Longitudinal Serum Proteomic and Metabolomic Profiling of Chronic Hepatitis B During Tenofovir Disoproxil Fumarate Therapy
| Author | Peixia Lin | en |
| Author | Zhaojun Jin | en |
| Author | Yimin Chen | en |
| Author | Jiaxin Jin | en |
| Author | Min Deng | en |
| Author | Dahai Wei | en |
| Issued Date | 2026-12-31 | en |
| Abstract | Background: Hepatitis B virus (HBV) infection remains a major global health burden. Although tenofovir disoproxil fumarate (TDF) effectively suppresses HBV replication, its precise mechanism of action remains incompletely understood. Objectives: This exploratory study aimed to track longitudinal serum proteomic and metabolomic alterations associated with effective TDF therapy in patients with chronic hepatitis B (CHB) and to elucidate their potential roles in mediating physiological processes and disease progression across different stages of therapy. Methods: Using data-independent acquisition (DIA) proteomics and untargeted metabolomics with ultra-high-performance liquid chromatography-quadrupole-Orbitrap tandem mass spectrometry (UHPLC-Q-Orbitrap MS/MS), we analyzed serum protein and metabolite profiles from 18 patients with CHB receiving TDF therapy. Samples were collected before treatment initiation (baseline, CO) and at weeks 12 (TDF-12) and 24 (TDF-24) of therapy. Results: Proteomic analysis identified 83 and 104 differentially expressed proteins at TDF-12 and TDF-24, respectively. Metabolomic profiling revealed 101 and 105 significantly altered metabolites at the same time points. Notably, at the predefined treatment response endpoint (week 24; HBV DNA < 30 IU/mL), integrated pathway analysis showed the greatest enrichment in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Key molecules, including fatty acid-binding protein 5 (FABP5), apolipoprotein A-V (APOA5), 3-hydroxybutyric acid (BHB), and leukotriene B4 (LTB4), were identified as candidate biomarkers warranting further investigation. Conclusions: To our knowledge, this is the first study to use an integrated, untargeted metabolomic and proteomic approach to characterize alterations in metabolites and proteins across different stages of TDF treatment in patients with CHB. These findings may provide a foundation for generating new hypotheses regarding the molecular mechanisms underlying the therapeutic response to TDF. | en |
| DOI | https://doi.org/10.5812/hepatmon-171094 | en |
| URI | https://brieflands.com/journals/hepatmon/articles/171094 | en |
| Keyword | Chronic Hepatitis B | en |
| Keyword | Tenofovir Disoproxil Fumarate | en |
| Keyword | Serum Metabolomics And Proteomics | en |
| Keyword | PPAR Signaling Pathway | en |
| Publisher | Brieflands | en |
| Title | Longitudinal Serum Proteomic and Metabolomic Profiling of Chronic Hepatitis B During Tenofovir Disoproxil Fumarate Therapy | en |
| Type | Research Article | en |