Abstract

Background: An outpatient prehabilitation strategy is feasible and effective in improving frailty in liver transplant (LT) candidates. We previously showed that attendance to physical therapy (PT) sessions results in a significant reduction in mortality, but were unable identify the frailty change threshold that yields such benefit. The aim of this study was to determine the impact of variation of frailty metrics on mortality and to identify a minimum clinically important difference that could provide a survival advantage to LT candidates with frailty.

Methods: LT candidates who attended PT consultation at our center between 2018 and 2022 were prospectively included. All patients received a personalized prehabilitation prescription and regular follow-up visits with a dedicated LT PT. Physical fitness assessment included the LFI and 6-min walk test (6MWT). Changes in LFI and 6MWT between PT visits were averaged and used as a measure of prehabilitation engagement/success. Multivariable survival models, including competing risks models against LT, were fit to investigate the impact of frailty metrics and prehabilitation engagement on mortality.

Results: A total of 1275 patients were prospectively included (59% male, age 57±11, BMI 30±7, MELD 14±6) and their data collected during 1973 PT visits (193 attended two visits, 162 attended three or more). Main indications for LT were alcohol (31%) and NAFLD (29%). Median LFI was 3.79 (3.21-4.41) and 23% were frail, whereas median 6MWT was 336 m (243-404) and 26% were frail; between-metrics agreement was 83%. In subjects who improved their LFI score (n=227/351), the absolute change was -0.38 (-0.17 to -0.84), whereas for 6MWT (n=209/332), the absolute change was 54 m (25-105). A total of 677 (55%) patients were waitlisted, LT occurred in 462 (37%) and death in 335 (26%). LFI improvement by 0.4 was associated with lower pre-transplant mortality (Table 1 and Figure 1). Sensitivity analyses restricted to patients with two or more LT PT visits did not change the findings. Surprisingly, improvement in 6MWT was not associated with a survival advantage.

Conclusion: Prehabilitation in LT candidates was associated with significant improvement in LFI and 6MWT. A minimum improvement in LFI by 0.4 was associated with better survival, independently of frailty status, and it could be used as an objective and clinically relevant on-training endpoint for frailty intervention.