medwireNews: Six weeks of exercise and nutritional support is a promising strategy for reducing postoperative morbidity in patients with sarcopenia undergoing major liver resection, the PREHEP study suggests.
“These data support a paradigm shift toward a more proactive and personalized approach in the perioperative care of patients with primary or secondary liver malignancies,” write Giammauro Berardi (San Camillo Forlanini Hospital, Rome, Italy) and colleagues in JAMA Surgery.
The study included 60 adults with sarcopenia who were scheduled for major liver resection and required a strategy to induce hypertrophy of the future liver remnant. The patients were a median of 69 years old, 53.3% were men, most were White, and 48.3% had comorbidities.
Eligible patients had a diagnosis of primary or secondary liver malignancy requiring major hepatectomy, which was defined as resection of at least three contiguous liver segments. Colorectal liver metastases were the most common etiology, occurring in 66.7% of the patients, followed by hepatocellular carcinoma (23.3%) and cholangiocarcinoma (10.0%).
A total of 86.7% of cases underwent portal vein embolization, 46.7% had a two-stage hepatectomy, and 33.3% received minimally invasive laparoscopy.
The investigators randomly assigned patients to receive either a 6-week prehabilitation program before hepatectomy (n=30) or standard care, proceeding directly to surgery (n=30).
Prehabilitation involved daily activity of either 30 minutes of brisk walking or 2000 or more additional steps daily, in addition to an inhospital strength and aerobic session with a trained physiotherapist for 60 minutes twice weekly. It also included twice-daily consumption of branched-chain amino acids and immune nutritional supplementation for the first 4 weeks, dropping to once daily for the remaining 2 weeks.
Berardi et al found that prehabilitation met the primary goal of the trial, significantly cutting the likelihood of morbidity at 90 days after surgery compared with the standard care group, as assessed by Clavien-Dindo classification and the Comprehensive Complication Index. The respective rates were 13.3% and 50.0%, giving an odds ratio (OR) of 0.15.
This gave an absolute risk reduction of 36.7 percentage points and a number needed to treat to prevent 90-day morbidity in one patient of three, they report.
The result was consistent when confounding factors, such as smoking status, alcohol consumption, cirrhosis, and laparoscopic or open surgery approaches, were accounted for (OR=0.18).
These findings support those of a previous study by the same group and “suggest that sarcopenia is not exclusively a marker of frailty but a modifiable risk factor through preoperative intervention,” the researchers say.
The prehabilitation group was also significantly less likely to show major morbidity than the standard care group, with corresponding rates of 0.0% versus 20.0%.
For other outcomes, including blood loss, need for transfusion, severity of complications, duration of hospital stay, and 90-day readmission rate, there was no significant difference between the two treatment groups.
The 90-day rate of complications was 31.7%; most (20%) of which were grade II on the Clavien-Dindo classification system, while 10% were grade IIIb or IV, including one death from postoperative liver failure in the standard care arm.
The researchers note that the patients’ BMI and triceps and subscapular skinfold thicknesses were lower than those reported for the general population, but their skeletal muscle index (SMI), hand grip strength, and gait speed test results were similar. The SMI and the handgrip strength test significantly improved over time in both men and women in the prehabilitation group but not in the standard care group.
Patients with sarcopenia often present with subclinical inflammation and other metabolic changes that may be affected by exercise and nutritional supplementation, the authors write. Therefore, “intervening during the interval between portal vein occlusion and definitive surgery provides a unique opportunity to modulate these factors,” they say.
In an invited commentary, Allan Tsung and colleagues, from the University of Virginia in Charlottesville, USA, write that the study is “promising,” but call for further studies with a multicenter design to “evaluate long-term outcomes, including sustained muscle strength, quality of life, and recurrence-free survival, to determine whether the observed short-term benefits translate into improved long-term prognosis.”
They conclude that the study “underlines the potential for sarcopenia screening and targeted prehabilitation to become part of standard of care.”
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JAMA Surg 2025; doi:10.1001/jamasurg.2025.3102
JAMA Surg 2025; doi:10.1001/jamasurg.2025.3076