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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.

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The Fibrosis-4 (FIB-4) index, a liver fibrosis biomarker, shows increased values with age. Using age-specific cutoffs is crucial to avoid overestimating fibrosis in older individuals.

Keywords:
B-PlateletsFIB-4P-ALTP-ASTliver fibrosisreference interval

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Area of Science:

  • Clinical Biochemistry
  • Hepatology
  • Biomarker Research

Background:

  • The Fibrosis-4 (FIB-4) index is a widely used non-invasive biomarker for assessing liver fibrosis.
  • A limitation of current FIB-4 index use is the lack of specified enzyme methods (aspartate transaminase (AST) and alanine transaminase (ALT)) in many studies.
  • Defining accurate reference values is essential for reliable FIB-4 index interpretation.

Purpose of the Study:

  • To establish age- and sex-specific reference intervals for the FIB-4 index.
  • To utilize data from the Nordic Reference Interval Project (NORIP) with traceable enzyme measurements.
  • To address the impact of age on FIB-4 index values and potential misinterpretations.

Main Methods:

  • Calculated reference intervals for the FIB-4 index using data from 1161 subjects in the NORIP study.
  • Determined 2.5th and 97.5th percentiles according to International Federation of Clinical Chemistry guidelines.
  • Analyzed age- and sex-specific reference intervals, with age categorized into 18-<39.9, 40-59.9, and 60-85 years.

Main Results:

  • Age was identified as the most significant factor influencing FIB-4 index values.
  • In individuals over 60 years, a substantial percentage exceeded thresholds for high risk (females: 7.5%, males: 18.2%) and intermediate risk (females: 84.2%, males: 77.6%).
  • These high proportions suggest a significant potential for false positives in low-prevalence populations.

Conclusions:

  • The FIB-4 index demonstrates a clear increase with advancing age.
  • Failure to implement age-specific decision values can lead to the overestimation of liver fibrosis in elderly patients.
  • Establishing age-stratified reference ranges is critical for accurate FIB-4 index interpretation in clinical practice.