Criteria Donor Grafts Research Articles

The Role of Normothermic Machine Perfusion in Extended Criteria Donor Grafts: A New Direction in Liver Graft Assessment and Preservation

Despite improvements in short-term and long-term outcomes of liver transplant patients, the discrepancy between the number of available livers and transplant candidates continues to increase. The use of expanded criteria donors is one strategy that can be used to address donor shortages. In recent years, preservation strategies such as normothermic machine perfusion (NMP) have been explored to improve the preservation of organs and test their viability before transplantation. We reviewed the recent literature and trials assessing the use of NMP in the setting of liver transplantation. Multiple feasibility trials have demonstrated the clinical prospect of NMP and proved its numerous advantages compared to conventional static cold storage. These advantages include preservation and viability assessment of high-risk donor allografts and grafts that would have otherwise been discarded. This review aims to address the topic of liver NMP in the setting of current and future applications in the setting of extended criteria donor grafts.

Application of extended criteria donor grafts in liver transplantation for acute-on-chronic liver failure: A retrospective cohort study.

There is no consensus on the usage of extended criteria donor (ECD) grafts in liver transplantation (LT) for acute-on-chronic liver failure (ACLF) patients. To summarize the experience of using ECD livers in ACLF-LT. A retrospective cohort study was conducted, enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021. The patients were divided into ECD and non-ECD groups for analysis. A total of 145 recipients were enrolled in this study, of which ECD and non-ECD recipients accounted for 53.8% and 46.2%, respectively. Donation after cardiac death (DCD) recipients accounted for the minority compared with donation after brain death (DBD) recipients (16.6% vs 83.4%). Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients. ECD grafts were associated with a significantly higher incidence of early allograft dysfunction (EAD) than non-ECD grafts (67.9% vs 41.8%, P = 0.002). Postoperative outcomes between DCD and DBD recipients were comparable (P > 0.05). ECD graft (P = 0.009), anhepatic phase (P = 0.034) and recipient gamma glutamyltransferase (P = 0.016) were independent risk factors for EAD. Recipient preoperative number of extrahepatic organ failures > 2 (P = 0.015) and intraoperative blood loss (P = 0.000) were independent predictors of poor post-LT survival. Although related to a higher risk of EAD, ECD grafts can be safely used in ACLF-LT. The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.

Utilization of hepatitis B surface antigen-positive donors in liver transplantation for recipients with hepatocellular carcinoma: a retrospective and propensity score matching analysis.

The use of extended criteria donor (ECD) grafts such as donor with infection of hepatitis B virus (HBV) is a potential solution for organ shortage. In this study, we aimed to evaluate the safety and long-term survival of utilization of hepatitis B surface antigen-positive (HBsAg+) donor livers in HCC patients using propensity score matching (PSM) analysis. Forty-eight donors with HBsAg-positive and 279 donors with HBsAg-negative were transplanted and enrolled in this study. PSM analysis were used to eliminate selection bias. Perioperative data and survival were collected and analyzed. PSM generated 44 patient pairs. When comparing intra- and post-operative data, no significant difference was found between groups (P>0.05). Patients with a HBsAg-positive donor had significantly worse progression-free survival (1-year: 65.9% vs. 90.9%; 3-year: 18.1% vs. 70.4%, P=0.0060) and overall survival (1-year: 84.1% and 95.4%; 3-year: 27.2% vs. 79.5%, P=0.0039). In multivariate analysis, donor HBsAg-positivity was an independent risk factor for survival and occurrence (P=0.005 and 0.025, respectively). In conclusion, with adequate antiviral prophylaxis and treatment, utilization of HBsAg positive liver grafts did not increase the incidence of early-stage complications. However, patient with an HBsAg-positive graft had poorer progression-free survival and overall survival.

Experimental and Clinical Aspects of Sevoflurane Preconditioning and Postconditioning to Alleviate Hepatic Ischemia-Reperfusion Injury: A Scoping Review.

Ischemia-reperfusion injury (IRI) is an inflammatory process inherent in organ transplantation procedures. It is associated with tissue damage and, depending on its intensity, can impact early graft function. In liver transplantation (LT), strategies to alleviate IRI are essential in order to increase the use of extended criteria donor (ECD) grafts, which are more susceptible to IRI, as well as to improve postoperative graft and patient outcomes. Sevoflurane, a commonly used volatile anesthetic, has been shown to reduce IRI. This scoping review aims to give a comprehensive overview of the existing experimental and clinical data regarding the potential benefits of sevoflurane for hepatic IRI (HIRI) and to identify any gaps in knowledge to guide further research. We searched Medline and Embase for relevant articles. A total of 380 articles were identified, 45 of which were included in this review. In most experimental studies, the use of sevoflurane was associated with a significant decrease in biomarkers of acute liver damage and oxidative stress. Administration of sevoflurane before hepatic ischemia (preconditioning) or after reperfusion (postconditioning) appears to be protective. However, in the clinical setting, results are conflicting. While some studies showed a reduction of postoperative markers of liver injury, the benefit of sevoflurane on clinical outcomes and graft survival remains unclear. Further prospective clinical trials remain necessary to assess the clinical relevance of the use of sevoflurane as a protective factor against HIRI.

313.6: Early Graft Disfunction After Hypothermic Oxygenated Machine Perfusion of ECD Criteria Liver Grafts: No Longer A Clinical Issue?

Introduction: Early allograft disfunction (EAD) continues to be an important issue in liver transplantation, varying from 15 to 30%. This rate is particularly high in case of extended criteria donor (ECD) grafts due to significant ischemia-reperfusion injury leading to EAD. This injury is substantially reduced by thermoregulated oxygenated machine perfusion. The aim of the paper was to assess the use of hypothermic oxygenated machine perfusion (HOPE) in ECD liver grafts in a high-volume liver transplantation center using a specific protocol. Method: Grafts with >30% macrosteatosis and with multiple ECD (at least 2 criteria) were perfused using dual HOPE (hepatic artery and portal vein perfusion), while HOPE (portal vein perfusion only) was used for the remaining ECD grafts. The main criteria to establish graft improvement were the improvement of arterial and portal perfusion flows, with lactate under 3 mmol/L throughout the procedure. Results: Between February 2016 and February 2022, 26 ECD liver grafts were harvested from DBD (donation after brain death) donors and benefitted from HOPE. Dual HOPE was used in 8 grafts (30.7%). Criteria for graft improvement were met in all grafts except 5 (19.2%), where lactate was over 3 mmol/L, with a median of 3.6 (range 3.5-6.1). The median follow-up was 5 months (range 2-44). No EAD was encountered. Conclusion: By using a combined protocol of HOPE and dual HOPE, ECD liver grafts may be safely used by avoiding early graft dysfunction.

Elevated effluent potassium concentrations predict the development of postreperfusion hyperkalemia in deceased liver transplantation: a retrospective cohort study

BackgroundPostreperfusion hyperkalemia (PRHK) has garnered increasing attention in regard to deceased liver transplantation (LT), especially for LT using the expanded criteria donor grafts. However, the impact of the effluent potassium (eK+) concentration on PRHK has been largely overlooked. We evaluated whether elevated eK+ concentrations are associated with PRHK in deceased LT.MethodsIn this single-institution, retrospective cohort study, we included all adults who underwent deceased LT with intraoperative eK+ concentration monitoring between November 2016 and December 2018. The eK+ concentrations were obtained from the effluent samples collected following a standard portal vein flush. PRHK was defined as any serum potassium (sK+) level of > 5.5 mmol/L following reperfusion. Logistic regression was performed to identify predictors for PRHK, and linear regression was used to examine predictors of the maximum percentage increase in the sK+ level following reperfusion.ResultsOf the 86 patients who met the inclusion criteria, 54 (62.8%) developed PRHK. Independent predictors for PRHK included greater graft weight (OR 1.283 [95% CI 1.029–1.599] per 100 g, P = 0.027), an elevated eK+ concentration (OR 1.291 [95% CI 1.068–1.561] per mol/L, P = 0.008), and a higher sK+ level before reperfusion (OR 4.459 [95% CI 1.543–12.884] per mol/L, P = 0.006). An eK+ concentration of more than 6.9 mmol/L had a sensitivity of 59.26% and a specificity of 78.12% for predicting PRHK (area under the receiver operating characteristic curve, 0.694). Multiple linear regression analyses indicated that the eK+ and sK+ levels before reperfusion were significant predictors of the maximum percentage increase in the sK+ level following reperfusion. In addition, PRHK was associated with an increased risk of postreperfusion significant arrhythmias, severe postreperfusion syndrome, and postoperative early allograft dysfunction.ConclusionsThis study shows that the eK+ concentration could predict the risk of PRHK in deceased LT. Further prospective studies are warranted to clarify these associations.

The First Series of Normothermic Machine Perfusion in India - The Way Ahead

Background: Normothermic machine perfusion (NMP) has revolutionized the field of liver transplant and is rapidly gaining popularity for utilising suboptimal livers, which were refused previously.Marginal liver with static cold storage (SCS) is associated with increased risk of primary non-function & early allograft dysfunction. NMP enables preservation of liver in "near-physiological" conditions.NMP promotes better utilisation of the resources to meet the increasing demand for organs. Case Series: We have used NMP (OrganOx) for three patients as summarized: Case 1 - Donor was a 65yr old elderly male, alcoholic since 35 yrs. Case 2 - The donor liver biopsy revealed 40-50% steatosis. Case 3 - The arrival of recipient was delayed by 6 hours. Perfusate fluid– PRBCs, Gelofusin, NaHCO3,Insulin,Bilesalts, Prostacyclins, Antibiotics and Nutrients. These donor livers were given a trial of NMP at 37°C. During NMP, perfusion fluid samples were assessed for arterial blood gases (pH, pO2, pCO2, HCO3), lactates, glucose,calcium and potassium every 30 minutes. Bile production was measured to assess liver function.As the measured indices were satisfactory, we have used the harvested organs for transplant. All the recipients fared well post-transplant with normothermic machine perfused organs. Conclusion: NMP addresses the dilemma of using extended criteria donor grafts. NMP optimises the donor liver utilization by improved preservation techniques, graft reconditioning and viability assessment before transplantation. Thus, our experience of NMP is promising and shows huge potential for future research.

A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion

No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = − 0.874, P < 0.001), AST (R = − 0.812, P = 0.004) and ALT (R = − 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts.

Effect of Aprotinin on Liver Injury after Transplantation of Extended Criteria Donor Grafts in Humans: A Retrospective Propensity Score Matched Cohort Analysis.

The number of patients awaiting liver transplantation still widely exceeds the number of donated organs available. Patients receiving extended criteria donor (ECD) organs are especially prone to an aggravated ischemia reperfusion syndrome during liver transplantation leading to massive hemodynamic stress and possible impairment in organ function. Previous studies have demonstrated aprotinin to ameliorate reperfusion injury and early graft survival. In this single center retrospective analysis of 84 propensity score matched patients out of 274 liver transplantation patients between 2010 and 2014 (OLT), we describe the association of aprotinin with postreperfusion syndrome (PRS), early allograft dysfunction (EAD: INR 1,6, AST/ALT > 2000 within 7–10 days) and recipient survival. The incidence of PRS (52.4% vs. 47.6%) and 30-day mortality did not differ (4.8 vs. 0%; p = 0.152) but patients treated with aprotinin suffered more often from EAD (64.3% vs. 40.5%, p = 0.029) compared to controls. Acceptable or poor (OR = 3.3, p = 0.035; OR = 9.5, p = 0.003) organ quality were independent predictors of EAD. Our data do not support the notion that aprotinin prevents nor attenuates PRS, EAD or mortality.

Use of the new preservation solution Custodiol-MP for ex vivo reconditioning of kidney grafts.

Organ shortage and the increasing use of extended criteria donor grafts for transplantation drives efforts for more efficient organ preservation strategies from simple cold storage toward dynamic organ reconditioning. The choice of a suitable preservation solution is of high relevance in different organ preservation or reconditioning situations. Custodiol-MP is a new machine perfusion solution giving the opportunity to add colloids according to organ requirements. The present study aimed to compare new Custodiol-MP with clinically established Belzer MPS solution. Porcine kidneys were ischemically predamaged and cold stored for 20 hours. Ex vivo machine reconditioning was performed either with Custodiol-MP (n = 6) or with Belzer MPS solution (n = 6) for 90 minutes with controlled oxygenated rewarming up to 20°C. Kidney function was evaluated using an established ex vivo reperfusion model. In this experimental setting, differences between both types of perfusion solutions could not be observed. Machine perfusion with Custodiol-MP resulted in higher creatinine clearance (7.4±8.6 mL/min vs. 2.8±2.5 mL/min) and less TNC perfusate levels (0.22±0.25 ng/mL vs. 0.09±0.08 ng/mL), although differences did not reach significance. For short-term kidney perfusion Custodiol-MP is safe and applicable. Particularly, the unique feature of flexible colloid supplementation makes the solution attractive in specific experimental and clinical settings.

The Role of Metabolomics in Current Concepts of Organ Preservation.

In solid organ transplantation (Tx), both survival rates and quality of life have improved dramatically over the last few decades. Each year, the number of people on the wait list continues to increase, widening the gap between organ supply and demand. Therefore, the use of extended criteria donor grafts is growing, despite higher susceptibility to ischemia-reperfusion injury (IRI) and consecutive inferior Tx outcomes. Thus, tools to characterize organ quality prior to Tx are crucial components for Tx success. Innovative techniques of metabolic profiling revealed key pathways and mechanisms involved in IRI occurring during organ preservation. Although large-scale trials are needed, metabolomics appears to be a promising tool to characterize potential biomarkers, for the assessment of graft quality before Tx and evaluate graft-related outcomes. In this comprehensive review, we summarize the currently available literature on the use of metabolomics in solid organ Tx, with a special focus on metabolic profiling during graft preservation to assess organ quality prior to Tx.

Effects of donor macrosteatosis and post transplant and post transplant complement activation on early allograft dysfunction in liver transplant patients

Presenter: Kelley Nunez PhD | Ochsner Health System Background: Liver transplantation provides a curative option for patients with underlying cirrhosis. However, organ shortage continues to increase waitlist mortality. To combat this, less than optimal organs have been used for transplantation. These extended criteria donor grafts are accompanied by increased risk of both graft failure and decreased patient survival. In this study, we investigated the impact of donor Macrosteatosis on early allograft dysfunction, complement activation, and inflammatory mediators in recipients. Methods: Cohort consisted of patients who received a liver transplant at Ochsner Medical Center from November 2011 – April 2019. Clinical variables and donor macrosteatosis percentages were retrospectively extracted from the electronic medical record. Recipient blood samples were collected immediately following liver transplantation in a subset of cohort. Multiple indices to determine early allograft dysfunction were calculated, and ELISA’s were performed on the blood samples for complement activation measurements and damage associated molecular proteins. Results: Cohort consisted of 1322 patients with median Donor age of 44, 58% male. Increases in donor Macrosteatosis led to significant increases in liver enzymes, INR, and bilirubin, all measures of liver damage. Higher levels of early allograft dysfunction were also found in patients receiving donor grafts with > 20% macrosteatosis. These patients had increased complement activation of both C3a and C5a, and significantly higher levels of the alarmin IL-33. Conclusion: Recipients that receive donor grafts with > 20% macrosteatosis have higher levels of liver damage, complement activation, and alarmin release. Proactive measures of lower complement activation may decrease presence of early allograft dysfunction.

Crucial Role of Extended Criteria Donors in Deceased Donor Single Kidney Transplantation to Face Chronic Shortage in the Heart of the Mediterranean Basin: A Single-Center Experience

BackgroundThe gap between organ availability and patients on the waiting list for deceased donor kidney transplants has resulted in the wide use of extended criteria donors (ECDs).We aimed to compare the surgical outcomes of single kidney transplantation (KT) performed at our institute with standard criteria donor (SCD) or ECD grafts, according to the Organ Procurement and Transplantation Network definition. Patients and methods. Our retrospective analysis studied 115 adult recipients of KT from January 2016 to July 2018, with kidney grafts procured from adult donors after brain or circulatory death, performed at our institute. Among the 2 recipients’ groups, we compared the incidence of early graft loss, delayed graft function, hospitalization, and surgical complications. We compared the evaluation of time to early graft loss with Kaplan-Meier estimators and curves; the hypothesis of no difference in time to graft loss between the 2 groups was tested using the log-rank statistics. ResultsOf the 103 deceased donor kidney transplants during the study period, 129 grafts were used after the regional network sharing allocation. More frequently, ECDs had a greater body mass index than SCDs (25.2 ± 3.9 vs 27.7 ± 5.0, P = .005) and type II diabetes mellitus (0% vs 18%, P = .002). KT recipients who received an ECD graft (73, 63.5%) were older (59.8 ± 9.8 vs 45.2 ± 15.4, P < .001) and presented a higher rate of delayed graft function (56% vs 24%, P = .001). Post-transplant graft loss did not differ among the 2 groups. ConclusionBased on clinical experience in a single transplant center, ECD use for KTs is crucial in facing the organ shortage, without impairing post-deceased donor kidney transplant outcomes.

Chronic Kidney Disease After Liver Transplantation: Impact of Extended Criteria Grafts.

The use of extended criteria donor (ECD) grafts has been associated with acute kidney injury (AKI) after liver transplantation. However, the relation between graft quality and development of chronic kidney disease (CKD) remains unknown. Therefore, the aim of this study was to analyze the impact of ECD grafts for CKD after liver transplantation. All patients (2007-2015) transplanted for end-stage liver disease at our center were assessed. Longterm kidney function was divided into 4 groups: no CKD (estimated glomerular filtration rate [eGFR], ≥60 mL/minute/1.73 m2 ), mild CKD (eGFR, 30-59 mL/minute/1.73 m2 ), severe CKD (eGFR, 15-29 mL/minute/1.73 m2 ), and end-stage renal disease (ESRD). Marginal donation after brain death (DBD) grafts (donor age, >70 years; body mass index, >35 kg/m2 ; cold storage, >12 hours) and donation after circulatory death (DCD) grafts were considered ECD grafts. Overall, 926 patients were included, and 43% received an ECD graft (15% marginal DBD; 28% DCD). After 5 years, 35% developed CKD; severe CKD and ESRD occurred in only 2% and 1%, respectively. CKD rates were comparable for all 3 graft groups (standard group, 36%; marginal DBD group, 29%; DCD group, 35%; standard versus marginal DBD groups, P=0.16; standard versus DCD group, P=0.80). None of the ECD criteria were identified as independent risk factors in a Cox regression model for CKD. Risk factors included recipient age, female sex, and preoperative kidney function. Furthermore, recipients who had severe acute kidney injury (AKI; Kidney Disease: Improving Global Outcomes stages 2 and 3) had a 1.8-fold increased risk for CKD. Longterm kidney function of recipients with severe AKI depended on the recovery of kidney function in the first postoperative week. In conclusion, there is no direct relation between the use of ECD grafts and CKD after liver transplantation. However, caution should be taken in recipients who experience severe AKI, regardless of graft type.

Tacrolimus overexposure in kidney transplant recipients during the first post-operative week: caution is required in older patients.

In liver transplantation, tacrolimus trough concentrations (Cmin) above 20 ng/mL during the first days led to worse outcome at 1 year but data in the kidney transplant (KT) era are scarce. The aim of this study was to evaluate the impact of tacrolimus overexposure during the first week post-transplantation on the kidney function (KF) of KT recipients. In this retrospective study, 105 KT recipients were attributed to overexposure group (OG) or normal group according to their Cmin during the first week of treatment. KF was evaluated by comparing the rate of delayed graft function (DGF) and by collecting plasma creatinine from day 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 and at 1 year. Risk factors for developing DGF were also investigated using a multivariate model. DGF was more frequent in OG (43% of patients; P = 0.027) which has higher plasma creatinine on day 7, 14, and 21. OG patients were older with more extended criteria donor's grafts. In the multivariate analysis, only cold ischemia time (CIT) remained associated with DGF (OR = 1.003), while TAC overexposure did not reach significance (P = 0.06; OR = 3.9). In this study, we confirmed the predominant role of CIT as a risk factor for the onset of DGF in kidney transplantation. 43% of KT recipients were overexposed with more DGF, especially older patients.

Outcomes of Liver Transplantation Using Organ Donation After Brain Death (DBD) versus Organ Donation After Cardiac Death (DCD): A Single Center Experience

Introduction: Donation after cardiac death (DCD) liver allografts have been associated with primary nonfunction, ischemic cholangiopathy, hepatic artery stenosis and a higher re-transplantation rate when compared with donation after brain death (DBD) allografts. The number of liver transplantation (LT) with DCD allografts has increased in the recent years. We present our experience with using this extended criteria donor grafts. Primary objective: To compare patient and graft survival between DBD and DCD allografts. Secondary objective: To compare biliary and vascular rates of LT complications between both groups. Methods: We retrospectively reviewed all LTs performed at a major transplant center from January 2012 to April 2017. We included patients who received a combined liver and kidney transplant (n = 29), and excluded patients who received a split LT (n =4). DCD and DBD allografts were compared using Chisquare, Fischer exact test, log-rank tests and Kaplan-Meier plot analysis. Results: A total of 409 patients were analyzed, 100 patients received DCD grafts, and 309 patients received DBD grafts. There was no significant difference in the recipient age, gender, BMI or donor age, gender and BMI of both groups. The DBD recipients had a higher biological (p = 0.001) and match MELD scores, (p = 0.005) while the DCD donors had a higher donor risk index (p < 0.0001). Cholangiopathy in the DCD group was 12.2% and 3.6% in the DBD group, p = 0.001. Although, the rate of non-anastomotic biliary strictures, however, was significantly different between both groups (Table 1), cholangiopathy did not appear to be significant in predicting patient or graft survival in a sub-group analysis. Patient survival in DCD recipients was 92.7% at 1 year, and 80.3% at 4 years versus 96% at 1 year and 88.5% at 4 years in DBD recipients, p = 0.27. Graft survival in DCD recipients was 88% at 1 year, and 76.3% at 4 years versus 94.1% at 1 year and 78.8% at 4 years in DBD recipients, p = 0.34 (Figure 1).Figure: Patient and graft survival Kaplan-Meier curves.Conclusion: With careful selection, LT outcomes of DCD organs are comparable to DBD organs.Figure: Demographics and outcomes by donor relationship.

Advances in Reducing Liver Allograft Injury

The shortage of organs for liver transplantation has led to the use of more extended criteria donor grafts and grafts recovered from Donation after circulatory death (DCD) donors. The former are more vulnerable to Ischemia-reperfusion injury (IRI) because of pre-existing pathology and the latter experience significant warm ischemia during organ recovery. Reducing the impact of IRI in extended criteria and DCD grafts is key to better outcomes in liver transplantation and could lead to expansion of the donor pool by increasing the utility of suboptimal organs. At each stage of the transplantation procedure there is opportunity to reduce the impact of IRI. This review discusses the underlying pathophysiology of IRI as it occurs in liver transplantation and summarises the advances that have been made in reducing human liver allograft injury through preconditioning, ex vivo conditioning and post-conditioning.

Postoperative Insulin-Like Growth Factor 1 Levels Reflect the Graft's Function and Predict Survival after Liver Transplantation.

BackgroundThe reduction of insulin-like growth factor 1 (IGF-1) plasma levels is associated with the degree of liver dysfunction and mortality in cirrhotic patients. However, little research is available on the recovery of the IGF-1 level and its prognostic role after liver transplantation (LT).MethodsFrom April 2010 to May 2011, 31 patients were prospectively enrolled (25/6 M/F; mean age±SEM: 55.2±1.4 years), and IGF-1 serum levels were assessed preoperatively and at 15, 30, 90, 180 and 365 days after transplantation. The influence of the donor and recipient characteristics (age, use of extended criteria donor grafts, D-MELD and incidence of early allograft dysfunction) on hormonal concentration was analyzed. The prognostic role of IGF-1 level on patient survival and its correlation with routine liver function tests were also investigated.ResultsAll patients showed low preoperative IGF-1 levels (mean±SEM: 29.5±2.1), and on postoperative day 15, a significant increase in the IGF-1 plasma level was observed (102.7±11.7 ng/ml; p<0.0001). During the first year after LT, the IGF-1 concentration remained significantly lower in recipients transplanted with older donors (>65 years) or extended criteria donor grafts. An inverse correlation between IGF-1 and bilirubin serum levels at day 15 (r = -0.3924, p = 0.0320) and 30 (r = -0.3894, p = 0.0368) was found. After multivariate analysis, early (within 15 days) IGF-1 normalization [Exp(b) = 3.913; p = 0.0484] was the only prognostic factor associated with an increased 3-year survival rate.ConclusionIGF-1 postoperative levels are correlated with the graft’s quality and reflect liver function. Early IGF-1 recovery is associated with a higher 3-year survival rate after LT.

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation.

Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liver disease (MELD) score helped to reduce waiting list mortality in liver transplantation (LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins (IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.

Does Multiorgan Versus Kidney-Only Cadaveric Organ Procurement Affect Graft Outcomes?

IntroductionThe majority of kidney grafts in most European countries still come from deceased donors who provide other organs. We analyzed whether multiorgan procurement portends a worse functional outcome compared with kidney-only harvesting. MethodsWe performed a retrospective analysis of 1043 consecutive brain-dead donor kidney transplantations performed at a single academic institution from September 2002 to June 2011. The graft outcomes using kidney-only donors (n = 243) were compared with multiorgan donor grafts (n = 800) analyzing donor age, gender, cause of death, duration of mechanical ventilation, renal function, and cold ischemic interval. We compared delayed graft function and serum creatinine values at 1, 3, 6, and 12 months posttransplantation as well as graft survivals. This methodology was also applied to the subset of expanded criteria donors: 179 kidney-only versus 474 multiorgan. The influence of donor variables on graft survival was also analyzed in a Cox regression model. Immunosuppressive regimens and preservation solutions were similar in both groups. ResultsKidney-only donors were older than their multiorgan counterparts (53.1 versus 44.8, P < .0005) and predominantly male (76.5% versus 62.6% male donors, P < .0005). Other donor variables were comparable. Kidney-only donor grafts showed a slightly higher incidence of delayed function (27.2 versus 21.1%, P = .049), but the mean serum creatinine values were similar at all intervals. No differences were observed in 7-year graft survival: 80.7% versus 79.9%. Expanded criteria donor grafts showed overlapping results, except for a higher rate of donor oligoanuria and a lower 1-month mean creatinine among kidney-only donors. Multivariate analysis revealed that the number of harvested organs did not influence graft survival. DiscussionImmediate and long-term outcomes of kidney grafts did not correlate with the number of organs harvested from the donor. The longer explantation time associated with multiorgan procurement did not seem to affect graft function.