Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency

David P. Dimmock, J. Kay Dunn, Annette Feigenbaum, Anthony Rupar, Rita Horvath, Peter Freisinger, Bénédicte Mousson de Camaret, Lee‐Jun Wong, Fernando Scaglia – 29 September 2008 – Deoxyguanosine kinase (DGUOK) deficiency is the commonest type of mitochondrial DNA depletion associated with a hepatocerebral phenotype. In this article, we evaluate predictors of survival and therapeutic options in patients with DGUOK deficiency.

Improved outcomes in patients with hepatitis C with difficult‐to‐treat characteristics: Randomized study of higher doses of peginterferon α‐2a and ribavirin

Michael W. Fried, Donald M. Jensen, Maribel Rodriguez‐Torres, Lisa M. Nyberg, Adrian M. Di Bisceglie, Timothy R. Morgan, Paul J. Pockros, Amy Lin, Lisa Cupelli, Frank Duff, Ka Wang, David R. Nelson – 26 September 2008 – Treatment response remains suboptimal for many patients with chronic hepatitis C, particularly those with genotype 1 and high levels of viremia. The efficacy of high‐dose regimens of peginterferon alfa‐2a and ribavirin was compared with conventional dose regimens in patients with features predicting poor treatment responses.

Molecular targeted therapies in hepatocellular carcinoma

Josep M. Llovet, Jordi Bruix – 26 September 2008 – Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several genomic alterations. There is evidence of aberrant activation of several signaling cascades such as epidermal growth factor receptor (EGFR), Ras/extracellular signal‐regulated kinase, phosphoinositol 3‐kinase/mammalian target of rapamycin (mTOR), hepatocyte growth factor/mesenchymal‐epithelial transition factor, Wnt, Hedgehog, and apoptotic signaling. Recently a multikinase inhibitor, sorafenib, has shown survival benefits in patients with advanced HCC.

Ammonia impairs neutrophil phagocytic function in liver disease

Debbie L. Shawcross, Gavin A. K. Wright, Vanessa Stadlbauer, Stephen J. Hodges, Nathan A. Davies, Caroline Wheeler‐Jones, Andrew A. Pitsillides, Rajiv Jalan – 26 September 2008 – Hyperammonemia is a feature of liver failure, which is associated with increased risk of infection. The aims of the present study were to determine in vitro, in rats fed an ammoniagenic diet and in patients with cirrhosis, whether induction of hyperammonemia results in neutrophil dysfunction.

Hepatitis C virus envelope components alter localization of hepatocyte tight junction–associated proteins and promote occludin retention in the endoplasmic reticulum

Ignacio Benedicto, Francisca Molina‐Jiménez, Olga Barreiro, Alejandra Maldonado‐Rodríguez, Jesús Prieto, Ricardo Moreno‐Otero, Rafael Aldabe, Manuel López‐Cabrera, Pedro L. Majano – 26 September 2008 – Hepatocyte tight junctions (TJ) play key roles in characteristic liver functions, including bile formation and secretion. Infection by hepatitis C virus (HCV) may cause alterations of the liver architecture and disruption of the bile duct, which ultimately can lead to cholestasis. Herein, we employed the HCV replicon system to analyze the effect of HCV on TJ organization.

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