Sensitivity of hepatitis C virus to cyclosporine A depends on nonstructural proteins NS5A and NS5B

Fiona Fernandes, Daniel S. Poole, Spencer Hoover, Rannveig Middleton, Adin‐Cristian Andrei, Justin Gerstner, Rob Striker – 28 June 2007 – HCV reoccurs after liver transplantation and increases mortality. Cyclosporine, but not tacrolimus, has potent antiviral effects against HCV replication in cell culture. To determine the conditions, if any, under which HCV is susceptible to cyclosporine in vivo, we selected for cyclosporine‐resistant mutant HCV in vitro. The resulting mutations were mapped to x‐ray crystallographic structures and sequence databases.

Sodium retention and ascites formation in a cholestatic mice model: Role of aldosterone and mineralocorticoid receptor?

Daniel Ackermann, David Mordasini, Lydie Cheval, Martine Imbert‐Teboul, Bruno Vogt, Alain Doucet – 27 June 2007 – Renal sodium retention in experimental liver cirrhosis originates from the distal nephron sensitive to aldosterone. The aims of this study were to (1) determine the exact site of sodium retention along the aldosterone‐sensitive distal nephron, and (2) to evaluate the role of aldosterone and mineralocorticoid receptor activation in this process. Liver cirrhosis was induced by bile duct ligation in either adrenal‐intact or corticosteroid‐clamped mice.

Triphasic decline of hepatitis C virus RNA during antiviral therapy

Harel Dahari, Ruy M. Ribeiro, Alan S. Perelson – 27 June 2007 – When patients chronically infected with hepatitis C virus (HCV) are placed on antiviral therapy with pegylated interferon (IFN)‐α or IFN‐α plus ribavirin (RBV), HCV RNA generally declines in a biphasic manner. However, a triphasic decline has been reported in a subset of patients. A triphasic decline consists of a first phase (1‐2 days) with rapid virus load decline, followed by a “shoulder phase” (4‐28 days) in which virus load decays slowly or remains constant, and a third phase of renewed viral decay.

Development and validation of a disease‐targeted quality of life instrument in chronic hepatitis B: The hepatitis B quality of life instrument, version 1.0

Brennan M. R. Spiegel, Roger Bolus, Steven Han, Myron Tong, Eric Esrailian, Jennifer Talley, Tram Tran, Jason Smith, Hetal A. Karsan, Francisco Durazo, Bruce Bacon, Paul Martin, Zobair Younossi, Siew Hwa‐Ong, Fasiha Kanwal – 27 June 2007 – Despite the increasing realization that health‐related quality of life (HRQOL) is an important outcome in chronic HBV infection, there are no validated, disease‐targeted instruments currently available.

On the TRAIL to therapeutic intervention in liver disease

Ingrid Herr, Peter Schemmer, Markus W. Büchler – 27 June 2007 – Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. The fact that HCC is resistant to conventional chemotherapy and is rarely amenable to radiotherapy leaves this disease with no effective therapeutic options and a very poor prognosis. Therefore, the development of more effective therapeutic tools and strategies is much needed.

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