• Andrew D Schreiner, Jingwen Zhang, William P Moran, David G Koch, Sherry Livingston, Chloe Bays, Justin Marsden, Patrick D Mauldin, and Mulugeta Gebregziabher.
• Medical University of South Carolina, Charleston, SC, USA. schrein@musc.edu.
• J Gen Intern Med. 2023 Aug 1; 38 (11): 245324602453-2460.

BackgroundAlanine aminotransferase (ALT) has long provided a cue for chronic liver disease (CLD) diagnostic evaluation, but the Fibrosis-4 Index (FIB-4), a serologic score used for predicting advanced fibrosis risk in CLD, may provide an alternative signal.ObjectiveCompare the predictive performance of FIB-4 with ALT for severe liver disease (SLD) events while adjusting for potential confounders.DesignRetrospective cohort study of primary care electronic health record data from 2012 to 2021.PatientsAdult primary care patients with at least two sets of ALT and other lab values necessary for calculating two unique FIB-4 scores, excluding those patients with an SLD prior to their index FIB-4 value.Main MeasuresThe occurrence of an SLD event, a composite of cirrhosis, hepatocellular carcinoma, and liver transplantation, was the outcome of interest. Categories of ALT elevation and FIB-4 advanced fibrosis risk were the primary predictor variables. Multivariable logistic regression models were developed to evaluate the association of FIB-4 and ALT with SLD, and the areas under the curve (AUC) for each model were compared.Key ResultsThe cohort of 20,828 patients included 14% with an abnormal index ALT (≥40 IU/L) and 8% with a high-risk index FIB-4 (≥2.67). During the study period, 667 (3%) patients suffered an SLD event. Adjusted multivariable logistic regression models demonstrated an association between high-risk FIB-4 (OR 19.34; 95%CI 15.50-24.13), persistently high-risk FIB-4 (OR 23.85; 95%CI 18.24-31.17), abnormal ALT (OR 7.07; 95%CI 5.81-8.59), and persistently abnormal ALT (OR 7.58; 95%CI 5.97-9.62) with SLD outcomes. The AUC of the index FIB-4 (0.847, p < 0.001) and combined FIB-4 (0.849, p < 0.001) adjusted models exceeded the index ALT adjusted model (0.815).ConclusionsHigh-risk FIB-4 scores demonstrated superior performance compared to abnormal ALT in predicting future SLD outcomes.© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.

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