ABSTRACT Background Post‐hepatectomy liver failure (PHLF) remains a limitation in the surgical treatment of liver cancer. The 90% partial hepatectomy (PH) rat model reliably induces biochemical PHLF and high mortality, providing a unique platform for identifying molecular pathways necessary for successful liver regeneration. This study aimed to characterize the early biomolecular mechanisms that support recovery following 90% PH. Methods Rats underwent 90% PH or sham surgery and were euthanised at 12, 24 or 48 h. A validated distress scoring system distinguished recovering animals from those progressing toward fatal PHLF. Liver tissue was analysed using high‐resolution LC–MS/MS proteomics to identify differentially regulated proteins and enriched pathways, and selected targets (Fga, Vegfa) were validated by Western blotting. Results At 12 h, recovering PH animals exhibited a pronounced acute‐phase response with significant upregulation of innate immune response ( p < 0.01), inflammatory response ( p < 0.0001), haemostatic ( p < 0.0001) and angiogenic pathways ( p < 0.01). At 24 h—the critical survival window—proteins regulating apoptosis signalling ( p < 0.01) and cellular stress ( p < 0.01) were significantly modulated. By 48 h, pathways related to RNA metabolism ( p < 0.001) and hepatocyte proliferation ( p < 0.04) were prominently upregulated. Western blotting confirmed increased expression of Fga and Vegfa, consistent with the proteomic data. Conclusion Recovery from 90% PH follows a tightly coordinated temporal sequence: an immediate acute inflammatory and coagulative response, followed by regulated apoptosis during the vulnerable 12–24‐h window, and the subsequent induction of hepatocellular proliferation. These findings identify molecular programs associated with recovery that stabilize hepatic function and enable the onset of regeneration. Insights from these temporal mechanisms may guide future biomarker development and therapeutic strategies to reduce PHLF after major liver resection.
Lund et al. (Wed,) studied this question.