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.
