Abstract
The Fibrosis-4 Index (FIB-4)non-invasively assesses fibrosis risk in chronic liver disease (CLD), but underdiagnosis limits FIB-4's application in primary care. To evaluate the association of FIB-4 risk with hazard of severe liver outcomes in primary care patients with and without diagnosed CLD. Retrospective cohort study of primary care data from 2007 to 2018. Adult patients with qualifying aminotransferase and platelet count results were included and a single FIB-4 score was calculated for each patient using the first of these values. Patients with a CLD diagnosis or outcome prior to their FIB-4 score were excluded. FIB-4 advanced fibrosis risk categorization (low, indeterminate, and high) was the primary predictor variable. Patients were followed from FIB-4 score to a severe liver outcome, a composite of cirrhosis, liver transplantation, and hepatocellular carcinoma. We analyzed the association of FIB-4 risk categories with hazard risk of a severe liver outcome using stratified Cox regression models, stratifying patients by known CLD. A total of 20,556 patients were followed for a mean 2,978 days (SD 1,201 days), and 4% of patients experienced a severe liver outcome. Of patients with low-, indeterminate-, and high-risk FIB-4 scores, 2%, 4%, and 20% suffered a severe liver outcome, respectively. In the overall adjusted model, high-risk FIB-4 scores were associated with hazard of severe liver disease (HR 6.64; 95% CI 5.58-7.90). High-risk FIB-4 scores were associated with severe liver outcomes for patients with known NAFLD (HR 7.32; 95% CI 3.44-15.58), other liver disease (HR 11.39; 95% CI 8.53-15.20), and no known CLD (HR 4.05; 95% CI 3.10-5.28). High-risk FIB-4 scores were strongly associated with risk of severe liver outcomes in patients with and without known CLD. Comprehensive FIB-4 application in primary care may signal silently advancing liver fibrosis.
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