Immune Tolerance After Liver Transplantation
4
Citation
115
Reference
10
Related Paper
Citation Trend
Keywords:
Immunosuppression
Immunosuppression
Basal (medicine)
Cite
Citations (20)
Post-transplant immunosuppression almost always includes a combination of drugs and approaches based on a patient's individual situation, organ transplanted, and current developments in the field. Depending on these factors, approaches could include Induction immunosuppression, Maintenance immunosuppression, or Anti-rejection immunosuppression.
Immunosuppression
Cite
Citations (0)
For children with liver transplants (LT), achieving an "ideal outcome" is a balancing act: too little immunosuppression begets graft injury; too much begets systemic complications. We aimed to delineate the parental perspective on this tightrope.Parents of children with LT completed an internet-based survey about their child's immunosuppression.Children of respondents (n = 82) were a median 4 years from primary LT (range 0-22); 73% were on immunosuppression monotherapy. Parents' top concerns were related to immunosuppression complications; 46% were more concerned about immunosuppression complications than rejection; only 17% were more concerned about rejection than immunosuppression complications. Among parents of children on immunosuppression monotherapy, 29% still worried more about immunosuppression complications than rejection, 48% expressed equal concern for both. Time since LT (0-4 vs. >4 years) was not associated with concern level for rejection or immunosuppression complications. Caregivers were significantly more certain that their child's immunosuppression regimen was correct to prevent rejection than to mitigate complications (p < .005).Caregivers of children with LTs reported higher levels of concern and uncertainty about immunosuppression complications than rejection risk. Understanding parent and patient perspectives on IS, and incorporating them into immunosuppression counseling and decision-making, is critical to achieving truly "ideal" long-term outcomes.
Immunosuppression
Regimen
Cite
Citations (2)
(1) Immunosuppression is responsible for excellent patient outcomes. (2) Immunosuppression withdrawal fails in most patients. (3) Patients who may benefit from immunosuppression withdrawal cannot currently be identified. (4) No data suggest that immunosuppression withdrawal decreases patient morbidity (ie, nephrotoxicity). (5) The minimization of immunosuppression instead of withdrawal may be adequate for improving patient outcomes.
Immunosuppression
Nephrotoxicity
Cite
Citations (15)
Abstract With the continued improvements in outcome following liver transplantation, the drawbacks associated with conventional immunosuppression regimens become increasingly apparent. Although up to 70% of patients develop a histological infiltrate of the graft (acute rejection), many of these will resolve spontaneously, and chronic rejection is rare. If a robust form of allograft acceptance or tolerance can be established, then immunosuppression can be withdrawn along with all the accompanying risks. The liver is already known to be associated with downregulated immune responses; the mechanism for this is unclear, but may be related to a number of mechanisms known to be involved in peripheral tolerance. There are many strategies being studied for achieving allograft tolerance, including the use of modern immunosuppressants, antibodies that target key molecules in the immune response, and recruitment of leukocytes to allografts. In the interim, it is necessary to look for safe protocols that allow trials of tolerance strategies without putting patients at increased risk.
Immunosuppression
Peripheral tolerance
Interim
Cite
Citations (15)
Objective To evaluate the significance of individual immunosuppression regime in liver transplant recipients with high risk factors. Methods Every liver transplant recipient received different immunosuppression regime based on different clinical conditions. Renal failure, acute rejection, bacterial, fungal and cytomegaloviral infection rate and hospital mortality were compared among the high risk recipients ( n =20) with individual immunosuppression regime, high risk recipients ( n =22) with routine immunosuppression regime and common recipients ( n =26) with routine regime. Results Renal failure, bacterial, fungal infection rate and hospital mortality were significantly different between high risk patients with individual immunosuppression regime and those with routine immunosuppression regime ( P 0.05 ). There was no significant difference in acute rejection and cytomegaloviral infection rate between two groups ( P 0.05 ). There was no significant difference in the above observed parameters between high risk recipients with individual immunosuppression regime and common recipients with routine regime ( P 0.05 ). Conclusion Individual immunosuppression regime can prolong the survival of the recipients with high risk factors and is proved to be more safe and reliable.
Immunosuppression
Cite
Citations (0)
Immunosuppression
Cite
Citations (4)
Purpose of review Conquering allograft rejection remains an elusive goal in spite of recent breakthroughs in the field of immunosuppression. Much of the problem lies in the toxicity and side-effects of long-term use of systemic immunosuppressant drugs, which are sometimes ineffective in controlling rejection, but also hinder establishment of transplant tolerance. In this review, we discuss novel technologies that use grafts engineered with immunomodulatory molecules as a means of inducing tolerance. Recent findings Several recent studies have demonstrated the feasibility of engineering cells, tissues, or solid organ grafts with immunoregulatory biologics to achieve long termgraft survival without the use of chronic immunosuppression. This approach was shown to primarily change the ratio of T effector versus CD4+CD25+FoxP3+ T regulatory cells within the graft microenvironment in favor of attaining localized tolerance induction and maintenance. Summary Localized immunomodulation using biologic-engineered allografts represent a new paradigm for achieving long-term graft survival in the absence of chronic use of immunosuppression. The manipulation of the graft, rather than the recipient, not only ensures short- and long-term safety by minimizing the adverse effects of immunosuppression, but also allows retention of immune competency critical for the ability of the recipient to fight infections and cancer.
Cite
Citations (6)
Life-long immunosuppression (IS) has always been considered the traditional approach in the management of transplant recipients to protect the hepatic graft from rejection. The liver is a tolerogenic organ with impressive immune regulatory mechanisms that maintain local and systemic immune tolerance to antigens, as well the capability to trigger effective immune responses against pathogens. The King's College team identified independent factors that were associated with sustained IS withdrawal: non-autoimmune liver disease; fewer donor—recipient human leucocyte antigen mismatches; and no previous acute rejection episode. From the reported data it is clear that it is possible safely to reduce and even discontinue IS therapy in up to 40% of selected liver allograft recipients. The identification of tolerance biomarkers is of central importance, in order to be able to develop a protocol that can be applied to all suitable patients.
Immunosuppression
Liver disease
Graft rejection
Cite
Citations (3)
Abstract A prospective identification of the estimated 20–50% of pediatric LTX recipients developing operational tolerance would be of great clinical advantage. So far markers of immune tolerance – T‐cell subpopulations or gene expression profiles – have been investigated only retrospectively in successfully weaned patients. Fifty children aged 8–265 months (median 89) were investigated 1–180 months (median 44) after LTX under ongoing immunosuppression. T‐cell subpopulations were measured during regular post‐transplant visits using FACS (Vδ1‐ vs. Vδ2‐γδ‐T cells and Tregs). A Vδ1/Vδ2‐γδ‐T‐cell ratio ≥1.42 previously reported in operational tolerance was found in 12 of 50 (24%) patients. In analogy, a Treg count ≥44 per μL was found in 35 of 50 (70%) patients and a Treg proportion ≥2.23% of CD 3 + ‐T cells in 39 of 50 (78%) patients. Only 9 of 50 patients (18%) fulfilled both criteria. The parameters Vδ1/Vδ2‐γδ‐T‐cell ratio and Tregs were not significantly correlated to each other or with donor type or immunosuppression. Vδ1/Vδ2‐γδ‐T‐cell ratio was more stable in serial examinations compared with Treg analyses. The observed proportion of 18% pediatric LTX patients with potential operational tolerance is in accordance with previous reports. However, clinical experience shows that rejections may happen even after long‐time weaning of immunosuppression. This suggests that operational tolerance is a dynamic process, with uncertain prediction by Vδ1/Vδ2‐γδ‐T‐cell ratio and/or Tregs under immunosuppression.
Immunosuppression
Cite
Citations (22)