A novel scoring system for prognostic prediction in d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure BALB/c mice

BMC Gastroenterol. 2009 Dec 30:9:99. doi: 10.1186/1471-230X-9-99.

Abstract

Background: 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. Therefore, a novel scoring system based on metabonomics combining with multivariate logistic regression was developed to predict the prognosis of FHF mouse model.

Methods: BALB/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.

Results: 28 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.

Conclusions: The 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Animals
  • Biomarkers / blood
  • Disease Models, Animal
  • Galactosamine / adverse effects
  • Lipopolysaccharides / adverse effects
  • Liver Failure, Acute / blood*
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / diagnosis*
  • Logistic Models
  • Male
  • Metabolomics / methods*
  • Mice
  • Mice, Inbred BALB C
  • Models, Statistical*
  • Phosphates / blood
  • Predictive Value of Tests
  • Prognosis
  • Ribitol / blood
  • Urea / blood

Substances

  • Biomarkers
  • Lipopolysaccharides
  • Phosphates
  • Ribitol
  • Galactosamine
  • Urea
  • 3-Hydroxybutyric Acid