Hepatitis C virus therapy in liver transplant recipients: Response predictors, effect on fibrosis progression, and importance of the initial stage of fibrosis

Bruno Roche, Mylene Sebagh, Maria Laura Canfora, Teresa Antonini, Anne‐Marie Roque‐Afonso, Valerie Delvart, Faouzi Saliba, Jean‐Charles Duclos‐Vallee, Denis Castaing, Didier Samuel – 24 November 2008 – Antiviral therapy after liver transplantation (LT) using interferon (IFN) and ribavirin (RBV) can achieve a sustained virological response (SVR) rate ranging from 20% to 45%. The aims of our study were to assess efficacy and tolerability of therapy, effect on fibrosis progression and the importance of the initial fibrosis stage to outcome.

Decline in native kidney function in liver transplant recipients is not associated with BK virus infection

Muna Salama, Neil Boudville, David Speers, Garry P. Jeffrey, Paolo Ferrari – 24 November 2008 – BK virus (BKV) infection is an established cause of allograft dysfunction in renal transplant recipients. The relationship between BKV infection and chronic kidney disease (CKD) post–orthotopic liver transplantation (OLT) is not well understood. This study aimed to determine the prevalence of BKV infection, its relationship to CKD and renal function loss over time in patients receiving OLT.

Genotype‐dependent sensitivity of hepatitis C virus to inhibitors of the p7 ion channel

Stephen Griffin, Corine StGelais, Ania M. Owsianka, Arvind H. Patel, David Rowlands, Mark Harris – 24 November 2008 – The hepatitis C virus (HCV) p7 protein plays a critical role during particle formation in cell culture and is required for virus replication in chimpanzees. The discovery that it displayed cation channel activity in vitro led to its classification within the “viroporin” family of virus‐coded ion channel proteins, which includes the influenza A virus (IAV) M2 protein.

Switch from type II to I Fas/CD95 death signaling on in vitro culturing of primary hepatocytes

Dorothée Walter, Kathrin Schmich, Sandra Vogel, Robert Pick, Thomas Kaufmann, Florian Christoph Hochmuth, Angelika Haber, Karin Neubert, Sabine McNelly, Fritz von Weizsäcker, Irmgard Merfort, Ulrich Maurer, Andreas Strasser, Christoph Borner – 24 November 2008 – Fas/CD95‐induced apoptosis of hepatocytes in vivo proceeds through the so‐called type II pathway, requiring the proapoptotic BH3‐only Bcl‐2 family member Bid for mitochondrial death signaling. Consequently, Bid‐deficient mice are protected from anti‐Fas antibody injection induced fatal hepatitis.

Liver‐specific ablation of integrin‐linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly

Vasiliki Gkretsi, Udayan Apte, Wendy M. Mars, William C. Bowen, Jian‐Hua Luo, Yu Yang, Yan P. Yu, Ann Orr, René St.‐Arnaud, Shoukat Dedhar, Klaus H. Kaestner, Chuanyue Wu, George K. Michalopoulos – 24 November 2008 – Hepatocyte differentiation and proliferation are greatly affected by extracellular matrix (ECM). Primary hepatocytes cultured without matrix dedifferentiate over time, but matrix overlay quickly restores differentiation. ECM also is critical in liver regeneration where ECM degradation and reconstitution are steps in the regenerative process.

An abnormal gene expression of the β‐adrenergic system contributes to the pathogenesis of cardiomyopathy in cirrhotic rats

Giulio Ceolotto, Italia Papparella, Antonietta Sticca, Sergio Bova, Maurizio Cavalli, Gabriella Cargnelli, Andrea Semplicini, Angelo Gatta, Paolo Angeli – 24 November 2008 – Decreased cardiac contractility and β‐adrenergic responsiveness have been observed in cirrhotic cardiomyopathy, but their molecular mechanisms remain unclear. To study β‐adrenergic–stimulated contractility and β‐adrenergic gene expression patterns, 20 Wistar Kyoto rats were treated with carbon tetrachloride to induce cirrhosis and 20 rats were used as controls.

Role of leisure‐time physical activity in nonalcoholic fatty liver disease: A population‐based study

Shira Zelber‐Sagi, Dorit Nitzan‐Kaluski, Rebecca Goldsmith, Muriel Webb, Izabel Zvibel, Ilana Goldiner, Laurie Blendis, Zamir Halpern, Ran Oren – 24 November 2008 – Physical activity (PA) is commonly recommended for nonalchoholic fatty liver disease (NAFLD) patients. However, there is limited evidence on the independent role of PA in NAFLD. The aim of this study was to examine the association between PA and NAFLD. We conducted a cross‐sectional study of a subsample (n = 375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for liver disease.

Comparison of a new enzymatic assay with a high‐performance liquid chromatography/ ultraviolet detection method for therapeutic drug monitoring of mycophenolic acid in adult liver transplant recipients

Benoit Blanchet, Fabrice Taieb, Filomena Conti, Halim Abbas, Idrissa Seydi, Laura Harcouet, Alain Dauphin, Yvon Calmus, Michel Tod – 24 November 2008 – Mycophenolic acid (MPA) is used to prevent graft rejection. The methods used for determining the plasma MPA concentration in liver transplant recipients are the enzyme‐multiplied immunoassay technique (EMIT), high‐performance liquid chromatography with ultraviolet detection (HPLC‐UV), and most recently mass spectrometry. EMIT has been reported to overestimate the MPA concentration by 30% to 35% in comparison with HPLC‐UV.

The difference in the fibrosis progression of recurrent hepatitis C after live donor liver transplantation versus deceased donor liver transplantation is attributable to the difference in donor age

Nazia Selzner, Nigel Girgrah, Les Lilly, Maha Guindi, Markus Selzner, George Therapondos, Oyedele Adeyi, Ian McGilvray, Mark Cattral, Paul D. Greig, David Grant, Gary Levy, Eberhard L. Renner – 24 November 2008 – Hepatitis C recurs universally after liver transplantation (LT). Whether its progression differs after live donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) is still debated.

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