IP Library Granted Patent US 8,460,943
Granted Patent B2
US 8,460,943 · App. 12/979,782 · Granted Jun 11, 2013

Detection and monitoring of liver damage

Inventors: Ariel E. Feldstein (Highland Heights, OH); Anna Wieckowska (Quebec, CA); Nizar Zein (Highland Heights, OH)
Assignee: The Cleveland Clinic Foundation
G01N33/566Y10S436/811
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Quick Facts
Patent No.
US 8,460,943
App. No.
12/979,782
Granted
Jun 11, 2013
Kind
B2
Abstract

A method of detecting liver damage in a subject comprises measuring the level of caspase-3 generated cytokeratin-18 fragments in the bodily sample. The level of measuring the level of caspase-3 generated cytokeratin-18 fragments is then correlated with liver disease progression.

Claims (33)

1. A method of assessing the degree of liver damage associated with non-alcoholic fatty liver disease in a subject with non-alcoholic fatty liver disease, the method comprising:

obtaining a bodily sample from the subject, wherein the bodily sample is selected from the group consisting of blood, plasma, and serum;

measuring the level of caspase generated cytokeratin-18 fragments in the bodily sample;

correlating the level of caspase generated cytokeratin-18 fragments with the degree of liver damage in the subject;

identifying the subject as having more severe liver damage the higher the measured level of caspase generated cytokeratin-18 fragments in the bodily sample compared to a predetermined value; and

administering to the subject having non-alcoholic fatty liver disease a therapeutic agent based on the identified severity of liver damage.

2. The method of claim 1 , the caspase generated cytokeratin-18 fragments being measured using an enzyme-linked immunosorbent assay (ELISA).

3. The method of claim 2 , the enzyme-linked immunosorbent assay measuring the level of caspase generated cytokeratin-18 fragments in units per liter (U/L), wherein the higher the U/L of caspase generated cytokeratin-18 fragments in the bodily sample the more severe the liver damage in the subject.

4. The method of claim 1 , wherein the higher the measured level of caspase generated cytokeratin-18 fragments in the bodily sample compared to a predetermined value, the more likely the subject has nonalcoholic steatohepatitis (NASH) than steatosis.

5. The method of claims 1 , wherein the higher the measured level of caspase generated cytokeratin-18 fragments in the bodily sample compared to a predetermined value, the more likely the subject has moderate to severe fibrosis than mild fibrosis.

6. The method of claim 1 , wherein a level of caspase generated cytokeratin-18 fragments are measured in the bodily sample and the level of caspase generated cytokeratin-18 fragments are correlated with the degree of liver damage in the subject, wherein the higher the measured level of caspase generated cytokeratin-18 fragments in the bodily sample compared to a predetermined value, the more severe the liver damage in the subject.

7. The method of claim 1 , wherein a level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 are measured in the bodily sample and the level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 are correlated with the degree of liver damage in the subject, wherein the higher the measured level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample compared to a predetermined value, the more severe the liver damage in the subject.

8. The method of claim 1 , wherein a level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 are measured in the bodily sample and the level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 are correlated with the degree of liver damage in the subject, wherein the higher the measured level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample compared to a predetermined value, the more severe the liver damage in the subject.

9. A method of assessing the degree of liver damage associated with non-alcoholic fatty liver disease in a subject with non-alcoholic fatty liver disease, the method comprising:

obtaining a bodily sample from the subject, wherein the bodily sample is selected from the group consisting of blood, plasma, and serum;

measuring the level of cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample;

correlating the level of cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 with the degree of liver damage in the subject;

identifying the subject as having more severe liver damage the higher the measured level of cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample compared to a predetermined value; and

administering to the subject having non-alcoholic fatty liver disease a therapeutic agent based on the identified severity of liver damage.

10. The method of claim 9 , the cytokeratin-18 fragments being measured using an enzyme-linked immunosorbent assay (ELISA).

11. The method of claim 10 , the enzyme-linked immunosorbent assay measuring the level of cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in units per liter (U/L), wherein the higher the U/L of cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample the more severe the liver damage in the subject.

12. The method of claim 9 , wherein the higher the measured level of cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample compared to a predetermined value, the more likely the subject has nonalcoholic steatohepatitis (NASH) than steatosis.

13. The method of claims 9 , wherein the higher the measured level of cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample compared to a predetermined value, the more likely the subject has moderate to severe fibrosis than mild fibrosis.

14. A method of assessing the degree of liver damage associated with non-alcoholic fatty liver disease in a subject with non-alcoholic fatty liver disease, the method comprising:

obtaining a bodily sample from the subject, wherein the bodily sample is selected from the group consisting of blood, plasma, and serum;

measuring the level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample;

correlating the level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 with the degree of liver damage in the subject;

identifying the subject as having more severe liver damage the higher the measured level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample compared to a predetermined value; and

administering to the subject having non-alcoholic fatty liver disease a therapeutic agent based on the identified severity of liver damage.

15. The method of claim 14 , the caspase generated cytokeratin-18 fragments being measured using an enzyme-linked immunosorbent assay (ELISA).

16. The method of claim 15 , the enzyme-linked immunosorbent assay measuring the level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in units per liter (U/L), wherein the higher the U/L of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample the more severe the liver damage in the subject.

17. The method of claim 14 , wherein the higher the measured level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample compared to a predetermined value, the more likely the subject has nonalcoholic steatohepatitis (NASH) than steatosis.

18. The method of claims 14 , wherein the higher the measured level of caspase generated cytokeratin-18 fragments which are cleaved at aspartic acid residue 396 in the bodily sample compared to a predetermined value, the more likely the subject has moderate to severe fibrosis than mild fibrosis.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded Feb 16, 2021
From: PDL BIOPHARMA, INC.
To: DEFINED DIAGNOSTICS, LLC (F/K/A WELLSTAT DIAGNOSTICS, LLC)
Reel/Frame 055314/0075 →
RELEASE OF SECURITY INTEREST Recorded Jan 19, 2021
From: WHITE OAK GLOBAL ADVISORS, LLC, AS ADMINISTRATIVE AGENT
To: DEFINED DIAGNOSTICS, LLC (F/K/A WELLSTAT DIAGNOSTICS, LLC)
Reel/Frame 055027/0238 →
SECURITY AGREEMENT Recorded Sep 17, 2013
From: WELLSTAT DIAGNOSTICS, LLC
To: PDL BIOPHARMA, INC.
Reel/Frame 031227/0194 →
SECURITY AGREEMENT Recorded Aug 16, 2013
From: WELLSTAT DIAGNOSTICS, LLC
To: WHITE OAK GLOBAL ADVISORS, LLC, AS ADMINISTRATIVE AGENT
Reel/Frame 031031/0075 →
Continuity (3)
Continuation 11804505 · May 18, 2007
Provisional Application 60801728 · May 19, 2006
Related Publication 20110151488A1 · Jun 23, 2011