Samenvatting

Introduction Reduced aerobic capacity and frailty are highly prevalent in liver transplant candidates and are associated with increased morbidity and mortality. Although exercise-based prehabilitation is safe and effective, adherence remains a challenge. Home-based prehabilitation may improve participation, especially when tailored to the patient’s fitness level and remotely monitored. This type of prehabilitation has shown promising results in other surgical groups1,2. However, their feasibility and effect in frail liver transplant candidates remain largely unknown. This study addresses this knowledge gap and contributes to the broader question of how best to prehabilitate highly frail patients. The aim of this study is to evaluate the effectiveness and feasibility of a remotely monitored bimodal (exercise + nutrition) prehabilitation program in frail patients with liver cirrhosis awaiting transplantation. Methods This ongoing investigator-initiated, single-center, single-arm, prospective clinical trial started in October 2024 at the University Medical Center Groningen, the Netherlands. Eligible patients with reduced aerobic capacity (i.e., VO₂ at the ventilatory anaerobic threshold ≤13 ml/kg/min and/or VO₂peak ≤18 ml/kg/min) participate in the bimodal lifestyle program. The program includes high-intensity interval training and endurance training based on Steep Ramp Test (SRT) results, resistance training, inspiratory muscle training, and protein supplementation. The SRT is regularly performed at home to monitor progress and adjust training intensity. Training includes two six-week home-based periods (12 weeks total, or until transplantation), followed by a final assessment at 18 weeks to evaluate the durability of the program’s effects. Primary outcome: Change in VO₂ at the ventilatory threshold and VO₂peak after six weeks of training. Secondary outcomes: Changes in sarcopenia (ultrasound, Liver Frailty Index), functional mobility, perceived fatigue, quality of life, number of hospital admissions, incidence of hepatic encephalopathy, microbiome composition, blood biomarkers, and postoperative outcomes. Feasibility is assessed through participation rate, adherence to prescribed training sessions and protein intake, and safety. Results At the time of submission, 41 patients were screened and 9 were included. The majority of exclusions were due to either adequate fitness or underlying liver disease without cirrhosis (e.g., ADPKD). The participation rate was 82%. Among those included, three have completed the first training period with available primary outcome data, three are currently in training, and three underwent liver transplantation before the first reassessment. While the primary outcomes showed variable patterns, consistent improvements in SRT performance were observed (figure 1). Adherence varied due to disease-related instability and intercurrent hospital admissions. It appears safe, since there have been no intervention-related adverse events until now. The other secondary outcomes are not available to present yet. Conclusion This early-phase study demonstrates that home-based, remotely monitored prehabilitation is feasible and acceptable in frail liver transplant candidates. Although consistent improvements in CPET outcomes could not be demonstrated because of variable results and incomplete data, measurable improvements in functional capacity were seen when assessed with the Steep Ramp Test. Conducting structured research in this vulnerable population was challenging, as clinical instability and hospital admissions often disrupted the intervention and assessments. However, these difficulties reflect the real-world fragility of liver transplant candidates. These interim findings underscore the need for flexible, patient-centered prehabilitation and support the potential of home-based approaches not only in liver transplant candidates but also in other highly vulnerable surgical populations. Recruitment is ongoing toward a target of 24 patients.