Subclinical Hepatic Injury and Dysfunction Following Surgery: Evidence From a Young and Aged Laparotomy Murine Model

Elderly patients represent a growing proportion of surgical cases and have elevated postoperative risks, partly due to age-related hepatic vulnerability. Conventional liver enzymes (ALT/AST) lack sensitivity for detecting early dysfunction, limiting perioperative assessment. We investigated whether sensitive biomarkers could reveal subclinical hepatic injury and metabolic dysfunction after surgical stress in aged mice. Young (3 months) and aged (24 months) C57BL/6J mice underwent standardized laparotomy with mesenteric vascular manipulation or sham anesthesia. At 48 h, liver histology, ALT, AST, cytokeratin-18 (CK18), microRNA-122 (miR-122), and tryptophan-kynurenine pathway metabolites (kynurenine, quinolinic acid) were measured. Histology and ALT/AST showed no significant changes across groups. In young mice, surgery did not alter miR-122 or CK18. In aged mice, surgery increased miR-122 (+175% p < 0.0001) and CK18 (+113% p < 0.0001) versus aged shams. Kynurenine rose modestly in young surgery mice (+24% p = 0.02) but markedly in aged surgery mice (+78% p < 0.0001), with a similar age-dependent quinolinic acid elevation (+24% p < 0.001). The quinolinic acid: kynurenine ratio decreased in aged surgery mice, indicating altered pathway flux. Surgical stress induces age-dependent subclinical hepatic injury and metabolic dysregulation detectable by miR-122, CK18, and kynurenine pathway metabolites, despite preserved histology and normal transaminases. These findings support incorporating sensitive biomarkers into the perioperative evaluation of older adults. Clinical implementation through commercially available assays and established laboratory platforms offers feasible pathways for improving geriatric surgical care.