Hepatitis B virus as a gene delivery vector activating foreign antigenic T cell response that abrogates viral expression in mouse models

Qiang Deng, Maryline Mancini‐Bourgine, Xiaoming Zhang, Marie‐Christine Cumont, Ren Zhu, Yu‐Chun Lone, Marie‐Louise Michel – 29 October 2009 – Chronic hepatitis B virus (HBV) infection is characterized by functionally impaired T cell responses. To ensure active immunotherapy, the immune response must be switched from exhausted T cells to functional effectors that can attain the liver and cure the viral infection. We thus designed a recombinant HBV (rHBV) containing a modified viral core gene that specifically delivers a foreign antigenic polyepitope to the liver.

Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma‐glutamyl transpeptidase levels

Robin Haring, Henri Wallaschofski, Matthias Nauck, Marcus Dörr, Sebastian E. Baumeister, Henry Völzke – 29 October 2009 – The aim of the present study was to investigate the association of serum gamma‐glutamyltransferase (GGT) levels with all‐cause mortality and to assess the impact of ultrasonographic findings of hepatic hyperechogenicity in that association. We used data from 4,160 subjects (2,044 men and 2,116 women) recruited for the population‐based Study of Health in Pomerania (SHIP) without baseline hepatitis B and C infections or liver cirrhosis.

Differential effects of progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1 mutations on canalicular localization of ATP8B1

Dineke E. Folmer, Vincent A. van der Mark, Kam S. Ho‐Mok, Ronald P.J. Oude Elferink, Coen C. Paulusma – 29 October 2009 – Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1), forming a spectrum of cholestatic disease. Whereas PFIC1 is a progressive, endstage liver disease, BRIC1 patients suffer from episodic periods of cholestasis that resolve spontaneously. At present it is not clear how the type and location of the mutations relate to the clinical manifestations of PFIC1 and BRIC1.

Modulation of glycosphingolipid metabolism significantly improves hepatic insulin sensitivity and reverses hepatic steatosis in mice

Nora Bijl, Milka Sokolović, Carlos Vrins, Mirjam Langeveld, Perry D. Moerland, Roelof Ottenhoff, Cindy P. A. A. van Roomen, Nike Claessen, Rolf G. Boot, Jan Aten, Albert K. Groen, Johannes M. F. G. Aerts, Marco van Eijk – 29 October 2009 – Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. The hyperinsulinemia that occurs as a consequence of insulin resistance is thought to be an important contributor to the development of fatty liver.

Calpain activation by hepatitis C virus proteins inhibits the extrinsic apoptotic signaling pathway

Yannick Simonin, Olivier Disson, Hervé Lerat, Etienne Antoine, Fabien Binamé, Arielle R. Rosenberg, Solange Desagher, Patrice Lassus, Paulette Bioulac‐Sage, Urszula Hibner – 29 October 2009 – An unresolved question regarding the physiopathology of hepatitis C virus (HCV) infection is the remarkable efficiency with which host defenses are neutralized to establish chronic infection. Modulation of an apoptotic response is one strategy used by viruses to escape immune surveillance.

Myeloperoxidase and superoxide dismutase 2 polymorphisms comodulate the risk of hepatocellular carcinoma and death in alcoholic cirrhosis

Pierre Nahon, Angela Sutton, Pierre Rufat, Marianne Ziol, Hassan Akouche, Christelle Laguillier, Nathalie Charnaux, Nathalie Ganne‐Carrié, Véronique Grando‐Lemaire, Gisèle N'Kontchou, Jean‐Claude Trinchet, Liliane Gattegno, Dominique Pessayre, Michel Beaugrand – 29 October 2009 – Alcohol increases reactive oxygen species (ROS) formation in hepatocyte mitochondria and by reduced nicotinamide adenine dinucleotide phosphate oxidases and myeloperoxidase (MPO) in Kupffer cells and liver‐infiltrating neutrophils.

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