesions in patients unable to develop a sufficient immune response directed against HPV.

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