Christine E Haugen1, Mara McAdams-DeMarco1,2, Elizabeth C Verna3, Robert S Rahimi4, Matthew R Kappus5, Michael A Dunn6, Michael L Volk7, Ahmet Gurakar8, Andres Duarte-Rojo9, Daniel R Ganger10, Jacqueline G O'Leary11, Daniela Ladner12, Jacqueline Garonzik-Wang1, Dorry L Segev1,2, Jennifer C Lai13. 1. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. 2. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland. 3. Center for Liver Disease and Transplantation, Columbia University Medical Center, New York, New York. 4. Department of Hepatology, Baylor University Medical Center, Dallas, Texas. 5. Department of Medicine, Duke University School of Medicine, Durham, North Carolina. 6. Center for Liver Diseases, Thomas A. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania. 7. Division of Gastroenterology and Hepatology, Loma Linda University Health, Loma Linda, California. 8. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. 9. Division of Gastroenterology and Hepatology, University of Arkansas Medical School, Little Rock. 10. Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 11. Division of Hepatology, Dallas Veterans Administration Medical Center, Dallas, Texas. 12. Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 13. Department of Medicine, University of California, San Francisco.
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.
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.
Authors: Ani Kardashian; Jin Ge; Charles E McCulloch; Matthew R Kappus; Michael A Dunn; Andres Duarte-Rojo; Michael L Volk; Robert S Rahimi; Elizabeth C Verna; Daniel R Ganger; Daniela Ladner; Jennifer L Dodge; Brian Boyarsky; Mara McAdams-DeMarco; Dorry L Segev; Jennifer C Lai Journal: Hepatology Date: 2020-10-30 Impact factor: 17.425
Authors: Gemma F Spiers; Tafadzwa Patience Kunonga; Alex Hall; Fiona Beyer; Elisabeth Boulton; Stuart Parker; Peter Bower; Dawn Craig; Chris Todd; Barbara Hanratty Journal: BMJ Open Date: 2021-03-22 Impact factor: 2.692
Authors: Jennifer C Lai; Puneeta Tandon; William Bernal; Elliot B Tapper; Udeme Ekong; Srinivasan Dasarathy; Elizabeth J Carey Journal: Hepatology Date: 2021-09 Impact factor: 17.298