{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Schreiner AD"],"funding":["NCATS NIH HHS","NIDDK NIH HHS"],"pagination":["917-922"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11096263"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["58(9)"],"pubmed_abstract":["<h4>Background and goals</h4>The Fibrosis-4 Index (FIB-4) has demonstrated a strong association with severe liver disease (SLD) outcomes in primary care, but previous studies have only evaluated this relationship using 1 or 2 FIB-4 scores. In this study, we determined the association of FIB-4 as a time-varying covariate with SLD risk using time-dependent Cox regression models.<h4>Study</h4>This retrospective cohort study included primary care patients with at least 2 FIB-4 scores between 2012 and 2021. The outcome was the occurrence of an SLD event, a composite of cirrhosis, complications of cirrhosis, hepatocellular carcinoma, and liver transplantation. The primary predictor was FIB-4 advanced fibrosis risk, categorized as low-(<1.3), indeterminate-(1.3≤FIB to 4<2.67), and high-risk (≥2.67). FIB-4 scores were calculated and the index, last, and maximum FIB-4s were identified. Time-dependent Cox regression models were used to estimate hazard ratios (HR) and their corresponding 95% CI with adjustment for potentially confounding covariates.<h4>Results</h4>In the cohort, 20,828 patients had a median of 5 (IQR: 3 to 11) FIB-4 scores each and 3% (n=667) suffered an SLD outcome during follow-up. Maximum FIB-4 scores were indeterminate-risk for 34% (7149) and high-risk for 24% (4971) of the sample, and 32% (6692) of patients had an increase in fibrosis risk category compared with their index value. The adjusted Cox regression model demonstrated an association between indeterminate- (hazard ratio 3.21; 95% CI 2.33-4.42) and high-risk (hazard ratio 20.36; 95% CI 15.03-27.57) FIB-4 scores with SLD outcomes.<h4>Conclusions</h4>Multiple FIB-4 values per patient are accessible in primary care, FIB-4 fibrosis risk assessments change over time, and high-risk FIB-4 scores (≥2.67) are strongly associated with severe liver disease outcomes when accounting for FIB-4 as a time-varying variable."],"journal":["Journal of clinical gastroenterology"],"pubmed_title":["FIB-4 as a Time-varying Covariate and Its Association With Severe Liver Disease in Primary Care: A Time-dependent Cox Regression Analysis."],"pmcid":["PMC11096263"],"funding_grant_id":["UL1 TR001450","R03 DK129558","K23 DK118200","P30 DK123704"],"pubmed_authors":["Schreiner AD","Livingston S","Bays C","Zhang J","Mauldin PD","Marsden J","Koch DG","Moran WP","Gebregziabher M"],"additional_accession":[]},"is_claimable":false,"name":"FIB-4 as a Time-varying Covariate and Its Association With Severe Liver Disease in Primary Care: A Time-dependent Cox Regression Analysis.","description":"<h4>Background and goals</h4>The Fibrosis-4 Index (FIB-4) has demonstrated a strong association with severe liver disease (SLD) outcomes in primary care, but previous studies have only evaluated this relationship using 1 or 2 FIB-4 scores. In this study, we determined the association of FIB-4 as a time-varying covariate with SLD risk using time-dependent Cox regression models.<h4>Study</h4>This retrospective cohort study included primary care patients with at least 2 FIB-4 scores between 2012 and 2021. The outcome was the occurrence of an SLD event, a composite of cirrhosis, complications of cirrhosis, hepatocellular carcinoma, and liver transplantation. The primary predictor was FIB-4 advanced fibrosis risk, categorized as low-(<1.3), indeterminate-(1.3≤FIB to 4<2.67), and high-risk (≥2.67). FIB-4 scores were calculated and the index, last, and maximum FIB-4s were identified. Time-dependent Cox regression models were used to estimate hazard ratios (HR) and their corresponding 95% CI with adjustment for potentially confounding covariates.<h4>Results</h4>In the cohort, 20,828 patients had a median of 5 (IQR: 3 to 11) FIB-4 scores each and 3% (n=667) suffered an SLD outcome during follow-up. Maximum FIB-4 scores were indeterminate-risk for 34% (7149) and high-risk for 24% (4971) of the sample, and 32% (6692) of patients had an increase in fibrosis risk category compared with their index value. The adjusted Cox regression model demonstrated an association between indeterminate- (hazard ratio 3.21; 95% CI 2.33-4.42) and high-risk (hazard ratio 20.36; 95% CI 15.03-27.57) FIB-4 scores with SLD outcomes.<h4>Conclusions</h4>Multiple FIB-4 values per patient are accessible in primary care, FIB-4 fibrosis risk assessments change over time, and high-risk FIB-4 scores (≥2.67) are strongly associated with severe liver disease outcomes when accounting for FIB-4 as a time-varying variable.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2026-06-03T23:29:41.571Z","creation":"2026-05-03T03:11:22.401Z"},"accession":"S-EPMC11096263","cross_references":{"pubmed":["37983873"],"doi":["10.1097/MCG.0000000000001935","10.1097/mcg.0000000000001935"]}}