Background : Although post-hepatectomy liver failure is a fatal complication, clinical diagnosis can only be made on or after postoperative day 5. This study aimed to identify earlier biomarkers for predicting the PHLF using integrated multi-omics analysis.

Methods : Twenty domestic female crossbreed pigs underwent sham operation (n=6), 70% (n=7) and 90% (n=7) partial hepatectomy (PH). Serum samples from all the animals were collected at five-time points (pre-operation, 6 h, 14 h, 30 h, and 48 h after the operation). A comprehensive multi-omics analysis was conducted on 164 proteins, 184 qualified lipids, and 109 metabolites derived from each omics study.

Results : An unsupervised Z-score heatmap clustering of all molecules showed a distinct trend between the sham, 70% PH, and 90% PH groups at each different time point. A supervised Z-score heatmap found 75 molecules not expressed in the sham group but showed significant changes between the 70% PH and 90% PH groups. Among them, seven potential biomarkers with an extreme difference (> 2-fold change) between the 70% PH and 90% PH groups were derived. Creatinine, methionine sulfoxide, and hypoxanthine showed significant different changes at 14 h between the groups (early markers). Lysophosphatidylethanolamine 22:4, oxalic acid, adiponectin, and angiotensinogen showed an increasing trend in the 90% PH group than in the 70% PH group, finally showing a significant difference at 48h between the groups (late markers).

Conclusions : Integrated multi-omics analyses revealed new potential biomarkers for predicting PHLF. We expect future clinical studies using these candidates may open new paths to earlier diagnosis for PHLF and become a basis for applying various treatments trials.