Too aggressive or not aggressive enough? Should a metric change center practice?

In an ideal system, all liver transplant centers would be created equal. Liver transplant candidates would be listed at their respective local centers, enjoy equal access to livers, similar transplant practices, and comparable transplant outcomes.

But in reality, transplant centers differ substantially, facing varying pressures that preclude the ideal. Internally, centers serve populations with different densities and disease etiologies that impact the number of candidates on the list relative to the availability and types of local donors. Candidate-donor mismatch, in turn, influences the disease severity of wait-list candidates leading to substantial geographic disparity. Median transplant MELD scores vary widely by center, ranging from 22 to 29. Externally, most centers compete with other centers within their donation service area for not only patients but also donor organs. Yet other centers experience no competition at all. These internal and external forces engender variability in transplant practice by center and motivate certain centers to push the envelope with respect to organ utilization. Arguably, one can surmise that these forces ultimately dictate differences in waitlist and transplant outcomes.

In this issue of AJT, Garonzik-Wang et al offer a novel description of the aggressive center that crystallizes differences in center practice (2). Although we previously described one extreme variation of transplant practice – high utilization of nationally distributed livers by 6 U.S. centers (1) – Garonzik-Wang et al provide a more detailed, multi-dimensional metric of “aggressiveness” by categorizing centers according to utilization of livers defined by eight donor characteristics associated with increased risk of either graft loss or disease transmission. Using an “aggressiveness score” cut-off of 6.5 (on a scale of 1 to 10) to include the top 30% most aggressive centers, the authors found that aggressive centers, compared to non-aggressive centers, were more likely to have larger wait-lists, a higher proportion of waitlisted patients with higher MELD scores (>15), higher transplant volume, and be located in competitive donation service areas. These factors strongly align with our intuition regarding transplant center behavior or “culture” and are important to describe, quantify, and report objectively.

Although at first blush, the aggressive phenotype appears to be driven by patient need, the fact that the median MELD score at transplant did not differ significantly between aggressive and non-aggressive centers (24 vs. 23, p=0.6) belies the depth and complexity of the factors that drive center behavior. There are also centers in UNOS regions with high transplant MELD scores (UNOS regions 1, 5, and 9) – a surrogate for patient need – that do not display aggressive behavior. As the authors speculate, additional factors including local mores and patient preferences, surgeon comfort and/or experience, center performance metrics, and financial incentives at the personal and institutional levels (2) may be equally potent, or potentially even the dominant drivers of aggressive organ acceptance and utilization practices.

Should centers measure themselves against this, or any other, ruler of aggressiveness to first examine and second regulate their liver acceptance practice? While Garonzik Wang et al proffer metrics for aggressiveness, they do not suggest guidelines for calibration. What defines too aggressive, or not aggressive enough, for a particular center? Presumably, mitigation of waitlist mortality should be the strongest motivator of aggressiveness. Previous investigators have reported that transplantation of extended criteria donor livers lowers adult waitlist mortality (3). This intuitively makes sense for a center in high match MELD regions. However, if a center systematically transplants at lower MELD scores, would aggressive behavior have the same impact on a center’s waitlist mortality? What is “appropriate” aggressiveness in one center, within one donation service area, in one region, may not be appropriate for another.

We believe that utilization of high-risk livers should be driven by center-specific waitlist mortality in order to justify the increased post-transplant risk inherently posed by these livers. Aggressiveness should somehow be calibrated according to patient need. While a description of center practice, as Garonzik Wang et al have provided, is an important first step, what is needed next is an objective assessment as to its impact on not only the actual recipients of high risk livers but on centers’ waitlist candidates.