FIB-4 and Severe Liver Disease Outcomes in Primary Care: A Stratified Cox Analysis

Abstract

Background: The Fibrosis-4 Index (FIB-4) non-invasively assesses fibrosis risk in chronic liver disease, but underdiagnosis limits FIB-4’s application in primary care. This study evaluates the association of FIB-4 risk with severe liver outcomes in primary care patients with and without diagnosed chronic liver disease. Methods: This retrospective cohort study of primary care data from 2007 to 2018 Included adult patients with qualifying aminotransferase and platelet count results. A single FIB-4 score was calculated for each patient using the first of these values. Patients with a chronic liver disease 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 with hazard risk of a severe liver outcome using stratified Cox regression models, stratifying patients by known chronic liver disease. Findings: 20,556 patients were followed for a mean 2,978 days (8·2 years; 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 6·54; 95% CI 5·49-7·77). High risk FIB-4 scores were associated with severe liver outcomes for patients with known NAFLD (HR 7·71; 95% CI 3·62-16·45), other liver disease (HR 11·12; 95% CI 8·33-14·82), and no known chronic liver disease (HR 4·04; 95% CI 3·10-5·28). Interpretation: High risk FIB-4 scores were strongly associated with risk of severe liver outcomes in patients with and without known chronic liver disease. Comprehensive FIB-4 application in primary care may signal silently advancing liver fibrosis. Funding Information: National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDKK23DK118200 PI: Schreiner). Declaration of Interests: All authors report no conflicts of interest with this work. Ethics Approval Statement: The Institutional Review Board at the Medical University of South Carolina (MUSC) approved this study.