Roles of Akt/PKB and IKK complex in constitutive induction of NF‐κB in hepatocellular carcinomas of transforming growth factor α/c‐myc transgenic mice

Valentina Factor, Aundrea L. Oliver, Ganesh R. Panta, Snorri S. Thorgeirsson, Gail E. Sonenshein, Marcello Arsura – 30 December 2003 – NF‐κB regulates liver cell death during development, regeneration, and neoplastic transformation. For example, we showed that oncogenic Ras‐ or Raf‐mediated transformation of rat liver epithelial cells (RLEs) led to altered NF‐κB regulation through IKK complex activation, which rendered these cells more resistant to TGF‐β1‐induced apoptosis.

Toll‐like receptor 4 is involved in the mechanism of early alcohol‐induced liver injury in mice

Takehiko Uesugi, Matthias Froh, Gavin E. Arteel, Blair U. Bradford, Ronald G. Thurman – 30 December 2003 – Chronic alcohol administration increases gut‐derived endotoxin in the portal blood, which activates Kupffer cells and causes liver injury. Mice (C3H/HeJ) with mutations in toll‐like receptor 4 (TLR4) are hyporesponsive to endotoxin. To test the hypothesis that TLR4 is involved in early alcohol‐induced liver injury, the long‐term intragastric ethanol feeding protocol developed by Tsukamoto and French for rats was adapted to mice.

High amino acid variability within the NS5A of hepatitis C virus (HCV) is associated with hepatocellular carcinoma in patients with HCV‐1b–related cirrhosis

Mireia Giménez‐Barcons, Sandra Franco, Yanette Suárez, Xavier Forns, Sergi Ampurdanès, Francesc Puig‐Basagoiti, Alberto Sánchez‐Fueyo, Josep‐Maria Barrera, Josep‐Maria Llovet, Jordi Bruix, José‐María Sánchez‐Tapias, Juan Rodés, Juan‐Carlos Saiz – 30 December 2003 – Interferon therapy may decrease the risk of hepatocellular carcinoma in patients with hepatitis C virus (HCV)‐related liver cirrhosis. Interaction of the cellular protein kinase PKR with the PKR‐binding domain (PKR‐bd) of HCV‐NS5A protein may affect cellular growth control and viral resistance to interferon therapy.

Peroxisome proliferator–activated receptor‐α−/− mice show enhanced hepatocyte proliferation in response to the hepatomitogen 1,4‐bis[2‐(3,5‐dichloropyridyloxy)] benzene, a ligand of constitutive androstane receptor

Amedeo Columbano, Giovanna M. Ledda‐Columbano, Monica Pibiri, Danilo Concas, Janardan K. Reddy, M. Sambasiva Rao – 30 December 2003 – Previously, we have suggested that liver cell proliferation induced by certain mitogens is dependent on their binding and activation of nuclear receptors of the steroid/thyroid superfamily.

Studies of murine schistosomiasis reveal interleukin‐13 blockade as a treatment for established and progressive liver fibrosis

Monica G. Chiaramonte, Allen W. Cheever, James D. Malley, Debra D. Donaldson, Thomas A. Wynn – 30 December 2003 – In several allergic, autoimmune, and infectious diseases, fibrosis is a major cause of morbidity and mortality. Here, using a model of infection‐induced liver fibrosis, we show that interleukin (IL)‐13 is required at all stages of Schistosomiasis mansoni infection to induce fibrosis. IL‐4 production was preserved in IL‐13–deficient mice, yet failed to significantly contribute to the fibrotic response in either acute or chronic infection.

Acquisition of susceptibility to hepatitis C virus replication in HepG2 cells by fusion with primary human hepatocytes: Establishment of a quantitative assay for hepatitis C virus infectivity in a cell culture system

Takayoshi Ito, Kotaro Yasui, Jun Mukaigawa, Asao Katsume, Michinori Kohara, Keiji Mitamura – 30 December 2003 – Hepatitis C virus (HCV) replicates in human and chimpanzee hepatocytes. To characterize the nature of HCV and evaluate antiviral agents, the development of an HCV replication system in a cell culture is essential. We developed a cell line derived from human hepatocytes by fusing them with a hepatoblastoma cell line, HepG2, and obtained several clones.

Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection

Robert A. de Man, Leonieke M. M. Wolters, Frederik Nevens, David Chua, Morris Sherman, Cing L. Lai, Adrian Gadano, Youngmee Lee, Fransesco Mazzotta, Neil Thomas, Deborah DeHertogh – 30 December 2003 – Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo‐controlled, dose‐escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow‐up was 24 weeks.

Familial intrahepatic cholestasis 1: Studies of localization and function

Peter Ujhazy, Daniel Ortiz, Suniti Misra, Shohua Li, James Moseley, Hugh Jones, Irwin M. Arias – 30 December 2003 – Mutations in the FIC1 gene constitute the molecular defect in familial intrahepatic cholestasis I (Fic1 [Byler's disease]) and benign recurrent intrahepatic cholestasis. This report describes the localization of Fic1 in rat liver and intestine, as well as biochemical and transfection studies that support its function as an energy‐dependent aminophospholipid translocase.

Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen–negative Chinese carriers

Jinlin Hou, Zhanghui Wang, Jinjun Cheng, Yulong Lin, George K. K. Lau, Jian Sun, Fuyuan Zhou, Jenny Waters, Peter Karayiannis, Kangxian Luo – 30 December 2003 – Previous studies have suggested that hepatitis B virus (HBV) variants may account for the presence of HBV DNA in hepatitis B surface antigen (HBsAg)‐negative patients (occult HBV infection). However, it is not known how widespread these variants are and how they influence the course of liver disease.

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