Association between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index

Christine E. Haugen; Mara McAdams-Demarco; Elizabeth C. Verna; Robert S. Rahimi; Matthew R. Kappus; Michael A. Dunn; Michael L. Volk; Ahmet Gurakar; Andres Duarte-Rojo; Daniel R. Ganger; Jacqueline G. O'Leary; Daniela Ladner; Jacqueline Garonzik-Wang; Dorry L. Segev; Jennifer C. Lai

doi:10.1001/jamasurg.2019.2845

Association between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index

Christine E. Haugen, Mara McAdams-Demarco, Elizabeth C. Verna, Robert S. Rahimi, Matthew R. Kappus, Michael A. Dunn, Michael L. Volk, Ahmet Gurakar, Andres Duarte-Rojo, Daniel R. Ganger, Jacqueline G. O'Leary, Daniela Ladner, Jacqueline Garonzik-Wang, Dorry L. Segev, Jennifer C. Lai^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

Importance: Among liver transplant candidates, obesity and frailty are associated with increased risk of death while they are on the wait-list. However, use of body mass index (BMI) may not detect candidates at a higher risk of death owing to the fact that ascites and muscle wasting are seen across transplant candidates of all BMI measurements. Objective: To evaluate whether the association between wait-list mortality and frailty varied by BMI of liver transplant candidates. Design, Setting, and Participants: A prospective cohort study was conducted at 9 liver transplant centers in the United States from March 1, 2012, to May 1, 2018, among 1108 adult liver transplant candidates without hepatocellular carcinoma. Exposures: At outpatient evaluation, the Liver Frailty Index score was calculated (grip strength, chair stands, and balance), with frailty defined as a Liver Frailty Index score of 4.5 or more. Candidates' BMI was categorized as nonobese (18.5-29.9), class 1 obesity (30.0-34.9), and class 2 or greater obesity (≥35.0). Main Outcomes and Measures: The risk of wait-list mortality was quantified using competing risks regression by candidate frailty, adjusting for age, sex, race/ethnicity, Model for End-stage Liver Disease Sodium score, cause of liver disease, and ascites, including an interaction with candidate BMI. Results: Of 1108 liver transplant candidates (474 women and 634 men; mean [SD] age, 55 [10] years), 290 (26.2%) were frail; 170 of 670 nonobese candidates (25.4%), 64 of 246 candidates with class 1 obesity (26.0%), and 56 of 192 candidates with class 2 or greater obesity (29.2%) were frail (P =.57). Frail nonobese candidates and frail candidates with class 1 obesity had a higher risk of wait-list mortality compared with their nonfrail counterparts (nonobese candidates: adjusted subhazard ratio, 1.54; 95% CI, 1.02-2.33; P =.04; and candidates with class 1 obesity: adjusted subhazard ratio, 1.72; 95% CI, 0.99-2.99; P =.06; P =.75 for interaction). However, frail candidates with class 2 or greater obesity had a 3.19-fold higher adjusted risk of wait-list mortality compared with nonfrail candidates with class 2 or greater obesity (95% CI, 1.75-5.82; P <.001; P =.047 for interaction). Conclusions and Relevance: This study's finding suggest that among nonobese liver transplant candidates and candidates with class 1 obesity, frailty was associated with a 2-fold higher risk of wait-list mortality. However, the mortality risk associated with frailty differed for candidates with class 2 or greater obesity, with frail candidates having a more than 3-fold higher risk of wait-list mortality compared with nonfrail patients. Frailty assessments may help to identify vulnerable patients, particularly those with a BMI of 35.0 or more, in whom a clinician's visual evaluation may be less reliable to assess muscle mass and nutritional status..

Original language	English (US)
Pages (from-to)	1103-1109
Number of pages	7
Journal	JAMA surgery
Volume	154
Issue number	12
DOIs	https://doi.org/10.1001/jamasurg.2019.2845
State	Published - Dec 2019

Funding

reported receiving grants from the National Institutes of Health during the conduct of the study. Dr McAdams-DeMarco reported receiving grants from the National Institute on Aging during the conduct of the study. Dr Verna reported receiving grants from Salix and personal fees from Gilead outside the submitted work. Dr Dunn reported receiving personal fees from Axcella Health Inc outside the submitted work. Dr Ganger reported receiving personal fees from Gilead outside the submitted work. Dr Ladner reported receiving grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported. Funding/Support: Funding for this study was provided by the National Institute of Diabetes and Digestive and Kidney Disease and the National Institute of Aging: grant numbers F32AG053025 (principal investigator [PI], Dr Haugen), R01AG055781 (PI, Dr McAdams-DeMarco), K24DK101828 (PI, Dr Segev), K23AG048337 (PI, Dr Lai), and R01AG059183 (PI, Dr Lai).

ASJC Scopus subject areas

Surgery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1001/jamasurg.2019.2845

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Haugen, C. E., McAdams-Demarco, M., Verna, E. C., Rahimi, R. S., Kappus, M. R., Dunn, M. A., Volk, M. L., Gurakar, A., Duarte-Rojo, A., Ganger, D. R., O'Leary, J. G., Ladner, D., Garonzik-Wang, J., Segev, D. L., & Lai, J. C. (2019). Association between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index. JAMA surgery, 154(12), 1103-1109. https://doi.org/10.1001/jamasurg.2019.2845

@article{40438b3e9afe434c9f23f8dafd5a3fdb,

title = "Association between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index",

abstract = "Importance: Among liver transplant candidates, obesity and frailty are associated with increased risk of death while they are on the wait-list. However, use of body mass index (BMI) may not detect candidates at a higher risk of death owing to the fact that ascites and muscle wasting are seen across transplant candidates of all BMI measurements. Objective: To evaluate whether the association between wait-list mortality and frailty varied by BMI of liver transplant candidates. Design, Setting, and Participants: A prospective cohort study was conducted at 9 liver transplant centers in the United States from March 1, 2012, to May 1, 2018, among 1108 adult liver transplant candidates without hepatocellular carcinoma. Exposures: At outpatient evaluation, the Liver Frailty Index score was calculated (grip strength, chair stands, and balance), with frailty defined as a Liver Frailty Index score of 4.5 or more. Candidates' BMI was categorized as nonobese (18.5-29.9), class 1 obesity (30.0-34.9), and class 2 or greater obesity (≥35.0). Main Outcomes and Measures: The risk of wait-list mortality was quantified using competing risks regression by candidate frailty, adjusting for age, sex, race/ethnicity, Model for End-stage Liver Disease Sodium score, cause of liver disease, and ascites, including an interaction with candidate BMI. Results: Of 1108 liver transplant candidates (474 women and 634 men; mean [SD] age, 55 [10] years), 290 (26.2%) were frail; 170 of 670 nonobese candidates (25.4%), 64 of 246 candidates with class 1 obesity (26.0%), and 56 of 192 candidates with class 2 or greater obesity (29.2%) were frail (P =.57). Frail nonobese candidates and frail candidates with class 1 obesity had a higher risk of wait-list mortality compared with their nonfrail counterparts (nonobese candidates: adjusted subhazard ratio, 1.54; 95% CI, 1.02-2.33; P =.04; and candidates with class 1 obesity: adjusted subhazard ratio, 1.72; 95% CI, 0.99-2.99; P =.06; P =.75 for interaction). However, frail candidates with class 2 or greater obesity had a 3.19-fold higher adjusted risk of wait-list mortality compared with nonfrail candidates with class 2 or greater obesity (95% CI, 1.75-5.82; P <.001; P =.047 for interaction). Conclusions and Relevance: This study's finding suggest that among nonobese liver transplant candidates and candidates with class 1 obesity, frailty was associated with a 2-fold higher risk of wait-list mortality. However, the mortality risk associated with frailty differed for candidates with class 2 or greater obesity, with frail candidates having a more than 3-fold higher risk of wait-list mortality compared with nonfrail patients. Frailty assessments may help to identify vulnerable patients, particularly those with a BMI of 35.0 or more, in whom a clinician's visual evaluation may be less reliable to assess muscle mass and nutritional status..",

author = "Haugen, {Christine E.} and Mara McAdams-Demarco and Verna, {Elizabeth C.} and Rahimi, {Robert S.} and Kappus, {Matthew R.} and Dunn, {Michael A.} and Volk, {Michael L.} and Ahmet Gurakar and Andres Duarte-Rojo and Ganger, {Daniel R.} and O'Leary, {Jacqueline G.} and Daniela Ladner and Jacqueline Garonzik-Wang and Segev, {Dorry L.} and Lai, {Jennifer C.}",

note = "Funding Information: reported receiving grants from the National Institutes of Health during the conduct of the study. Dr McAdams-DeMarco reported receiving grants from the National Institute on Aging during the conduct of the study. Dr Verna reported receiving grants from Salix and personal fees from Gilead outside the submitted work. Dr Dunn reported receiving personal fees from Axcella Health Inc outside the submitted work. Dr Ganger reported receiving personal fees from Gilead outside the submitted work. Dr Ladner reported receiving grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported. Funding Information: Funding/Support: Funding for this study was provided by the National Institute of Diabetes and Digestive and Kidney Disease and the National Institute of Aging: grant numbers F32AG053025 (principal investigator [PI], Dr Haugen), R01AG055781 (PI, Dr McAdams-DeMarco), K24DK101828 (PI, Dr Segev), K23AG048337 (PI, Dr Lai), and R01AG059183 (PI, Dr Lai). Publisher Copyright: {\textcopyright} 2019 American Medical Association. All rights reserved.",

year = "2019",

month = dec,

doi = "10.1001/jamasurg.2019.2845",

language = "English (US)",

volume = "154",

pages = "1103--1109",

journal = "JAMA surgery",

issn = "2168-6254",

publisher = "American Medical Association",

number = "12",

}

Haugen, CE, McAdams-Demarco, M, Verna, EC, Rahimi, RS, Kappus, MR, Dunn, MA, Volk, ML, Gurakar, A, Duarte-Rojo, A , Ganger, DR, O'Leary, JG, Ladner, D, Garonzik-Wang, J, Segev, DL & Lai, JC 2019, 'Association between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index', JAMA surgery, vol. 154, no. 12, pp. 1103-1109. https://doi.org/10.1001/jamasurg.2019.2845

TY - JOUR

T1 - Association between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index

AU - Haugen, Christine E.

AU - McAdams-Demarco, Mara

AU - Verna, Elizabeth C.

AU - Rahimi, Robert S.

AU - Kappus, Matthew R.

AU - Dunn, Michael A.

AU - Volk, Michael L.

AU - Gurakar, Ahmet

AU - Duarte-Rojo, Andres

AU - Ganger, Daniel R.

AU - O'Leary, Jacqueline G.

AU - Ladner, Daniela

AU - Garonzik-Wang, Jacqueline

AU - Segev, Dorry L.

AU - Lai, Jennifer C.

N1 - Funding Information: reported receiving grants from the National Institutes of Health during the conduct of the study. Dr McAdams-DeMarco reported receiving grants from the National Institute on Aging during the conduct of the study. Dr Verna reported receiving grants from Salix and personal fees from Gilead outside the submitted work. Dr Dunn reported receiving personal fees from Axcella Health Inc outside the submitted work. Dr Ganger reported receiving personal fees from Gilead outside the submitted work. Dr Ladner reported receiving grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported. Funding Information: Funding/Support: Funding for this study was provided by the National Institute of Diabetes and Digestive and Kidney Disease and the National Institute of Aging: grant numbers F32AG053025 (principal investigator [PI], Dr Haugen), R01AG055781 (PI, Dr McAdams-DeMarco), K24DK101828 (PI, Dr Segev), K23AG048337 (PI, Dr Lai), and R01AG059183 (PI, Dr Lai). Publisher Copyright: © 2019 American Medical Association. All rights reserved.

PY - 2019/12

Y1 - 2019/12

N2 - Importance: Among liver transplant candidates, obesity and frailty are associated with increased risk of death while they are on the wait-list. However, use of body mass index (BMI) may not detect candidates at a higher risk of death owing to the fact that ascites and muscle wasting are seen across transplant candidates of all BMI measurements. Objective: To evaluate whether the association between wait-list mortality and frailty varied by BMI of liver transplant candidates. Design, Setting, and Participants: A prospective cohort study was conducted at 9 liver transplant centers in the United States from March 1, 2012, to May 1, 2018, among 1108 adult liver transplant candidates without hepatocellular carcinoma. Exposures: At outpatient evaluation, the Liver Frailty Index score was calculated (grip strength, chair stands, and balance), with frailty defined as a Liver Frailty Index score of 4.5 or more. Candidates' BMI was categorized as nonobese (18.5-29.9), class 1 obesity (30.0-34.9), and class 2 or greater obesity (≥35.0). Main Outcomes and Measures: The risk of wait-list mortality was quantified using competing risks regression by candidate frailty, adjusting for age, sex, race/ethnicity, Model for End-stage Liver Disease Sodium score, cause of liver disease, and ascites, including an interaction with candidate BMI. Results: Of 1108 liver transplant candidates (474 women and 634 men; mean [SD] age, 55 [10] years), 290 (26.2%) were frail; 170 of 670 nonobese candidates (25.4%), 64 of 246 candidates with class 1 obesity (26.0%), and 56 of 192 candidates with class 2 or greater obesity (29.2%) were frail (P =.57). Frail nonobese candidates and frail candidates with class 1 obesity had a higher risk of wait-list mortality compared with their nonfrail counterparts (nonobese candidates: adjusted subhazard ratio, 1.54; 95% CI, 1.02-2.33; P =.04; and candidates with class 1 obesity: adjusted subhazard ratio, 1.72; 95% CI, 0.99-2.99; P =.06; P =.75 for interaction). However, frail candidates with class 2 or greater obesity had a 3.19-fold higher adjusted risk of wait-list mortality compared with nonfrail candidates with class 2 or greater obesity (95% CI, 1.75-5.82; P <.001; P =.047 for interaction). Conclusions and Relevance: This study's finding suggest that among nonobese liver transplant candidates and candidates with class 1 obesity, frailty was associated with a 2-fold higher risk of wait-list mortality. However, the mortality risk associated with frailty differed for candidates with class 2 or greater obesity, with frail candidates having a more than 3-fold higher risk of wait-list mortality compared with nonfrail patients. Frailty assessments may help to identify vulnerable patients, particularly those with a BMI of 35.0 or more, in whom a clinician's visual evaluation may be less reliable to assess muscle mass and nutritional status..

AB - Importance: Among liver transplant candidates, obesity and frailty are associated with increased risk of death while they are on the wait-list. However, use of body mass index (BMI) may not detect candidates at a higher risk of death owing to the fact that ascites and muscle wasting are seen across transplant candidates of all BMI measurements. Objective: To evaluate whether the association between wait-list mortality and frailty varied by BMI of liver transplant candidates. Design, Setting, and Participants: A prospective cohort study was conducted at 9 liver transplant centers in the United States from March 1, 2012, to May 1, 2018, among 1108 adult liver transplant candidates without hepatocellular carcinoma. Exposures: At outpatient evaluation, the Liver Frailty Index score was calculated (grip strength, chair stands, and balance), with frailty defined as a Liver Frailty Index score of 4.5 or more. Candidates' BMI was categorized as nonobese (18.5-29.9), class 1 obesity (30.0-34.9), and class 2 or greater obesity (≥35.0). Main Outcomes and Measures: The risk of wait-list mortality was quantified using competing risks regression by candidate frailty, adjusting for age, sex, race/ethnicity, Model for End-stage Liver Disease Sodium score, cause of liver disease, and ascites, including an interaction with candidate BMI. Results: Of 1108 liver transplant candidates (474 women and 634 men; mean [SD] age, 55 [10] years), 290 (26.2%) were frail; 170 of 670 nonobese candidates (25.4%), 64 of 246 candidates with class 1 obesity (26.0%), and 56 of 192 candidates with class 2 or greater obesity (29.2%) were frail (P =.57). Frail nonobese candidates and frail candidates with class 1 obesity had a higher risk of wait-list mortality compared with their nonfrail counterparts (nonobese candidates: adjusted subhazard ratio, 1.54; 95% CI, 1.02-2.33; P =.04; and candidates with class 1 obesity: adjusted subhazard ratio, 1.72; 95% CI, 0.99-2.99; P =.06; P =.75 for interaction). However, frail candidates with class 2 or greater obesity had a 3.19-fold higher adjusted risk of wait-list mortality compared with nonfrail candidates with class 2 or greater obesity (95% CI, 1.75-5.82; P <.001; P =.047 for interaction). Conclusions and Relevance: This study's finding suggest that among nonobese liver transplant candidates and candidates with class 1 obesity, frailty was associated with a 2-fold higher risk of wait-list mortality. However, the mortality risk associated with frailty differed for candidates with class 2 or greater obesity, with frail candidates having a more than 3-fold higher risk of wait-list mortality compared with nonfrail patients. Frailty assessments may help to identify vulnerable patients, particularly those with a BMI of 35.0 or more, in whom a clinician's visual evaluation may be less reliable to assess muscle mass and nutritional status..

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JO - JAMA surgery

JF - JAMA surgery

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ER -

Association between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index

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