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.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT05281211.