Non-Invasive Method for Assessing Liver Fibrosis Progression

Abstract

The present invention relates to a non-invasive method for assessing liver fibrosis progression in an individual, said method comprising the steps of calculating the ratio of fibrosis level to cause duration and to a non-invasive method for assessing liver fibrosis progression in an individual, said method comprising the steps of measuring, at two different times t 1 and t 2 , the fibrosis levels FL (t 1 ) and FL (t 2 ) and calculating the ratio FL (t 2 )−FL (t 1 ) to (t 2 −t 1 ) and to a non-invasive method for assessing if an individual is a slow, medium or fast fibroser.

1 .- 14 . (canceled) 
     
     
         15 . A non-invasive method for assessing liver fibrosis progression in an individual comprising:
 measuring a fibrosis level in a patient; and   calculating a ratio of fibrosis level to cause duration.   
     
     
         16 . The method of  claim 15 , further comprising:
 measuring at two different times t1 and t2 fibrosis levels FL(t1) and FL(t2); and   calculating a ratio FL(t 2 )−FL(t 1 ) to (t 2 −t 1 ).   
     
     
         17 . The method of  claim 15 , further comprising:
 a) measuring in a sample of the individual at least one variable or score further defined as:
 biological variables further defined as α-2 macroglobulin (α2M), Hyaluronic acid (HA), Apolipoprotein A1 (ApoA1), Type III procollagen N-terminal propeptide (P3P), γ-glutamyltranspeptidase (GGT), Bilirubin, β-globulin, γ-globulin (GLB), Platelets (PLT), Prothrombin time (PT), Prothrombin index (PI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Urea, Sodium (NA), Glycemia, Triglycerides, Albumin (ALB), Alkaline phosphatase (ALP), Human cartilage glycoprotein 39 (YKL-40), Tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), Matrix metalloproteinase 2 (MMP-2), Ferritin, TGFβ1, Laminin, βγ-block, Haptoglobin, C-Reactive protein (CRP), and/or cholesterol, 
 complex biological variable; 
 clinical variables further defined as age at first contact, age, cause duration, firm liver, Splenomegaly, Ascites, collateral circulation, cause of CLD, and/or oesophageal varices (EV grade); 
 score further defined as Metavir F stage, Area of fibrosis (AOF), fractal dimension, Fibrosis score, PGA score, PGAA score, Hepascore, Aspartate-aminotransferase to platelet ratio index (APRI), and/or European Liver Fibrosis (ELF), and/or 
 combinations thereof: and 
   b) combining the selected variables in a mathematical function, further defined as a multiple linear regression function, a non-linear regression function, or simple mathematic function.   
     
     
         18 . The method of  claim 17 , further comprising measuring in a sample of the individual at least two variables or scores. 
     
     
         19 . The method of  claim 18 , further comprising measuring in a sample of the individual at least three variables or scores. 
     
     
         20 . The method of  claim 17 , wherein AST/ALT is measured. 
     
     
         21 . The method of  claim 17 , wherein the mathematical function is an arithmetic operation. 
     
     
         22 . The method of  claim 21 , wherein the arithmetic operation is division. 
     
     
         23 . The method of  claim 17 , wherein liver fibrosis progression is assessed by measuring Metavir F progression established by:
 measuring in any combination:
 at least one biological variable further defined as Type III procollagen N-terminal propeptide (P3P), Hyaluronic acid (HA), Prothrombin index (PI), γ-glutamyl transpeptidase (GGT) and/or βγ-block; 
 at least one complex biological variable further defined as AST/ALT; 
 at least one clinical variable further defined as age at first contact and/or cause duration; 
 at least one score further defined as a fibrosis score, AOF, and/or fractal dimension; and/or 
   combining the selected variables in the mathematical function.   
     
     
         24 . The method of  claim 17 , wherein the liver fibrosis progression is assessed by measuring the area of fibrosis (AOF) progression established by:
 measuring in any combination:
 at least one biological variable further defined as α-2 macroglobulin (α2M), Hyaluronic acid (HA), β-globulin, Prothrombin index (PI) and/or βγ-block; 
 the complex biological variable AST/ALT; 
 at least one clinical variable further defined as age at first contact, age, cause duration, sex, firm liver, Splenomegaly, Ascites, Collateral circulation and/or cause of CLD; and/or 
 at least one score further defined as Metavir F stage, area of fibrosis (AOF), FibroMeter™, PGA score and/or PGAA score; and 
   combining the selected variables in the mathematical function.   
     
     
         25 . The method of  claim 17 , wherein the variables comprise in any combination:
 the biological variable β-globulins;   the complex biological variable AST/ALT;   the clinical variable cause duration; and/or   the score Area of fibrosis (AOF) or Metavir F stage.   
     
     
         26 . The method of  claim 17 , wherein the variables comprise in any combination:
 at least one biological variables chosen among β-globulins or Prothrombin index (PI);   the complex biological variable AST/ALT; and/or   at least one clinical variable chosen among age at first contact, cause duration, or firm liver.   
     
     
         27 . The method of  claim 17 , wherein the variables comprise in any combination:
 at least one biological variable defined as β-globulins and/or α-2 macroglobulin (α2M);   the complex biological variable AST/ALT; and/or   at least one clinical variable further defined as age at first contact or cause duration.   
     
     
         28 . A method for assessing an individual comprising performing at least once the method of  claim 15 . 
     
     
         29 . The method of  claim 28 , further defined as a method of assessing if an individual is a fast fibroser, using binary logistic regression, and a fast fibroser is identified as having an increased AOF progression, younger inclusion age and older start age or alternatively cause duration by stepwise binary logistic regression. 
     
     
         30 . The method of  claim 28 , further defined as a method of assessing if an individual is a slow, medium or fast fibroser using discriminant analyses and the individual is ranked as a slow, medium or fast fibroser with reference to a ranking of patients determined by statistical analysis. 
     
     
         31 . The method of  claim 28 , further defined as a method of assessing if an individual is at risk of suffering or is suffering from a condition further defined as chronic liver disease, a hepatitis viral infection, a hepatoxicity, a liver cancer, a non alcoholic fatty liver disease (NAFLD), an autoimmune disease, a metabolic liver disease and/or a disease with secondary involvement of the liver.