Study of FibroTest and hyaluronic acid biological variation in healthy volunteers and comparison of serum hyaluronic acid biological variation between chronic liver diseases of different etiology and fibrotic stage using confidence intervals

Clin Biochem. 2015 Jul;48(10-11):652-7. doi: 10.1016/j.clinbiochem.2015.03.020. Epub 2015 Apr 8.


Objectives: Personalized ranges of liver fibrosis serum biomarkers such as FibroTest or hyaluronic acid could be used for early detection of fibrotic changes in patients with progressive chronic liver disease. Our aim was to generate reliable biological variation estimates for these two biomarkers with confidence intervals for within-subject biological variation and reference change value.

Design and methods: Nine fasting healthy volunteers and 66 chronic liver disease patients were included. Biological variation estimates were calculated for FibroTest in healthy volunteers, and for hyaluronic acid in healthy volunteers and chronic liver disease patients stratified by etiology and liver fibrosis stage.

Results: In healthy volunteers, within-subject biological coefficient of variation (with 95% confidence intervals) and index of individuality were 20% (16%-28%) and 0.6 for FibroTest and 34% (27%-47%) and 0.79 for hyaluronic acid, respectively. Overall hyaluronic acid within-subject biological coefficient of variation was similar among non-alcoholic fatty liver disease and chronic hepatitis C with 41% (34%-52%) and 45% (39%-55%), respectively, in contrast to chronic hepatitis B with 170% (140%-215%). Hyaluronic acid within-subject biological coefficients of variation were similar between F0-F1, F2 and F3 liver fibrosis stages in non-alcoholic fatty liver disease with 34% (25%-49%), 41% (31%-59%) and 34% (23%-62%), respectively, and in chronic hepatitis C with 34% (27%-47%), 33% (26%-45%) and 38% (27%-65%), respectively. However, corresponding hyaluronic acid indexes of individuality were lower in the higher fibrosis stages.

Conclusion: Non-overlapping confidence intervals of biological variation estimates allowed us to detect significant differences regarding hyaluronic acid biological variation between chronic liver disease subgroups.

Keywords: Biological variation; Chronic liver diseases (CLDs); Confidence intervals; FibroTest (FT); Hyaluronic acid (HA); Index of individuality; Liver fibrosis biomarkers; Reference change values (RCVs).

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Confidence Intervals
  • End Stage Liver Disease / blood*
  • End Stage Liver Disease / diagnosis*
  • End Stage Liver Disease / etiology
  • Female
  • Follow-Up Studies
  • Healthy Volunteers
  • Humans
  • Hyaluronic Acid / blood*
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / etiology
  • Male
  • Middle Aged
  • Young Adult


  • Biomarkers
  • Hyaluronic Acid