Hepatic venous pressure gradient identifies patients at risk of severe hepatitis C recurrence after liver transplantation

Alejandro Blasco, Xavier Forns, José A. Carrión, Juan Carlos García‐Pagán, Rosa Gilabert, Antoni Rimola, Rosa Miquel, Miquel Bruguera, Juan‐Carlos García‐Valdecasas, Jaime Bosch, Miquel Navasa – 22 February 2006 – Liver biopsy is essential in the follow‐up of HCV‐infected liver transplant recipients. The aim of this study was to prospectively compare percutaneous (PLB) versus transjugular liver biopsy (TLB) in the assessment of liver damage.

Characterization of the hepatitis C virus E2 epitope defined by the broadly neutralizing monoclonal antibody AP33

Alexander W. Tarr, Ania M. Owsianka, Judith M. Timms, C. Patrick McClure, Richard J. P. Brown, Timothy P. Hickling, Thomas Pietschmann, Ralf Bartenschlager, Arvind H. Patel, Jonathan K. Ball – 22 February 2006 – The mouse monoclonal antibody (MAb) AP33, recognizing a 12 amino acid linear epitope in the hepatitis C virus (HCV) E2 glycoprotein, potently neutralizes retroviral pseudoparticles (HCVpp) carrying genetically diverse HCV envelope glycoproteins. Consequently, this antibody and its epitope are highly relevant to vaccine design and immunotherapeutic development.

Zonal gene expression in murine liver: Lessons from tumors

Stephan Hailfinger, Maike Jaworski, Albert Braeuning, Albrecht Buchmann, Michael Schwarz – 22 February 2006 – Gene expression in hepatocytes within the liver lobule is differentially regulated along the portal to central axis; however, the mechanisms governing the processes of zonation within the lobule are unknown. A model for zonal heterogeneity in normal liver is proposed, based on observations of differential expression of genes in liver tumors from mice that harbor activating mutations in either Catnb (which codes for β‐catenin) or Ha‐ras.

Improved prognosis for patients hospitalized with esophageal varices in Sweden 1969–2002

Knut Stokkeland, Lena Brandt, Anders Ekbom, Rolf Hultcrantz – 22 February 2006 – Liver cirrhosis may be complicated by the development of esophageal varices. The treatment of esophageal varices has changed radically during the last 30 years. Our aim was to study whether the prognosis for patients with esophageal varices had improved in Sweden between 1969 and 2002.

The use of vasoconstrictors in patients with cirrhosis: Type 1 HRS and beyond

Richard Moreau, Didier Lebrec – 22 February 2006 – In patients with cirrhosis and type 1 hepatorenal syndrome (HRS), systemic vasodilation, which is mainly attributable to splanchnic vasodilation, plays a critical role in the activation of endogenous vasoconstrictor systems, resulting in renal vasoconstriction and functional renal failure. It has been suggested that the use of splanchnic (and systemic) vasoconstrictors such as terlipressin (a vasopressin analog) or alpha‐1‐adrenoceptor agonists (midodrine or noradrenaline) may improve renal function in patients with type 1 HRS.

A novel function for a micro RNA: Negative regulators can do positive for the hepatitis C virus

Nicole Appel, Ralf Bartenschlager – 22 February 2006 – MicroRNAs are small RNA molecules that regulate messenger RNA (mRNA) expression. MicroRNA 122 (miR‐122) is specifically expressed and highly abundant in the human liver. We show that the sequestration of miR‐122 in liver cells results in marked loss of autonomously replicating hepatitis C viral RNAs. A genetic interaction between miR‐122 and the 5′ noncoding region of the viral genome was revealed by mutational analyses of the predicted microRNA binding site and ectopic expression of miR‐122 molecules containing compensatory mutations.

Ascorbic acid improves the intrahepatic endothelial dysfunction of patients with cirrhosis and portal hypertension

Manuel Hernández‐Guerra, Juan C. García‐Pagán, Juan Turnes, Pablo Bellot, Ramón Deulofeu, Juan G. Abraldes, Jaime Bosch – 22 February 2006 – Patients with cirrhosis show intrahepatic endothelial dysfunction, characterized by an impaired flow‐dependent vasorelaxation. This alteration is responsible for the marked postprandial increase in portal pressure and is attributed to an insufficient release of nitric oxide (NO).

Targeted delivery of ribavirin improves outcome of murine viral fulminant hepatitis via enhanced anti‐viral activity

Gary A. Levy, Gord Adamson, M. James Phillips, Louise A. Scrocchi, Laisum Fung, Pieter Biessels, Nancy F. Ng, Anand Ghanekar, Andrea Rowe, Max Xuezhong Ma, Adam Levy, Cheryl Koscik, William He, Reginald Gorczynski, Steve Brookes, Caroline Woods, Ian D. McGilvray, David Bell – 22 February 2006 – Side effects of interferon–ribavirin combination therapy limit the sustained viral response achievable in hepatitis C virus (HCV) patients. Coupling ribavirin to macromolecular carriers that target the drug to the liver would reduce systemic complications.

Conversion from tacrolimus to cyclosporine in liver transplanted patients with diabetes mellitus

Jérôme Dumortier, Sophie Bernard, Yves Bouffard, Olivier Boillot – 22 February 2006 – Adverse effects associated with calcineurin inhibitors may impact their clinical utility in some patients. This study characterizes the clinical outcomes of liver transplanted (LT) patients who experienced diabetes mellitus (DM) on tacrolimus‐based regimen and were converted to cyclosporine‐based therapy. Since January 2002, all patients with DM on a tacrolimus‐based regimen were recruited and converted to cyclosporine‐based therapy, after a 6‐month minimal follow‐up after LT.

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