Enhanced liver fibrosis (ELF) score: Reference ranges, biological variation in healthy subjects, and analytical considerations.

BACKGROUND: The Enhanced Liver Fibrosis score has been recognized as a non-invasive test for liver fibrosis. However, reference intervals, biological variation and analytical performance have not been studied in detail so far. The aim was to acquire data that are essential for correct interpretation.

METHODS: A total of 40 apparently healthy volunteers were evaluated for reference ranges of serum concentration of hyaluronic acid, aminoterminal propeptide of type III collagen, and tissue inhibitor of metalloproteases-1, and calculated ELF score. A subgroup of 20 subjects was evaluated repeatedly for 7 weeks. For all variables, reference intervals, within-subject and between-subject biological variations, reference change values, and the indexes of individuality were assessed. Analytical performance (intermediate precision) and interlaboratory comparison were also evaluated.

RESULTS: The reference ranges were 5.1-62.7 μg/L for HA, 3.56-12.6 μg/L for PIIINP, 143.6-265.3 μg/L for TIMP-1, and 7.14-9.55 for the ELF score. The within-subject variations were 32.7, 10.6, 4.2, and 3.2% for HA, PIIINP, TIMP-1, and ELF score, respectively. Similarly, the between-subject variations were 59.0, 13.3, 12.8, and 5.2%. For the ELF score, RCV was 10.1% and II was 0.62. The intermediate precisions were <5%, <6%, and <10% for HA, PIIINP, and TIMP-1, respectively.

CONCLUSION: The reference range of the ELF score overlap with the area defined as moderate fibrosis by the manufacturer. High biological variation of HA was diminished by the natural logarithm in the calculation of the ELF score. The use of the ELF score has suitable analytical and acceptable biological performance characteristics for clinical practice. However, the transfer of results evaluated in healthy persons to the populations with chronic liver diseases deserves caution.