Predicting liver regeneration following major resection

TY - JOUR

T1 - Predicting liver regeneration following major resection

AU - Dehlke, Karolin

AU - Krause, Linda

AU - Tyufekchieva, Silvana

AU - Murtha-Lemekhova, Anastasia

AU - Mayer, Philipp

AU - Vlasov, Artyom

AU - Klingmüller, Ursula

AU - Mueller, Nikola S

AU - Hoffmann, Katrin

N1 - © 2022. The Author(s).

PY - 2022/8/4

Y1 - 2022/8/4

N2 - Breakdown of synthesis, excretion and detoxification defines liver failure. Post-hepatectomy liver failure (PHLF) is specific for liver resection and 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. This study combined a time-dependent cytokine and growth factor profiling dataset of a training (30 patients) and a validation (14 patients) cohorts undergoing major liver resection with statistical and predictive models identifying individual pathway signatures. 2319 associations were tested. Primary hepatocytes isolated from patient tissue samples were stimulated and their proliferation was analysed through DNA content assay. Common expression trajectories of cytokines and growth factors with strong correlation to PHLF, morbidity and mortality were identified despite highly individual perioperative dynamics. Especially, dynamics of EGF, HGF, and PLGF were associated with mortality. PLGF was additionally associated with PHLF and complications. A global association-network was calculated and validated to investigate interdependence of cytokines and growth factors with clinical attributes. Preoperative cytokine and growth factor signatures were identified allowing prediction of mortality following major liver resection by regression modelling. Proliferation analysis of corresponding primary human hepatocytes showed associations of individual regenerative potential with clinical outcome. Prediction of PHLF was possible on as early as first postoperative day (POD1) with AUC above 0.75. 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.

AB - Breakdown of synthesis, excretion and detoxification defines liver failure. Post-hepatectomy liver failure (PHLF) is specific for liver resection and 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. This study combined a time-dependent cytokine and growth factor profiling dataset of a training (30 patients) and a validation (14 patients) cohorts undergoing major liver resection with statistical and predictive models identifying individual pathway signatures. 2319 associations were tested. Primary hepatocytes isolated from patient tissue samples were stimulated and their proliferation was analysed through DNA content assay. Common expression trajectories of cytokines and growth factors with strong correlation to PHLF, morbidity and mortality were identified despite highly individual perioperative dynamics. Especially, dynamics of EGF, HGF, and PLGF were associated with mortality. PLGF was additionally associated with PHLF and complications. A global association-network was calculated and validated to investigate interdependence of cytokines and growth factors with clinical attributes. Preoperative cytokine and growth factor signatures were identified allowing prediction of mortality following major liver resection by regression modelling. Proliferation analysis of corresponding primary human hepatocytes showed associations of individual regenerative potential with clinical outcome. Prediction of PHLF was possible on as early as first postoperative day (POD1) with AUC above 0.75. 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.

KW - Cytokines

KW - Hepatectomy/adverse effects

KW - Humans

KW - Liver Failure/etiology

KW - Liver Function Tests

KW - Liver Neoplasms/surgery

KW - Liver Regeneration

KW - Postoperative Complications

KW - Retrospective Studies

U2 - 10.1038/s41598-022-16968-9

DO - 10.1038/s41598-022-16968-9

M3 - SCORING: Journal article

C2 - 35927556

VL - 12

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

M1 - 13396

ER -