Abstract

BackgroundIt is frequently important to identify the prognosis of fulminant hepatic failure (FHF) patients as this will influence patient management and candidacy for liver transplantation. Therefore, a novel scoring system based on metabonomics combining with multivariate logistic regression was developed to predict the prognosis of FHF mouse model.MethodsBALB/c mice were used to construct FHF model. Parts of plasma were collected at 4, 5, and 6-h time points after treatment, respectively, and detected using gas chromatography/time-of-flight mass spectrometry (GC/TOFMS). The acquired data were processed using partial least square discriminant analysis (PLS-DA). The metabolic markers identified were used to construct a scoring system by multivariate regression analysis.Results28 mice of survival group and 28 of dead group were randomly selected and analyzed. PLS regression analysis showed that both the PLS models of 5 h and 6 h after d-galactosamine/lipopolysaccharide treatment demonstrated good performances. Loadings plot suggested that phosphate, beta-hydroxybutyrate (HB), urea, glucose and lactate concentrations in plasma had the highest weightings on the clustering differences at the three time points. By the multivariate logistic regression analysis, the death/survival index (DSI) was constructed based on relative concentrations of HB, urea and phosphate. It provided general accurate rate of prediction of 93.3% in the independent samples.ConclusionsThe novel scoring system based on metabonomics combining with multivariate logistic regression is accurate in predicting the prognosis of FHF mouse model and may be referred in clinical practice as a more useful prognostic tool with other available information.

Highlights

  • It is frequently important to identify the prognosis of fulminant hepatic failure (FHF) patients as this will influence patient management and candidacy for liver transplantation

  • We reported the dynamics of metabolic profiles in dgalactosamine/lipopolysaccharide (GalN/LPS)-treated BALB/c mouse model, and identified 5 biomarkers including phosphate, β-hydroxybutyrate (HB), urea, glucose and lactate which may constitute a set of markers for the early diagnosis and prognosis of FHF [12,13]

  • We have developed a novel scoring system that is highly accurate in predicting the prognosis of FHF mouse model

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Summary

Introduction

It is frequently important to identify the prognosis of fulminant hepatic failure (FHF) patients as this will influence patient management and candidacy for liver transplantation. A novel scoring system based on metabonomics combining with multivariate logistic regression was developed to predict the prognosis of FHF mouse model. Individual compounds including lactate, phosphorus among others were proposed to predict patient outcome in FHF [4,5]. Their prognostic value is debatable [6]. Application of multivariate models has been improved prediction accuracy of FHF outcome. Better prognostic model to identify FHF patients who are likely to survive is needed

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