The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Development of a novel frailty index to predict mortality in patients with end‐stage liver disease
Open accessAbstract
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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“Finally, malnutrition [105], frailty [106, 107] and especially sarcopenia [108, 109, 110, 111] have become increasingly important in patients with advanced chronic liver disease and should be evaluated and treated in each patient.”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [106]
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Cites
Frailty in Older Adults: Evidence for a Phenotype
Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W. J., Burke, G., et al. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.3.m146 · Cited by 24,907 · cited 10×
“(1), good (2), fair (3), poor (4), or very poor (5).”
BackgroundMethodInfluentialAssessment of Older People: Self-Maintaining and Instrumental Activities of Daily Living
Lawton, M. P., & Brody, E. M. (1969) · The Gerontologist · doi:10.1093/geront/9.3_part_1.179 · Cited by 18,540
A Proportional Hazards Model for the Subdistribution of a Competing Risk
Fine, J. P., & Gray, R. J. (1999) · Journal of the American Statistical Association · doi:10.1080/01621459.1999.10474144 · Cited by 14,290 · cited 2×
“not available for competing risk regression.((12)) However, in our cohort, the estimates of waitlist mortality, our primary outcome, were similar at 3, 6, and 12 months (Supporting Table S2).”
ResultGuralnik, J. M., Simonsick, E. M., Ferrucci, L., Glynn, R. J., Berkman, L. F., Blazer, D. G., Scherr, P. A., & Wallace, R. B. (1994) · Journal of Gerontology · doi:10.1093/geronj/49.2.m85 · Cited by 9,792 · cited 3×
“Balance, seconds <30 seconds is impaired((16)) 30 (30-30) 0.”
ResultA Model to Predict Survival in Patients With End–Stage Liver Disease
Kamath, P. S., Wiesner, R. H., Malinchoc, M., Kremers, W. K., Therneau, T. M., Kosberg, C. L., D’Amico, G., Dickson, R. E., & Kim, W. R. (2001) · Hepatology · doi:10.1053/jhep.2001.22172 · Cited by 5,066 · cited 6×
“The MELD score has proven, time and time again, to predict mortality in patients with cirrhosis.((1,15)) However, clinicians have long recognized that, at a given MELD score, the clinical manifestations of patients with ESLD are highly heterogeneous.”
BackgroundMethodInfluentialGait speed and survival in older adults.
Studenski, S. (2011) · JAMA · doi:10.1001/jama.2010.1923 · Cited by 4,558 · cited 3×
“Given the inherent sex differences in grip strength((8)) and walk speed((9)) norms, we converted grip strength and walk speed into sexspecific z-scores for use in the prediction modeling:”
MethodResultLower-extremity function in persons over the age of 70 years as a predictor of subsequent disability
Guralnik, J. M., Ferrucci, L., Simonsick, E. M., Salive, M. E., & Wallace, R. B. (1995) · New England Journal of Medicine · doi:10.1056/nejm199503023320902 · Cited by 4,083
Collins, P. G. S., Reitsma, J. B., Altman, D. G., & Moons, K. G. M. (2015) · British Journal of Cancer · doi:10.1038/bjc.2014.639 · Cited by 3,319
Collins, G. S., Reitsma, J. B., Altman, D. G., & Moons, K. G. M. (2015) · Annals of Internal Medicine · doi:10.7326/m14-0697 · Cited by 3,267
Internal validation of predictive models
Steyerberg, E. W., Harrell, F. E., Borsboom, G. J. J. M., Eijkemans, M. J. C., Vergouwe, Y., & Habbema, J. D. F. (2001) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(01)00341-9 · Cited by 2,746 · cited 1×
“This was a deliberate choice, given that studies have demonstrated that this combination of selection methods is equivalent to cross-validation and bootstrapping and is preferred to internal validation.((10,25)) External validation, however, remains the gold standard to assess the true validity of this index when appl…”
Method
Research works printed but not linked: 1
- 2005, Model building in PROC PHREG with automatic variable selection and information criteria, Stat Data Anal, SUGI 30, 206
Cited by
Sorted by citations
From discoveries in ageing research to therapeutics for healthy ageing
Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019) · Nature · doi:10.1038/s41586-019-1365-2 · Cited by 1,389
Contemporary Epidemiology of Chronic Liver Disease and Cirrhosis
Moon, A. M., Singal, A. G., & Tapper, E. B. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2019.07.060 · Cited by 1,200
Lai, J. C., Tandon, P., Bernal, W., Tapper, E. B., Ekong, U., Dasarathy, S., & Carey, E. J. (2021) · Hepatology · doi:10.1002/hep.32049 · Cited by 742
“(90,91) Poor performance according to some scales (e.g., ADLs), however, suggests a greater burden of functional deficits than others (e.g., walk speed).”
BackgroundSelf-citationMELD 3.0: The Model for End-Stage Liver Disease Updated for the Modern Era
Kim, W. R., Mannalithara, A., Heimbach, J. K., Kamath, P. S., Asrani, S. K., Biggins, S. W., Wood, N. L., Gentry, S. E., & Kwong, A. J. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.08.050 · Cited by 654
Current treatment of non‐alcoholic fatty liver disease
Paternostro, R., & Trauner, M. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13531 · Cited by 305
Metadata
- Authors
- Lai, J. C., Covinsky, K. E., Dodge, J. L., Boscardin, W. J., Segev, D. L., Roberts, J. P., & Feng, S.
- Affiliations
- University of California, San Francisco (US)
- Johns Hopkins University (US)
- Corresponding author
- Lai, Jennifer C.
- ORCID
- Venue
- Hepatology
- Published
- 2017-06-28
- Volume
- 66
- Issue
- 2
- Pages
- 564-574
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC5519430
- OpenAlex
- W2606209221
- Cited by
- 556
- References
- 34
- Citations by year
- 2026: 75 · 2025: 62 · 2024: 71 · 2023: 62 · 2022: 50 · 2021: 69 · 2020: 60 · 2019: 59 · 2018: 35 · 2017: 10
- FWCI
- 27.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American College of Gastroenterology (K23AG048337, P30 DK026743, P30AG044281)
- National Institutes of Health
- University of California, San Francisco (P30 AG044281, P30DK026743)
- National Institute on Aging (K23AG048337, R01AG042504, R03AG045072, P30AG044281)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK101828, P30DK026743)
- Liver Center, University of California, San Francisco (P30 DK026743, DK026743)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- frailty index, end-stage liver disease, liver cirrhosis, waitlist mortality, MELD-Na, liver transplantation, mortality prediction, grip strength, chair stand, balance, net reclassification improvement, instrumental activities of daily living, walking speed, exhaustion, physical activity
- MeSH terms
- Activities of Daily Living, Cause of Death, Disability Evaluation, Female, Humans, Liver Cirrhosis, Male, Middle Aged, Physical Fitness, Predictive Value of Tests, Prognosis, Retrospective Studies, Severity of Illness Index, Waiting Lists, Reproducibility of Results, Cohort Studies, Survival Rate, Liver Transplantation, Databases, Factual, Risk Assessment, End Stage Liver Disease
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