Back to results
US 6,986,995 B2Granted
Methods of diagnosing liver fibrosis
AssigneePrometheus Laboratories Inc.
InventorsSteven L. Rose, Esther H. Oh, Michael J. Walsh
Life of this patent
Estimating the term…
Abstract
The present invention provides a method of diagnosing the presence or severity of liver fibrosis in an individual by detecting α2-macroglobulin (α2-MG) in a sample from the individual; detecting hyaluronic acid (HA) in a sample from the individual; detecting tissue inhibitor of metalloproteinases-1 (TIMP-1) in a sample from the individual; and diagnosing the presence or severity of liver fibrosis in the individual based on the presence or level of α2-MG, HA and TIMP-1.
Claims63
A method of diagnosing the presence or severity of liver fibrosis in an individual, comprising the steps of:
- (a) detecting α2-macroglobulin (α2-MG) in a sample from said individual;
- (b) detecting hyaluronic acid (HA) in a sample from said individual;
- (c) detecting tissue inhibitor of metalloproteinases-1 (TIMP-1) in a sample from said individual;
- and
- (d) diagnosing the presence or severity of liver fibrosis in said individual based on the presence or level of α2-MG, HA and TIMP-1.
2 more elements
A method of differentiating F0–F1 fibrosis from F2–F4 fibrosis in an individual, comprising the steps of:
- (a) contacting an appropriate dilution of a sample from said individual with anti-α2-MG antibody under conditions suitable to form a first complex of α2-MG and anti-α2-MG antibody;
- (b) washing said first complex to remove unbound molecules;
- (c) determining the amount of α2-MG-containing first complex;
- (d) contacting an appropriate dilution of a sample from said individual with a HA-binding protein (HABP) under conditions suitable to form a second complex of HA and HABP;
- (e) washing said second complex to remove unbound molecules;
- (f) determining the amount of HA-containing second complex;
- (g) contacting an appropriate dilution of a sample from said individual with anti-TIMP-1 antibody under conditions suitable to form a third complex of TIMP-1 and anti-TIMP-1 antibody;
- (h) washing said third complex to remove unbound molecules;
- (i) determining the amount of TIMP-1-containing third complex;
- and
- (j) differentiating F0–F1 fibrosis from F2–F4 fibrosis in said individual based on the amounts of α2-MG, HA and TIMP-1-containing complexes.
8 more elements
A method of monitoring the efficacy of anti-fibrotic therapy in a patient, comprising the steps of:
- (a) detecting α2-macroglobulin (α2-MG) in a sample from a patient administered an anti-fibrotic therapy;
- (b) detecting hyaluronic acid (HA) in a sample from said patient;
- (c) detecting tissue inhibitor of metalloproteinases-1 (TIMP-1) in a sample from said patient;
- and
- (d) determining the presence or severity of liver fibrosis in said patient based on the presence or level of α2-MG, HA and TIMP-1, thereby monitoring the efficacy of anti-fibrotic therapy.
2 more elements
A method of differentiating F0–F1 fibrosis from F2–F4 fibrosis in an individual, comprising the steps of:
- (a) determining an α2-MG level in a sample from said individual;
- (b) determining a HA level in a sample from said individual;
- (c) determining a TIMP-1 level in a sample from said individual;
- and
- (d) diagnosing said individual as having F0–F1 fibrosis when said α2-MG level is below an α2-MG cut-off value X1, said HA level is below a HA cut-off value Y1 or said TIMP-1 level is below a TIMP-1 cut-off value Z1,
- diagnosing said individual as having F2–F4 fibrosis when said α2-MG level is above an α2-MG cut-off value X2, said HA level is above a HA cut-off value Y2 and said TIMP-1 level is above a TIMP-1 cut-off value Z2,
- and diagnosing said individual as having an indeterminate status when said α2-MG level is above X1, said HA level is above Y1, and said TIMP-1 level is above Z1 but said α2-MG level is below X2, said HA level is below Y2 or said TIMP-1 level is below Z2.
4 more elements
A method of diagnosing the presence or severity of liver fibrosis in an individual, comprising the steps of:
- (a) comparing a level of a first fibrotic marker α2-MG in said individual to a cut-off value X1 to determine whether said individual is positive for α2-MG;
- (b) comparing a level of a second fibrotic marker HA in said individual to a cut-off value Y1 to determine whether said individual is positive for HA;
- (c) comparing a level of a third fibrotic marker TIMP-1 in said individual to a cut-off value Z1 to determine whether said individual is positive for TIMP-1;
- and
- (d) diagnosing the presence or severity of liver fibrosis in said individual based on positivity or negativity for α2-MG, HA, and TIMP-1.
- wherein in a population having about 40% liver fibrosis prevalence, X1, Y1 and Z1 are independently selected to diagnose the presence or severity of liver fibrosis in said individual with more than 91% accuracy in about 70% of the population assayed.
3 more elements
A method of diagnosing the presence or severity of liver fibrosis in an individual, comprising the steps of:
- (a) comparing a level of a first fibrotic marker α2-MG in said individual to a cut-off value X1 to determine whether said individual is positive for α2-MG;
- (b) comparing a level of a second fibrotic marker HA in said individual to a cut-off value Y1 to determine whether said individual is positive for HA;
- (c) comparing a level of a third fibrotic marker TIMP-1 in said individual to a cut-off value Z1 to determine whether said individual is positive for TIMP-1;
- and
- (d) diagnosing the presence or severity of liver fibrosis in said individual based on positivity or negativity for α2-MG, HA, and TIMP-1,
- wherein said cut-off values X1, Y1, and Z1 are independently selected to achieve an optimized clinical parameter selected from the group consisting of sensitivity, specificity, negative predictive value, positive predictive value, and accuracy.
3 more elements
A method of diagnosing the presence or severity of liver fibrosis in an individual, comprising the steps of:
- (a) comparing a level of a first fibrotic marker α2-MG in said individual to a cut-off value X1 to determine whether said individual is positive for α2-MG, wherein said individual is positive for α2-MG when said level of α2-MG is above X1;
- (b) comparing a level of a second fibrotic marker HA in said individual to a cut-off value Y1 to determine whether said individual is positive for HA, wherein said individual is positive for HA when said level of HA is above Y1;
- (c) comparing a level of a third fibrotic marker TIMP-1 in said individual to a cut-off value Z1 to determine whether said individual is positive for TIMP-1, wherein said individual is positive for TIMP-1 when said level of TIMP-1 is above Z1,
- wherein any individual positive for α2-MG, HA, and TIMP-1 as compared to X1, Y1, and Z1, respectively, is further evaluated for positivity for α2-MG, HA, and TIMP-1 using a second set of cut-off values X2, Y2, and Z2 comprising:
- (d) comparing the level of α2-MG in said individual to X2, wherein said individual is positive for α2-MG when said level of α2-MG is above X2;
- (e) comparing the level of HA in said individual to Y2, wherein said individual is positive for HA when said level of HA is above Y2;
- (f) comparing the level of TIMP-1 in said individual to Z2, wherein said individual is positive for TIMP-1 when said level of TIMP-1 is above Z2;
- and
- (g) diagnosing the presence or severity of liver fibrosis in said individual based on positivity or negativity for α2-MG, HA, and TIMP-1, wherein said cut-off values X2, Y2, and Z2 are greater than or equal to X1, Y1, and Z1, respectively,
- wherein said individual is diagnosed as having liver fibrosis when said individual is positive for α2-MG, HA, and TIMP-1 as compared to X2, Y2, and Z2, respectively, and
- wherein said individual is diagnosed as having an indeterminate status when said individual is negative for α2-MG, HA, or TIMP-1 as compared to X2, Y2, and Z2, respectively.
8 more elements
Dependencies are inferred from the claim text.