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Prognostic Value of the TLM3 Biomarker Panel for Early Fibrosis Development in MASLD Within the General Population
Koen C van Son1,2,3, Jelle C B C de Jong4, Serdar Özsezen4
1Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Background & Aims:
Fibrotic MASLD is associated with increased morbidity and mortality, often remaining asymptomatic until advanced stages of disease. Predicting fibrosis onset and progression would improve risk stratification and treatment allocation. This study aims to investigate whether a previously identified fibrosis biomarker panel for active fibrogenesis (TLM3) can serve as a prognostic marker panel for fibrosis development in a population at cardiometabolic risk of fibrotic MASLD.
Methods:
The temporal dynamics of a molecular fibrosis gene expression signature associated with histologically proven fibrosis development was investigated in a diet-induced MASLD mouse model (LDLr-/-.Leiden). The corresponding proteins were measured in baseline serum from individuals at risk of MASLD from the general population HELIUS-cohort and correlated with established fibrosis proxies (ELF, VCTE and FIB4) at 7 years follow-up.
Results:
The molecular fibrosis gene expression signature was upregulated in a murine MASLD model before the onset of histopathological features of fibrosis. In humans, serum levels of IGFBP7, Ssc5D, Sema4D, VCAN, THBS1 and TNC at baseline correlated with fibrosis proxies at follow-up. IGFBP7 at baseline was able to predict new onset fibrosis, defined as ELF ≥ 9.8 at follow-up in participants with ELF < 9.8 at baseline, with an area under the curve (AUC) of 0.79 (95% CI: 0.64-0.94).
Conclusion:
Together, these findings indicate the potential predictive capacity of the TLM3 biomarker panel in early stages of MASLD-fibrosis, both in a murine model as well as in individuals from the general population at risk of MASLD.
Insights
A new biomarker panel (TLM3) shows promise in predicting early stages of metabolic dysfunction-associated steatotic liver disease (MASLD) fibrosis. This aids in identifying at-risk individuals for better fibrosis management.
Area of Science:
- Hepatology
- Biomarker Discovery
- Metabolic Syndrome
Background:
- Fibrotic MASLD significantly increases morbidity and mortality, often detected late.
- Early prediction of fibrosis is crucial for risk stratification and treatment.
Purpose of the Study:
- To evaluate the TLM3 biomarker panel's potential for predicting fibrosis development in individuals at risk for MASLD.
- To assess TLM3's prognostic capacity for early-stage MASLD fibrosis.
Main Methods:
- Investigated a fibrosis gene expression signature in a diet-induced MASLD mouse model.
- Measured serum protein levels of the TLM3 panel in a human cohort at risk for MASLD.
- Correlated baseline biomarker levels with fibrosis proxies (ELF, VCTE, FIB4) at 7-year follow-up.
Main Results:
- The fibrosis signature was upregulated in mice before histological fibrosis onset.
- Baseline serum levels of IGFBP7, Ssc5D, Sema4D, VCAN, THBS1, and TNC correlated with fibrosis proxies.
- IGFBP7 baseline levels predicted new-onset fibrosis with an AUC of 0.79.
Conclusions:
- The TLM3 biomarker panel demonstrates predictive capacity for early MASLD-fibrosis.
- Findings support TLM3's utility in both animal models and at-risk human populations.
- This panel may improve early detection and management of MASLD fibrosis.
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