Blood metabolic panels for identifying significant fibrosis and inflammation in patients with MASLD.

Journal: Cell reports. Medicine
Published Date: Dec 19, 2025

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) remains a prevalent condition with limited diagnostic and therapeutic options. This study aims to identify metabolic signatures of disease progression and develop non-invasive diagnostic models through three independent cohorts (including two cohorts confirmed by biopsy and one cohort confirmed by ultrasound) involving 293 participants for detecting significant fibrosis (≥F2) and mild to severe inflammatory activity (≥I2) using multiple machine learning techniques. The fibrosis panel shows area under the receiver operating characteristic curve (AUROC) of 0.928 (95% confidence interval [CI]: 0.835-0.978), 0.829 (0.732-0.902), and 0.806 (0.724-0.872) in the discovery cohort, validation cohort 1, and validation cohort 2, respectively, outperforming the fibrosis-4 index (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), non-alcoholic fatty liver disease fibrosis score (NFS), liver stiffness measurement (LSM), and combination of hoMa, Ast and CK18 (MACK-3). The inflammation panel achieves AUROCs of 0.894 (0.791-0.957) and 0.776 (0.673-0.859) in the discovery cohort and validation cohort 1, respectively. The key metabolites guanidinoacetic acid (GAA) and sebacic acid (SA) demonstrate therapeutic efficacy in mice. These validated panels provide accurate stratification of MASLD severity, and GAA/SA offer therapeutic potential, advancing both diagnosis and treatment strategies.

Authors

  • Yan Huang
    Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX.
  • Jiaqi Li
    Department of Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China.
  • Shuying Song
    Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Bingying Du
    Department of Neurology, First Affiliated Hospital of Naval Medical University, Shanghai, China.
  • Yutang Cao
    School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Yangyang Wang
  • Haoshuang Fu
    Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Tianhui Zhou
    Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Shuwu Yu
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Yameng Liu
    School of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, People's Republic of China.
  • Kanglong Wang
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Zhujun Cao
    Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: [email protected].
  • Xiaozhen Guo
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: [email protected].
  • Cen Xie
    Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: [email protected].
  • Qing Xie
    Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Keywords

No keywords available for this article.

External Resources

Popular Topics
Recent Journals