A randomized, controlled, prehabilitation intervention to maximize early recovery (PRIMER) in liver transplantation

Abstract

Frailty and impaired functional status are associated with adverse outcomes on the liver transplant (LT) waitlist and after transplantation. Prehabilitation prior to LT has rarely been tested. We conducted a 2-arm patient-randomized pilot trial to evaluate the feasibility and efficacy of a 14-week behavioral intervention to promote physical activity prior to LT. Thirty patients were randomized 2:1 to intervention (n = 20) versus control (n = 10). The intervention arm received financial incentives and text-based reminders linked to wearable fitness trackers. Daily step goals were increased by 15% in 2-week intervals. Weekly check-ins with study staff assessed barriers to physical activity. The primary outcomes were feasibility and acceptability. Secondary outcomes included mean end-of-study step counts, short physical performance battery, grip strength, and body composition by phase angle. We fit regression models for secondary outcomes with the arm as the exposure adjusting for baseline performance. The mean age was 61, 47% were female, and the median Model for End-stage Liver Disease sodium (MELD-Na) was 13. One-third were frail or prefrail by the liver frailty index, 40% had impaired mobility by short physical performance battery, nearly 40% had sarcopenia by bioimpedance phase angle, 23% had prior falls, and 53% had diabetes. Study retention was 27/30 (90%; 2 unenrolled from intervention, 1 lost to follow-up in control arm). Self-reported adherence to exercise during weekly check-ins was about 50%; the most common barriers were fatigue, weather, and liver-related symptoms. End-of-study step counts were nearly 1000 steps higher for intervention versus control: adjusted difference 997, 95% CI, 147–1847; p = 0.02. On average, the intervention group achieved daily step targets 51% of the time. A home-based intervention with financial incentives and text-based nudges was feasible, highly accepted, and increased daily steps in LT candidates with functional impairment and malnutrition.

Physical activity decreases in patients on the liver transplant waiting list and influences postoperative outcome—a prospective cohort study

“…A recent systematic review on prehabilitation in patients awaiting LT did not detect an impact on adverse clinical outcomes including mortality due to sparse data ( 33 ). This lack of findings might also be confounded by not having identified the beneficial exercise intervention or prehabilitation program so far in these patients ( 34 ).…”

Sarcopenic obesity in patients awaiting liver transplant: Unique challenges for nutritional recommendations

“…It is important to note that nutrition alone is insufficient to improve functional status in patients with CLD, malnutrition, and frailty[ 1 ]. Recent studies on prehabilitation in patients preparing for liver transplantation have shown that interventions such as increased daily step count, and introduction of strength exercises is safe, feasible, and can improve aerobic and functional capacity[ 48 , 49 ].…”

(P)rehabilitation in advanced chronic liver disease (advCLD): From basic exercise concepts to implementation challenges

“…Home-based protocols are more accessible for participants, where exercise programming often requires no additional equipment and can be performed with minimal or even no supervision. However, home-based interventions also present challenges as well, including lower exercise adherence rates than traditional facility-based programs, perhaps owing to low rates of intrinsic motivation in the absence of in-person accountability, although this has been addressed by having a supervised portion of an in-home digital therapeutic-based intervention 14,15,17 . Despite these limitations, home-based exercise programs can lead to clinically meaningful improvement in both frailty and physical performance and should be considered in the right clinical setting, especially if time, cost, or exercise resource access barriers are identified before exercise prescription development (Figure 1).…”