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

**Authors:** Yong Deng, Juan Mo, Liu Chun, Ning Wang, Jing Cao, Amy Micaela Montufar Mejia, Domenica Camila Montufar Mejia, Muhammad Adil Malik, Dama Faniriantsoa Henrio Marcellin, Xiaowu Li, Zhong Chen

PMC · DOI: 10.1186/s12879-026-12709-9 · BMC Infectious Diseases · 2026-02-04

## TL;DR

The study found that higher levels of a protein called TIM4 in the blood are linked to more severe chronic hepatitis B, suggesting it could help predict disease severity.

## Contribution

The study identifies TIM4 as a potential new biomarker for assessing severity in chronic hepatitis B patients.

## Key findings

- Serum TIM4 levels were significantly higher in chronic hepatitis B patients compared to healthy controls.
- TIM4 was positively correlated with liver damage markers like ALT, AST, and bilirubin.
- TIM4 showed moderate predictive value for severe CHB with an AUC of 0.640.

## Abstract

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.

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.

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).

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.

Not applicable. This is a cross-sectional study and was therefore not registered as a clinical trial.

## Linked entities

- **Proteins:** TIMD4 (T cell immunoglobulin and mucin domain containing 4)
- **Diseases:** chronic hepatitis B (MONDO:0005344), hepatitis B (MONDO:0005344)

## Full-text entities

- **Genes:** TIMD4 (T cell immunoglobulin and mucin domain containing 4) [NCBI Gene 91937] {aka SMUCKLER, TIM4}
- **Diseases:** chronic hepatitis B. (MESH:D019694)

## Full text

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## Figures

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## References

3 references — full list in the complete paper: https://tomesphere.com/paper/PMC12958702/full.md

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Source: https://tomesphere.com/paper/PMC12958702