Ischemia reperfusion injury (IRI) predisposes to the formation of donor-specific antibodies, a factor contributing to chronic rejection and late allograft loss.
Vascular endothelial growth factor (VEGF) is a potent secreted mitogen critical for physiologic and tumor angiogenesis.Regulation of VEGF occurs at several levels, including transcription, mRNA stabilization, translation, and differential cellular localization of various isoforms.Recent advances in our understanding of posttranscriptional regulation of VEGF include identification of the stabilizing mRNA binding protein, HuR, and the discovery of internal ribosomal entry sites in the 5'UTR of the VEGF mRNA.Monoclonal anti-VEGF antibody was recently approved for use in humans, but suffers from the need for high systemic doses.RNA interference (RNAi) technology is being used in vitro and in animal models with promising results.Here, we review the literature on post-transcriptional regulation of VEGF and describe recent progress in targeting these mechanisms for therapeutic benefit.
Abstract Non‐alcoholic steatohepatitis ( NASH ) is rapidly becoming the leading indication for liver transplantation ( LT ) in the United States. While post‐transplantation outcomes are similar to other indications for transplant, recent evidence has suggested that reduction in risk factors for post‐transplant metabolic syndrome may impose a significant survival benefit in this patient population. Cardiovascular mortality is the leading cause of death following transplantation for NASH . While pre‐transplant pharmacologic and surgical approaches have been utilized to reduce cardiovascular risk factors following transplantation, the effectiveness of these treatment approaches in the post‐transplant setting is poorly defined. Studies are urgently needed in the treatment of this rapidly growing population.
The techniques of liver transplantation have evolved significantly over the last few decades, and the development of collaborative, multidisciplinary care has become a key component of successful outcomes in transplant recipients. Fundamentals of organ allocation, hepatic anatomy, surgical technique, and risks of complications must be understood by all clinicians caring for liver transplant patients. Each phase of the transplant operation has unique physiologic circumstances, each with its own potential for success or failure. Biliary complications are most common, followed by hepatic arterial, portal venous, and hepatic venous complications. New techniques, especially the introduction of living donor liver transplantation (LDLT), have been used to further expand the donor pool and provide excellent long-term patient outcomes. The development of piggyback techniques also facilitated the capability of split liver and LDLT. As the retrohepatic vena cava must stay with the donor, all living donor transplants are completed using piggyback techniques.
