Role of Steatosis in Preventing Post-hepatectomy Liver Failure After Major Resection: Findings From an Animal Study.

Abstract

Background/aim: Post-hepatectomy liver failure (PHLF) and hepatic steatosis are evident shortly after extensive partial hepatectomy (PH) in rodents. This study aimed to extrapolate the protein expression and biological pathways involved in recovering PHLF (rPHLF) and non-recovering PHLF (nrPHLF).

Methods: Rats were randomly assigned to 90% PH or sham surgery. rPHLF was distinguished from nrPHLF using a quantitative scoring system. The sham (n = 6), rPHLF (n = 8), and nrPHLF (n = 13) groups were compared 24 h post-PH. Proteomics was used to assess protein variations and to investigate differentially regulated biological pathways. Stereological methods were used to quantify hepatic lipid content. The plasma triglyceride levels were measured.

Results: rPHLF demonstrated substantial downregulation of proteins involved in lipid metabolism compared to nrPHLF (P < 0.001). Several proteins associated with lipogenesis, beta-oxidation, lipolysis, membrane trafficking, and inhibition of cell proliferation were markedly downregulated in rPHLF.The hepatic lipid proportion was significantly higher for rPHLF (61% of hepatocyte volume, 95% confidence interval [CI]: 48%-82%) than for nrPHLF (32% of hepatocyte volume, 95% CI: 22%-39%). The median lipid volume per hepatocyte in rPHLF was 2815 μm³ (95% CI: 2208-3774 μm³) and 1759 μm³ in nrPHLF (95% CI: 1188-2134 μm³). Lipid droplets were not detected in the sham-operated rats. No significant differences in plasma triglyceride levels were found between the groups (P > 0.08).

Conclusion: The degree of hepatic steatosis is a promising prognostic indicator for early liver regeneration and nrPHLF onset immediately following extensive PH. Intrahepatic lipid accumulation appears to be linked to the coordinated downregulation of proteins integral to lipid metabolism and cellular transport.