A metabolite-augmented FIB-4 machine learning panel achieves superior liver fibrosis staging in chronic liver disease
Accurate, non-invasive liver fibrosis detection is essential for chronic liver disease management, particularly with rising metabolic dysfunction-associated liver disease (MASLD) and chronic hepatitis B (CHB). While the Fibrosis-4 (FIB-4) index is widely used, its performance for advanced fibrosis is limited. We develop Met-FIB using metabolomics and machine learning, integrating FIB-4 parameters (age, aspartate aminotransferase, alanine aminotransferase, and platelet count) with tyrosine and taurocholic acid identified in a CHB discovery cohort (n = 3,251). Validation includes one CHB cohort (n = 729) and two MASLD cohorts (n = 149, n = 155). Met-FIB outperforms FIB-4, FibroScan, and other serum markers across all fibrosis stages. In CHB, Met-FIB achieves 96.3% rule-out sensitivity and 85.4% rule-in specificity for significant fibrosis, with rule-in specificity reaching 98.6% and 98.8% for advanced fibrosis and cirrhosis. In MASLD, corresponding values are 93.9% and 90.2% for significant fibrosis, with >97.9% specificity for late-stage disease. Met-FIB demonstrates clinical utility for non-invasive fibrosis staging across diverse etiologies.
Authors
- Mengci Li (ORCID: https://orcid.org/0000-0002-8181-2232)
- Keke Ding (ORCID: https://orcid.org/0000-0002-5261-4843)
- Xianzhang Huang (ORCID: https://orcid.org/0000-0003-4320-9181)
- Xinliang Zhang (ORCID: https://orcid.org/0000-0001-8513-3328)
- Zheng Zhang (ORCID: https://orcid.org/0000-0003-1470-6998)
- Huanming Xiao (ORCID: https://orcid.org/0000-0002-8739-0720)
- Tao Sun (ORCID: https://orcid.org/0000-0003-4163-1098)
- Alice Pik-Shan Kong
- V. W.S. Wong
- Kejun Zhou
- Xiaoning Wang
- Tianbiao Yang
- Xufei Peng
- Ping Liu
- Yuanyuan Chen
- Xiaoling Chi
- Wei Jia
- Tianlu Chen
- Quan Liu
- Xin Deng
- Guoxiang Xie
Institutions
- Ningbo University (CN)
- Guangzhou University of Chinese Medicine (CN)
- Sun Yat-sen University (CN)
- Shenzhen Institute of Information Technology (CN)
- Chinese University of Hong Kong (HK)
- Anhui Medical University (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Shanghai Sixth People's Hospital (CN)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- Shuguang Hospital (CN)
- Second Affiliated Hospital of Anhui Medical University (CN)
- Shenzhen Third People’s Hospital (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1016/j.xcrm.2026.102726
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Research Grants Council, University Grants Committee
- Science and Technology Department of Zhejiang Province