Synergistic combination of biomarkers for detecting and assessing hepatic fibrosis

An in vitro process for determining whether or not the stage of hepatic fibrosis of a patient infected with one or more hepatitis viruses has passed beyond the stage of hepatic fibrosis that is a score F1 according to the Metavir fibrosis scores system, said process comprising the following steps:

• i) selecting different biological markers, the selected different biological markers consisting of:
• a) hyaluronic acid and the protein CXCL10;
• and
• b) zero, one, two, three or four additional markers selected from the list of markers comprised of the age, body mass index, viral load and the stiffness of the liver;
• ii) quantifying the different biological markers selected in step i)
• by measuring in vitro the concentration of each of hyaluronic acid and the concentration of protein CXCL10 in a sample of biological fluid obtained in advance from said patient;
• and
• when one, two, three or four additional markers are selected from said list of step i)b) above, and when this (or these) additional marker(s) is (are) or includes (include) one or more markers selected from the age, body mass index and stiffness of the liver:
• by collecting the value of quantification of this or each of these additional markers that was determined in advance for or on said patient;
• when one, two, three or four additional markers are selected from said list of step i)b) above, and when this (or these) additional marker(s) is (are) or includes (include) the viral load:
• by measuring this viral load in vitro in a sample of biological fluid obtained in advance from said patient, or by collecting the value of this viral load that was determined in advance for said patient;
• and
• iii) comparing the values of quantification obtained in step ii) to their values, or to the distribution of their values, in the predefined reference cohorts according to the stage of hepatic fibrosis, in order to classify said patient into the one of these reference cohorts to which they most probably belong, said reference cohorts including or being:
• a first reference cohort in which the stage of hepatic fibrosis of the individuals does not pass beyond said stage of hepatic fibrosis, which according to the Metavir score system is a score of F1;
• and
• a second reference cohort in which the stage of hepatic fibrosis of the individuals passes beyond said stage of hepatic fibrosis, which according to the Metavir score system is a score of F1;
• classification into said first cohort indicating that the stage of hepatic fibrosis of said patient has not passed beyond the stage of hepatic fibrosis, which according to the Metavir score system is a score of F1;
• classification into said second cohort indicating that the stage of hepatic fibrosis of said patient has passed beyond the stage of hepatic fibrosis, which according to the Metavir score system is a score of F1.