A novel scoring system for prognostic prediction in d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure BALB/c mice.
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.
Feng
Bo
B
Hepatology Institute, Peking University People's Hospital, No. 11 Xizhimen South Street, Beijing 100044, PR China. xyfyfb_1@sina.com
Wu
Sheng Ming
SM
Lv
Sa
S
Liu
Feng
F
Chen
Hong Song
HS
Gao
Yan
Y
Dong
Fang Ting
FT
Wei
Lai
L
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D005688:Galactosamine / Q000009:adverse effects; D008070:Lipopolysaccharides / Q000009:adverse effects; D017114:Liver Failure, Acute / Q000097:blood* / Q000139:chemically induced / Q000175:diagnosis*; D016015:Logistic Models; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D015233:Models, Statistical; D010710:Phosphates / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D012255:Ribitol / Q000097:blood; D014508:Urea / Q000097:blood
D015415:Biomarkers; D008070:Lipopolysaccharides; D010710:Phosphates; D012255:Ribitol; D005688:Galactosamine; D014508:Urea; D020155:3-Hydroxybutyric Acid