Validated Early Detection Metrics Reduce the Population Requiring Liver Fibrosis Screening

Current guideline-defined indicators for fibrosis screening identify a large proportion of the general population, burdening health care resources. We aimed to evaluate and refine indicators for fibrosis screening.

We included adults aged 18-80 years from the National Health and Nutrition Examination Survey 2017-2020 data with a body mass index ≥18.5 kg/m² without excessive alcohol use. We obtained the weighted proportions of individuals across stratified screening indicators and targeted only subgroups with ≥10% liver stiffness measurement (LSM ≥8 kPa) risk for screening. These refined criteria were validated and linked with liver-related events in 4 general-population cohorts.

The derivation cohort included 5904 adults (8.9% LSM ≥8 kPa). Current guidelines identified 60%-76% as screening-eligible, yielding an LSM ≥8 kPa prevalence of 11%-14% among those screening eligible and 2% among those not eligible. Our refined strategy targeted 22% for screening, increasing prevalence to 28% among those screening-eligible, while maintaining low prevalence (4%) in those not eligible. In the pooled validation cohort (n = 13,295; 7.0% LSM ≥8 kPa), 14% met the refined criteria. Results remained consistent across thresholds: LSM ≥8, ≥10, and ≥12 kPa prevalence among screening-eligible individuals was 22%, 13%, and 8%, respectively, and 4%, 2%, and 1% among those not eligible. In the UK Biobank (n = 282,852), individuals meeting the refined criteria had an approximately 6-fold higher 10-year risk of incident cirrhosis (0.99% vs 0.18%) and liver-related death (0.40% vs 0.07%).

Current recommendations target 60%-76% of adults for fibrosis screening. Our refined strategy reduced this to 10%-22%, achieving significantly higher disease prevalence among those eligible for screening, while maintaining a very low risk of increased LSM or liver-related events in those not eligible for screening.