Perioperative Determinants of Postoperative Morbidity After Liver Resection: From Morphofunctional Vulnerability to...

Background: Postoperative morbidity after liver resection remains considerable despite advances in surgical and perioperative care. Risk stratification has traditionally focused on surgical factors, although patient-related vulnerability and the postoperative inflammatory response may also play a critical role. This study aimed to evaluate the relative contribution of perioperative factors, including morphofunctional vulnerability (skeletal muscle index [SMI] and GLIM-defined malnutrition), surgical variables, and inflammatory biomarkers, in predicting postoperative outcomes after liver resection. Methods: We conducted a retrospective single-center study including patients who underwent liver resection between 2017 and 2021. Preoperative morphofunctional assessment included skeletal muscle index (SMI) measured at the L3 level on computed tomography and nutritional status defined according to GLIM criteria. Perioperative variables included surgical factors and postoperative inflammatory and immune biomarkers. Outcomes were overall complications within 90 days, major complications (Clavien-Dindo ≥ III), and severe morbidity defined by a Comprehensive Complication Index (CCI) ≥ 26.2. Multivariable logistic regression analyses were performed to identify independent predictors. Results: A total of 253 patients were analysed. Overall complications occurred in 35.6% of patients, with major complications in 14.6% and severe morbidity in 17.4%. Low SMI was present in 56.1% of patients. In multivariable analysis, low SMI independently predicted postoperative complications (OR 2.23, 95% CI 1.14-4.38; p = 0.02), along with the open surgical approach, operative time ≥ 193 min, and elevated C-reactive protein on postoperative day 3. For major complications (Clavien-Dindo ≥ III), low SMI remained a strong independent predictor (OR 4.28, 95% CI 2.76-10.40; p = 0.001), together with surgical factors and lymphopenia on postoperative day 3. In contrast, GLIM-defined malnutrition was independently associated with severe morbidity (CCI ≥ 26.2) (OR 2.95, 95% CI 1.44-6.06; p = 0.003). Conclusions: Postoperative morbidity after liver resection is determined by a combination of perioperative factors, including patient-related morphofunctional vulnerability, surgical complexity, and postoperative inflammatory response. Skeletal muscle depletion is primarily associated with the occurrence of complications, whereas GLIM-defined malnutrition appears to influence their severity. These findings support a comprehensive perioperative approach to risk stratification and highlight the potential role of targeted prehabilitation strategies aimed at improving surgical resilience and postoperative outcomes.