Anton I. Skaro

Ischemic Cholangiopathy After Controlled Donation After Cardiac Death Liver Transplantation: A Meta-analysis

OBJECTIVE To conduct a meta-analysis to enhance understanding of the risks of biliary complications, particularly ischemic cholangiopathy (IC), after donation after cardiac death (DCD) compared with donation after brain death (DBD) liver transplantation. BACKGROUND Biliary complications after liver transplantation have profound health and economic implications which merit further investigation. METHODS The MEDLINE (1950–2009), EMBASE, and Cochrane Library databases were searched and supplemented by review of conference proceedings and publication bibliographies. All original single institution studies reporting outcomes for DCD and DBD liver transplant recipients were considered. Odds ratios (OR) and 95% confidence intervals (CI) based on random effects models were calculated. RESULTS Eleven publications, all retrospective cohort studies, involving 489 DCD and 4455 DBD recipients, were included. Donation after cardiac death recipients had a 2.4 times increased odds of biliary complications (95% CI= 1.8–3.4) and a 10.8 times increased odds of IC (95% CI = 4.8–24.2).Ischemic cholangiopathy was present in 16% of DCD compared with 3% of DBD recipients. Donation after cardiac death recipients also experienced higher odds of 1-year patient mortality (OR = 1.6, 95% CI = 1.04–2.5) and graft failure (OR = 2.1, 95% CI = 1.5–2.8). CONCLUSIONS Donation after cardiac death liver transplantation is marred by inferior outcomes including higher rates of biliary complications and IC as well as increased mortality and graft failure. Despite current federal mandates to increase DCD donation, these serious complications translate into poor outcomes for individuals and increased healthcare costs. These risks should be considered in decisions regarding the utilization of these grafts.

Cardiovascular Risk Assessment of the Liver Transplant Candidate

Liver transplantation (LT) candidates today are increasingly older, have greater medical acuity, and have more cardiovascular comorbidities than ever before. Steadily rising model for end-stage liver disease (MELD) scores at the time of transplant, resulting from high organ demand, reflect the escalating risk profiles of LT candidates. In addition to advanced age and the presence of comorbidities, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually demonstrate increased cardiac output and a compromised ventricular response to stress, a condition termed cirrhotic cardiomyopathy. These cardiac disturbances are likely mediated by decreased beta-agonist transduction, increased circulating inflammatory mediators with cardiodepressant properties, and repolarization changes. Low systemic vascular resistance and bradycardia are also commonly seen in cirrhosis and can be aggravated by beta-blocker use. These physiologic changes all contribute to the potential for cardiovascular complications, particularly with the altered hemodynamic stresses that LT patients face in the immediate post-operative period. Post-transplant reperfusion may result in cardiac death due to a multitude of causes, including arrhythmia, acute heart failure, and myocardial infarction. Recognizing the hemodynamic challenges encountered by LT patients in the perioperative period and how these responses can be exacerbated by underlying cardiac pathology is critical in developing recommendations for the pre-operative risk assessment and management of these patients. The following provides a review of the cardiovascular challenges in LT candidates, as well as evidence-based recommendations for their evaluation and management.

The impact of ischemic cholangiopathy in liver transplantation using donors after cardiac death: The untold story

BACKGROUND Liver transplantation (LT) from donation after cardiac death (DCD) donors is increasingly being used to address organ shortages. Despite encouraging reports, standard survival metrics have overestimated the effectiveness of DCD livers. We examined the mode, kinetics, and predictors of organ failure and resource utilization to more fully characterize outcomes after DCD LT. METHODS We reviewed the outcomes for 32 DCD and 237 donation after brain death (DBD) LT recipients at our institution. RESULTS Recipients of DCD livers had a 2.1 times greater risk of graft failure, a 2.5 times greater risk of relisting, and a 3.2 times greater risk of retransplantation compared with DBD recipients. DCD recipients had a 31.6% higher incidence of biliary complications and a 35.8% higher incidence of ischemic cholangiopathy. Ischemic cholangiography was primarily implicated in the higher risk of graft failure observed after DCD LT. DCD recipients with ischemic cholangiography experienced more frequent rehospitalizations, longer hospital stays, and required more invasive biliary procedures. CONCLUSION Related to higher complication rates, DCD recipients necessitated greater resource utilization. This more granular data should be considered in the decision to promote DCD LT. Modification of liver allocation policy is necessary to address those disadvantaged by a failing DCD graft.

A comprehensive risk assessment of mortality following donation after cardiac death liver transplant – An analysis of the national registry

BACKGROUND & AIMS Organ scarcity has resulted in increased utilization of donation after cardiac death (DCD) donors. Prior analysis of patient survival following DCD liver transplantation has been restricted to single institution cohorts and a limited national experience. We compared the current national experience with DCD and DBD livers to better understand survival after transplantation. METHODS We compared 1113 DCD and 42,254 DBD recipients from the Scientific Registry of Transplant Recipients database between 1996 and 2007. Patient survival was analyzed using the Kaplan-Meier methodology and Cox regression. RESULTS DCD recipients experienced worse patient survival compared to DBD recipients (p<0.001). One and 3 year survival was 82% and 71% for DCD compared to 86% and 77% for DBD recipients. Moreover, DCD recipients required re-transplantation more frequently (DCD 14.7% vs. DBD 6.8%, p<0.001), and re-transplantation survival was markedly inferior to survival after primary transplant irrespective of graft type. Amplification of mortality risk was observed when DCD was combined with cold ischemia time >12h (HR = 1.81), shared organs (HR = 1.69), recipient hepatocellular carcinoma (HR=1.80), recipient age >60 years (HR = 1.92), and recipient renal insufficiency (HR = 1.82). CONCLUSIONS DCD recipients experience significantly worse patient survival after transplantation. This increased risk of mortality is comparable in magnitude to, but often exacerbated by other well-established risk predictors. Utilization decisions should carefully consider DCD graft risks in combination with these other factors.

The increased costs of donation after cardiac death liver transplantation: caveat emptor.

Objective:To determine the effect of donation after cardiac death (DCD) livers on post-transplantation costs. Background:DCD livers are increasingly being used to expand the donor pool despite higher complication rates. Although complications after liver transplantation have profound financial implications, the effect of DCD livers on post-transplantation costs has not been studied. Methods:We estimated direct medical care costs based on inpatient and outpatient hospital costs for 28 DCD and 198 donation after brain death (DBD) liver recipients. Organ acquisition and physician costs were excluded. Results:Donor and recipient demographics were comparable for DCD and DBD transplants. One-year, post-transplantation costs were higher for DCD recipients (124.9% of DBD costs, P = 0.04). DCD costs remained higher (125.2% of DBD costs, P = 0.009) after adjusting for recipient characteristics. Furthermore, DCD post-transplantation costs were 30% higher than DBD costs after adjusting for pre-transplantation costs (P = 0.02). Biliary complications (DCD 58% vs. DBD 21%; P < 0.001) and, specifically, ischemic cholangiopathy (DCD 44% vs. DBD 1.6%; P < 0.001) occurred more frequently after DCD transplantation. Moreover, DCD recipients underwent retransplantation more often (DCD 21% vs. DBD 7.1%, P = 0.02). One-year costs were increased for recipients with ischemic cholangiopathy or retransplantation by 53% (P = 0.01) and 107% (P < 0.001), respectively. However, DCD costs continued to be higher when retransplanted patients were excluded (120% of DBD costs, P = 0.02). Conclusions:Higher rates of graft failure and biliary complications translate into markedly increased direct medical care costs for DCD recipients. These important financial implications should be considered in decisions regarding the use of DCD livers.

Resolution of Recurrent Focal Segmental Glomerulosclerosis after Retransplantation

The authors of this letter describe the successful retransplantation of an allograft that was failing in its first recipient owing to recurrent primary focal segmental glomerulosclerosis. In the second recipient, all evidence of the nephrotic syndrome resolved.

Impact of Anemia after Renal Transplantation on Patient and Graft Survival and on Rate of Acute Rejection

BACKGROUND AND OBJECTIVES The impact of posttransplantation anemia on patient survival, renal allograft survival, and rate of acute rejection is not known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 1023 patients who underwent kidney transplantation at one center from January 1992 through June 2003 were retrospectively analyzed. Posttransplantation anemia was defined as mean hemoglobin <11 g/dl after 3 mo after transplantation. Data on demographics, pretransplantation dialysis, previous transplant history, pretransplantation hemoglobin, degree of HLA mismatch, and donor characteristics were collected. Some of the posttransplantation data that were collected in addition to the hemoglobin included delayed graft function; diabetes; hypertension; induction and maintenance of immunosuppressive regimen; posttransplantation infections; and use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, statins, aspirin, and beta blockers. Cox regression models were used to assess the effects of posttransplantation anemia on each outcome: Mortality, graft survival, and rate of acute rejection. Median follow-up time was 4 yr. RESULTS During the entire follow-up period, there were 89 (9%) deaths, 143 (14%) acute rejection episodes, and 235 (23%) kidney losses. In multivariate Cox regression models, being anemic after transplantation, after the first 90 d, was associated with increased overall mortality and increased renal allograft loss. Posttransplantation anemia was also associated with increased acute rejection rates. CONCLUSIONS This study shows that posttransplantation anemia is associated with worse patient and graft survival and higher rates of acute rejection when compared with nonanemic renal transplant recipients.

Perception versus reality ?: Virtual crossmatch - How to overcome some of the technical and logistic limitations

The goal of this work was to evaluate concordance between (a) actual flow cytometric crossmatch (FCXM) that is performed by the OPO laboratory servicing our transplant center and (b) virtual XM (vXM) prediction based on antibody identification by solid‐phase methods performed in our laboratory.

Outcomes and Native Renal Recovery Following Simultaneous Liver-Kidney Transplantation

With the increase in patients having impaired renal function at liver transplant due to MELD, accurate predictors of posttransplant native renal recovery are needed to select candidates for simultaneous liver–kidney transplantation (SLK). Current UNOS guidelines rely on specific clinical criteria for SLK allocation. To examine these guidelines and other variables predicting nonrecovery, we analyzed 155 SLK recipients, focusing on a subset (n = 78) that had post‐SLK native GFR (nGFR) determined by radionuclide renal scans. The 77 patients not having renal scans received a higher number of extended criteria donor organs and had worse posttransplant survival. Of the 78 renal scan patients, 31 met and 47 did not meet pre‐SLK UNOS criteria. The UNOS criteria were more predictive than our institutional criteria for all nGFR recovery thresholds (20–40 mL/min), although at the most conservative cut‐off (nGFR ≤ 20) it had low sensitivity (55.3%), specificity (75%), PPV (67.6%) and NPV (63.8%) for predicting post‐SLK nonrecovery. On multivariate analysis, the only predictor of native renal nonrecovery (nGFR ≤ 20) was abnormal pre‐SLK renal imaging (OR 3.85, CI 1.22–12.5). Our data support the need to refine SLK selection utilizing more definitive biomarkers and predictors of native renal recovery than current clinical criteria.

Comparative effectiveness of donation after cardiac death versus donation after brain death liver transplantation: Recognizing who can benefit

Due to organ scarcity and wait‐list mortality, transplantation of donation after cardiac death (DCD) livers has increased. However, the group of patients benefiting from DCD liver transplantation is unknown. We studied the comparative effectiveness of DCD versus donation after brain death (DBD) liver transplantation. A Markov model was constructed to compare undergoing DCD transplantation with remaining on the wait‐list until death or DBD liver transplantation. Differences in life years, quality‐adjusted life years (QALYs), and costs according to candidate Model for End‐Stage Liver Disease (MELD) score were considered. A separate model for hepatocellular carcinoma (HCC) patients with and without MELD exception points was constructed. For patients with a MELD score <15, DCD transplantation resulted in greater costs and reduced effectiveness. Patients with a MELD score of 15 to 20 experienced an improvement in effectiveness (0.07 QALYs) with DCD liver transplantation, but the incremental cost‐effectiveness ratio (ICER) was >