Elevated serum TIM4 is associated with disease severity and serves as a potential predictive biomarker in chronic hepatitis B

BACKGROUND: Chronic hepatitis B (CHB), caused by persistent hepatitis B virus infection, is largely immune-mediated, and biomarkers to identify patients at risk for severe disease are needed. METHODS: In a hospital-based cross-sectional study at the Department of Infectious Disease, The First Hospital of Changsha City (January 2024-October 2025), we enrolled 119 CHB patients (89 non-severe and 30 severe) and 41 healthy controls. Serum T-cell immunoglobulin and mucin domain-containing protein 4 (TIM4) was quantified by enzyme-linked immunosorbent assay (ELISA), and associations with routine laboratory indices and severe CHB were evaluated using correlation analyses, logistic regression, and receiver operating characteristic (ROC) curves. RESULTS: Serum TIM4 was significantly higher in CHB patients than in controls (p < 0.01) and was higher in severe than in non-severe CHB (p < 0.05). TIM4 correlated positively with alanine aminotransferase, aspartate aminotransferase, and bilirubin levels (p < 0.05) and negatively correlated with platelet count (p < 0.01). In both univariate and multivariate (age- and sex-adjusted) analyses, TIM4 was associated with severe CHB (OR = 1.005, p = 0.022). ROC analysis demonstrated an AUC of 0.640 (p = 0.022). CONCLUSION: Serum TIM4 levels are elevated in CHB and are associated with disease severity. TIM4 may serve as a supplementary biomarker for severity assessment; however, further multi-center and longitudinal studies are required to confirm its clinical value. TRIAL REGISTRATION: Not applicable. This is a cross-sectional study and was therefore not registered as a clinical trial.