Development of a novel frailty index to predict mortality in patients with end‐stage liver disease
Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End‐Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and...
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Published in | Hepatology (Baltimore, Md.) Vol. 66; no. 2; pp. 564 - 574 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Wiley Subscription Services, Inc
01.08.2017
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Subjects | |
Online Access | Get full text |
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Abstract | Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End‐Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and enhance mortality prediction in patients with cirrhosis. Consecutive outpatients listed for liver transplantation at a single transplant center without MELD exceptions were assessed with candidate frailty measures. Best subset selection analyses with Cox regression identified subsets of frailty measures that predicted waitlist mortality (=death or delisting because of sickness). We selected the frailty index by balancing statistical accuracy with clinical utility. The net reclassification index (NRI) evaluated the %patients correctly reclassified by adding the frailty index to MELDNa. Included were 536 patients with cirrhosis with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final frailty index consisted of: grip strength, chair stands, and balance. The ability of MELDNa and the frailty index to correctly rank patients according to their 3‐month waitlist mortality risk (i.e., concordance‐statistic) was 0.80 and 0.76, respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings (P = 0.005) and 3% of nondeaths/delistings (P = 0.17) with a total NRI of 19% (P < 0.001). Compared to those with robust frailty index scores (<20th percentile), cirrhotics with poor frailty index scores (>80th percentile) were more impaired by gait speed, difficulty with Instrumental Activities of Daily Living, exhaustion, and low physical activity (P < 0.001 for each). Conclusion: Our frailty index for patients with cirrhosis, comprised of three performance‐based metrics, has construct validity for the concept of frailty and improves risk prediction of waitlist mortality over MELDNa alone. (Hepatology 2017;66:564–574). |
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AbstractList | Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End-Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and enhance mortality prediction in patients with cirrhosis. Consecutive outpatients listed for liver transplantation at a single transplant center without MELD exceptions were assessed with candidate frailty measures. Best subset selection analyses with Cox regression identified subsets of frailty measures that predicted waitlist mortality (=death or delisting because of sickness). We selected the frailty index by balancing statistical accuracy with clinical utility. The net reclassification index (NRI) evaluated the %patients correctly reclassified by adding the frailty index to MELDNa. Included were 536 patients with cirrhosis with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final frailty index consisted of: grip strength, chair stands, and balance. The ability of MELDNa and the frailty index to correctly rank patients according to their 3-month waitlist mortality risk (i.e., concordance-statistic) was 0.80 and 0.76, respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings (P = 0.005) and 3% of nondeaths/delistings (P = 0.17) with a total NRI of 19% (P < 0.001). Compared to those with robust frailty index scores (<20th percentile), cirrhotics with poor frailty index scores (>80th percentile) were more impaired by gait speed, difficulty with Instrumental Activities of Daily Living, exhaustion, and low physical activity (P < 0.001 for each).
Our frailty index for patients with cirrhosis, comprised of three performance-based metrics, has construct validity for the concept of frailty and improves risk prediction of waitlist mortality over MELDNa alone. (Hepatology 2017;66:564-574). Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End‐Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and enhance mortality prediction in patients with cirrhosis. Consecutive outpatients listed for liver transplantation at a single transplant center without MELD exceptions were assessed with candidate frailty measures. Best subset selection analyses with Cox regression identified subsets of frailty measures that predicted waitlist mortality (=death or delisting because of sickness). We selected the frailty index by balancing statistical accuracy with clinical utility. The net reclassification index (NRI) evaluated the %patients correctly reclassified by adding the frailty index to MELDNa. Included were 536 patients with cirrhosis with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final frailty index consisted of: grip strength, chair stands, and balance. The ability of MELDNa and the frailty index to correctly rank patients according to their 3‐month waitlist mortality risk (i.e., concordance‐statistic) was 0.80 and 0.76, respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings (P = 0.005) and 3% of nondeaths/delistings (P = 0.17) with a total NRI of 19% (P < 0.001). Compared to those with robust frailty index scores (<20th percentile), cirrhotics with poor frailty index scores (>80th percentile) were more impaired by gait speed, difficulty with Instrumental Activities of Daily Living, exhaustion, and low physical activity (P < 0.001 for each). Conclusion: Our frailty index for patients with cirrhosis, comprised of three performance‐based metrics, has construct validity for the concept of frailty and improves risk prediction of waitlist mortality over MELDNa alone. (Hepatology 2017;66:564–574). Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End-Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and enhance mortality prediction in patients with cirrhosis. Consecutive outpatients listed for liver transplantation at a single transplant center without MELD exceptions were assessed with candidate frailty measures. Best subset selection analyses with Cox regression identified subsets of frailty measures that predicted waitlist mortality (=death or delisting because of sickness). We selected the frailty index by balancing statistical accuracy with clinical utility. The net reclassification index (NRI) evaluated the %patients correctly reclassified by adding the frailty index to MELDNa. Included were 536 patients with cirrhosis with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final frailty index consisted of: grip strength, chair stands, and balance. The ability of MELDNa and the frailty index to correctly rank patients according to their 3-month waitlist mortality risk (i.e., concordance-statistic) was 0.80 and 0.76, respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings (P = 0.005) and 3% of nondeaths/delistings (P = 0.17) with a total NRI of 19% (P < 0.001). Compared to those with robust frailty index scores (<20th percentile), cirrhotics with poor frailty index scores (>80th percentile) were more impaired by gait speed, difficulty with Instrumental Activities of Daily Living, exhaustion, and low physical activity (P < 0.001 for each). CONCLUSIONOur frailty index for patients with cirrhosis, comprised of three performance-based metrics, has construct validity for the concept of frailty and improves risk prediction of waitlist mortality over MELDNa alone. (Hepatology 2017;66:564-574). Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End‐Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and enhance mortality prediction in patients with cirrhosis. Consecutive outpatients listed for liver transplantation at a single transplant center without MELD exceptions were assessed with candidate frailty measures. Best subset selection analyses with Cox regression identified subsets of frailty measures that predicted waitlist mortality (=death or delisting because of sickness). We selected the frailty index by balancing statistical accuracy with clinical utility. The net reclassification index (NRI) evaluated the %patients correctly reclassified by adding the frailty index to MELDNa. Included were 536 patients with cirrhosis with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final frailty index consisted of: grip strength, chair stands, and balance. The ability of MELDNa and the frailty index to correctly rank patients according to their 3‐month waitlist mortality risk (i.e., concordance‐statistic) was 0.80 and 0.76, respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings ( P = 0.005) and 3% of nondeaths/delistings ( P = 0.17) with a total NRI of 19% ( P < 0.001). Compared to those with robust frailty index scores (<20th percentile), cirrhotics with poor frailty index scores (>80th percentile) were more impaired by gait speed, difficulty with Instrumental Activities of Daily Living, exhaustion, and low physical activity ( P < 0.001 for each). Conclusion : Our frailty index for patients with cirrhosis, comprised of three performance‐based metrics, has construct validity for the concept of frailty and improves risk prediction of waitlist mortality over MELDNa alone. (H epatology 2017;66:564–574). |
Author | Dodge, Jennifer L. Covinsky, Kenneth E. Roberts, John P. Boscardin, W. John Feng, Sandy Segev, Dorry L. Lai, Jennifer C. |
AuthorAffiliation | e Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD d Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA b Department of Medicine, Division of Geriatrics, University of California-San Francisco, San Francisco, CA c Department of Surgery, Division of Transplant Surgery, University of California-San Francisco, San Francisco, CA a Department of Medicine, Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA |
AuthorAffiliation_xml | – name: d Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA – name: a Department of Medicine, Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA – name: e Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD – name: b Department of Medicine, Division of Geriatrics, University of California-San Francisco, San Francisco, CA – name: c Department of Surgery, Division of Transplant Surgery, University of California-San Francisco, San Francisco, CA |
Author_xml | – sequence: 1 givenname: Jennifer C. surname: Lai fullname: Lai, Jennifer C. email: Jennifer.lai@ucsf.edu organization: University of California‐San Francisco – sequence: 2 givenname: Kenneth E. surname: Covinsky fullname: Covinsky, Kenneth E. organization: University of California‐San Francisco – sequence: 3 givenname: Jennifer L. surname: Dodge fullname: Dodge, Jennifer L. organization: University of California‐San Francisco – sequence: 4 givenname: W. John surname: Boscardin fullname: Boscardin, W. John organization: University of California‐San Francisco – sequence: 5 givenname: Dorry L. surname: Segev fullname: Segev, Dorry L. organization: Johns Hopkins University School of Medicine – sequence: 6 givenname: John P. surname: Roberts fullname: Roberts, John P. organization: University of California‐San Francisco – sequence: 7 givenname: Sandy surname: Feng fullname: Feng, Sandy organization: University of California‐San Francisco |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28422306$$D View this record in MEDLINE/PubMed |
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Notes | Potential conflict of interest: Dr. Lai consults for Third Rock Ventures. Supported by an American College of Gastroenterology Junior Faculty Development Award, P30AG044281 (UCSF Older Americans Independence Center), K23AG048337 (Paul B. Beeson Career Development Award in Aging Research), P30 DK026743 (UCSF Liver Center), and NIH R01AG042504 and K24DK101828. These funding agencies played no role in the analysis of the data or the preparation of this manuscript. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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Snippet | Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End‐Stage... Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End-Stage... |
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SubjectTerms | Activities of Daily Living Balance Cause of Death Cirrhosis Cohort Studies Databases, Factual Death Disability Evaluation End Stage Liver Disease - diagnosis End Stage Liver Disease - mortality End Stage Liver Disease - surgery Female Frailty Gait Hepatology Humans Liver cirrhosis Liver Cirrhosis - pathology Liver Cirrhosis - physiopathology Liver diseases Liver Transplantation Male Malnutrition Middle Aged Mortality Physical activity Physical Fitness - physiology Predictive Value of Tests Prognosis Reclassification Reproducibility of Results Retrospective Studies Risk Assessment Severity of Illness Index Sodium Survival Rate Transplantation Transplants & implants Waiting Lists - mortality |
Title | Development of a novel frailty index to predict mortality in patients with end‐stage liver disease |
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