Indirect action of tumor necrosis factor‐alpha in liver injury during the CD8+ T cell response to an adeno‐associated virus vector in mice

Matthew Giannandrea, Robert H. Pierce, Ian Nicholas Crispe – 28 May 2009 – CD8+ T cells can cause hepatocellular injury by two distinct mechanisms. In addition to their direct cytotoxic effect, there is also collateral liver injury, which occurs when cells are killed in an antigen‐independent manner. Whereas immune effector cytokines interferon‐gamma (IFNγ) and tumor necrosis factor‐alpha (TNFα) have both been implicated in various forms of hepatitis, their respective roles in direct and/or collateral liver damage remains unclear.

Variants in interferon‐alpha pathway genes and response to pegylated interferon‐Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long‐term treatment against cirrhosis trial

Tania Mara Welzel, Timothy R. Morgan, Herbert L. Bonkovsky, Deepa Naishadham, Ruth M. Pfeiffer, Elizabeth C. Wright, Amy A. Hutchinson, Andrew T. Crenshaw, Arman Bashirova, Mary Carrington, Myhanh Dotrang, Richard K. Sterling, Karen L. Lindsay, Robert J. Fontana, William M. Lee, Adrian M. Di Bisceglie, Marc G. Ghany, David R. Gretch, Stephen J. Chanock, Raymond T. Chung, Thomas R.

Extracellular matrix modulates sensitivity of hepatocytes to fibroblastoid dedifferentiation and transforming growth factor β–induced apoptosis

Patricio Godoy, Jan G. Hengstler, Iryna Ilkavets, Christoph Meyer, Anastasia Bachmann, Alexandra Müller, Gregor Tuschl, Stefan O. Mueller, Steven Dooley – 28 May 2009 – Hepatocytes in culture are a valuable tool to investigate mechanisms involved in the response of the liver to cytokines. However, it is well established that hepatocytes cultured on monolayers of dried stiff collagen dedifferentiate, losing specialized liver functions.

Role of adenosine monophosphate‐activated protein kinase–p70 ribosomal S6 kinase‐1 pathway in repression of liver X receptor‐alpha–dependent lipogenic gene induction and hepatic steatosis by a novel class of dithiolethiones

Seong Hwan Hwahng, Sung Hwan Ki, Eun Ju Bae, Hyun Eun Kim, Sang Geon Kim – 28 May 2009 – Dithiolethiones, a novel class of adenosine monophosphate‐activated protein kinase (AMPK) activators, prevent insulin resistance through AMPK‐dependent p70 ribosomal S6 kinase‐1 (S6K1) inhibition. There is no known effect of S6K1 for liver X receptor‐alpha (LXRα)‐mediated lipogenic gene expression and steatosis, a cause of chronic liver disease.

Overexpression of insulin receptor substrate‐1 and hepatitis Bx genes causes premalignant alterations in the liver

Lisa Longato, Suzanne de la Monte, Noriyoshi Kuzushita, Masayoshi Horimoto, Arlin B. Rogers, Betty L. Slagle, Jack R. Wands – 28 May 2009 – Activation of the insulin (IN)/insulin receptor substrate‐1 (IRS‐1)/mitogen‐associated protein kinase (MAPK) and the Wnt/β‐catenin signaling cascades occurs frequently in hepatocellular carcinoma (HCC) associated with persistent viral infection.

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