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-...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.展开更多
Background:To date,definitions of liver dysfunction(LD)after hepatic resection rely on late postoperative time points.Further,the used parameters are markedly influenced by perioperative management.Thus,we aimed to es...Background:To date,definitions of liver dysfunction(LD)after hepatic resection rely on late postoperative time points.Further,the used parameters are markedly influenced by perioperative management.Thus,we aimed to establish a very early postoperative score to predict postoperative mortality.Methods:Liver related parameters were evaluated after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis(mCRC)and subsequent validation in a prospective set of 482 consecutive patients from 4 independent institutions undergoing hepatic resection was performed.Results:C-reactive protein(CRP,AUC=0.739,P<0.001)and antithrombinⅢ-activity(ATⅢ,AUC=0.844,P<0.001)on the first postoperative day(POD)were found to be elevated in patients with LD.Cut-off values for CRP at 3 mg/dL and for ATⅢat 60%significantly identified high-risk patients for postoperative LD and mortality(P<0.001)and thus defined the 3-60 criteria on POD1.The 3-60 criteria showed superior sensitivity and specificity compared to established criteria for LD[3-60 criteria:total positive patients:26 patients(70%mortality detected),odds ratio(OR):48.8;International Study Group for Liver Surgery:total positive patients:43(70%mortality detected),OR:23.3;Peak7:total positive patients:9(30%mortality detected),OR:27.8;50-50:total positive patients:9(30%mortality detected),OR:27.8].These results could be validated in a multi-center analysis and ultimately the 3-60 criteria remained an independent predictor of postoperative mortality upon multivariable analysis.Conclusions:The 3-60 criteria on POD1 predict postoperative LD and mortality early after liver resection with a comparable or better accuracy than established criteria,allowing for immediate identification of high-risk patients.展开更多
基金supported by the Austrian government“Bürgermeisterfonds,Vienna,Austria”(18129)NIH(R01DK122813)+2 种基金the Austrian Science Fund(FWF)(P-32064)“City of Vienna Fund for Innovative Interdisciplinary Cancer Research”(21041)supported by means of the IHPBA Kenneth Warren Fellowship during conducting this study.
文摘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.
文摘Background:To date,definitions of liver dysfunction(LD)after hepatic resection rely on late postoperative time points.Further,the used parameters are markedly influenced by perioperative management.Thus,we aimed to establish a very early postoperative score to predict postoperative mortality.Methods:Liver related parameters were evaluated after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis(mCRC)and subsequent validation in a prospective set of 482 consecutive patients from 4 independent institutions undergoing hepatic resection was performed.Results:C-reactive protein(CRP,AUC=0.739,P<0.001)and antithrombinⅢ-activity(ATⅢ,AUC=0.844,P<0.001)on the first postoperative day(POD)were found to be elevated in patients with LD.Cut-off values for CRP at 3 mg/dL and for ATⅢat 60%significantly identified high-risk patients for postoperative LD and mortality(P<0.001)and thus defined the 3-60 criteria on POD1.The 3-60 criteria showed superior sensitivity and specificity compared to established criteria for LD[3-60 criteria:total positive patients:26 patients(70%mortality detected),odds ratio(OR):48.8;International Study Group for Liver Surgery:total positive patients:43(70%mortality detected),OR:23.3;Peak7:total positive patients:9(30%mortality detected),OR:27.8;50-50:total positive patients:9(30%mortality detected),OR:27.8].These results could be validated in a multi-center analysis and ultimately the 3-60 criteria remained an independent predictor of postoperative mortality upon multivariable analysis.Conclusions:The 3-60 criteria on POD1 predict postoperative LD and mortality early after liver resection with a comparable or better accuracy than established criteria,allowing for immediate identification of high-risk patients.
