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Age- and sex-specific reference values for FIB-4 derived from the Nordic Reference Interval Project (NORIP)
Lena Hamelius1, Gunnar Nordin1, Per Bjellerup1
1Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Introduction:
The Fibrosis-4 (FIB-4) index is a non-invasive biomarker that is widely used to assess liver fibrosis. A limitation is that the enzyme methods (aspartate transaminase (AST) and alanine transaminase (ALT)) are not specified in studies. The aim of the present study was to define reference values for FIB-4 index using Nordic Reference Interval Project data where the results for P-AST and P-ALT are traceable to the IFCC reference measurement procedures.
Material And Methods:
FIB-4 values from 1161 subjects (550 males and 611 females) in the NORIP study were used to calculate reference intervals for the index. The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines.
Results:
Age (18-<39.9, 40-59.9 and 60-85 years) and sex-specific reference intervals were calculated. Of the components used to calculate the FIB-4 index the age had the greatest impact. In the cohort older than 60 years, 7.5% of the females and 18.2% of the males were above the 2.67 limit for high risk of advanced fibrosis. In the same age group 84.2% of the females and 77.6% of the males had FIB-4 values above the 1.3 limit for intermediate risk and further evaluation required. These are very high proportions which means that a very large proportion of the patients will have false positive results when testing populations with a low disease prevalence.
Conclusion:
FIB-4 index increases with age, potentially leading to overestimation of fibrosis in elderly patients if age specific decision values are not used.
