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Hepatology. 2017 Aug;66(2):564-574. doi: 10.1002/hep.29219. Epub 2017 Jun 28.

Development of a novel frailty index to predict mortality in patients with end-stage liver disease.

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Department of Medicine, Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA.
Department of Medicine, Division of Geriatrics, University of California-San Francisco, San Francisco, CA.
Department of Surgery, Division of Transplant Surgery, University of California-San Francisco, San Francisco, CA.
Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA.
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.


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).

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