Uric acid and anti‐TNF antibody improve mitochondrial dysfunction in ob/ob mice

Inmaculada García‐Ruiz, Cristina Rodríguez‐Juan, Teresa Díaz‐Sanjuan, Pilar del Hoyo, Francisco Colina, Teresa Muñoz‐Yagüe, José A. Solís‐Herruzo – 29 August 2006 – The mechanisms responsible for low mitochondrial respiratory chain (MRC) activity in the liver of patients with nonalcoholic steatohepatitis are unknown. In this study, we examined the cause of this dysfunction in ob/ob mice.

Critical role of acidic sphingomyelinase in murine hepatic ischemia‐reperfusion injury

Laura Llacuna, Montserrat Marí, Carmen Garcia‐Ruiz, José C. Fernandez‐Checa, Albert Morales – 29 August 2006 – The molecular mechanisms of hepatic ischemia/reperfusion (I/R) damage are incompletely understood. We investigated the role of ceramide in a murine model of warm hepatic I/R injury. This sphingolipid induces cell death and participates in tumor necrosis factor (TNF) signaling.

Proteomic profiling of cholangiocarcinoma: Diagnostic potential of SELDI‐TOF MS in malignant bile duct stricture

Christopher J. Scarlett, Alex J. Saxby, AiQun Nielsen, Cameron Bell, Jaswinder S. Samra, Thomas Hugh, Robert C. Baxter, Ross C. Smith – 29 August 2006 – Proteomic techniques promise to improve the diagnosis of cholangiocarcinoma (CC) in both tissue and serum as histological diagnosis and existing serum markers exhibit poor sensitivities. We explored the use of surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF MS) to identify potential protein biomarkers of CC. Twenty‐two resected CC samples were compared with adjacent noninvolved bile duct tissue.

CD4+ immune escape and subsequent T‐cell failure following chimpanzee immunization against hepatitis C virus

Montserrat Puig, Kathleen Mihalik, John C. Tilton, Ollie Williams, Michael Merchlinsky, Mark Connors, Stephen M. Feinstone, Marian E. Major – 29 August 2006 – Hepatitis C is a major cause of chronic liver disease, with 170 million individuals infected worldwide and no available vaccine. We analyzed the effects of an induced T‐cell response in 3 chimpanzees, targeting nonstructural proteins in the absence of neutralizing antibodies. In all animals the specific T‐cell response modified the outcome of infection, producing a 10‐ to 1,000‐fold reduction in peak virus titers.

Peginterferon alpha‐2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B

Karsten Wursthorn, Marc Lutgehetmann, Maura Dandri, Tassilo Volz, Peter Buggisch, Bernhard Zollner, Thomas Longerich, Peter Schirmacher, Frauke Metzler, Myrga Zankel, Conrad Fischer, Graeme Currie, Carol Brosgart, Joerg Petersen – 29 August 2006 – Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for persistent infection of hepatocytes. The aim of this study was to determine changes in intrahepatic cccDNA in patients with chronic hepatitis B (CH‐B) during 48 weeks of antiviral therapy and its correlation to virological, biochemical, and histological parameters.

Investigation of the Lith1 candidate genes ABCB11 and LXRA in human gallstone disease

Clemens Schafmayer, Jürgen Tepel, Andre Franke, Stephan Buch, Sören Lieb, Marcus Seeger, Frank Lammert, Bernd Kremer, Ulrich R. Fölsch, Fred Fändrich, Stefan Schreiber, Jochen Hampe – 29 August 2006 – Genetic susceptibility in the causation of gallbladder diseases was recognized as early as 1937. A major gallstone susceptibility locus (Lith1) was identified in 1995 by quantitative trait locus mapping in mice. Two attractive positional and functional candidate genes in LXRA and ABCB11 are located in this interval. ABCB11 is associated with progressive familial cholestasis.

Lack of UCP2 reduces fas‐mediated liver injury in ob/ob mice and reveals importance of cell‐specific UCP2 expression

Péter Fülöp, Zoltán Derdák, Anthony Sheets, Edmond Sabo, Eric P. Berthiaume, Murray B. Resnick, Jack R. Wands, György Paragh, György Baffy – 29 August 2006 – Fatty liver is vulnerable to conditions that challenge hepatocellular energy homeostasis. Lipid‐laden hepatocytes highly express uncoupling protein‐2 (UCP2), a mitochondrial carrier that competes with adenosine triphosphate (ATP) synthesis by mediating proton leak. However, evidence for a link between UCP2 expression and susceptibility of liver to acute injury is lacking.

Hepatitis C virus entry: Molecular biology and clinical implications

Heidi Barth, T. Jake Liang, Thomas F. Baumert – 29 August 2006 – With an estimated 170 million infected individuals, hepatitis C virus (HCV) has a major impact on public health. A vaccine protecting against HCV infection is not available, and current antiviral therapies are characterized by limited efficacy, high costs, and substantial side effects. Binding of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between virus and the target cell that is required for the initiation of infection.

Efficacy of peginterferon alpha‐2b in chronic hepatitis delta: Relevance of quantitative RT‐PCR for follow‐up

Corinne Castelnau, Frédéric Le Gal, Marie‐Pierre Ripault, Emmanuel Gordien, Michelle Martinot‐Peignoux, Nathalie Boyer, Bach‐Nga Pham, Sarah Maylin, Pierre Bedossa, Paul Dény, Patrick Marcellin, Elyanne Gault – 29 August 2006 – Hepatitis delta virus (HDV) can cause severe acute and chronic liver disease in patients infected by hepatitis B virus. Interferon alpha at high doses, although poorly efficient, is the only treatment reported to provide some benefit in chronic hepatitis delta. Pegylated interferon alpha (PEG‐IFN) has not yet been evaluated.

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