Peripheral cytotoxic immune profiles in hepatobiliary surgical patients

Perforin and granzyme B are key effector molecules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Their expression profiles in hepatobiliary surgical patients and the relative contributions of disease-specific versus host factors remain unclear.

In this retrospective cross-sectional study, 245 consecutive hepatobiliary surgical inpatients were enrolled. Six flow cytometric markers (CD3⁺, CD8⁺, and CD16⁺56⁺ subsets expressing perforin or granzyme B) were analyzed across six disease categories. Group comparisons were performed with and without age adjustment. Correlation, receiver operating characteristic (ROC), principal component analysis (PCA), and clustering analyses were conducted.

NK cells showed consistently high cytotoxic marker expression, exceeding T-cell subsets. No significant differences were observed across disease groups, even after age adjustment (all p > 0.05). All markers were positively correlated with age (ρ = 0.197-0.422; all p ≤ 0.002), indicating a dominant effect of immunosenescence. In acute pancreatitis (AP), CD8⁺Perforin⁺ was higher in severe cases and showed moderate discriminative performance [area under the curve (AUC) = 0.744; sensitivity 100%, specificity 50.0%]. CD8⁺Granzyme B⁺ correlated with bilirubin, albumin, AST, and lymphocyte count (all p ≤ 0.001). PCA identified two independent immune axes (T-cell and NK-cell cytotoxicity), and clustering revealed three immune phenotypes not associated with disease category.

Peripheral cytotoxic marker expression is primarily driven by age rather than disease category in hepatobiliary surgical patients. CD8⁺Perforin⁺ shows potential as a marker for pancreatitis severity, while immune profiling reveals distinct but disease-independent cytotoxic phenotypes.