The Marburg I variant (G534E) of the factor VII–activating protease determines liver fibrosis in hepatitis C infection by reduced proteolysis of platelet‐derived growth factor BB

Hermann E. Wasmuth, Carmen G. Tag, Eddie Van de Leur, Claus Hellerbrand, Tobias Mueller, Thomas Berg, Gero Puhl, Peter Neuhaus, Didier Samuel, Christian Trautwein, Sandip M. Kanse, Ralf Weiskirchen – 24 February 2009 – Genetic risk factors play an important role for the progression of liver fibrosis in chronic hepatitis C virus (HCV) infection, but functional data on specific alleles and their related proteins are limited.

HCV796: A selective nonstructural protein 5B polymerase inhibitor with potent anti‐hepatitis C virus activity In Vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus

Norman M. Kneteman, Anita Y. M. Howe, Tiejun Gao, Jamie Lewis, Dan Pevear, Gary Lund, Donna Douglas, David F. Mercer, D. Lorne J. Tyrrell, Frederick Immermann, Inder Chaudhary, John Speth, Stephen A. Villano, John O'Connell, Marc Collett – 24 February 2009 – Anti‐hepatitis C virus (HCV) drug development has been challenged by a lack of experience with inhibitors inclusive of in vitro, animal model, and clinical study.

Is the iron donor lipocalin 2 implicated in the pathophysiology of hereditary hemochromatosis?

Hua Huang, Shizuo Akira, Manuela M. Santos – 24 February 2009 – Under normal conditions, iron is taken up by the cells through the transferrin‐mediated pathway. However, in hereditary hemochromatosis, a common iron‐overloading disorder associated with mutations in the HFE gene, iron in plasma exceeds transferrin‐binding capacity, and non–transferrin‐bound iron (NTBI) appears in the circulation of patients with iron overload. NTBI can be taken up by hepatocytes through a transferrin‐independent pathway.

Functional linkage of cirrhosis‐predictive single nucleotide polymorphisms of toll‐like receptor 4 to hepatic stellate cell responses

Jinsheng Guo, Johnny Loke, Feng Zheng, Feng Hong, Steven Yea, Masayuki Fukata, Mirko Tarocchi, Olivia T. Abar, Hongjin Huang, John J. Sninsky, Scott L. Friedman – 24 February 2009 – In a recent study, a single nucleotide polymorphism (SNP) of the Toll‐like receptor 4 (TLR4) gene (c.1196C>T [rs4986791, p.T399I]) emerged as conferring protection from fibrosis progression compared to a major, wild‐type (WT) CC allele (p.T399).

Tbx3 promotes liver bud expansion during mouse development by suppression of cholangiocyte differentiation

Timo H.‐W. Lüdtke, Vincent M. Christoffels, Marianne Petry, Andreas Kispert – 24 February 2009 – After specification of the hepatic endoderm, mammalian liver organogenesis progresses through a series of morphological stages that culminate in the migration of hepatocytes into the underlying mesenchyme to populate the hepatic lobes. Here, we show that in the mouse the transcriptional repressor Tbx3, a member of the T‐box protein family, is required for the transition from a hepatic diverticulum with a pseudo‐stratified epithelium to a cell‐emergent liver bud.

Foxl1 is a marker of bipotential hepatic progenitor cells in mice

Sara D. Sackett, Zhaodong Li, Reginald Hurtt, Yan Gao, Rebecca G. Wells, Karrie Brondell, Klaus H. Kaestner, Linda E. Greenbaum – 24 February 2009 – The liver contains a population of small bipotential facultative progenitor cells that reconstitute liver function when mature hepatocytes or cholangiocytes are unable to proliferate. Mesenchymal markers, including members of the forkhead transcription factor gene family, have been detected in hepatic progenitor cells.

Mesenchymal origin of hepatic stellate cells, submesothelial cells, and perivascular mesenchymal cells during mouse liver development

Kinji Asahina, Shirley Y. Tsai, Peng Li, Mamoru Ishii, Robert E. Maxson, Henry M. Sucov, Hidekazu Tsukamoto – 24 February 2009 – The knowledge concerning fetal hepatic stellate cells (HSCs) is scarce, and their cell lineage and functions are largely unknown. The current study isolated fetal liver mesenchymal cells from a mouse expressing β‐galactosidase under the control of Msx2 promoter by fluorescence‐activated cell sorting (FACS) and surveyed marker genes by microarray analysis.

Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: A pathological analysis

Valérie Paradis, Stéphane Zalinski, Emna Chelbi, Nathalie Guedj, Françoise Degos, Valérie Vilgrain, Pierre Bedossa, Jacques Belghiti – 24 February 2009 – Metabolic syndrome (MS) is a newly identified risk factor in chronic liver disease (CLD) and hepatocellular carcinoma (HCC). The aim of this study was to analyze the pathological characteristics of HCC and nontumoral liver in patients with MS as the only risk factor for liver disease in comparison with those that developed in the course of other CLDs in order to provide further insight into the physiopathology of HCC associated with MS.

Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease

Feng Hong, Svetlana Radaeva, Hong‐na Pan, Zhigang Tian, Richard Veech, Bin Gao – 23 February 2009 – Fatty liver, formerly associated predominantly with excessive alcohol intake, is now also recognized as a complication of obesity and an important precursor state to more severe forms of liver pathology including ischemia/reperfusion injury. No standard protocol for treating fatty liver exists at this time.

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