Metabolomic Profiling of Hepatitis B-Associated Liver Disease Progression: Chronic Hepatitis B, Cirrhosis, and Hepatocellular Carcinoma
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Information and Data Collection
2.2. Serum Preparation for Nuclear Magnetic Resonance (NMR)
2.3. 1H-NMR Data Processing and Multivariate Statistical Analysis
3. Results
3.1. The Clinical Characteristics of the Study Population of Patients with the Progression of HBV-Associated Liver Disease
3.2. The Identification of Serum Metabolites in Patients with the Progression of HBV-Associated Liver Disease
3.3. The Multivariate Analysis of Serum Metabolite Data from Patients with the Progression of HBV-Associated Liver Disease
3.4. Correlated Metabolites of Six Core Discriminatory Metabolites in the Progression of HBV-Associated Liver Disease
3.5. Metabolic Pathways Affected by the Progression of HBV-Associated Liver Disease
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Criteria | CHB (n = 64) | CHB-LC (n = 35) | CHB-HCC (n = 15) | p-Value |
---|---|---|---|---|
Age (years) | 49 (23–75) | 51 (32–74) | 51 (33–83) | 0.6551 |
Gender (Male) | 48 (75.0) | 24 (68.6) | 14 (93.3) | 0.2661 |
Hypertension | 9 (14.1) | 8 (22.9) | 3 (20.0) | 0.1889 |
Diabetes Mellitus | 10 (15.6) | 4 (11.4) | 2 (13.3) | 0.3528 |
Hyperlipidemia | 5 (7.8) | 2(5.7) | 1 (6.6) | 0.5002 |
Body Mass Index (kg/m2) | 24.8 (18.1–44.4) | 24.0 (18.1–29.0) | 23.1 (16.5–28.4) | 0.1778 |
Stiffness (kPa) | 5.85 (3.3–9.9) | 12.4 (14.7–46.4) | 13.0 (6.0–33.8) | <0.0001 |
Total Bilirubin (mg/dL) | 0.75 (0.2–12.7) | 0.95 (0.2–4.9) | 1.3 (0.4–19.9) | 0.02144 |
Albumin (mg/dL) | 4.2 (2.9–4.8) | 4.0 (2.2–5.2) | 2.9 (2.1–4.3) | 0.002864 |
AST (IU/dL) | 54 (12–2290) | 52.5 (20–1430) | 90 (51–369) | 0.01426 |
ALT (IU/dL) | 84 (4–2140) | 42.5 (15–1402) | 52 (11–759) | 0.2416 |
GGT (mg/dL) | 37 (11–767) | 53.5 (9–889) | 163 (13–535) | 0.02091 |
Platelet (103/μL) | 206 (106–465) | 167 (22–300) | 159 (64–360) | 0.007749 |
INR | 1.06 (0.93–1.37) | 1.16 (0.93–1.96) | 1.24 (0.96–2.27) | 0.005469 |
Creatinine (mg/dL) | 0.75 (0.46–4.29) | 0.72 (0.50–3.52) | 0.90 (0.36–5.11) | 0.3903 |
HBeAg (+) | 31 (48.4) | 15 (42.9) | 5 (33.3) | 0.5657 |
HBV DNA (IU/L) | 2 × 106 (0–1 × 109) | 7 × 105 (0–2 × 108) | 1 × 106 (4.0 × 101–1 × 107) | 0.2458 |
Metabolites | f. Value | p Value | FDR | Fisher’s LSD |
---|---|---|---|---|
Pyruvate | 52.265 | 9.27 × 10−17 | 5.84 × 10−15 | 2-1; 3-1; 3-2 |
Tyrosine | 24.954 | 1.09 × 10−9 | 3.43 × 10−18 | 2-1; 3-1; 3-2 |
Lactate | 17.216 | 3.02 × 10−7 | 6.35 × 10−6 | 2-1; 3-1; 3-2 |
Propylene glycol | 15.883 | 8.46 × 10−7 | 1.33 × 10−5 | 2-1; 3-1 |
Isoleucine | 15.075 | 1.59 × 10−6 | 2.01 × 10−5 | 1-3; 2-3 |
Taurine | 14.629 | 2.27 × 10−6 | 2.38 × 10−5 | 2-1; 1-3; 2-3 |
TMAO | 13.295 | 6.60 × 10−6 | 5.19 × 10−5 | 2-1; 3-1 |
Histamine | 8.857 | 0.00026851 | 0.0018796 | 1-3; 2-3 |
2-Hydroxybutyrate | 8.0749 | 0.00052966 | 0.0033368 | 1-3; 2-3 |
N-Nitrosodimethylamine | 6.6211 | 0.0019149 | 0.010967 | 1-3; 2-3 |
Mannitol | 5.8654 | 0.0037796 | 0.019843 | 1-3; 2-3 |
Glutamate | 5.7421 | 0.0042263 | 0.020481 | 1-3; 2-3 |
Valine | 5.3763 | 0.0058952 | 0.025792 | 1-2; 1-3 |
Glutamine | 5.3315 | 0.006141 | 0.025792 | 1-3; 2-3 |
Tryptophan | 4.7257 | 0.010707 | 0.042159 | 1-3; 2-3 |
Glucitol | 4.6325 | 0.011668 | 0.043241 | 2-3 |
5,6-Dihydrothymine | 13.607 | 5.13 × 10−6 | 4.62 × 10−5 | 2-1; 3-1; 3-2 |
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Oh, J.; Baritugo, K.-A.G.; Kim, J.; Park, G.; Han, K.J.; Lee, S.; Sung, G.-H. Metabolomic Profiling of Hepatitis B-Associated Liver Disease Progression: Chronic Hepatitis B, Cirrhosis, and Hepatocellular Carcinoma. Metabolites 2025, 15, 504. https://doi.org/10.3390/metabo15080504
Oh J, Baritugo K-AG, Kim J, Park G, Han KJ, Lee S, Sung G-H. Metabolomic Profiling of Hepatitis B-Associated Liver Disease Progression: Chronic Hepatitis B, Cirrhosis, and Hepatocellular Carcinoma. Metabolites. 2025; 15(8):504. https://doi.org/10.3390/metabo15080504
Chicago/Turabian StyleOh, Junsang, Kei-Anne Garcia Baritugo, Jayoung Kim, Gyubin Park, Ki Jun Han, Sangheun Lee, and Gi-Ho Sung. 2025. "Metabolomic Profiling of Hepatitis B-Associated Liver Disease Progression: Chronic Hepatitis B, Cirrhosis, and Hepatocellular Carcinoma" Metabolites 15, no. 8: 504. https://doi.org/10.3390/metabo15080504
APA StyleOh, J., Baritugo, K.-A. G., Kim, J., Park, G., Han, K. J., Lee, S., & Sung, G.-H. (2025). Metabolomic Profiling of Hepatitis B-Associated Liver Disease Progression: Chronic Hepatitis B, Cirrhosis, and Hepatocellular Carcinoma. Metabolites, 15(8), 504. https://doi.org/10.3390/metabo15080504