Global challenges in liver disease

Roger Williams – 29 August 2006 – Immigration, cheap air travel, and globalization are all factors contributing to a worldwide spread of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. End‐stage chronic liver disease (ESLD) as a result of co‐infection with HBV/HCV is now the major cause of death for individuals who have been infected with the HIV virus. The high incidence of HCV infection in Egypt—the legacy left from the mass use of tartar emetic to eradicate schistosomiasis, as in other high prevalence areas—will take years to reduce.

Ischemic preconditioning of the murine liver protects through the Akt kinase pathway

Kunihiko Izuishi, Allan Tsung, Mohammad Akram Hossain, Masao Fujiwara, Hisao Wakabayashi, Tsutomu Masaki, Timothy R. Billiar, Hajime Maeta – 29 August 2006 – Hepatic ischemia‐reperfusion (I/R) injury occurs in the settings of transplantation, trauma, and elective liver resection. Ischemic preconditioning has been used as a strategy to reduce inflammation and organ damage from I/R of the liver. However, the mechanisms involved in this process are poorly understood.

Involvement of integrin‐linked kinase in carbon tetrachloride–induced hepatic fibrosis in rats

Yining Zhang, Tadashi Ikegami, Akira Honda, Teruo Miyazaki, Bernard Bouscarel, Marcos Rojkind, Ichinosuke Hyodo, Yasushi Matsuzaki – 29 August 2006 – Integrin‐linked kinase (ILK) is a multidomain focal adhesion protein implicated in signal transduction between integrins and growth factor receptors. Although its expression is upregulated in pulmonary and renal fibrosis, its role in the development of hepatic fibrosis remains to be determined.

Hypercholesterolemia in rats with hepatomas: Increased oxysterols accelerate efflux but do not inhibit biosynthesis of cholesterol

Takeshi Hirayama, Akira Honda, Yasushi Matsuzaki, Teruo Miyazaki, Tadashi Ikegami, Mikio Doy, Guorong Xu, Michael Lea, Gerald Salen – 29 August 2006 – Hypercholesterolemia is an important paraneoplastic syndrome in patients with hepatoma, but the nature of this defect has not yet been identified. We investigated the molecular mechanisms of hypercholesterolemia in a hepatoma‐bearing rat model. Buffalo rats were implanted in both flanks with Morris hepatoma 7777 (McA‐RH7777) cells. After 4 weeks, tumor weight was 5.5 ± 1.7 g, and serum cholesterol level increased from 60 ± 2 to 90 ± 2 mg/dL.

Disruption of the Arnt gene in endothelial cells causes hepatic vascular defects and partial embryonic lethality in mice

Sun Hee Yim, Yatrik Shah, Shuhei Tomita, H. Douglas Morris, Oksana Gavrilova, Gilles Lambert, Jerrold M. Ward, Frank J. Gonzalez – 29 August 2006 – Vascular endothelial cells (ECs) play a critical role in angiogenesis and organogenesis, especially in embryonic liver development. Hypoxia‐inducible transcription factors (Hifs) are a key trigger of hypoxic signals, a primary stimulus of angiogenesis. The aryl hydrocarbon receptor nuclear translocator (Arnt), also called Hif‐1β, serves as an obligate heterodimerization partner of Hif‐1α and Hif‐2α.

HLA class II alleles, genotypes, haplotypes, and amino acids in primary biliary cirrhosis: A large‐scale study

Peter T. Donaldson, Anna Baragiotta, Michael A. Heneghan, Annarosa Floreani, Carla Venturi, James A. Underhill, David E.J. Jones, Oliver F.W. James, Margaret F. Bassendine – 29 August 2006 – Twin and family studies suggest there is a significant genetic component to primary biliary cirrhosis (PBC). However, the inability to replicate reported associations has been a recurring problem, with the only consistently reported genetic association that between PBC and HLA‐DRB1*0801. However, recently even this has been questioned, and a number of novel associations have also been reported.

Matrix metalloproteinase‐9 is an important factor in hepatic regeneration after partial hepatectomy in mice

Eric W. Olle, Xiaodan Ren, Shannon D. McClintock, Roscoe L. Warner, Michael P. Deogracias, Kent J. Johnson, Lisa M. Colletti – 29 August 2006 – Partial hepatectomy triggers hepatocyte proliferation, hepatic matrix remodeling, and hepatocyte apoptosis, all of which are important processes in the regenerating liver. Previous studies have shown an increase in the levels of matrix metalloproteinases gelatinase A (MMP‐2) and gelatinase B (MMP‐9) after partial hepatectomy. The goal of this study was to investigate the role of MMP‐9 in liver regeneration after partial hepatectomy.

Patterns of viral decline during PEG‐interferon alpha‐2b therapy in HBeAg‐positive chronic hepatitis B: Relation to treatment response

Martijn J. ter Borg, Monika van Zonneveld, Stefan Zeuzem, Hakan Senturk, Ulus S. Akarca, Christopher Simon, Bettina E. Hansen, Bart L. Haagmans, Robert A. de Man, Solko W. Schalm, Harry L.A. Janssen, HBV 99‐01 Study Group – 29 August 2006 – In chronic hepatitis B, it is difficult to predict an early therapeutic response. We investigated the viral decline during therapy with pegylated interferon alpha‐2b (PEG‐IFN) with or without lamivudine in 266 HBeAg‐positive chronic hepatitis B patients.

Pegylated interferon alpha‐2b as monotherapy or in combination with ribavirin in chronic hepatitis delta

Grazia Anna Niro, Alessia Ciancio, Giovanni Battista Gaeta, Antonina Smedile, Aldo Marrone, Antonella Olivero, Maria Stanzione, Ezio David, Giuseppina Brancaccio, Rosanna Fontana, Francesco Perri, Angelo Andriulli, Mario Rizzetto – 29 August 2006 – Therapy of chronic hepatitis delta with standard interferon therapy has met with limited efficacy. This study was designed to examine the efficacy and safety of peginterferon with or without ribavirin.

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