Immunosuppression in liver transplant.

The increasing potency of immunosuppression (IS) agents resulted in significantly decreased rates of steroid resistant rejection and rejection related graft loss in liver transplantation (LT). Currently, more than two thirds of late mortality after LT is unrelated to graft function. However, the increased benefit of more potent IS drugs, coupled with the prolonged survival of transplant recipients led to longer patients exposure to these drugs and their unwanted adverse effects, creating a double-edged sword. In this article the authors describe the mechanism of action and the adverse effects of the most commonly used immunosuppressed drugs, and the most commonly used IS regimens for both induction and maintenance regimens. The balance between the ideal IS regimen to prevent rejection and the need to minimize the dose of IS drugs in order to prevent the adverse effects related to its use requires the knowledge of the science and the experience with the art of medicine. The different protocols aimed at protecting renal function and preventing the development of de novo cancer and metabolic syndrome are discussed here. The main causes of mortality late after liver transplant are associated with prolonged use of IS medications, and clear evidence exists about over-immunosuppression of recipients of liver transplant. The current status of strategies of IS minimization and withdrawal are reviewed in this article, with evaluation of its benefits and pitfalls.

Stretching the boundaries for liver transplant in the 21st century.

Given the high waiting list mortality, there is a clear need to identify strategies to increase the number of livers for transplantation. Some strategies require policy changes, whereas others depend on a better understanding of available opportunities. We divided the strategies to increase the number of livers for transplantation into two categories-those aiming to increase the use of organs considered to be of suboptimal quality, and those aiming to increase the use of organs considered to be of suboptimal size. Enough evidence suggests that, if considered in the context of other donor and recipient variables, grafts from elderly donors are a safe option. The severity of steatosis, and not simply its presence, is an important factor in contemplating the utility of steatotic grafts. Use of organs that have steatosis together with other factors that define extended-criteria organs should be avoided, particularly prolonged cold ischaemia time. Donation after circulatory death has an important role in increasing the donor pool, given the wide availability of organs from donors with this cause of death. This type of donation is hampered by a higher risk of ischaemia-reperfusion injury than other types of donation, which can result in graft complications and potential graft loss. Different types of machine perfusion have the potential to overcome these issues, and further research is needed to establish the best techniques and most cost-effective models. Despite the scarcity of data, the availability of safe and highly effective antiviral therapies means that the use of donors infected with hepatitis C virus (HCV) in recipients who are HCV negative can be considered as a strategy to increase the donor pool. Although data on transplantations using livers from living donors in patients with a Model for End-Stage Liver Disease (MELD) score higher than 20-24 are scarce, outcomes are similar to those achieved in patients with lower MELD scores, at least in reference centres. Increased use of split livers is an option if donors and recipients are carefully selected.

International Liver Transplantation Society Consensus Statement on Immunosuppression in Liver Transplant Recipients.

Effective immunosupression management is central to achieving optimal outcomes in liver transplant recipients. Current immunosuppression regimens and agents are highly effective in minimizing graft loss due to acute and chronic rejection but can also produce a substantial array of toxicities. The utilization of immunosuppression varies widely, contributing to the wide disparities in posttransplant outcomes reported between transplant centers. The International Liver Transplantation Society (ILTS) convened a consensus conference, comprised of a global panel of expert hepatologists, transplant surgeons, nephrologists, and pharmacologists to review the literature and experience pertaining to immunosuppression management to develop guidelines on key aspects of immunosuppression. The consensus findings and recommendations of the ILTS Consensus guidelines on immunosuppression in liver transplant recipients are presented in this article.

The New Era of Hepatitis C: Therapy in Liver Transplant Recipients.

Hepatitis C virus (HCV) is the leading cause of end-stage liver disease in both Europe and the United States and is the most common reason for liver transplant. In the absence of antiviral therapy, recurrent infection is the norm with subsequent graft hepatitis and impaired survival. Whether it may be better to postpone therapy in patients in whom higher risk of failure and toxicity is coupled with lower chance of liver function improvement likely depends on several factors, including waiting time, center allocation policy, presence of hepatocellular carcinoma and local prevalence of anti-HCV-positive donors.