Prehabilitation with Exercise and Nutrition to Reduce Morbidity of Major Hepatectomy in Patients with Sarcopenia: The PREHEP Randomized Clinical Trial

Importance: Sarcopenia is an emerging predictor of complications after liver surgery. Strategies to mitigate its impact are crucial to improving postoperative outcomes. Objective: To determine whether a 6-week multimodal prehabilitation program combining physical exercise and nutritional support reduces postoperative morbidity in patients with sarcopenia who are undergoing major hepatectomy. Design, Setting, and Participants: This study is a single-center, open-label, randomized clinical trial conducted from April 2022 to January 2025. Adult patients with sarcopenia scheduled for major liver resection and requiring future liver remnant hypertrophy were randomized (1:1) to receive either structured prehabilitation or standard care. The trial was conducted in a tertiary hepatobiliary referral center in Italy. Enrolled adult patients had radiologically and functionally confirmed sarcopenia. Most patients underwent portal vein embolization and right hepatectomy. Interventions: The intervention group received a 6-week program while awaiting future liver remnant hypertrophy including daily walking, supervised biweekly in-hospital exercise, and branched-chain amino acid and immune nutritional supplementation. The control group received standard perioperative care. Main Outcomes and Measures: The primary outcome was 90-day postoperative morbidity, assessed by Clavien-Dindo classification. Results: A total of 70 adult patients with radiologically and functionally confirmed sarcopenia were enrolled, and 60 (median [IQR] age, 69 [63-75] years; 32 male [53.3%]) were included in the final analysis. Most patients (52 [86.7%]) underwent portal vein embolization, and 63 (88.3%) underwent right hepatectomy. Overall morbidity was significantly lower in the prehabilitation group (4 of 30 [13.3%] vs 15 of 30 [50%]; odds ratio, 0.15; 95% CI, 0.04-0.55; P =.004), with an absolute risk reduction of 36.7% and number needed to treat of 3. All major complications occurred in the control group (6 of 30 [20%]; d = 0.40; P =.02). Muscle mass and strength improved significantly only in the prehabilitation arm. Conclusions and Relevance: Results of this randomized clinical trial reveal that a 6-week structured prehabilitation program significantly reduced postoperative morbidity in patients with sarcopenia undergoing major liver resection. These findings support integrating exercise and nutritional interventions into preoperative care for high-risk surgical patients to improve surgical outcomes.