METHODS TO PREDICT LIVER DISEASE MORTALITY USING LIPOPROTEIN LP-Z
Described herein are methods for the determination of patient mortality from alcoholic hepatitis in biosamples by NMR spectroscopy and more specifically for the determination of a Z index score based on lipoprotein constituent LP-Z in blood plasma and serum.
1 . A method to predict patient mortality to alcoholic hepatitis comprising:
acquiring an NMR spectrum of a biosample obtained from the subject;
programmatically determining the concentration of LP-Z and total apoB-containing lipoproteins in the sample based on the NMR spectrum of the sample, wherein the NMR spectrum of the sample includes LP-X and LP-Z; and
calculating a Z index score.
2 . The method of claim 1 , wherein the acquiring step of the method comprises:
producing a measured lipid signal lineshape for an NMR spectrum of the biosample obtained from a subject; and
generating a calculated lineshape for the sample.
3 . The method of claim 2 , wherein the calculated lineshape is based on derived concentrations of lipoprotein components comprising LP-X and LP-Z.
4 . The method of claim 3 , wherein the derived concentration of each of the lipoprotein components is a function of a reference spectrum for that component and a calculated reference coefficient.
5 . The method of claim 2 , wherein generating step comprises calculating the reference coefficients for the calculated lineshape based on a linear least squares fit technique.
6 . The method of claim 2 , further comprising:
determining that the degree of correlation between the initial calculated lineshape of the sample and a measured lineshape of the sample; and
determining the presence of LP-Z based on the calculated lineshape if the degree of correlation between the calculated lineshape and the measured lineshape of the sample is above a predetermined threshold.
7 . The method of claim 1 , wherein the Z index score comprises a concentration of lipoprotein LP-Z, LDL, and VLDL.
8 . The method of claim 1 , wherein the Z index is a ratio of LP-Z concentration to total apoB-containing lipoproteins concentration.
9 . The method of claim 1 , wherein the Z index is calculated by the following equation:
Z index=([ LP - Z ])/([ VLDL ]+[ LDL ]+[ LP - Z ]).
10 . The method of claim 1 , wherein a Z index of greater than 0.6 predicts patient mortality will occur in 90 days or less.
11 . The method of claim 1 , wherein the method predicts a likelihood of patient mortality within 90 days.
12 . The method of claim 1 , wherein the method predicts a likelihood of survival or patient response to treatment.
13 . The method of claim 1 , further comprising, before the programmatic determination,
placing the sample of the subject in an NMR spectrometer;
deconvolving the NMR spectrum; and
calculating NMR derived measurements of a plurality of selected lipoprotein parameters based on the deconvolved NMR spectrum.
14 . The method of claim 1 , further comprising producing a report listing the concentrations of the lipoprotein constituents present in the sample and likelihood of mortality.
15 . The method of claim 1 , wherein the biosample is one of blood, serum, plasma, cerebral spinal fluid, or urine.
16 . A NMR analyzer comprising:
a NMR spectrometer;
a probe in communication with the spectrometer; and
a controller in communication with the spectrometer configured to obtain NMR signal of a defined single peak region of NMR spectra associated with LP-Z of a fluid specimen in the probe and generate a patient report providing a LP-Z level.
17 . The analyzer of claim 16 , wherein the controller is in communication with at least one local or remote processor, wherein the at least one processor is configured to:
(i) obtain a composite NMR spectrum of a fitting region of the fluid specimen; and
(ii) deconvolve the composite NMR spectrum using a defined deconvolution model to generate the LP-Z level.
18 . The analyzer of claim 17 , wherein the deconvolution model comprises at least one of high density lipoprotein (HDL) components, low density lipoprotein (LDL) components, VLDL (very low density lipoprotein)/chylomicron components, LP-X, LP-Y and LP-Z.
19 . The analyzer of claim 16 , wherein the probe is a flow probe.
20 . The analyzer of claim 16 , wherein the fluid specimen is an in vitro plasma biosample.
21 . The analyzer of claim 16 , wherein the fluid specimen is a biosample of blood, serum, plasma, cerebral spinal fluid, or urine.