Thrombospondin-2 as a Predictive Biomarker for Hepatocellular Carcinoma after Hepatitis C Virus Elimination by Direct-Acting Antiviral
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Regimens of DAA Treatment
2.3. Patient Follow-Up
2.4. Enzyme-Linked Immunosorbent Assay (ELISA) of Serum TSP-2
2.5. Statistical Analysis
3. Results
3.1. Serum TSP-2 Levels Are Capable of Identifying CHC Patients Who Have a High Risk of HCC Development after HCV Elimination by DAA Treatment
3.2. Serum TSP-2 Levels Reflect Liver Fibrosis and Inflammation in CHC Patients after HCV Elimination by DAA Treatment
3.3. The AFT Score Composed of AFP, TSP-2 and the FIB-4 Index Stratifies Patients According to the HCC Risk after DAA Treatment
3.4. The TSP-2 and AFT Scores Stratified Patients According to HCC Risk in the Validation Cohort
3.5. Serum TSP-2 Level Identifies Patients with a High Risk of HCC Occurrence among Patients with FIB-4 Index < 3.25
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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Factor | Unit | All (N = 524) | Missing (N) | Non HCC (N = 500) | HCC (N = 24) | p Value |
---|---|---|---|---|---|---|
Age | Years Old | 70 (62–77) | 0 | 70 (61–76) | 71 (65–79) | 0.171 |
Sex | Male/Female | 204/320 | 0 | 192/308 | 12/12 | 0.255 |
HCV Group | 1/2/Other | 406/117/1 | 0 | 386/113/1 | 20/4/0 | 0.771 |
HCV-RNA(Pre) | Log IU/mL | 6.2 (5.6–6.5) | 2 | 6.2 (5.6–6.5) | 6.2 (5.4–6.6) | 0.976 |
BMI(Pre) | kg/m2 | 22.4 (20.4–24.3) | 29 | 22.4 (20.4–24.3) | 22.9 (20.6–26.0) | 0.322 |
WBC | /μL | 4700 (3890–5680) | 48 | 4700 (3900–5690) | 4290 (3530–5650) | 0.409 |
Hb | g/dL | 13.1 (12.0–14.2) | 48 | 13.1 (12.0–14.2) | 12.2 (10.7–13.7) | 0.071 |
Plt | ×104/μL | 16.8 (13.4–20.9) | 1 | 16.9 (13.5–21.0) | 13.8 (10.4–20.0) | 0.046 |
AST | U/L | 23 (19–28) | 1 | 23 (19–28) | 27 (24–34) | 0.083 |
ALT | U/L | 17 (12–24) | 1 | 17 (12–24) | 20 (15–27) | 0.367 |
T-bil | mg/dL | 0.7 (0.6–1.0) | 1 | 0.7 (0.6–1.0) | 0.8 (0.6–1.0) | 0.030 |
eGFR | mL/min/1.73 m2 | 68.9 (60–80) | 48 | 69 (60–80) | 66.3 (60.9–80.4) | 0.742 |
CRP | mg/dL | 0.1 (0.02–0.1) | 113 | 0.1 (0.02–0.1) | 0.1 (0.05–0.1) | 0.149 |
HbA1c | % | 5.5 (5.2–5.9) | 75 | 5.5 (5.2–5.9) | 5.3 (5.0–5.8) | 0.725 |
Alb | g/dL | 4.1 (3.9–4.3) | 8 | 4.1 (3.9–4.3) | 4.0 (3.7–4.2) | 0.011 |
Hyaluronic Acid | ng/mL | 84 (39–163) | 184 | 81 (38–156) | 149 (103–339) | 0.031 |
AFP | ng/mL | 4.0 (2.7–5.9) | 16 | 4.0 (2.6–5.5) | 6.0 (3.3–10) | <0.0001 |
DCP | mAU/mL | 18 (14–21) | 160 | 18 (14–21) | 16 (11–20) | 0.386 |
FIB-4 index | 2.3 (1.7–3.2) | 1 | 2.3 (1.6–3.2) | 3.5 (2.4–4.3) | 0.0007 | |
TSP-2 | ng/μL | 44.9 (29.0–72.4) | 0 | 44.2 (28.3–71.2) | 78.2 (44.1–111) | <0.0001 |
Factor | Unit | Univariate Analysis p Value | Multivariate Analysis p Value |
---|---|---|---|
Age | Years Old | 0.175 | |
Sex | 0.244 | ||
HCV Group | 0.700 | ||
HCV-RNA(Pre) | Log IU/mL | 0.981 | |
BMI(Pre) | kg/m2 | 0.369 | |
WBC | /μL | 0.412 | |
Hb | g/dL | 0.078 | |
Plt | ×104/μL | 0.056 | |
AST | U/L | 0.106 | |
ALT | U/L | 0.343 | |
T-bil | mg/dL | 0.042 | |
eGFR | mL/min/1.73 m2 | 0.723 | |
CRP | mg/dL | 0.228 | |
HbA1c | % | 0.740 | |
Alb | g/dL | 0.011 | |
Hyaluronic Acid | ng/mL | 0.109 | |
AFP | ng/mL | <0.0001 | <0.0001 |
DCP | mAU/mL | 0.399 | |
FIB-4 index | 0.006 | 0.015 | |
TSP-2 | ng/μL | 0.0002 | 0.003 |
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Matsumae, T.; Kodama, T.; Tahata, Y.; Myojin, Y.; Doi, A.; Nishio, A.; Yamada, R.; Nozaki, Y.; Oshita, M.; Hiramatsu, N.; et al. Thrombospondin-2 as a Predictive Biomarker for Hepatocellular Carcinoma after Hepatitis C Virus Elimination by Direct-Acting Antiviral. Cancers 2023, 15, 463. https://doi.org/10.3390/cancers15020463
Matsumae T, Kodama T, Tahata Y, Myojin Y, Doi A, Nishio A, Yamada R, Nozaki Y, Oshita M, Hiramatsu N, et al. Thrombospondin-2 as a Predictive Biomarker for Hepatocellular Carcinoma after Hepatitis C Virus Elimination by Direct-Acting Antiviral. Cancers. 2023; 15(2):463. https://doi.org/10.3390/cancers15020463
Chicago/Turabian StyleMatsumae, Takayuki, Takahiro Kodama, Yuki Tahata, Yuta Myojin, Akira Doi, Akira Nishio, Ryoko Yamada, Yasutoshi Nozaki, Masahide Oshita, Naoki Hiramatsu, and et al. 2023. "Thrombospondin-2 as a Predictive Biomarker for Hepatocellular Carcinoma after Hepatitis C Virus Elimination by Direct-Acting Antiviral" Cancers 15, no. 2: 463. https://doi.org/10.3390/cancers15020463