Hepatitis B virus X protein increases expression of p21Cip‐1/WAF1/MDA6 and p27Kip‐1 in primary mouse hepatocytes, leading to reduced cell cycle progression

Liang Qiao, Kevin Leach, Robert McKinstry, Donna Gilfor, Adly Yacoub, Jong Sung Park, Steven Grant, Philip B. Hylemon, Paul B. Fisher, Paul Dent – 30 December 2003 – Previously, we have linked prolonged intense mitogen‐activated protein kinase (MAP kinase; MAPK) signaling in hepatocytes to increased expression of p21Cip‐1/WAF1/MDA6 (p21) and p16INK4a (p16), that leads to a p21‐dependent growth arrest. In this study, we investigated the impact of hepatitis B virus X protein (pX) expression on MAPK‐modulated cell cycle progression in primary mouse hepatocytes.

Bile acid feeding increased proliferative activity and apical bile acid transporter expression in both small and large rat cholangiocytes

Gianfranco Alpini, Yoshiyuki Ueno, Shannon S. Glaser, Marco Marzioni, Jo Lynne Phinizy, Heather Francis, Gene LeSage – 30 December 2003 – Bile acids (BA) enter cholangiocytes by the Na+‐dependent apical BA transporter (ABAT). By this mechanism, taurocholate (TC) and taurolithocholate (TLC) increase cholangiocyte proliferation. No in vivo studies exist regarding the anatomical sites involved in BA‐regulation of cholangiocyte growth. Specific cholangiocyte subpopulations participate in BA‐regulated proliferation.

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.

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.

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.

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.

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.

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.

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.

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