Sirolimus‐based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma

Christian Toso, Shaheed Merani, David L. Bigam, A.M. James Shapiro, Norman M. Kneteman – 26 March 2010 – Liver transplantation is an important treatment option for selected patients with nonresectable hepatocellular carcinoma (HCC). Several reports have suggested a lower risk of posttransplant tumor recurrence with the use of sirolimus and a higher one with calcineurin inhibitors, but the selection of an ideal immunosuppression protocol is still a matter of debate.

Nucleotide‐binding oligomerization domain containing 2 (NOD2) variants are genetic risk factors for death and spontaneous bacterial peritonitis in liver cirrhosis

Beate Appenrodt, Frank Grünhage, Martin G. Gentemann, Lydia Thyssen, Tilman Sauerbruch, Frank Lammert – 26 March 2010 – Spontaneous bacterial peritonitis (SBP), a severe complication in patients with advanced liver cirrhosis, has been attributed to bacterial translocation from the intestine. Variants of the NOD2 (nucleotide‐binding oligomerization domain containing 2) gene have been associated with impaired mucosal barrier function in Crohn disease. We hypothesized that the risk of acquiring SBP is increased in patients with cirrhosis carrying NOD2 variants.

The emerging role of T cell immunoglobulin mucin‐1 in the mechanism of liver ischemia and reperfusion injury in the mouse

Yoichiro Uchida, Bibo Ke, Maria Cecilia S. Freitas, Haofeng Ji, Danyun Zhao, Elizabeth R. Benjamin, Nader Najafian, Hideo Yagita, Hisaya Akiba, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski – 26 March 2010 – The T cell immunoglobulin and mucin domain‐containing molecules (TIM) protein family, which is expressed by T cells, plays a crucial role in regulating host adaptive immunity and tolerance. However, its role in local inflammation, such as innate immunity‐dominated organ ischemia–reperfusion injury (IRI), remains unknown.

HFE C282Y homozygotes are at increased risk of breast and colorectal cancer

Nicholas J. Osborne, Lyle C. Gurrin, Katrina J. Allen, Clare C. Constantine, Martin B. Delatycki, Christine E. McLaren, Dorota M. Gertig, Gregory J. Anderson, Melissa C. Southey, John K. Olynyk, Lawrie W. Powell, John L. Hopper, Graham G. Giles, Dallas R. English – 26 March 2010 – The evidence that mutations in the HFE gene for hemochromatosis are associated with increased cancer risk is inconsistent. The Melbourne Collaborative Cohort Study is a prospective cohort study that commenced recruitment in 1990.

Targeting mitogen‐activated protein kinase kinase with the inhibitor PD0325901 decreases hepatocellular carcinoma growth in vitro and in mouse model systems

Matthew Hennig, Michele T. Yip‐Schneider, Sabrina Wentz, Huangbing Wu, S. K. Hekmatyar, Patrick Klein, Navin Bansal, C. Max Schmidt – 26 March 2010 – Hepatocellular carcinoma (HCC) is a common cause of death from solid organ malignancy worldwide. Extracellular signal‐regulated/mitogen‐activated protein kinase kinase (MEK) signaling is a critical growth regulatory pathway in HCC. Targeting MEK with a novel small molecule inhibitor, PD0325901, may inhibit HCC tumorigenesis.

Consistent beneficial effects of killer cell immunoglobulin‐like receptor 2DL3 and group 1 human leukocyte antigen‐C following exposure to hepatitis C virus

Susanne Knapp, Usama Warshow, Doha Hegazy, Louise Brackenbury, I. Neil Guha, Andrew Fowell, Ann‐Margaret Little, Graeme J. Alexander, William M.C. Rosenberg, Matthew E. Cramp, Salim I. Khakoo – 26 March 2010 – Natural killer cells are a key component in the immune control of viral infections. Their functions are controlled by inhibitory receptors for major histocompatability complex (MHC) class I, including the killer cell immunoglobulin‐like receptors (KIR).

Peginterferon alpha‐2a is associated with higher sustained virological response than peginterferon alfa‐2b in chronic hepatitis C: Systematic review of randomized trials

Tahany Awad, Kristian Thorlund, Goran Hauser, Davor Stimac, Mahasen Mabrouk, Christian Gluud – 26 March 2010 – A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (peginterferon alpha‐2a or peginterferon alfa‐2b) is most effective. We performed a systematic review of head‐to‐head randomized trials to assess the benefits and harms of the two treatments.

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