Intra-laboratory analytical variability of biochemical markers of fibrosis (Fibrotest) and activity (Actitest) and reference ranges in healthy blood donors

Abstract

Combinations of tests comprising alpha2-macroglobulin, haptoglobin, apolipoprotein Al, gamma-glutamyltransferase, total bilirubin (Fibrotest) and alanine aminotransferase (Actitest) are being developed as alternatives to liver biopsy in patients with chronic hepatitis C. The aim of this study was to assess in the same laboratory the impact of parameter assay variations on Fibrotest and Actitest results and intra-patient reproducibility of the two tests. The stability of the samples for each test was studied after storage at -80 degrees C and -20 degrees C. Within-run, between-run and total imprecision for each parameter assay, and for Fibrotest and Actitest results, were determined. Transferability of assay results between different analyzers was studied. Intra-patient reproducibility was assessed in 55 hospitalized patients. Fibrotest and Actitest reference ranges were determined in 300 blood donors (reference group). The stability of the parameters was affected by serum storage at -20 degrees C only. The impact of parameter analytical variability on Fibrotest and Actitest results was less than 10% and intra-patient reproducibility was acceptable (p > 0.05). The transferability between different analyzers of results of assays performed under the same standardized and calibration conditions was excellent. Fibrotest and Actitest reference ranges in blood donors were (mean+/-SE) 0.075+/-0.004 and 0.068+/-0.004, respectively. The low intra-laboratory and intra-patient variability in Fibrotest and Actitest results confirm Fibrotest and Actitest reliability.

Intra-individual fasting versuspostprandial variation of biochemical markers of liver fibrosis (FibroTest) and activity (ActiTest)

“…However, these markers should replace liver biopsy for routine estimation of liver injury in chronic liver diseases. The variability of the components and of FT-AT has been already studied for the pre-analytical and analytical steps [26], as well as for the interlaboratory variability [25]. …”

“…The logarithmic expression of results in the algorithm used for FibroTest and ActiTest calculations minimizes the influence of analytical imprecision, in particular for GGT, ALT and total bilirubin. Variability in the same patient of 2 FT and AT results at an interval of 4 days was also acceptable in spite of isolated wider variations in components results [26]. The influence of gender was observed for all parameters except haptoglobin.…”

“…The influence of gender was observed for all parameters except haptoglobin. ALT activity, as previously described, GGT activity, α 2 -macroglobulin, and haptoglobin levels were influenced by body mass index [26]. …”

“…For FT, AT, and their six components, the inter- and intra laboratory variability has been shown to be acceptable without significant consequence on predictive values when pre-analytical and analytical recommendations were applied [25,26]. …”

Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does it take two to tango?

“…Although the impact of patient age on the performance of direct serum markers has never been thoroughly investigated, the still limited available evidence suggests that the same panel of direct markers performs with higher sensitivity and specificity in a paediatric cohort35 than in an adult cohort34 of patients with NAFLD. Although the applicability and the interlaboratory reproducibility of different tests have been shown to be satisfactory for use in clinical practice,42 43 the interpretation of each test requires a critical analysis in order to avoid false-positive or false-negative results 44…”