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

Abstract

Background Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the MELDNa score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and enhance mortality prediction in cirrhotics. Methods Consecutive outpatients listed for LT 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 due to 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. Results Included were 536 cirrhotics with median MELDNa of 18. 107(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-mo waitlist mortality risk (i.e., C-statistic) was 0.80 and 0.76, respectively, but 0.82 for MELDNa + Frailty Index together. Compared with MELDNa alone, MELDNa + Frailty Index correctly re-classified 16% of deaths/delistings (p=0.005) and 3% of non-deaths/delistings (p=0.17) with a total NRI of 19% (p<0.001). Compared to those with robust Frailty Index scores (<20%ile), cirrhotics with poor Frailty Index Scores (>80%ile) were more impaired by gait speed, IADL difficulty, exhaustion, and low physical activity [p<0.001 for each]. Conclusions Our Frailty Index for cirrhotics, comprised of 3 performance-based metrics, has construct validity for the concept of frailty and improves risk prediction of waitlist mortality over MELDNa alone.

Hepatic encephalopathy impacts the predictive value of the Fried Frailty Index

“…To avoid the pitfalls of subjective assessments of frailty, the field of liver transplantation may be moving toward the strictly objective measures such as the Liver Frailty Index (hand-grip, chair-stands, and balance). 8 However, our data show that the relative impact of HE and cognitive dysfunction will not diminish for objective measures and will need to be addressed even as our frailty indices improve and become more standardized.…”

“…Frailty tools measure many features, including disability (i.e. activities of daily living 5,8 ), physical function (i.e. hand-grip, walk-speed 9 ), and muscle bulk / sarcopenia (i.e.…”

Physical frailty after liver transplantation

“…While we did not directly measure health-related quality of life (HRQoL) using standardized HRQoL instruments in this study, we have previously demonstrated that the Liver Frailty Index is strongly correlated with Activities of Daily Living and Instrumental Activities of Daily Living, both of which are crucial components of HRQoL. 9 …”

“…9 Briefly, patients with cirrhosis who were listed and active for liver transplantation at the University of California, San Francisco and seen as outpatients were eligible for enrollment. At enrollment, all participants underwent assessment of frailty pretransplant.…”

“…9 It has advantages over other frailty assessment tools that have been studied in cirrhotic patients in that it is entirely performance-based, is scored on a continuous scale (making it suitable for investigating longitudinal changes in frailty posttransplant), and perhaps most importantly, is directed towards dimensions of frailty—malnutrition, muscle wasting, and neuromotor coordination—that are most likely to be impacted by end-stage liver disease.…”