Implementing a Height-Based Rule for the Allocation of Pediatric Donor Livers to Adults: A Liver Simulated Allocation Model Study

In liver transplantation, adult women are more likely to die on the waiting list and less likely to receive a deceased donor transplant compared with adult men.⁽¹⁾ The reasons for these disparities include incorporation of creatinine in the Model for End-Stage Liver Disease (MELD), candidate anthropometrics, and differences in access to transplantation. Although policy interventions aimed at improving donor–recipient size matching are not enough to address all factors described above, they could be immediately implemented before more systematic allocation changes.

In an analysis of the Scientific Registry of Transplant Recipients (SRTR) database, weighting for candidate anthropometric measurements was found to increase waitlist mortality risks for women by 125.8%.⁽¹⁾ Candidate height has a disproportionate impact (even more so than the MELD score) on a candidate’s success in receiving a transplant. In our previous analyses, we found that 166 cm in adults is a height threshold below which waitlist mortality begins to increase.⁽²⁾ Moreover, height-based interventions at this threshold would disproportionately benefit women as 72% of adult women and 9% of adult men on the waiting list had heights <166 cm.⁽²⁾ The allocation of pediatric donor grafts represents a potential area to implement this policy because adult women who received first offers of pediatric grafts had similar waitlist mortality rates as men and more appropriate donor–recipient size matching.⁽³⁾

Therefore, we hypothesized that a height-based rule for allocating pediatric grafts to adult candidates, after all pediatric candidates are exhausted, might help alleviate this sex-based disparity. To test this hypothesis, we used the liver simulated allocation model (LSAM) to simulate a height-based rule superimposed on the acuity circles (AC) allocation scheme.

Methods

This study used SRTR data from July 1, 2013, through June 30, 2016, applied toward LSAM, version 2019. LSAM (SRTR, Minneapolis, MN) is the software package used by SRTR to perform event-based simulations of US liver allocations.⁽⁴⁾ The simulation time was 3 years with 10 replications of each scheme. Settings were adjusted so that the total number of transplants remained similar under all simulations. Candidates whose disease trajectory was censored because of transplant had their trajectory imputed, to death or end of simulation, with those of similar candidates. The primary outcomes of interest were numbers of transplants and waitlist deaths.

The AC+166 scheme maintains prioritization of children over non–Status 1 adults and only changes the order within which adults are prioritized. We define the sex gap as the difference between the percentages of men and women who received transplants during the simulation period (number of transplants/number of total waitlist candidates).

Across the 10 replications over 3 years of simulation, the means for each primary outcome were calculated and presented unless otherwise stated. Results under AC+166 were compared with AC via paired t tests. We considered P < 0.001 as statistical significance as multiple tests were performed.

Results

Each LSAM replication had an average of 48,989 candidates: 36.4% were adult women. Of the women, 71.8% and 9.8% of men had a height of <166 cm. Each LSAM replication had an average 21,972 donors, and 10.0% were pediatric donors where our rule could be applied.

When compared with the AC scheme, the AC+166 scheme was projected to significantly increase the number of transplants in adults with heights <166 cm (5742 versus 5844; P < 0.001) and adult women (6417 versus 6498; P < 0.001). Conversely, the number of transplants in adults with heights ≥166 cm (12,370 versus 12,261; P < 0.001) and adult men (11,694 versus 11,607; P < 0.001) were projected to decrease significantly. When compared with AC, AC+166 resulted in no changes in the overall numbers of transplants for both adults (18,112 versus 18,106; P = 0.58) and children (1843 versus 1841; P = 0.70).

When compared with AC, AC+166 resulted in no statistically significant changes in waitlist deaths in adults with heights <166 cm (1371 versus 1348; P = 0.02), adult women (1505 versus 1483; P = 0.04), adults with heights ≥166 cm (2510 versus 2525; P = 0.03), and adult men (2376 versus 2391; P = 0.03). When compared with AC, AC+166 resulted in no changes in overall waitlist deaths for adults (3881 versus 3874; P = 0.44) and children (76 versus 76; P = 0.90).

In the AC scheme, the average numbers of transplants for adult women (6417) and adult men (11,694) comprised 33.8% and 35.3% of all candidates, respectively, for a difference of 1.6%. In the AC+166 scheme, adult women gained an average of 81 transplants, whereas adult men lost an average of 87 transplants. These changes in the average numbers of transplants comprised 34.2% of adult women and 35.1% of adult men candidates under AC+166 for a difference of 0.9%. The AC+166 scheme eliminated 41.7% of the sex gap in the percentages of adults who received transplants.

Conclusions

We simulated a height-based rule on pediatric graft allocation to adults with a goal of closing the disparities faced by adult women. Although this does not address all of the factors contributing to sex-based disparities, this rule represents one that could be implemented immediately. In our AC+166 scheme, we narrowed the sex gap in transplant rates by shifting size-appropriate grafts and increasing the number of women receiving transplants by 81. In practical terms, for women to close the sex gap or to achieve the average transplant rate for all adults, women would have to gain approximately 179 transplants. For women to match the transplant rates for adult men under the AC scheme, women would have to gain approximately 282 transplants. The AC+166 scheme effectively reduced this sex gap by an average of 41.7%: the percentage of women who received a transplant increased by 0.4%, whereas that for men decreased by 0.3%.

Furthermore, our simulations showed the AC+166 scheme would result in no significant changes in waitlist deaths. Although the percentage of women who received transplants did increase significantly, the lack of changes in waitlist mortality for women indicate that the pediatric grafts that end up being allocated to women may have taken place in areas with relatively low MELD scores. Although this finding may be attributed to the maldistribution of pediatric transplant services in low MELD areas, this also confirmed that the AC+166 scheme is only a first step and further policy modifications may be necessary to have a substantial impact on waitlist mortality. Fortunately, our height-based rule was applied after pediatric candidates were exhausted to avoid harm to children, who were disadvantaged under region-based allocation.⁽⁵⁾

There are several limitations to this analysis. The SRTR data were from 2013 through 2016. The characteristics of patients who received transplants have shifted since 2016, resulting in a different case mix of cirrhosis etiologies and demographics. Moreover, the LSAM accept/decline model was fit before AC and may not reflect current organ acceptance/rejection behaviors. Third, the LSAM is not able to simulate split-liver transplants, which is another avenue by which the sex gap could be closed that simultaneously helps children. By allocating splitable livers to pediatric candidates who only require the left lateral segment, the remaining right trisegment would be a good match for smaller candidates who require a smaller donor liver. Lastly, the shift from region-based to AC allocation is projected to increase the proportion of pediatric grafts allocated to children from 46% to 77%.⁽⁵⁾ Our height-based rule, therefore, applies for an even more limited number of pediatric grafts, limiting its potential impact.

Despite these limitations, our study demonstrates the utility of a height-based intervention to begin to achieve sex parity. Further modifications to AC, such as the prioritization of adult donors <166 cm for adult candidates <166 cm within each MELD band, may close the sex gap even further.