Predicting Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Receiving Finite Periods of Antiviral Therapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Patients and Methods
2.1. Patients
2.2. Clinical and Virological Variables
2.3. Antiviral Treatment Methods
2.4. Statistical Analysis
3. Results
3.1. Demographic Characteristics of Treatment-Naïve Patients with CHB Infection Receiving NAs
3.2. Stepwise Selection for HCC after NAs
3.3. HCC Assessment Using the CGMH HCC Predictive Scoring System
3.4. HCC Assessment Using the PAGE-B Predictive Scoring System
3.5. Kaplan–Meier Survival Curve for Cumulative HCC Risk Determined Using the CGMH HCC Predictive Scoring System
3.6. Kaplan–Meier Survival Curve for Cumulative HCC Risk Determined Using the PAGE-B Predictive Scoring System
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Characteristics | Patients with CHB Receiving NAs without HCC | Patients with CHB Receiving NAs with HCC | p Value | ||
---|---|---|---|---|---|
N = 757 | N = 33 | ||||
N | % | N | % | ||
Age | |||||
Mean ± SD | 48.40 ± 12.84 | 53.46 ± 8.34 | 0.025 | ||
Median (IQR) | 48.94 (39.38, 57.03) | 53.61 (45.79, 58.36) | 0.015 | ||
Gender | 0.028 | ||||
Female | 226 | 29.9% | 4 | 12.1% | |
Male | 531 | 70.2% | 29 | 87.9% | |
Laboratory data | |||||
Alpha-fetoprotein (ng/mL) | |||||
Mean ± SD | 24.15 ± 83.76 | 11.14 ± 18.26 | 0.373 | ||
Median (IQR) | 4.30 (3.00, 9.20) | 4.00 (3.00, 7.00) | 0.966 | ||
Aspartate aminotransferase (U/L) | |||||
Mean ± SD | 175.51 ± 306.87 | 74.36 ± 68.01 | 0.059 | ||
Median (IQR) | 72.00 (44.00, 148.00) | 49.00 (39.00, 80.00) | 0.016 | ||
Alanine aminotransferase (U/L) | |||||
Mean ± SD | 245.98 ± 393.09 | 81.45 ± 76.87 | 0.017 | ||
Median (IQR) | 115.00 (60.00, 232.00) | 50.00 (37.00, 103.00) | <.0001 | ||
Total Bilirubin (mg/dL) | |||||
Mean ± SD | 1.50 ± 2.98 | 1.22 ± 2.12 | 0.593 | ||
Median (IQR) | 0.80 (0.50, 1.10) | 0.70 (0.50, 1.20) | 0.603 | ||
International normalized ratio | |||||
Mean ± SD | 1.18 ± 0.81 | 1.14 ± 0.15 | 0.761 | ||
Median (IQR) | 1.00 (1.00, 1.10) | 1.10 (1.00, 1.20) | 0.059 | ||
Platelet (103/μL) | |||||
Mean ± SD | 178.16 ± 72.86 | 141.64 ± 50.73 | 0.005 | ||
Median (IQR) | 174.00 (140.00, 210.0) | 144.00 (117.00, 165.0) | 0.001 | ||
HBV DNA titer | |||||
HBV DNA (copies/mL) | |||||
Mean ± SD | 917.82 ± 5672.48 | 166.67 ± 799.77 | 0.448 | ||
Median (IQR) | 25.30 (1.51, 640.20) | 4.09 (1.24, 23.63) | 0.018 | ||
logHBV DNA | |||||
Mean ± SD | 7.30 ± 1.61 | 6.77 ± 1.00 | 0.058 | ||
Median (IQR) | 7.40 (6.18, 8.81) | 6.61 (6.09, 7.37) | 0.018 | ||
Relapse after NA withdraw | 0.002 | ||||
No | 233 | 30.8% | 2 | 6.1% | |
Yes | 524 | 69.2% | 31 | 93.9% | |
Courses of NA treatment | 0.655 | ||||
1 | 575 | 76.0% | 27 | 81.8% | |
2 | 149 | 19.7% | 6 | 18.2% | |
3 | 27 | 3.6% | 0 | 0.0% | |
4 | 6 | 0.8% | 0 | 0.0% | |
Antiviral treatment strategies | |||||
Peginterferon in combination with entecavir | 0.240 | ||||
No | 722 | 95.4% | 30 | 90.9% | |
Yes | 35 | 4.6% | 3 | 9.1% | |
Entecavir monotherapy followed by NA switching or addition | 0.065 | ||||
No | 353 | 46.6% | 10 | 30.3% | |
Yes | 404 | 53.4% | 23 | 69.7% | |
Entecavir monotherapy | 0.018 | ||||
No | 318 | 42.0% | 7 | 21.2% | |
Yes | 439 | 58.0% | 26 | 78.8% | |
Tenofovir monotherapy switching to or addition of other NAs | 0.856 | ||||
No | 657 | 86.8% | 29 | 87.9% | |
Yes | 100 | 13.2% | 4 | 12.1% | |
Initial lamivudine or telbivudine therapy | 0.042 | ||||
No | 602 | 79.5% | 31 | 93.9% | |
Yes | 155 | 20.5% | 2 | 6.1% | |
Peginterferon monotherapy | 0.275 | ||||
No | 694 | 91.7% | 32 | 97.0% | |
Yes | 63 | 8.3% | 1 | 3.0% | |
HBeAg | 0.418 | ||||
Negative | 499 | 65.9% | 24 | 72.7% | |
Positive | 258 | 34.1% | 9 | 27.3% | |
Anti-HBe | 0.044 | ||||
Negative | 240 | 31.7% | 5 | 15.2% | |
Positive | 517 | 68.3% | 28 | 84.9% | |
Liver Cirrhosis | <.0001 | ||||
No | 591 | 78.1% | 7 | 21.2% | |
Yes | 166 | 21.9% | 26 | 78.8% | |
HBV Genotype | |||||
Genotype B | 0.004 | ||||
No | 177 | 23.4% | 15 | 45.5% | |
Yes | 580 | 76.6% | 18 | 54.6% | |
Genotype C | 0.008 | ||||
No | 586 | 77.4% | 19 | 57.6% | |
Yes | 171 | 22.6% | 14 | 42.4% | |
HBV viral point mutation | |||||
G1719T | 0.034 | ||||
No | 712 | 94.1% | 28 | 84.9% | |
Yes | 45 | 5.9% | 5 | 15.2% | |
G172A/C | 0.506 | ||||
No | 747 | 98.7% | 33 | 100.0% | |
Yes | 10 | 1.3% | 0 | 0.0% | |
C1730G | 0.005 | ||||
No | 575 | 76.0% | 18 | 54.6% | |
Yes | 182 | 24.0% | 15 | 45.5% | |
A1752G | 0.519 | ||||
No | 486 | 64.2% | 23 | 69.7% | |
Yes | 271 | 35.8% | 10 | 30.3% | |
T1753C/A | 0.713 | ||||
No | 659 | 87.1% | 28 | 84.9% | |
Yes | 98 | 13.0% | 5 | 15.2% | |
A1762T | 0.003 | ||||
No | 428 | 56.5% | 10 | 30.3% | |
Yes | 329 | 43.5% | 23 | 69.7% | |
G1764A | 0.001 | ||||
No | 413 | 54.6% | 8 | 24.2% | |
Yes | 344 | 45.4% | 25 | 75.8% | |
C1766T | 0.038 | ||||
No | 711 | 93.9% | 28 | 84.9% | |
Yes | 46 | 6.1% | 5 | 15.2% | |
T1768A | 0.022 | ||||
No | 715 | 94.5% | 28 | 84.9% | |
Yes | 42 | 5.6% | 5 | 15.2% | |
C1799G | 0.012 | ||||
No | 176 | 23.3% | 14 | 42.4% | |
Yes | 581 | 76.8% | 19 | 57.6% | |
G1896A | 0.829 | ||||
No | 243 | 32.1% | 10 | 30.3% | |
Yes | 514 | 67.9% | 23 | 69.7% | |
G1899A | 0.574 | ||||
No | 604 | 79.8% | 25 | 75.8% | |
Yes | 153 | 20.2% | 8 | 24.2% |
Factor | aHR * | 95% CI | p Value | Assigned Points | |
---|---|---|---|---|---|
Genotype C | 2.23 | 1.09 | 4.55 | 0.029 | 2 |
Relapse after NA withdraw | 6.96 | 1.64 | 29.62 | 0.009 | 7 |
Male | 4.19 | 1.43 | 12.33 | 0.009 | 4 |
Liver Cirrhosis | 11.14 | 4.79 | 25.92 | <0.0001 | 11 |
T1768A | 3.21 | 1.19 | 8.69 | 0.022 | 3 |
CGMH Predictive Scoring System | Number of Patients without HCC | Number of Patients with HCC | HCC Incidence |
---|---|---|---|
0 | 36 | 0 | 0.00% |
2 | 13 | 0 | 0.00% |
3 | 5 | 0 | 0.00% |
4 | 104 | 0 | 0.00% |
5 | 1 | 0 | 0.00% |
6 | 32 | 0 | 0.00% |
7 | 93 | 1 | 1.06% |
9 | 29 | 1 | 3.33% |
11 | 227 | 3 | 1.30% |
12 | 7 | 0 | 0.00% |
13 | 39 | 2 | 4.88% |
14 | 4 | 0 | 0.00% |
15 | 19 | 1 | 5.00% |
16 | 8 | 0 | 0.00% |
17 | 7 | 0 | 0.00% |
18 | 23 | 1 | 4.17% |
20 | 16 | 1 | 5.88% |
21 | 3 | 0 | 0.00% |
22 | 70 | 12 | 14.63% |
23 | 2 | 1 | 33.33% |
24 | 16 | 7 | 30.43% |
25 | 2 | 1 | 33.33% |
27 | 1 | 2 | 66.67% |
Total | 757 | 33 | 4.17% |
CGMH Predictive Scoring | Group | HCC Risk | |
---|---|---|---|
Score | No HCC, N (%) | HCC, N (%) | |
0–12 | Low risk | 547 (99.09%) | 5 (0.91%) |
13–20 | Moderate risk | 116 (95.87%) | 5 (4.13%) |
≥21 | High risk | 94 (80.34%) | 23 (19.66%) |
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Lin, C.-L.; Wu, S.-Y.; Lai, M.-W.; Hsu, C.-W.; Chen, W.-M.; Jao, A.-T.; Chien, C.-H.; Hu, C.-C.; Chien, R.-N.; Yeh, C.-T. Predicting Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Receiving Finite Periods of Antiviral Therapy. Cancers 2023, 15, 3343. https://doi.org/10.3390/cancers15133343
Lin C-L, Wu S-Y, Lai M-W, Hsu C-W, Chen W-M, Jao A-T, Chien C-H, Hu C-C, Chien R-N, Yeh C-T. Predicting Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Receiving Finite Periods of Antiviral Therapy. Cancers. 2023; 15(13):3343. https://doi.org/10.3390/cancers15133343
Chicago/Turabian StyleLin, Chih-Lang, Szu-Yuan Wu, Ming-Wei Lai, Chao-Wei Hsu, Wan-Ming Chen, An-Tzu Jao, Cheng-Hung Chien, Ching-Chih Hu, Rong-Nan Chien, and Chau-Ting Yeh. 2023. "Predicting Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Receiving Finite Periods of Antiviral Therapy" Cancers 15, no. 13: 3343. https://doi.org/10.3390/cancers15133343