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.

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.

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.

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.

Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post‐hepatectomy in mice

Hanh‐Tu Lieu, Marie‐Thérèse Simon, Thao Nguyen‐Khoa, Messeret Kebede, Alexandre Cortes, Luis Tebar, Andrew J. H. Smith, Rosemary Bayne, Stephen P. Hunt, Christian Bréchot, Laurence Christa – 28 November 2006 – Reg2/RegIIIβ is the murine homologue of the human secreted HIP/PAP C‐type lectin. HIP/PAP transgenic mice were protected against acetaminophen‐induced acute liver failure and were stimulated to regenerate post‐hepatectomy. To assess the role of Reg2, we used Reg2−/− mice in a model of fulminant hepatitis induced by Fas and in the post‐hepatectomy regeneration.

Engineered measles virus as a novel oncolytic viral therapy system for hepatocellular carcinoma

Boris Blechacz, Patrick L. Splinter, Suzanne Greiner, Rae Myers, Kah‐Whye Peng, Mark J. Federspiel, Stephen J. Russell, Nicholas F. LaRusso – 28 November 2006 – The oncolytic measles virus Edmonston strain (MV‐Edm), a nonpathogenic virus targeting cells expressing abundant CD46, selectively destroys neoplastic tissue. Clinical development of MV‐Edm would benefit from noninvasive monitoring strategies to determine the speed and extent of the spread of the virus in treated patients and the location of virus‐infected cells.

Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation

Inmaculada Fernández, Juan Carlos Meneu, Francisco Colina, Ignacio García, Raquel Muñoz, Gregorio Castellano, Antonio Fuertes, Manuel Abradelo, Carlos Lumbreras, Enrique Moreno, José Antonio Solís‐Herruzo – 28 November 2006 – Treatment of recurrent hepatitis C in liver transplant is controversial. The aim of our study was to evaluate the clinical and histological efficacy of pegylated interferon alpha 2b (PEG‐IFN) and ribavirin therapy of recurrent hepatitis C after liver transplantation (LT).

Model for end‐stage liver disease (MELD) exception guidelines: Results and recommendations from the MELD exception study group and conference (MESSAGE) for the approval of patients who need liver transplantation with diseases not considered by the standar

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