Faculty Bibliography

A causal link has been proposed between presumed consent (PC) and increased donation; we hypothesized that too much heterogeneity exists in transplantation systems to support this inference. We explored variations in PC implementation and other potential factors affecting donation rates. In-depth interviews were performed with senior transplant physicians from 13 European PC countries. Donation was always discussed with family and would not proceed against objections. Country-specific, nonconsent factors were identified that could explain differences in donation rates. Because the process of donation in PC countries does not differ dramatically from the process in non-PC countries, it seems unlikely that PC alone increases donation rates.

Model for End-stage Liver Disease (MELD)-based allocation of deceased donor livers allows exceptions for patients whose score may not reflect their true mortality risk. We hypothesized that organ procurement organizations (OPOs) may differ in exception practices, use of exceptions may be increasing over time, and exception patients may be advantaged relative to other patients. We analyzed longitudinal MELD score, exception and outcome in 88 981 adult liver candidates as reported to the United Network for Organ Sharing from 2002 to 2010. Proportion of patients receiving an HCC exception was 0-21.4% at the OPO-level and 11.9-18.8% at the region level; proportion receiving an exception for other conditions was 0.0%-13.1% (OPO-level) and 3.7-9.5 (region-level). Hepatocellular carcinoma (HCC) exceptions rose over time (10.5% in 2002 vs. 15.5% in 2008, HR = 1.09 per year, p<0.001) as did other exceptions (7.0% in 2002 vs. 13.5% in 2008, HR = 1.11, p<0.001). In the most recent era of HCC point assignment (since April 2005), both HCC and other exceptions were associated with decreased risk of waitlist mortality compared to nonexception patients with equivalent listing priority (multinomial logistic regression odds ratio [OR] = 0.47 for HCC, OR = 0.43 for other, p<0.001) and increased odds of transplant (OR = 1.65 for HCC, OR = 1.33 for other, p<0.001). Policy advantages patients with MELD exceptions; differing rates of exceptions by OPO may create, or reflect, geographic inequity.

Liver transplantation has evolved over the past four decades into the most effective method to treat end-stage liver failure and one of the most expensive medical technologies available. Accurate understanding of the financial implication of recipient severity of illness is crucial to assessing the economic impact of allocation policies. A novel database of linked clinical data from the Organ Procurement and Transplantation Network with cost accounting data from the University HealthSystem Consortium was used to analyze liver transplant costs for 15,813 liver transplants. This data was then utilized to consider the economic impact of alternative allocation systems designed to increase sharing of liver allografts using simulation results. Transplant costs were strongly associated with recipient severity of illness as assessed by the MELD score (p < 0.0001); however, this relationship was not linear. Simulation analysis of the reallocation of livers from low MELD patients to high MELD using a two-tiered regional sharing approach (MELD 15/25) resulted in 88 fewer deaths annually at estimated cost of $17,056 per quality-adjusted life-year saved. The results suggest that broader sharing of liver allografts offers a cost-effective strategy to reduce the mortality from end stage liver disease.

BACKGROUND:The 2004 International Society for Heart and Lung Transplantation consensus report specified an entity of histopathologic antibody-mediated rejection (hAMR) but did not define specific histologic criteria. Therefore, there is no gold standard for hAMR diagnosis. METHODS:In May 2009 we performed a survey of pathologists from cardiac transplant centers in the United States and Canada assessing practices regarding hAMR investigation. RESULTS:Of 94 centers who responded to our survey (77% response rate), 90% reported investigating for hAMR, and 80% of those reported having a defined protocol. Of centers with a defined protocol, 23% investigated all biopsies for hAMR. Of those who investigated for hAMR selectively, the most common triggers were clinical suspicion (61%) or suggestive histologic findings (36%). Sixteen different stains were used for hAMR investigation, the most common being C4d by immunofluorescence (38%), immunohistochemistry (38%) or both (21%). CONCLUSIONS:We found wide variation in pathologists' practices regarding hAMR diagnosis. A consensus document regarding hAMR is needed to better align our collective protocols, understand this disease process and to optimize patient care.

BACKGROUND:The acceptance and implementation of the International Society for Heart and Lung Transplantation's most recently adopted grading system (ISHLT-2004), which supplanted the ISHLT-1990 system for diagnosing cardiac allograft rejection, are unknown. METHODS:We performed an online survey of pathologists at cardiac transplant centers in the United States and Canada to determine how cardiac transplant rejection is reported. The survey consisted of a series of questions related to biopsy volume, the rejection grading system used, and reasons why that grading system was used. RESULTS:Survey responses were obtained from 96 of 122 centers in the United States and Canada. Eighty-seven percent of respondents reported adopting the ISHLT-2004 grading system, either exclusively or in combination with other grading systems. Overall, 45% of respondents use only the ISHLT-2004 grading system, 40% issue reports containing both the ISHLT-2004 and the ISHLT-1990 grading systems, 12% use only the ISHLT-1990 system, and 3% use either the ISHLT-2004 or the ISHLT-1990 system in combination with an older scoring system. The primary reasons for not using the ISHLT-2004 grading system exclusively were (1) the perceived preference of cardiologists and cardiac surgeons at that particular center (77%) and (2) a belief that the ISHLT-2004 grading system is not as informative as the ISHLT-1990 grading system (62%). CONCLUSIONS:There is appreciable variability in the system(s) used for reporting rejection among North American cardiac transplant centers. Understanding the reasons behind this variability will be crucial for the optimization of future grading systems for cardiac allograft rejection.