Human leukocyte antigen (HLA)‐B*57:01‐restricted activation of drug‐specific T cells provides the immunological basis for flucloxacillin‐induced liver injury

Manal M. Monshi, Lee Faulkner, Andrew Gibson, Rosalind E. Jenkins, John Farrell, Caroline J. Earnshaw, Ana Alfirevic, Karin Cederbrant, Ann K. Daly, Neil French, Munir Pirmohamed, B. Kevin Park, Dean J. Naisbitt – 17 September 2012 – The role of the adaptive immune system in adverse drug reactions that target the liver has not been defined. For flucloxacillin, a delay in the reaction onset and identification of human leukocyte antigen (HLA)‐B*57:01 as a susceptibility factor are indicative of an immune pathogenesis.

Dating the origin and dispersal of hepatitis B virus infection in humans and primates

Dimitrios Paraskevis, Gkikas Magiorkinis, Emmanouil Magiorkinis, Simon Y.W. Ho, Robert Belshaw, Jean‐Pierre Allain, Angelos Hatzakis – 17 September 2012 – The origin of hepatitis B virus (HBV) infection in humans and other primates remains largely unresolved. Understanding the origin of HBV is crucial because it provides a framework for studying the burden, and subsequently the evolution, of HBV pathogenicity with respect to changes in human population size and life expectancy.

Toll‐like receptor 2 and palmitic acid cooperatively contribute to the development of nonalcoholic steatohepatitis through inflammasome activation in mice

Kouichi Miura, Ling Yang, Nico van Rooijen, David A. Brenner, Hirohide Ohnishi, Ekihiro Seki – 17 September 2012 – Innate immune signaling associated with Toll‐like receptors (TLRs) is a key pathway involved in the progression of nonalcoholic steatohepatitis (NASH). Here we show that both TLR2 and palmitic acid are required for activation of the inflammasome, interleukin (IL)‐1α, and IL‐1β, resulting in the progression of NASH. Wild‐type (WT) and TLR2−/− mice were fed a choline‐deficient amino acid–defined (CDAA) diet for 22 weeks to induce NASH.

Preserving the morphology and evaluating the quality of liver grafts by hypothermic machine perfusion: A proof‐of‐concept study using discarded human livers

Diethard Monbaliu, Qiang Liu, Louis Libbrecht, Rita De Vos, Katrien Vekemans, Charlotte Debbaut, Olivier Detry, Tania Roskams, Jos van Pelt, Jacques Pirenne – 17 September 2012 – The wider use of livers from expanded criteria donors and donation after circulatory death donors may help to improve access to liver transplantation. A prerequisite for safely using these higher risk livers is the development of objective criteria for assessing their condition before transplantation.

Donor polymorphisms of toll‐like receptor 4 associated with graft failure in liver transplant recipients

William S. Oetting, Weihua Guan, David P. Schladt, Robert E. Leduc, Pamala A. Jacobson, Arthur J. Matas, Srinath Chinnakotla, Bernd Schröppel, Barbara T. Murphy, Ajay K. Israni – 15 September 2012 – There have been many reports showing significant associations between recipient genetic variants and allograft outcomes, including acute rejection and graft failure, but less is known about the contribution of the donor genotype.

Declining liver utilization for transplantation in the United States and the impact of donation after cardiac death

Eric S. Orman, A. Sidney Barritt, Stephanie B. Wheeler, Paul H. Hayashi – 11 September 2012 – Worsening donor liver quality resulting in decreased organ utilization may be contributing to the recent decline in liver transplants nationally. We sought to examine trends in donor liver utilization and the relationship between donor characteristics and nonuse. We used the United Network for Organ Sharing database to review all deceased adult organ donors in the United States from whom at least 1 solid organ was transplanted into a recipient. Trends in donor characteristics were examined.

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