Predicting liver regeneration after major resection

Background Disruption of synthesis, excretion and detoxification functions defines liver failure. After liver resection, post-hepatectomy liver failure (PHLF) is a rightfully feared complication due to high lethality and limited therapeutic success. Individual cytokine and growth factor profiles may represent potent predictive markers for recovery of liver function. We aimed to investigate these profiles in post-hepatectomy regeneration.

Methods A time-dependent cytokine and growth factor profiling dataset of a training (30 patients) and a validation (14 patients) cohorts undergoing major liver resection were combined with statistical and predictive models identifying individual pathway signatures. 2319 associations were tested.

Results Expression trajectories of cytokines and growth factors with strong correlation to PHLF, morbidity and mortality were identified despite highly individual perioperative dynamics. EGF drop, HGF trajectory and PLGF fluctuations were associated with mortality. PLGF fluctuations were associated with PHLF and complications. A global-association-network was calculated and validated according to the types of underlying risk-factors. Preoperative cytokine and growth factor signatures were identified for prediction of mortality following major liver resection by regularized regression modelling. Subsequently, prediction of PHLF was possible as early as on POD1 (AUC over 0.75). Elastic-net-model could predict mortality on POD1 (AUC=0.75). Proliferation analysis of corresponding primary human hepatocytes showed significant associations of individual regenerative potential with clinical outcome.

Conclusion Prediction of PHLF and mortality is possible on POD1 with liquid-biopsy based risk profiling. Further utilization of these models would allow tailoring of interventional strategies according to individual profiles.

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022