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

Christine E. Haugen, Mara Ann McAdams Demarco, Elizabeth C. Verna, Robert 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, Dorry Segev, Jennifer C. Lai

Research output: Contribution to journalLetter

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 languageEnglish (US)
JournalJAMA surgery
DOIs
StateAccepted/In press - Jan 1 2019

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Body Mass Index
Obesity
Transplants
Mortality
Liver
Ascites
Muscles
End Stage Liver Disease
Hand Strength
Nutritional Status
Liver Diseases
Hepatocellular Carcinoma
Cohort Studies
Outpatients
Sodium
Outcome Assessment (Health Care)
Prospective Studies

ASJC Scopus subject areas

  • Surgery

Cite this

Association between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index. / Haugen, Christine E.; McAdams Demarco, Mara Ann; Verna, Elizabeth C.; Rahimi, Robert; Kappus, Matthew R.; Dunn, Michael A.; Volk, Michael L.; Gurakar, Ahmet; Duarte-Rojo, Andres; Ganger, Daniel R.; O'Leary, Jacqueline G.; Ladner, Daniela; Garonzik, Jacqueline; Segev, Dorry; Lai, Jennifer C.

In: JAMA surgery, 01.01.2019.

Research output: Contribution to journalLetter

Haugen, CE, McAdams Demarco, MA, Verna, EC, Rahimi, R, Kappus, MR, Dunn, MA, Volk, ML, Gurakar, A, Duarte-Rojo, A, Ganger, DR, O'Leary, JG, Ladner, D, Garonzik, J, Segev, D & Lai, JC 2019, 'Association between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index', JAMA surgery. https://doi.org/10.1001/jamasurg.2019.2845
Haugen, Christine E. ; McAdams Demarco, Mara Ann ; Verna, Elizabeth C. ; Rahimi, Robert ; Kappus, Matthew R. ; Dunn, Michael A. ; Volk, Michael L. ; Gurakar, Ahmet ; Duarte-Rojo, Andres ; Ganger, Daniel R. ; O'Leary, Jacqueline G. ; Ladner, Daniela ; Garonzik, Jacqueline ; Segev, Dorry ; Lai, Jennifer C. / Association between Liver Transplant Wait-list Mortality and Frailty Based on Body Mass Index. In: JAMA surgery. 2019.
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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 {McAdams Demarco}, {Mara Ann} and Verna, {Elizabeth C.} and Robert Rahimi 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 and Dorry Segev and Lai, {Jennifer C.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1001/jamasurg.2019.2845",
language = "English (US)",
journal = "JAMA Surgery",
issn = "2168-6254",
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}

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 Ann

AU - Verna, Elizabeth C.

AU - Rahimi, Robert

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, Jacqueline

AU - Segev, Dorry

AU - Lai, Jennifer C.

PY - 2019/1/1

Y1 - 2019/1/1

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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