Lipidomic Signatures of Post-Hepatectomy Liver Failure Using Porcine Hepatectomy Models

Abstract

Introduction: Clinical diagnosis of post-hepatectomy liver failure (PHLF) can only be made on or after 5th postoperative day. Biomarker for early diagnosis is considered as a critical unmet need. Method: Pigs underwent sham operation (n=6), 70% (n=7) and 90% (n=7) partial hepatectomy (PH). A comprehensive lipidomic analysis was conducted using sera collected at pre-operation (PO), 14 h, 30 h, and 48 h after PH using nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Results: Of the 184 quantified lipids, 14 lipids showed significant differences between the two resection groups starting at 30 h after surgery. Four phosphatidylcholine (PC) plasmalogen species (p-16:0/16:0, p-18:0/18:2, p-18:0/20:4, and p-18:0/22:6) and PC 32:2 significantly increased in the 90% PH group while these returned to PO level after 30 h in the 70% PH group, presumably implying the failure markers. However, eight triacylglycerol (TG) species (40:0, 42:1, 42:0, 44:1, 44:2, 46:1, 46:2, and 48:3) and sphingomyelin d18:1/20:0 showed an opposite trend, wherein they significantly decreased in the 90% PH group while these in the 70% PH group were abruptly increased until 30 h but returned to near PO levels at 48 h , implying the recovery markers. Same trends were also observed in PC plasmalogen and TG classes in addition to selected individual lipid species. Conclusions: Characteristic lipidomic signatures of PHLF could be identified using large animal models. These candidates have potentials to serve as a tool for early diagnosis and may open new path to the study to overcome PHLF.