Early identification of cirrhosis risk in type 2 diabetes using the Fibrosis-4 index: evidence from a large U.S. cohort

Cirrhosis remains a leading cause of liver-related morbidity and mortality and is often diagnosed only at advanced stages. Individuals with type 2 diabetes mellitus (T2DM) are at increased risk, yet systematic screening for early fibrosis is rarely implemented. We evaluated whether the Fibrosis-4 (FIB-4) index, a widely used non-invasive biomarker, can identify elevated cirrhosis risk near the time of T2DM diagnosis. We conducted a retrospective cohort study using the NIH All of Us Research Program database. Adults with newly diagnosed T2DM and laboratory data for FIB-4 calculation within ± 365 days of diagnosis were included. Cases were participants who subsequently developed cirrhosis; controls were those who did not. FIB-4 distributions were compared using Wilcoxon rank-sum tests. Cox proportional hazards models assessed the association between FIB-4 and time to cirrhosis. Discriminative ability was evaluated using receiver operating characteristic (ROC) analysis, and Kaplan–Meier curves compared time-to-event outcomes by FIB-4 category. Among 9,253 participants (136 cases, 9,117 controls), median FIB-4 was higher in cases (1.38; 95% CI: 1.25–1.48) than controls (1.00; 95% CI: 0.99–1.01; p < 0.001). Higher FIB-4 was associated with increased cirrhosis risk in Cox regression analyses (adjusted HR = 1.16 per 1‑unit increase; 95% CI 1.08–1.24; p < 0.001). ROC analysis yielded an AUROC of 0.66, indicating moderate discriminative ability, with an optimal cutoff of 1.23 derived for internal stratification. Kaplan–Meier analysis showed shorter time to cirrhosis for FIB-4 ≥ 1.23 (log-rank p < 0.001). FIB-4 measured near T2DM diagnosis may serve as an early signal for cirrhosis risk. Incorporating FIB-4 into diabetes care pathways could enable timely referral and intervention, improving long-term liver outcomes. Not applicable. FIB-4 scores are elevated at type 2 diabetes diagnosis among patients who later develop cirrhosis. FIB-4 demonstrates moderate discriminative ability for cirrhosis risk in patients with type 2 diabetes. Sensitivity and adjusted analyses confirm the robustness of FIB-4 associations with cirrhosis risk. FIB-4 may be a practical first-line, non-invasive liver screening tool in diabetes care. Early cirrhosis risk detection may improve MASLD outcomes in diabetes. This study demonstrates that FIB-4, a simple and low-cost biomarker, can identify early cirrhosis risk in individuals newly diagnosed with type 2 diabetes, addressing a critical gap in MASLD detection as a first-line risk stratification tool rather than a diagnostic test. These findings are particularly relevant for primary care and endocrinology providers managing high-risk populations. Incorporating FIB-4 into electronic health records and clinical decision support systems could enable earlier intervention and reduce long-term liver-related complications. Given moderate predictive performance and variability across racial groups, future implementation should include population-specific validation and strategies to ensure equitable access to screening. People with type 2 diabetes are at higher risk for liver disease, but this often goes unnoticed until serious damage has already occurred. In our study, we looked at whether a simple blood test called the Fibrosis-4 (FIB-4) index could help spot early signs of liver scarring (cirrhosis) in these patients. Using data from over 9,000 people in the NIH All of Us Research Program, we found that those who eventually developed cirrhosis had higher FIB-4 scores around the time they were first diagnosed with diabetes. This suggests that liver damage may already be starting when diabetes is diagnosed. The FIB-4 test uses routine lab results—age, liver enzymes, and platelet count—and is easy to calculate. It doesn’t require expensive imaging or invasive procedures. We also found that the test worked better in some racial groups than others, highlighting the need for more research to ensure fair and accurate screening for everyone. Our findings suggest that adding the FIB-4 test to regular diabetes care could help doctors catch liver problems earlier and take steps to prevent serious complications.