Evaluating the Associations Between the Liver Frailty Index and Karnofsky Performance Status With Waitlist Mortality

Abstract

Background. Frailty has emerged as a critical determinant of mortality in patients with cirrhosis. Currently, the United Network for Organ Sharing registry only includes the Karnofsky Performance Status (KPS) scale, which captures a single component of frailty. We determined the associations between frailty, as measured by the Liver Frailty Index (LFI), and KPS with waitlist mortality. Methods. Included were 247 adult patients with cirrhosis listed for liver transplantation without hepatocellular carcinoma from February 2014 to June 2019, who underwent outpatient assessments using the LFI and KPS within 30 days of listing. “Frail” was defined using the established LFI cutoff of ≥4.4. Competing risk models assessed associations between the LFI and KPS with waitlist mortality (death/delisting for sickness). Results. At a median 8 months follow-up, 25 (10%) patients died/were delisted. In this cohort, median Model for End-Stage Liver Disease-Sodium was 17, LFI was 3.9 (interquartile range 3.4–4.5), and KPS was 80 (interquartile range 70–90). In multivariable analysis, LFI (sub-hazard ratio 1.07, per 0.1 unit; 95% confidence interval, 1.01-1.12) was associated with waitlist mortality while KPS was not (sub-hazard ratio 1.00, per 10 units; 95% confidence interval, 0.78-1.29). Conclusions. Our data suggest that frailty, as measured by the LFI, may be more appropriate at capturing mortality risk than KPS and provide evidence in support of using the LFI more broadly in clinical transplant practice in the outpatient setting.

Association of Frailty With Health-Related Quality of Life in Liver Transplant Recipients

“…Compared with those without frailty, patients with frailty differed significantly by race and ethnicity and etiology of cirrhosis, with higher percentages of non-Hispanic White individuals (87% vs 64%) and individuals with nonalcoholic fatty liver disease (NAFLD) (44% vs 25%), and were less likely to have HCC (24% vs 38%; P = .02), but were similar by age, sex, and body mass index (calculated as weight in kilograms divided by height in meters squared). Median (IQR) Model of End-stage Liver Disease/sodium scores at assessment (21 [15-26] vs 17 [12][13][14][15][16][17][18][19][20][21][22]; P < .001) and transplant (26 [19][20][21][22][23][24][25][26][27][28][29][30][31] vs 21 [15][16][17][18][19][20][21][22][23][24][25][26][27]; P < .001) were significantly higher in those with frailty vs without frailty, as were rates of ascites (60% vs 34%; P < .001) and hepatic encephalopathy (67% vs 51%; P = .02). The median (IQR) time from assessment to transplant was 1.7 months (0.5-3.6) in those with frailty and 2.8 (1.2-5.6) in those without frailty (P = .02) (Table 1).…”

“…While prior studies have established the association between the Karnofsky Performance Status (KPS), a metric that has been used in hepatology literature as a surrogate for frailty, and posttransplant mortality, 20 the present study potentially advances the field by using an objective, performance-based metric of frailty that seems to be a more accurate metric of frailty than the KPS and avoids the weaknesses of a subjective metric, such as KPS, that renders it less suitable for transplant decision-making. 21,22 In patients with cirrhosis, the frail phenotype has been conceptualized to be predominantly associated with the combination of undernutrition, muscle wasting, and neuromotor discoordination. 23,24 These factors are respectively represented by the 3 tests of the LFI: grip strength, chair stands, and balance.…”

“…The results of the final analysis suggest that the presence of frailty at 1 year posttransplant was associated with worse physical HRQL that was nearly twice what is considered clinically important and independent of many of the pretransplant baseline characteristics that we believed may have otherwise confounded this association. While prior studies have established the association between the Karnofsky Performance Status (KPS), a metric that has been used in hepatology literature as a surrogate for frailty, and posttransplant mortality, the present study potentially advances the field by using an objective, performance-based metric of frailty that seems to be a more accurate metric of frailty than the KPS and avoids the weaknesses of a subjective metric, such as KPS, that renders it less suitable for transplant decision-making …”

Nutrition, frailty assessment, and interventions for the liver transplant candidate

“…[8] As this assessment includes subjectivity, it may be influenced by factors not accurately tied to physical performance, thereby skewing risk assessment for individual patients. [8] The LFI (https://liverfrailtyindex.ucsf.edu/) objectively measures physical frailty, using grip strength, chair stands, and balance testing to categorize patients as robust, prefrail, or frail. [3] The LFI improves risk prediction of 3-month waitlist mortality for LT compared with the model for end-stage liver disease alone and predicts post-transplant functional status.…”

Sarcopenia and Frailty in Liver Cirrhosis

“…The LFI is composed of three performance-based tests (GS, chair stands and balance) [ 79 ]. Its usefulness in liver transplant patients was reported from overseas, and its usefulness in HCC patients was also reported from Japan [ 79 , 80 , 81 , 82 , 83 , 84 , 85 ]. The LFI can be closely linked to muscle atrophy in CLD patients [ 83 ].…”