Jeffrey B. Halldorson

Center competition and outcomes following liver transplantation

In the United States, livers for transplantation are distributed within donation service areas (DSAs). In DSAs with multiple transplant centers, competition among centers for organs and recipients may affect recipient selection and outcomes in comparison with DSAs with only 1 center. The objective of this study was to determine whether competition within a DSA is associated with posttransplant outcomes and variations in patients wait‐listed within the DSA. United Network for Organ Sharing data for 38,385 adult cadaveric liver transplant recipients undergoing transplantation between January 1, 2003 and December 31, 2009 were analyzed to assess differences in liver recipients and donors and in posttransplant survival by competition among centers. The main outcome measures that were studied were patient characteristics, actual and risk‐adjusted graft and patient survival rates after transplantation, organ quality as quantified by the donor risk index (DRI), wait‐listed patients per million population by DSA, and competition as quantified by the Hirschman‐Herfindahl index (HHI). Centers were stratified by HHI levels as no competition or as low, medium (or mid), or high competition. In comparison with DSAs without competition, the low‐, mid‐, and high‐competition DSAs (1) performed transplantation for patients with a higher risk of graft failure [hazard ratio (HR) = 1.24, HR = 1.26, and HR = 1.34 (P < 0.001 for each)] and a higher risk of death [HR = 1.21, HR = 1.23, and HR = 1.34 (P < 0.001 for each)] and for a higher proportion of sicker patients as quantified by the Model for End‐Stage Liver Disease (MELD) score [10.0% versus 14.8%, 20.1%, and 28.2% with a match MELD score of 31‐40 (P < 0.001 for each comparison)], (2) were more likely to use organs in the highest risk quartile as quantified by the DRI [18.3% versus 27.6%, 20.4%, and 31.7% (P ≤ 0.001 for each)], and (3) listed more patients per million population [18 (median) versus 34 (P = not significant), 37 (P = 0.005), and 45 (P = 0.0075)]. Significant variability in patient selection for transplantation is associated with market variables characterizing competition among centers. These findings suggest both positive and negative effects of competition among health care providers. Liver Transpl 19:96–104, 2013.

A Randomized Clinical Trial Testing the Anti-Inflammatory Effects of Preemptive Inhaled Nitric Oxide in Human Liver Transplantation

Decreases in endothelial nitric oxide synthase derived nitric oxide (NO) production during liver transplantation promotes injury. We hypothesized that preemptive inhaled NO (iNO) would improve allograft function (primary) and reduce complications post-transplantation (secondary). Patients at two university centers (Center A and B) were randomized to receive placebo (nu200a=u200a20/center) or iNO (80 ppm, nu200a=u200a20/center) during the operative phase of liver transplantation. Data were analyzed at set intervals for up to 9-months post-transplantation and compared between groups. Patient characteristics and outcomes were examined with the Mann-Whitney U test, Student t-test, logistic regression, repeated measures ANOVA, and Cox proportional hazards models. Combined and site stratified analyses were performed. MELD scores were significantly higher at Center B (22.5 vs. 19.5, p<0.0001), surgical times were greater at Center B (7.7 vs. 4.5 hrs, p<0.001) and warm ischemia times were greater at Center B (95.4 vs. 69.7 min, p<0.0001). No adverse metabolic or hematologic effects from iNO occurred. iNO enhanced allograft function indexed by liver function tests (Center B, p<0.05; and p<0.03 for ALT with center data combined) and reduced complications at 9-months (Center A and B, pu200a=u200a0.0062, ORu200a=u200a0.15, 95% CI (0.04, 0.59)). ICU (pu200a=u200a0.47) and hospital length of stay (pu200a=u200a0.49) were not decreased. iNO increased concentrations of nitrate (p<0.001), nitrite (p<0.001) and nitrosylhemoglobin (p<0.001), with nitrite being postulated as a protective mechanism. Mean costs of iNO were

Differential Rates of Ischemic Cholangiopathy and Graft Survival Associated With Induction Therapy in DCD Liver Transplantation

1,020 per transplant. iNO was safe and improved allograft function at one center and trended toward improving allograft function at the other. ClinicalTrials.gov with registry number 00582010 and the following URL:http://clinicaltrials.gov/show/NCT00582010.

Pseudoaneurysm After Combined Kidney/Pancreas Transplantation Presenting with Sentinel Bleeding: A Case Report and Review

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan–Meier estimated 5‐year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first‐year posttransplant from IC. Our program has almost exclusively utilized either anti‐thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (pu2009=u20090.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (pu2009=u20090.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era.

ECD kidney transplantation outcomes are improved when matching donors to recipients using a novel creatinine clearance match ratio (CCMR)

BACKGROUNDnVascular complications, most commonly arterial or venous thrombosis, are one of the most common causes of early graft loss after pancreas transplantation. However, only a few cases of pseudoaneurysm formation have been reported.nnnCASE REPORTnThis case report is unique for the presentation of pancreatic graft pseudoaneurysm with a sentinel retroperitoneal bleed as well as the failure to achieve diagnosis by ultrasound or standard cut CT scanning. The case emphasizes the importance of clinical suspicion and the need for dedicated fine-cut CT angiography or standard percutaneous angiography for diagnosis. The site of the anastomosis precluded minimally invasive treatment options and open repair with graft salvage was accomplished with minimal morbidity.nnnCONCLUSIONSnAlthough pseudoaneurysm after pancreas transplantation is uncommon, unexplained post-operative bleeding, even in the stable patient, should raise the suspicion of a sentinel bleeding event necessitating urgent angiography. Rapid diagnosis and treatment can prevent potential life- and graft-threatening rebleeding. The choice between minimally invasive and open surgical repair should be individualized depending on the site of the lesion.

The effects of Share 35 on the cost of liver transplantation

Improved outcomes have been associated with various methods of size matching between expanded criteria (ECD) donors and recipients. A novel method for improved functional based matching was developed utilizing manipulation of Cockcroft‐Gault estimated creatinine clearances for donor and recipient. We hypothesized that optimal clearance‐based matches would have superior outcomes for both immediate graft function and long‐term graft survival. For the analysis, recipients of ECD kidneys in the Scientific Registry of Transplant Recipients (SRTR) transplanted between October 1, 1987 and August 31, 2011 were included. Univariate and multivariate analyses predicted the hazard ratio of graft failure and the odds ratio of requiring dialysis within the first week. A total of 25,640 ECD kidney transplants were analyzed. On multivariate analysis, higher creatinine clearance match ratio (CCMR) was associated with increased graft failure and odds of requiring dialysis within the first week (comparing highest ratio quintile versus lowest ratio quintile: HR 1.43, p < 0.001; OR 2.08, p < 0.001). This study suggests that ECD kidneys have improved outcomes when the recipient/donor CCMR is optimized.

Serum Alkaline Phosphatase and Bilirubin Are Early Surrogate Markers for Ischemic Cholangiopathy and Graft Failure in Liver Transplantation From Donation After Circulatory Death

On June 18, 2013, the United Network for Organ Sharing (UNOS) instituted a change in the liver transplant allocation policy known as “Share 35.” The goal was to decrease waitlist mortality by increasing regional sharing of livers for patients with a model for end‐stage liver disease (MELD) score of 35 or above. Several studies have shown Share 35 successful in reducing waitlist mortality, particularly in patients with high MELD. However, the MELD score at transplant has increased, resulting in sicker patients, more complications, and longer hospital stays. Our study aimed to explore factors, along with Share 35, that may affect the cost of liver transplantation. Our results show Share 35 has come with significantly increased cost to transplant centers across the nation, particularly in regions 2, 5, 10, and 11. Region 5 was the only region with a median MELD above 35 at transplant, and cost was significantly higher than other regions. Several other recipient factors had changes with Share 35 that may significantly affect the cost of liver transplant. While access to transplantation for the sickest patients has improved, it has come at a cost and regional disparities remain. Financial implications with proposed allocation system changes must be considered.

Extracorporeal Delivery of rAAV with Metabolic Exchange and Oxygenation

Liver transplantation with the use of donation after circulatory death (DCD) is associated with ischemic cholangiopathy (IC) often leading to graft loss. We hypothesized that serial postoperative analysis of alkaline phosphatase and bilirubin might identify patients who would later on develop ischemic cholangiopathy and/or graft loss, allowing early recognition and potentially retransplantation. The University of Washington DCD experience totals 89 DCD liver transplantations performed from 2003 to 2011 with Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively; 84/89 patients transplanted with DCD livers lived ≥ 60 days after transplantation and were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week, 1 month, and 2 months after transplantation were analyzed. Two-month serum bilirubin and alkaline phosphatase proved to have the strongest associations with development of IC and graft failure. Two-month alkaline phosphatase of <100 U/L had a negative predictive value of 97% for development of IC. Two-month alkaline phosphatase demonstrated an inflection starting at >300 U/L strongly associated with development of IC (P < .0001). Serum bilirubin at 2 months was most strongly associated with graft failure within the 1st year with a strong inflection point at 2.5 mg/dL (P = .0001). All jaundiced recipients at 60 days after transplantation (bilirubin >2.5 mg/dL) developed graft failure within the 1st year (P < .0001). Use of these early surrogate markers could facilitate prioritization and early retransplantation for DCD liver recipients with allografts destined for failure.

D-MELD, a strong and accurate tool to guide donor-2-recipient matching.

Over the past decade much progress has been made towards the treatment of disease with recombinant adeno-associated viral vectors, ranging from cancer to muscular dystrophies, and autoimmune diseases to cystic fibrosis. Given inherent challenges of vector delivery we developed a system incorporating commercially available dialysis equipment. This concept was evaluated in vitro utilizing rAAV expressing the reporter gene human placental alkaline phosphatase. A number of pre-circulating conditions were assessed. Vector recovery was evaluated by quantitative vector genome analysis and cellular transduction assays. A dialysis circulation time course was established, and results were recorded across varied conditions ranging from approximately 2 to 90% retention of viable vector. This approach is unique in that it focuses on efficient localized, isolated and continual delivery of vector to target tissues, provides for the preservation of tissue integrity with dialysis for metabolic exchange and allows for the transfer of oxygen through a secondary membrane post-dialysis.