Identifying a clinically relevant cutoff for height that is associated with a higher risk of waitlist mortality in liver transplant candidates
2019; Elsevier BV; Volume: 20; Issue: 3 Linguagem: Inglês
10.1111/ajt.15644
ISSN1600-6143
Autores Tópico(s)Liver Disease Diagnosis and Treatment
ResumoHeight explains a substantial proportion of gender-based disparity in waitlist mortality among liver transplant candidates. We sought to identify a clinically relevant height cutoff below which waitlist mortality increases significantly. We examined all nonstatus one adult liver transplant candidates from 2010 to 2014. We used a recursive application of the minimum P value approach with univariate competing risk regressions (deceased donor liver transplantation as the competing risk) to detect differences in waitlist mortality with regards to height. Of 69 883 candidates, 36% (24 819) were women and 64% (45 064) were men. Median height for all was 173 cm: 163 cm in women, 178 cm in men. The optimal search method of recursively evaluating smaller height intervals yielded 166 cm as the optimal height cutoff. Using height <166 cm as the cutoff, 72% of women and 9% of men met criteria. Compared to candidates ≥166 cm, "short stature" candidates had higher rates of death/delisting (28% vs 24%) and lower rates of transplantation (38% vs 44%) (P < .01 for both). After adjustment for clinical and demographic characteristics, height <166 cm remained associated with an 8% increased risk of waitlist mortality (95% CI 1.03-1.14, P < .01). Short candidate height may be a motivation to explore split livers or living donors as accelerated liver transplantation options. Height explains a substantial proportion of gender-based disparity in waitlist mortality among liver transplant candidates. We sought to identify a clinically relevant height cutoff below which waitlist mortality increases significantly. We examined all nonstatus one adult liver transplant candidates from 2010 to 2014. We used a recursive application of the minimum P value approach with univariate competing risk regressions (deceased donor liver transplantation as the competing risk) to detect differences in waitlist mortality with regards to height. Of 69 883 candidates, 36% (24 819) were women and 64% (45 064) were men. Median height for all was 173 cm: 163 cm in women, 178 cm in men. The optimal search method of recursively evaluating smaller height intervals yielded 166 cm as the optimal height cutoff. Using height <166 cm as the cutoff, 72% of women and 9% of men met criteria. Compared to candidates ≥166 cm, "short stature" candidates had higher rates of death/delisting (28% vs 24%) and lower rates of transplantation (38% vs 44%) (P < .01 for both). After adjustment for clinical and demographic characteristics, height <166 cm remained associated with an 8% increased risk of waitlist mortality (95% CI 1.03-1.14, P < .01). Short candidate height may be a motivation to explore split livers or living donors as accelerated liver transplantation options. The Model for End-Stage Liver Disease (MELD) and its derivative MELD-Sodium (MELDNa) have been in use since 2002 to prioritize liver transplant waitlist candidates. Although derived from four objective laboratory tests, the MELDNa score does not fully capture some of the nuanced clinical factors that many populations face on the waitlist. Our group has previously demonstrated that anatomic size differences, such as height and weight, substantially contribute to the gender-based waitlist mortality disparity seen among liver transplant candidates.1Lai JC Terrault NA Vittinghoff E Biggins SW. Height contributes to the gender difference in wait-list mortality under the MELD-based liver allocation system.Am J Transplant. 2010; 10: 2658-2664Crossref PubMed Scopus (74) Google Scholar We have also previously demonstrated that adult women who received pediatric donor liver offers are more likely to be transplanted with size-matched grafts than adult women who received adult donor liver offers.2Ge J Gilroy R Lai JC. Receipt of a pediatric liver offer as the first offer reduces waitlist mortality for adult women.Hepatology. 2018; 68: 1101-1110Crossref PubMed Scopus (15) Google Scholar What has been lacking in the literature is a specific threshold for height below which short women (and to a certain extent, short men) experience significantly higher risk for mortality.3Nephew LD Goldberg DS Lewis JD Abt P Bryan M Forde KA. Exception points and body size contribute to gender disparity in liver transplantation.Clin Gastroenterol Hepatol. 2017; 15 (e2.): 1286-1293Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar To facilitate patient and provider decision-making surrounding donor organ acceptance, we sought to identify a clinically relevant cutoff for waitlist candidate height, below which waitlist mortality increases dramatically. We examined all nonstatus one adult liver transplant waitlist candidates in the United States from January 1, 2010 to December 31, 2014 using the United Network for Organ Sharing (UNOS) registry database. Following previously documented methods to identify prognostic variables, we utilized the minimum P value method with univariate competing risk regressions (with deceased donor liver transplantation [DDLT] as the competing risk) to detect differences in waitlist mortality with regard to height. To search for the optimal cutoff, we conducted iterative and recursive applications of the minimum P value approach with successively smaller height intervals.4Mazumdar M Glassman JR. Categorizing a prognostic variable: review of methods, code for easy implementation and applications to decision-making about cancer treatments.Stat Med. 2000; 19: 113-132Crossref PubMed Scopus (298) Google Scholar We then used multivariable competing risk regressions to associate the identified clinically relevant height cutoff with waitlist mortality, adjusting for the following clinical and demographic variables: gender, age, ethnicity/race, diagnosis, blood type, listing MELD score, and listing region. The data reported here have been supplied by UNOS. The interpretation and reporting of these data are the responsibility of the authors of this letter. Of the 69 883 waitlist candidates included in this analysis, 36% (24 819) were women and 64% (45 064) were men. Median height for the entire waitlist pool was 173 cm: 163 cm for women on the waitlist, 178 cm in men on the waitlist. In univariate competing risk regressions, each centimeter increase in waitlist candidate height was associated with an 1% decreased risk of waitlist mortality (95% confidence interval [CI] 0.99-0.99, P < .01). The optimal search method of evaluating successively smaller height intervals yielded 166 cm as the height cutoff below which mortality risk increases significantly (Figure 1). Using height <166 cm as the cutoff to define "short stature," 72% of the women and 9% of the men who were waitlist candidates met criteria. Compared to candidates with heights ≥166 cm, short stature candidates were more likely to be Hispanic (23% vs 12%) or Asian (8% vs 3%), have blood type O (48% vs 46%), be listed for nonalcoholic fatty liver disease (13% vs 9%) or Hepatitis B (16% vs 9%), or were located in a region with higher MELD scores at transplantation (56% vs 50%). Compared to candidates ≥166 cm, short stature candidates had higher rates of death/delisting (28% vs 24%) and lower rates of DDLT (38% vs 44%) [P < .01 for both]. After adjustment for these clinical characteristics, height <166 cm remained associated with 8% increased risk of waitlist mortality (95% CI 1.03-1.14, P < .01) compared to candidates with height ≥166 cm. In this analysis, we identified a height cutoff of 166 cm (5 feet 5 inches) as a clinically relevant value below which liver transplant waitlist candidate experience a significantly increased risk for waitlist mortality. Using the cutoff of 166 cm, the majority (81%) of women met criteria for "short stature." In addition, the criteria also demonstrated that candidates of "short stature" were, regardless of gender, more likely to be ethnic minorities, notably Hispanic or Asian, or be listed in regions with higher MELD scores at transplantation. Anatomic size (as proxied by candidate height) and size matching play a major role in timely deceased donor liver transplantation. This, in turn, has previously been demonstrated to contribute to and exacerbate the gender-based waitlist mortality disparity seen in the MELD era. Identification of a precise height cutoff (166 cm) under which waitlist mortality significantly increases may facilitate proposals to prioritize organs from pediatric or adult donors with short stature to candidates <166 cm tall. This line of research also raises the possibility that gender, height, and/or other candidate-related physical characteristics should be considered in addition to or in conjunction with the current MELDNa score for allocation purposes. At a minimum, this cutoff can facilitate clinical decision-making to motivate patients to accept extended criteria donor livers, such as split livers, and seek living donors as options to expand access to liver transplantation, especially for the most vulnerable candidates on the waitlist. This analysis was funded by R01AG059183/K23AG048337 (National Institute on Aging, Lai) and by 5T32DK060414-17 (National Institute of Diabetes and Digestive and Kidney Diseases, Ge). The funding agencies played no role in the analysis of the data or the preparation of this letter. The authors of this letter have no conflicts of interest to disclose as described by the American Journal of Transplantation. Ge: Study concept and design; acquisition of data; analysis and interpretation of data; drafting of letter; critical revision of the letter for important intellectual content; statistical analysis. Lai: Study concept and design; acquisition of data; analysis and interpretation of data; drafting of letter; critical revision of the letter for important intellectual content; obtained funding; study supervision. The data reported here have been supplied by the United Network for Organ Sharing as the contractor for the Organ Procurement and Transplantation Network. The interpretation and reporting of these data are the responsibility of the author(s) and should in no way be seen as an official policy of or interpretation by the OPTN or the United States Government.
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