Development and Validation of a Nomogram Based on Perioperative Factors to Predict Post-hepatectomy Liver Failure.
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ABSTRACT: Background and aims
Post-hepatectomy liver failure (PHLF) is a severe complication and main cause of death in patients undergoing hepatectomy. The aim of this study was to build a predictive model of PHLF in patients undergoing hepatectomy.Methods
We retrospectively analyzed patients undergoing hepatectomy at Zhongshan Hospital, Fudan University from July 2015 to June 2018, and randomly divided them into development and internal validation cohorts. External validation was performed in an independent cohort. Least absolute shrinkage and selection operator (commonly referred to as LASSO) logistic regression was applied to identify predictors of PHLF, and multivariate binary logistic regression analysis was performed to establish the predictive model, which was visualized with a nomogram.Results
A total of 492 eligible patients were analyzed. LASSO and multivariate analysis identified three preoperative variables, total bilirubin (p=0.001), international normalized ratio (p<0.001) and platelet count (p=0.004), and two intraoperative variables, extent of resection (p=0.002) and blood loss (p=0.004), as independent predictors of PHLF. The area under receiver operating characteristic curve (referred to as AUROC) of the predictive model was 0.838 and outperformed the model for end-stage liver disease score, albumin-bilirubin score and platelet-albumin-bilirubin score (AUROCs: 0.723, 0.695 and 0.663, respectively; p<0.001 for all). The optimal cut-off value of the predictive model was 14.7. External validation showed the model could predict PHLF accurately and distinguish high-risk patients.Conclusions
PHLF can be accurately predicted by this model in patients undergoing hepatectomy, which may significantly contribute to the postoperative care of these patients.
SUBMITTER: Xu B
PROVIDER: S-EPMC8237151 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AbstractIn humans, thrombocytopenic patients have increased incidence of post-hepatectomy liver failure (PHLF), but existing evidence is heterogeneous. Our objective was to determine if preoperative platelet count or antiplatelet drugs were associated with PHLF.Patients who underwent hepatic resection in the University Hospitals of Geneva, Switzerland, from 01.12.2009 to 18.12.2018 were identified. Platelet count at day 0, postoperative days (POD) 1, 3, and 5 were retrieved. Occurrence of PHLF according to the ISGLS definition was determined. Logistic regression was performed to determine if platelet count or antiplatelet drug were predictors for PHLF.Five hundred ninety seven patients were included. Eighty patients (17.8%) had a preoperative platelet count <150 (G/l) and 24 patients (5.3%) had a platelet count <100 (G/l). Thirty five patients (5.9%) were under antiplatelet drug. Platelet count significantly decreased at POD 1 and POD 3 when compared to preoperative platelet count (182?±?71.61 (G/l) vs 212?±?85.26 (G/l), P?<?.0001; 162?±?68.5 (G/l) vs 212?±?85.26 (G/l), P?<?.0001). At POD 5, post-operative platelet count did not significantly differ from its preoperative value. Forty three patients (11.2%) suffered from PHLF. Their platelet count was not significantly different than patients without PHLF (211?±?89.7 (G/l) vs 211?±?83.5 (G/l), P?=?.671). One patient with PHLF had a platelet count <100 (G/l) and 5 had a count <150 (G/l). Univariate logistic regression did not identify preoperative thrombocytopenia (<100 (G/l) or <150 (G/l)), postoperative thrombocytopenia, or the presence of antiagregant drug, as predictors of PHLF. We did not identify preoperative or postoperative thrombocytopenia as predictor of PHLF in a cohort of 597 patients.
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Project description:BackgroundAdequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data.MethodsConsecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF.ResultsFor 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram.ConclusionsThe combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram.Trial registrationClinicaltrials.gov Identifier: NCT04076631.
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Project description:This study aimed to establish a radiomics-based nomogram for predicting severe (grade B or C) post-hepatectomy liver failure (PHLF) in patients with huge (≥ 10 cm) hepatocellular carcinoma (HCC). One hundred eighty-six patients with huge HCC (training dataset, n = 131 and test dataset, n = 55) that underwent curative hepatic resection were included in this study. The least absolute shrinkage and selection operator (LASSO) approach was applied to develop a radiomics signature for grade B or C PHLF prediction using the training dataset. A multivariable logistic regression model was used by incorporating radiomics signature and other clinical predictors to establish a radiomics nomogram. Decision tree analysis was performed to stratify the risk for severe PHLF. The radiomics signature consisting of nine features predicted severe PHLF with AUCs of 0.766 and 0.745 for the training and test datasets. The radiomics nomogram was generated by integrating the radiomics signature, the extent of resection and the model for end-stage liver disease (MELD) score. The nomogram exhibited satisfactory discrimination ability, with AUCs of 0.842 and 0.863 for the training and test datasets, respectively. Based on decision tree analysis, patients were divided into three risk classes: low-risk patients with radiomics score < -0.247 and MELD score < 10 or radiomics score ≥ - 0.247 but underwent partial resections; intermediate-risk patients with radiomics score < - 0.247 but MELD score ≥10; high-risk patients with radiomics score ≥ - 0.247 and underwent extended resections. The radiomics nomogram could predict severe PHLF in huge HCC patients. A decision tree may be useful in surgical decision-making for huge HCC hepatectomy.
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Project description:ObjectivesThis study aimed to develop and externally validate a nomogram for predicting liver metastasis after radical resection in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsA total of 247 PDAC patients who underwent radical resection were retrospectively reviewed from January 2015 to March 2022 at Ningbo Medical Centre Lihuili Hospital Eastern Section, and used as a training cohort to develop the nomogram. 83 PDAC patients from the Ningbo Medical Centre Lihuili Hospital Xingning Section were enrolled as the validation cohort. The postoperative liver metastasis was recorded during the follow-up, and the liver metastasis-free survival was defined as the time from operation to the date of liver metastasis diagnosis or death. The nomogram was established based on independent prognostic factors selected by LASSO and multivariate Cox regression model. The performance was assessed using the concordance index (C-index) and calibration curves. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to determine the clinical utility of the nomogram model.ResultsFrom the training cohort of 247 patients, a total of 132 patients developed liver metastasis during the follow-up, the 1-, 2- and 3- year liver metastasis-free survival were 52.4%, 43.5% and 40% respectively. The LASSO and multivariate Cox regression analysis indicated that postoperative CA125 (hazard ratio [HR] = 1.007, p <0.001), tumor differentiation (HR = 1.640, p = 0.010), tumor size (HR = 1.520, p = 0.029), lymph node ratio (HR = 1.897, p = 0.002) and portal/superior mesenteric/splenic vein invasion degree (PV/SMV/SV) (HR = 2.829, p <0.001) were the independent factors of liver metastasis. A nomogram with independent factors was developed and the C-index was 0.760 (95% confidence interval [CI], 0.720-0.799) and 0.739 (95% CI, 0.669-0.810) in the training and validation cohorts, respectively. The areas under curve (AUC) of the nomogram at 1-, 2- and 3-year were 0.815, 0.803 and 0.773 in the training cohort, and 0.765, 0.879 and 0.908 in the validation cohort, respectively, higher than those in TNM stage. Decision curve analysis (DCA) analysis revealed that the nomogram model provided superior net benefit in clinical utility. Liver metastasis-free survival curves showed a significant discriminatory ability for liver metastasis risk based on the nomogram (p <0.001).ConclusionsThe nomogram showed high accuracy in predicting liver metastasis for PDAC after radical resection, and may serve as a clinical support tool to guide personalized and prescient intervention.
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Project description:The pathophysiology of post-hepatectomy liver failure is not entirely understood but is rooted in the disruption of normal hepatocyte regeneration and homeostasis. Current investigations of post-hepatectomy liver failure and regeneration are focused on evaluation of circulating hepatic function parameters (transaminases, cholestasis, and coagulation parameters), volumetry and hepatic hemodynamics. However, identification of biochemical factors associated with regeneration and post hepatectomy liver failure is crucial for understanding the pathophysiology and identification of patients at risk. The objective of the present systematic review was to identify circulating factors associated with liver regeneration and post hepatectomy liver failure in patients undergoing hepatectomy. The quantitative analysis was intended if studies provided sufficient data. Electronic databases (MEDLINE via PubMed, Web of Knowledge, Cochrane Library and WHO International Clinical Trials Registry Platform) were searched for publications on cell signaling factors in liver regeneration and post-hepatectomy liver failure following liver resection in clinical setting. No date restriction was given. No language restriction was used. Studies were assessed using MINORS. This study was registered at PROSPERO (CRD42020165384) prior to data extraction. In total 1953 publications were evaluated for titles and abstracts after exclusion of duplicates. Full texts of 167 studies were further evaluated for inclusion. 26 articles were included in the review and 6 publications were included in the meta-analyses. High levels of serum hyaluronic acid even preoperatively are associated with PHLF but especially increased levels early after resection are predictive of PHLF with high sensitivity and specificity. Postoperative elevation of HA to levels between 100 and 500 ng/ml is increased the risk for PHLF ([OR] = 246.28, 95% [CI]: 11.82 to 5131.83; p = 0.0004) Inteleukin-6 levels show contradicting result in association with organ dysfunction. HGF positively correlates with liver regeneration. Overall, due to heterogeneity, scarcity, observational study design and largely retrospective analysis, the certainty of evidence, assessed with GRADE, is very low. High levels of serum hyaluronic acid show a strong association with PHLF and increased levels after resection are predictive of PHLF with high sensitivity and specificity, even on POD1. Interleukin-6 levels need to be studied further due to contradictive results in association with organ dysfunction. For HGF, no quantitative analysis could be made. Yet, most studies find positive correlation between high HGF levels and regeneration. Prospective studies investigating HGF and other growth factors, hyaluronic acid and interleukins 1 and 6 in correlation with liver regeneration measured sequentially through e.g. volumetry, and liver function parameters, preferably expanding the analysis to include dynamic liver function tests, are needed to sufficiently illustrate the connection between biomolecule levels and clinical outcomes.
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Project description:The liver's regenerative capacity is unique, but too small a segment can overwhelm its ability to simultaneously regenerate and support the host, resulting in liver dysfunction and death. Here we tested a temporary Xenogeneic Heterotopic Auxiliary Liver Transplant (XHALT) from Gal-KO miniature swine in a baboon model of Post-Hepatectomy Liver Failure (PHLF) by 90%- hepatectomy. Immunosuppression consisted of CVF, ATG, FK 506 and steroids. 90%-hepatectomized animals died within 4-5 days with the clinical picture of PHLF, (high LFTs and bilirubin, ascites, encephalopathy and coagulopathy). The 10% remnants had macroscopic and histological evidence of severe steatosis and absence of hepatocyte replication. In contrast, the addition of XHALT prolonged survival up to 11 days, with the cause of death being sepsis, rather than liver failure. The remnant liver appeared grossly normal, and on histology, there was no evidence of fatty infiltration, but there was pronounced Ki-67 staining. In conclusion, temporary auxiliary xenografts have the potential to support a small for size liver graft while it grows to adequate size or provide an opportunity for organ recovery in acute liver failure.
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