Jennifer C Lai1, Jennifer L Dodge2, Matthew R Kappus3, Michael A Dunn4, Michael L Volk5, Andres Duarte-Rojo6, Daniel R Ganger7, Robert S Rahimi8, Charles E McCulloch9, Christine E Haugen10, Mara McAdams-DeMarco11, Daniela P Ladner12, Dorry L Segev10, Elizabeth C Verna13. 1. Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, San Francisco, CA. Electronic address: Jennifer.lai@ucsf.edu. 2. Division of Transplant Surgery, Department of Surgery, University of California-San Francisco, San Francisco, CA. 3. Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, Durham, NC. 4. Center for Liver Diseases, Thomas A. Starzl Transplantation Institute, and Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA. 5. Division of Gastroenterology & Hepatology, and Transplantation Institute, Loma Linda University Health, Loma Linda, CA. 6. Division of Gastroenterology & Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR. 7. Division of Gastroenterology and Hepatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. 8. Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Baylor Scott and White, Dallas, TX, USA. 9. Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA. 10. Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD. 11. Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 12. Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL. 13. Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY.
Abstract
BACKGROUND & AIMS: To date, studies evaluating the association between frailty and mortality in patients with cirrhosis have been limited to assessments of frailty at a single time point. We aimed to evaluate changes in frailty over time and their association with death/delisting in patients too sick for liver transplantation. METHODS: Adults with cirrhosis, listed for liver transplantation at 8 US centers, underwent ambulatory longitudinal frailty testing using the liver frailty index (LFI). We used multilevel linear mixed-effects regression to model and predict changes in LFI (ΔLFI) per 3 months, based on age, gender, model for end-stage liver disease (MELD)-Na, ascites, and hepatic encephalopathy, categorizing patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk. RESULTS: We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe worsening of frailty had worse baseline LFI and were more likely to have non-alcoholic fatty liver disease, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted because of sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELD-Na, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI 1.35-3.09). CONCLUSION: Worsening frailty was significantly associated with death/delisting independent of baseline frailty and MELD-Na. Notably, patients who experienced improvements in frailty had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty. LAY SUMMARY: Frailty, as measured at a single time point, is predictive of death in patients with cirrhosis, but whether changes in frailty over time are associated with death is unknown. In a study of over 1,000 patients with cirrhosis who underwent frailty testing, we demonstrate that worsening frailty is strongly linked with mortality, regardless of baseline frailty and liver disease severity. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.
BACKGROUND & AIMS: To date, studies evaluating the association between frailty and mortality in patients with cirrhosis have been limited to assessments of frailty at a single time point. We aimed to evaluate changes in frailty over time and their association with death/delisting in patients too sick for liver transplantation. METHODS: Adults with cirrhosis, listed for liver transplantation at 8 US centers, underwent ambulatory longitudinal frailty testing using the liver frailty index (LFI). We used multilevel linear mixed-effects regression to model and predict changes in LFI (ΔLFI) per 3 months, based on age, gender, model for end-stage liver disease (MELD)-Na, ascites, and hepatic encephalopathy, categorizing patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk. RESULTS: We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe worsening of frailty had worse baseline LFI and were more likely to have non-alcoholic fatty liver disease, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted because of sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELD-Na, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI 1.35-3.09). CONCLUSION: Worsening frailty was significantly associated with death/delisting independent of baseline frailty and MELD-Na. Notably, patients who experienced improvements in frailty had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty. LAY SUMMARY: Frailty, as measured at a single time point, is predictive of death in patients with cirrhosis, but whether changes in frailty over time are associated with death is unknown. In a study of over 1,000 patients with cirrhosis who underwent frailty testing, we demonstrate that worsening frailty is strongly linked with mortality, regardless of baseline frailty and liver disease severity. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.
Authors: Jennifer C Lai; Kenneth E Covinsky; Jennifer L Dodge; W John Boscardin; Dorry L Segev; John P Roberts; Sandy Feng Journal: Hepatology Date: 2017-06-28 Impact factor: 17.425
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