Genomics of liver transplant injury and regeneration

Abstract

While improved surgical techniques, post-operative care, and immunosuppression regimens have reduced morbidity and mortality associated with orthotopic liver transplantation (OLT), further improvement of outcomes requires personalized treatment and a better understanding of genomic mechanisms involved. Gene expression profiles of ischemia/reperfusion (I/R) injury, regeneration, and rejection, may suggest mechanisms for development of better predictive tools and treatments. The liver is unique in its regenerative potential, recovering lost mass and function after injury from ischemia, resection, and rejection. I/R injury, an inevitable consequence of perfusion cessation, cold storage, and reperfusion, is regulated by the interaction of the immune system, inflammatory cytokines, and reduced microcirculatory blood flow in the liver. Rejection, a common post-operative complication, is mediated by the recipient's immune system through T-cell-dependent responses activating proinflammatory and apoptotic pathways. Characterizing distinctive gene expression signatures for these events can identify therapies to reduce injury, promote regeneration, and improve outcomes. While certain markers of liver injury and regeneration have been observed in animals, many of these are unverified in human studies. Further investigation of these genomic signatures and mechanisms through new technology offers promise, but continues to pose a significant challenge. An overview of the current fund of knowledge in this area is reviewed.