Method for Discriminating Symptom of Hepatic Disease

Patent metadata

Field	Value
Publication number	US-2018100867-A1
Application number	US-201615565027-A
Country	US
Kind code	A1
Filing date	Apr 8, 2016
Priority date	Apr 10, 2015
Publication date	Apr 12, 2018
Grant date	—

Abstract

Provided is a noninvasive method for determining the presence of a symptom of a hepatic disease such as nonalcoholic fatty liver disease with a higher diagnostic accuracy. A method for discriminate between nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), the method comprising: (1) a step of measuring the quantities of marker molecules contained in blood collected from a subject; (2) a step of determining an index value from a normalized score calculated based on the quantities of the marker molecules belonging to the same group; and (3) a step of determining that the subject is possibly affected with NASH in the case that the index value is larger than a reference value.

First claim

1 . A method for discriminating between nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), the method comprising:
(1) a step of measuring quantities of marker molecules contained in blood collected from a subject, wherein the marker molecules to be measured are (A) at least two marker molecules selected from Group 1 consisting of PROS1, CLU, ANG, APOC3, APOD, CFHR1, cortisol, EGFR, HPN, IGFBP3, IL1B, IL23A, MET, MMP10, tetranectin, TTR, VDBP, and VEGFR-2, at least two marker molecules selected from Group 2 consisting of VCAM1, HA, CTSD, COL4, COL4-7S, ALB, AFP, AXL, CCL19, CGB, CSF1, FAS, Mac-2bp, CA19-9, NRCAM, OPG, VWF, and YKL-40, at least two marker molecules selected from Group 3 consisting of AST, PSAT, LEP, ICAM1, CK-18, GSTA1, ALT, INS IVD , INS MAP , 6Ckine, AGT, CRP, CXCL10, FABP4, G6PI, HSP-60, P3NP, and testosterone, or at least two marker molecules selected from Group 4 consisting of AREG, BDNF, CD40-L, EREG, FGF2, HBEGF, IGFBP2, MMP9, PAI-1, PDGFB, PLGF, SAP, TGFA, TGFB1, THBS1, and VTN, or, (B) at least two marker molecules selected from one of two groups selected from the Group 1, the Group 2, the Group 3, and the Group 4 and at least two marker molecules selected from the other; (2) a step of determining an index value from a normalized score calculated based on the quantities of the marker molecules, wherein the normalized score based on the quantities of the marker molecules belonging to the same group is calculated by using the following formula 1:

M
=

1
N



∑

i
=
1

N



1

1
+

exp


(

-

α
i



m
i

-

mean


(

m
i

)

sd


(

m
i

)

)





α
i

=

{

1

(

mean


(

m
i
NASH

)

>

mean


(

m
i
NAFL

)

)

-
1

(
otherwise
)

(

formula



1

)

wherein M denotes a normalized score; N denotes a number of marker molecules; m i denotes the quantity of each marker molecule measured; mean (m i ) denotes a predetermined mean of a quantity of each marker molecule; sd (m i ) denotes a predetermined standard deviation for each marker molecule; mean (m i NASH ) denotes a predetermined mean of a quantity of each marker molecule for patients affected with NASH; and mea

Assignees

• Social Welfare Organization Saiseikai Imp Gift Foundation Inc
• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Okanoue Takeshi
• Yoshimura Keito
• Iwasaki Tsuyoshi
• Yamazaki Kazuto
• Ebise Hayao
• Ichihara Junji

Classifications

• G01N33/6869

  Interleukin · CPC title

• G01N2333/70542

  CD106 · CPC title

• G01N33/6863

  Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors · CPC title

• G01N2800/085

  Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin · CPC title

• G01N33/6893 Primary

  related to diseases not provided for elsewhere · CPC title