{"doi":"10.21037/hbsn-24-464","title":"Plasma GLP-1 and metabolic dynamics during human liver regeneration and their association with posthepatectomy liver failure","abstract":"Background: Metabolic regulation is critical during liver regeneration in rodents, but human data are limited. We investigated perioperative dynamics of circulating metabolites and plasma levels of glucagon-like peptide-1 (GLP-1) and GLP-2, in patients undergoing liver resections, exploring their associations with the histological phenotype of metabolic dysfunction-associated steatotic liver disease (MASLD) and posthepatectomy liver failure (PHLF). Methods: Eighty-one and 75 patients from two centers between 2012 and 2023 were studied. Targeted quantitative metabolomic assay of 180 circulating metabolites, perioperative GLP-1, GLP-2, and standard lipid parameter level evaluation was employed. An exploratory PHLF prediction model was developed, including GLP-1 as a metabolic parameter. Results: Significant alterations of 44 metabolites by postoperative day (POD) 1 and 40 by POD5 were observed, mainly among phospholipid species. Unsupervised clustering identified two metabolic clusters, with one encompassing 93% of PHLF patients by POD5 (P<0.001). Standard plasma lipid parameters displayed consistent decrease after hepatectomy, independent from MASLD phenotype, with the lowest levels in PHLF patients. Postoperative GLP-1 and GLP-2 dynamics displayed a reciprocal pattern, indicating adaptive change in secretion. Preoperative GLP-1 levels were significantly increased in PHLF (P=0.02). Furthermore, incorporation of GLP-1 into the established aspartate aminotransferase to platelet ratio index (APRI) + albumin-bilirubin (ALBI) score, improved PHLF prediction [area under the curve (AUC): 0.833, 95% confidence interval (CI): 0.660-0.964]. Conclusions: Significant metabolic changes occur during human liver resection, particularly in phospholipid metabolism, along with distinct perioperative dynamics of GLP-1 and GLP-2, closely linked to PHLF and independent of the histological phenotype of MASLD. Additionally, we provide exploratory results on the predictive value of GLP-1 for PHLF, emphasizing a holistic model of liver function assessment highlighting the metabolic component of human liver regeneration.","journal":"HepatoBiliary Surgery and Nutrition","year":2025,"id":518876,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9629,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1386781,"name":"Jan Philipp Jonas","orcid":"0000-0002-3134-9040","position":1,"is_corresponding":false},{"id":1075663,"name":"David Pereyra","orcid":"0000-0001-6700-9163","position":2,"is_corresponding":false},{"id":1075664,"name":"Jonas Santol","orcid":"0000-0002-8097-9735","position":3,"is_corresponding":false},{"id":5740,"name":"Hubert Hackl","orcid":"0000-0003-4055-3841","position":4,"is_corresponding":false},{"id":1387231,"name":"Tamara Kalchbrenner","orcid":null,"position":5,"is_corresponding":false},{"id":1386782,"name":"Johannes Laengle","orcid":"0000-0003-4771-1398","position":6,"is_corresponding":false},{"id":1386783,"name":"V. Podrascanin","orcid":"0009-0004-9684-8918","position":7,"is_corresponding":false},{"id":1387232,"name":"Florian Lehner","orcid":null,"position":8,"is_corresponding":false},{"id":1387233,"name":"Istvan Levente Viragos-Toth","orcid":null,"position":9,"is_corresponding":false},{"id":1386784,"name":"Wolfgang Hulla","orcid":"0000-0001-8189-4621","position":10,"is_corresponding":false},{"id":1387234,"name":"Verena Ruso","orcid":null,"position":11,"is_corresponding":false},{"id":230197,"name":"Rory L. Smoot","orcid":"0000-0001-8543-661X","position":12,"is_corresponding":false},{"id":1387235,"name":"Friedrich Laengle","orcid":null,"position":13,"is_corresponding":false},{"id":1075667,"name":"Thomas Gruenberger","orcid":"0000-0002-2671-0540","position":14,"is_corresponding":false},{"id":669044,"name":"Alice Assinger","orcid":"0000-0002-5670-5910","position":15,"is_corresponding":false},{"id":363545,"name":"Patrick Starlinger","orcid":"0000-0002-4666-5337","position":16,"is_corresponding":false},{"id":1266229,"name":"Markus Ammann","orcid":null,"position":0,"is_corresponding":true}],"reference_count":1,"raw_metadata":null,"created_at":"2026-07-19T02:49:14.184995Z","pmid":"39925909","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}