Blockade of Janus kinase‐2 signaling ameliorates mouse liver damage due to ischemia and reperfusion

Maria Cecilia S. Freitas, Yoichiro Uchida, Danyun Zhao, Bibo Ke, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski – 25 January 2010 – Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling is one of the major pathways for cytokine signal transduction. However, the role of the JAK/STAT pathway in liver ischemia/reperfusion is not clear. This study focuses on Janus kinase‐2 (JAK2), which functions upstream of signal transducer and activator of transcription 1 (STAT1) in JAK/STAT, and its role in the mechanism of liver ischemia/reperfusion injury (IRI).

Coronary artery disease in orthotopic liver transplantation: Pretransplant assessment and management

Javed Ehtisham, Mario Altieri, Ephrem Salamé, Eric Saloux, Isabelle Ollivier, Martial Hamon – 25 January 2010 – The prevalence of coronary artery disease in end‐stage liver disease is only now being recognized. Liver transplant patients are a high risk subgroup for coronary artery disease, even if asymptomatic. Coronary artery disease is a predictor of poor outcomes; therefore, identification of those at risk must be a key clinical priority.

Kupffer cells promote hepatic steatosis via interleukin‐1β–dependent suppression of peroxisome proliferator‐activated receptor α activity

Rinke Stienstra, Fredy Saudale, Caroline Duval, Shohreh Keshtkar, Johanna E. M. Groener, Nico van Rooijen, Bart Staels, Sander Kersten, Michael Müller – 25 January 2010 – Kupffer cells have been implicated in the pathogenesis of various liver diseases. However, their involvement in metabolic disorders of the liver, including fatty liver disease, remains unclear. The present study sought to determine the impact of Kupffer cells on hepatic triglyceride storage and to explore the possible mechanisms involved.

Lack of interleukin‐6/glycoprotein 130/signal transducers and activators of transcription‐3 signaling in hepatocytes predisposes to liver steatosis and injury in mice

Daniela C. Kroy, Naiara Beraza, Darjus F. Tschaharganeh, Leif E. Sander, Stephanie Erschfeld, Arne Giebeler, Christian Liedtke, Hermann E. Wasmuth, Christian Trautwein, Konrad L. Streetz – 25 January 2010 – A deregulated cytokine balance is involved in triggering the sequence from steatosis to nonalcoholic steatohepatitis, ultimately leading to liver fibrosis and cancer. To better define the role of proinflammatory interleukin‐6 (IL‐6)‐type cytokines in hepatocytes we investigated the role of IL‐6 and its shared receptor, glycoprotein 130 (gp130), in a mouse model of steatohepatitis.

Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications

Elisa Fabbrini, Shelby Sullivan, Samuel Klein – 25 January 2010 – Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). Steatosis, the hallmark feature of NAFLD, occurs when the rate of hepatic fatty acid uptake from plasma and de novo fatty acid synthesis is greater than the rate of fatty acid oxidation and export (as triglyceride within very low‐density lipoprotein). Therefore, an excessive amount of intrahepatic triglyceride (IHTG) represents an imbalance between complex interactions of metabolic events.

Calcineurin inhibitor tacrolimus does not interfere with the suppression of hepatitis C virus infection by interferon‐α

Qiuwei Pan, Herold J. Metselaar, Petra de Ruiter, Jaap Kwekkeboom, Hugo W. Tilanus, Harry L. A. Janssen, Luc J. W. van der Laan – 25 January 2010 – Immunosuppression considerably affects hepatitis C virus (HCV) recurrence and the outcome of antiviral treatment after liver transplantation. Recent findings have suggested that the calcineurin inhibitor tacrolimus (Tac), unlike cyclosporine A (CsA), interferes with the antiviral activity of interferon‐α (IFN‐α) in vitro.

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