Interactive effects of platelet-to-lymphocyte ratio and FIB-4 index for risk stratification of liver fibrosis in metabolic dysfunction-associated steatotic liver disease: performance assessment comparing interactive models with traditional composite scores.

BACKGROUND: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease globally, and the accurate assessment of hepatic fibrosis is crucial for guiding therapeutic decisions. This study aimed to investigate the diagnostic value of the interaction between the platelet-to-lymphocyte ratio (PLR) and the Fibrosis-4 (FIB-4) index for predicting significant hepatic fibrosis in patients with MASLD.

METHODS: This retrospective study analyzed 358 MASLD patients who underwent liver biopsy at two university-affiliated hospitals between January 2020 and December 2024. Based on histopathology, significant fibrosis was defined as fibrosis stage ≥F2. Four predictive models were constructed: PLR alone, FIB-4 alone, a combined PLR + FIB-4 model, and a PLR × FIB-4 interaction model. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI), and compared against traditional non-invasive scores.

RESULTS: Among the 358 patients, 168 (46.9%) had significant fibrosis. PLR was positively correlated with the FIB-4 index (r = 0.542, p < 0.001), and this correlation strengthened with increasing fibrosis severity. The interaction model demonstrated the best diagnostic performance, yielding an AUC of 0.824 (95% CI: 0.778-0.870) for significant fibrosis, with 78.6% sensitivity and 78.9% specificity. For predicting advanced fibrosis (≥F3), its AUC was 0.852 (95% CI: 0.803-0.901). Compared to the APRI-FIB-4 composite score, the interaction model significantly improved reclassification (NRI: 0.142, p = 0.008) and discrimination (IDI: 0.067, p = 0.003). A three-tier risk stratification strategy based on the model also showed excellent clinical utility (p for trend <0.001). Bootstrap internal validation (n = 1,000) confirmed the model's stability and calibration.

CONCLUSION: The PLR × FIB-4 interaction model is a novel and effective tool for the non-invasive assessment of hepatic fibrosis in patients with MASLD. This model significantly outperforms individual markers and traditional scoring systems and demonstrates excellent risk stratification capability, holding significant promise for supporting individualized clinical management.