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Subclinical Hepatic Injury and Dysfunction Following Surgery: Evidence From a Young and Aged Laparotomy Murine Model
Kenneth Meza Monge1, Kevin M Najarro1, Rachel H McMahan1
1Division of G.I., Trauma, and Endocrine Surgery, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Summary
Sensitive biomarkers like microRNA-122 and cytokeratin-18 detect subclinical liver injury in aged mice after surgery. These markers, along with kynurenine pathway metabolites, reveal age-dependent hepatic dysfunction missed by conventional tests.
Area of Science:
- Geriatric Medicine
- Surgical Oncology
- Hepatology
Background:
- Elderly patients face higher surgical risks due to age-related liver vulnerability.
- Conventional liver enzymes (ALT/AST) are insensitive to early hepatic dysfunction in older adults.
- Perioperative assessment of liver health in aging populations requires more sensitive methods.
Purpose of the Study:
- To investigate if sensitive biomarkers can detect subclinical hepatic injury and metabolic dysfunction after surgical stress in aged mice.
- To compare the response of young and aged mice to surgical stress using novel biomarkers.
- To assess the utility of microRNA-122, cytokeratin-18, and tryptophan-kynurenine pathway metabolites in evaluating perioperative liver health.
Main Methods:
- Young and aged mice underwent laparotomy with mesenteric vascular manipulation or sham anesthesia.
- Liver histology, ALT, AST, microRNA-122 (miR-122), cytokeratin-18 (CK18), and tryptophan-kynurenine metabolites were measured 48 hours post-surgery.
- Comparative analysis was performed between young/aged mice and sham/surgery groups.
Main Results:
- Histology and ALT/AST levels remained unchanged across all groups.
- Aged mice undergoing surgery showed significant increases in miR-122 and CK18 compared to aged sham controls.
- Surgical stress in aged mice led to marked elevations in kynurenine and quinolinic acid, with altered pathway flux.
Conclusions:
- Surgical stress induces age-dependent subclinical hepatic injury and metabolic dysregulation in mice.
- Sensitive biomarkers (miR-122, CK18, kynurenine pathway) can detect this injury, unlike conventional liver enzymes.
- These findings support the clinical implementation of sensitive biomarkers for improved perioperative care in older adults.
