Biopsychosocial Perioperative Care, Perioperative Stress, and Peripheral T-Cell Subset Recovery After Laparoscopic Hepatectomy for Hepatocellular Carcinoma: A Retrospective Propensity-Weighted Cohort Study.

Abstract

Background: Laparoscopic hepatectomy for hepatocellular carcinoma (HCC) imposes substantial surgical and psychological stress, with potential neuroendocrine and immune consequences. Whether integrated biopsychosocial perioperative care is associated with differences across several perioperative domains remains unclear.

Objective: This study aimed to evaluate the association of a structured biopsychosocial (BPS) perioperative programme with psychological distress, stress hormones, cellular immunity, postoperative recovery, sleep, safety, and 18-month oncological outcomes after laparoscopic hepatectomy for HCC.

Methods: This single-centre retrospective cohort included 343 consecutive patients treated between January 2022 and January 2025; 169 received BPS care plus conventional management and 174 received conventional care alone. Anxiety, depression, stress hormones, T-lymphocyte subsets, recovery, pain, opioid use, sleep, complications, recurrence, and survival were assessed longitudinally. Linear mixed-effects models and propensity-score overlap weighting with multivariable adjustment were used; time-to-event outcomes were analysed using Cox models. The anxiety (Self-Rating Anxiety Scale, SAS) and depression (Self-Rating Depression Scale, SDS) trajectories were prespecified as the co-primary outcomes. Propensity-score overlap weighting used covariates measured before programme allocation, and multiplicity was controlled within prespecified outcome families using the Benjamini-Hochberg false-discovery-rate procedure.

Results: After weighting, all measured covariates were balanced (maximum standardised mean difference 0.03). SAS and SDS trajectories favoured BPS care (group × time, both P<0.001), with adjusted discharge differences of -4.3 and -2.7 points, respectively. At postoperative day 7, the adjusted CD4+/CD8+ difference was +0.26 (95% CI 0.20-0.32). Length of stay was shorter by 1.1 days (95% CI -1.6 to -0.7), and 1-month PSQI was lower by 1.45 points (95% CI -1.78 to -1.12). Thirty-day complications, recurrence, and mortality were not statistically different. Peripheral-blood T-cell subset proportions index circulating composition and may not represent tissue or tumour-microenvironment antitumour immunity. After false-discovery-rate correction, all co-primary and secondary endpoints remained significant, whereas the safety and 18-month oncological endpoints did not.

Conclusion: Structured BPS perioperative care was associated with favourable differences across several domains of postoperative recovery after laparoscopic hepatectomy for HCC. These findings support prospective multicentre randomised evaluation of integrated biopsychosocial care. The findings support integrated biopsychosocial care as a complement to, not a replacement for, established enhanced-recovery pathways.