Influenza Vaccination Reduces the Risk of Liver Cancer in Patients with Chronic Kidney Disease: A Nationwide Population-Based Cohort Study
Abstract
:1. Introduction
2. Methods
2.1. Patient Selection Process and the Primary Endpoint
2.2. Potential Confounders
2.3. Statistical Analysis
3. Results
4. Discussion
4.1. Main Findings
4.2. Mechanism of Liver Cancer Development in Patients with CKD
4.3. Mechanism Underlying the Association between Incidence of Liver Cancer and Influenza Vaccination
4.4. Effect of Influenza Vaccination in Patients with Different Characteristics
5. Limitations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Whole Cohort (n = 12,985) | Unvaccinated (n = 7490) | Vaccinated (n = 5495) | p a | ||||
---|---|---|---|---|---|---|---|
n | % | n | % | n | % | ||
Age, years (Mean ± SD) | 70.98 (9.40) | 70.09 (10.26) | 72.18 (7.90) | <0.001 | |||
55–64 | 3989 | 30.72 | 2877 | 38.41 | 1112 | 20.24 | <0.001 |
65–74 | 4541 | 34.97 | 2139 | 28.56 | 2402 | 43.71 | |
≥75 | 4455 | 34.31 | 2474 | 33.03 | 1981 | 36.05 | |
Gender | |||||||
Female | 5712 | 43.99 | 3333 | 44.50 | 2379 | 43.29 | 0.172 |
Male | 7273 | 56.01 | 4157 | 55.50 | 3116 | 56.71 | |
CCI Index + | |||||||
0 | 1491 | 11.48 | 876 | 11.70 | 615 | 11.19 | 0.013 |
1 | 2043 | 15.73 | 1166 | 15.57 | 877 | 15.96 | |
2 | 2876 | 22.15 | 1589 | 21.21 | 1287 | 23.42 | |
≥3 | 6575 | 50.64 | 3859 | 51.52 | 2716 | 49.43 | |
Diabetes | |||||||
No | 6310 | 48.59 | 3355 | 44.79 | 2955 | 53.78 | <0.001 |
Yes | 6675 | 51.41 | 4135 | 55.21 | 2540 | 46.22 | |
Hypertension | |||||||
No | 2555 | 19.68 | 1387 | 18.52 | 1168 | 21.26 | <0.001 |
Yes | 10,430 | 80.32 | 6103 | 81.48 | 4327 | 78.74 | |
Dyslipidemia | |||||||
No | 6337 | 48.80 | 3386 | 45.21 | 2951 | 53.70 | <0.001 |
Yes | 6648 | 51.20 | 4104 | 54.79 | 2544 | 46.30 | |
Statin | |||||||
<28 days | 7972 | 61.39 | 4786 | 63.90 | 3186 | 57.98 | <0.001 |
28–365 days | 2683 | 20.66 | 1576 | 21.04 | 1107 | 20.15 | |
>365 days | 2330 | 17.94 | 1128 | 15.06 | 1202 | 21.87 | |
Metformin | |||||||
<28 days | 10,266 | 79.06 | 6045 | 80.71 | 4221 | 76.82 | <0.001 |
28–365 days | 1331 | 10.25 | 804 | 10.73 | 527 | 9.59 | |
>365 days | 1388 | 10.69 | 641 | 8.56 | 747 | 13.59 | |
RAASI | |||||||
<28 days | 4114 | 31.68 | 2792 | 37.28 | 1322 | 24.06 | <0.001 |
28–365 days | 3751 | 28.89 | 2344 | 31.30 | 1407 | 25.61 | |
>365 days | 5120 | 39.43 | 2354 | 31.43 | 2766 | 50.34 | |
Aspirin | |||||||
<28 days | 6715 | 51.71 | 4478 | 59.79 | 2237 | 40.71 | <0.001 |
28–365 days | 3149 | 24.25 | 1702 | 22.72 | 1447 | 26.33 | |
>365 days | 3121 | 24.04 | 1310 | 17.49 | 1811 | 32.96 | |
Level of Urbanization | |||||||
Urban | 8785 | 67.65 | 5350 | 71.43 | 3435 | 62.51 | <0.001 |
Suburban | 2806 | 21.61 | 1488 | 19.87 | 1318 | 23.99 | |
Rural | 1394 | 10.74 | 652 | 8.70 | 742 | 13.50 | |
Monthly income (TWD) | |||||||
0 | 1596 | 12.29 | 901 | 12.03 | 695 | 12.65 | <0.001 |
1–21,000 | 4486 | 34.55 | 2397 | 32.00 | 2089 | 38.02 | |
21,000–33,300 | 3788 | 29.17 | 1996 | 26.65 | 1792 | 32.61 | |
≥33,301 | 3115 | 23.99 | 2196 | 29.32 | 919 | 16.72 |
All Group (n = 12,985) | Unvaccinated (Total Follow-Up 21,919.2 Person-Years) | Vaccinated (Total Follow-Up 33,990.2 Person-Years) | Adjusted HR † (95% C.I.) | ||||||
---|---|---|---|---|---|---|---|---|---|
No. of Patients with Cancer | Incidence Rate (per 105 Person-Years) (95% C.I.) | No. of Patients with Cancer | Incidence Rate (Per 105 Person-Years) (95% C.I.) | ||||||
Whole cohort | |||||||||
All season | 162 | 739.1 | (625.3, | 852.9) | 123 | 361.9 | (297.9, | 425.8) | 0.45 (0.35, 0.58) *** |
Age, 55–64 a | |||||||||
All season | 82 | 760.1 | (595.6, | 924.7) | 22 | 244.5 | (142.3, | 346.7) | 0.28 (0.17, 0.46) *** |
Age, 65–74 b | |||||||||
All season | 43 | 701.0 | (491.5, | 910.5) | 63 | 398.2 | (299.9, | 496.5) | 0.53 (0.35, 0.79) ** |
Age, ≥75 c | |||||||||
All season | 37 | 740.4 | (501.8, | 978.9) | 38 | 414.4 | (282.6, | 546.1) | 0.57 (0.35, 0.91) * |
Female d | |||||||||
All season | 60 | 622.6 | (465.1, | 780.2) | 39 | 260.3 | (178.6, | 342.1) | 0.39 (0.26, 0.60) *** |
Male e | |||||||||
All season | 102 | 830.4 | (669.3, | 991.6) | 84 | 441.9 | (347.4, | 536.4) | 0.49 (0.36, 0.67) *** |
Unvaccinated | Vaccinated | p for Trend | |||
---|---|---|---|---|---|
1 | 2–3 | ≥4 | |||
Adjusted HR (95%C.I.) | Adjusted HR (95%C.I.) | Adjusted HR (95%C.I.) | Adjusted HR (95%C.I.) | ||
Main model † | 1.00 | 0.86 (0.63, 1.17) | 0.45 (0.31, 0.63) *** | 0.21 (0.14, 0.33) *** | <0.001 |
Additional covariates ‡ | |||||
Main model + Statin | 1.00 | 0.89 (0.65, 1.21) | 0.47 (0.33, 0.67) *** | 0.23 (0.15, 0.35) *** | <0.001 |
Main model + Metformin | 1.00 | 0.86 (0.63, 1.18) | 0.45 (0.32, 0.64) *** | 0.22 (0.14, 0.33) *** | <0.001 |
Main model + RAA | 1.00 | 0.91 (0.67, 1.23) | 0.47 (0.33, 0.67) *** | 0.23 (0.15, 0.36) *** | <0.001 |
Main model + Aspirin | 1.00 | 0.91 (0.67, 1.24) | 0.49 (0.34, 0.69) *** | 0.24 (0.16, 0.36) *** | <0.001 |
Subgroup effects | |||||
Age, years | |||||
55–64 | 1.00 | 0.50 (0.27, 0.92) * | 0.33 (0.16, 0.69) ** | 0.07 (0.02, 0.27) *** | <0.001 |
65–74 | 1.00 | 1.22 (0.75, 1.99) | 0.58 (0.34, 0.97) * | 0.23 (0.13, 0.42) *** | <0.001 |
≥75 | 1.00 | 0.98 (0.55, 1.75) | 0.42 (0.21, 0.84) * | 0.38 (0.18, 0.80) * | 0.002 |
Sex | |||||
Female | 1.00 | 0.90 (0.55, 1.47) | 0.36 (0.19, 0.67) *** | 0.11 (0.04, 0.27) *** | <0.001 |
Male | 1.00 | 0.85 (0.57, 1.26) | 0.50 (0.33, 0.77) ** | 0.28 (0.17, 0.45) *** | <0.001 |
CCI Index + | |||||
0 | 1.00 | 1.00 (0.27, 3.65) | 0.75 (0.23, 2.44) | 0.46 (0.14, 1.54) | 0.204 |
1 | 1.00 | 0.57 (0.23, 1.40) | 0.65 (0.28, 1.47) | 0.23 (0.08, 0.62) ** | 0.004 |
2 | 1.00 | 0.75 (0.38, 1.47) | 0.57 (0.29, 1.11) | 0.20 (0.09, 0.45) *** | <0.001 |
≥3 | 1.00 | 0.89 (0.60, 1.32) | 0.28 (0.16, 0.49) *** | 0.17 (0.09, 0.32) *** | <0.001 |
Diabetes | |||||
No | 1.00 | 0.88 (0.56, 1.38) | 0.54 (0.33, 0.87) * | 0.23 (0.13, 0.39) *** | <0.001 |
Yes | 1.00 | 0.81 (0.53, 1.23) | 0.34 (0.20, 0.57) *** | 0.20 (0.10, 0.38) *** | <0.001 |
Dyslipidemia | |||||
No | 1.00 | 0.80 (0.53, 1.19) | 0.37 (0.23, 0.59) *** | 0.21 (0.13, 0.35) *** | <0.001 |
Yes | 1.00 | 0.97 (0.60, 1.57) | 0.59 (0.35, 1.01) | 0.22 (0.10, 0.45) *** | <0.001 |
Hypertension | |||||
No | 1.00 | 0.80 (0.42, 1.54) | 0.52 (0.26, 1.03) | 0.20 (0.09, 0.45) *** | <0.001 |
Yes | 1.00 | 0.87 (0.61, 1.24) | 0.42 (0.27, 0.63) *** | 0.21 (0.13, 0.35) *** | <0.001 |
Statin | |||||
<28 days | 1.00 | 0.90 (0.63, 1.28) | 0.43 (0.28, 0.65) *** | 0.24 (0.15, 0.39) *** | <0.001 |
28–365 days | 1.00 | 0.80 (0.29, 2.18) | 0.77 (0.30, 1.92) | 0.24 (0.07, 0.87) * | 0.040 |
>365 days | 1.00 | 0.97 (0.40, 2.36) | 0.47 (0.17, 1.32) | 0.17 (0.05, 0.60) ** | 0.003 |
Metformin | |||||
<28 days | 1.00 | 0.82 (0.57, 1.16) | 0.42 (0.28, 0.63) *** | 0.19 (0.11, 0.31) *** | <0.001 |
28–365 days | 1.00 | 1.15 (0.44, 2.99) | 0.86 (0.31, 2.38) | 0.59 (0.20, 1.80) | 0.346 |
>365 days | 1.00 | 1.05 (0.42, 2.59) | 0.42 (0.15, 1.19) | 0.24 (0.09, 0.69) ** | 0.003 |
RAASI | |||||
<28 days | 1.00 | 0.86 (0.52, 1.41) | 0.36 (0.18, 0.70) ** | 0.09 (0.03, 0.28) *** | <0.001 |
28–365 days | 1.00 | 1.19 (0.67, 2.11) | 0.42 (0.20, 0.88) * | 0.36 (0.17, 0.77) ** | 0.002 |
>365 days | 1.00 | 0.83 (0.47, 1.44) | 0.63 (0.37, 1.07) | 0.28 (0.15, 0.50) *** | <0.001 |
Aspirin | |||||
<28 days | 1.00 | 0.83 (0.54, 1.26) | 0.53 (0.33, 0.85) ** | 0.14 (0.06, 0.31) *** | <0.001 |
28–365 days | 1.00 | 1.10 (0.59, 2.05) | 0.45 (0.21, 0.96) * | 0.08 (0.02, 0.36) *** | <0.001 |
>365 days | 1.00 | 1.15 (0.56, 2.36) | 0.54 (0.24, 1.20) | 0.57 (0.30, 1.10) | 0.043 |
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Hao, W.-R.; Yang, T.-Y.; Chen, C.-C.; Lin, K.-J.; Chiu, C.-C.; Fang, Y.-A.; Jian, W.; Lei, M.-H.; Yeh, H.-T.; Hsu, M.-H.; et al. Influenza Vaccination Reduces the Risk of Liver Cancer in Patients with Chronic Kidney Disease: A Nationwide Population-Based Cohort Study. Vaccines 2022, 10, 2008. https://doi.org/10.3390/vaccines10122008
Hao W-R, Yang T-Y, Chen C-C, Lin K-J, Chiu C-C, Fang Y-A, Jian W, Lei M-H, Yeh H-T, Hsu M-H, et al. Influenza Vaccination Reduces the Risk of Liver Cancer in Patients with Chronic Kidney Disease: A Nationwide Population-Based Cohort Study. Vaccines. 2022; 10(12):2008. https://doi.org/10.3390/vaccines10122008
Chicago/Turabian StyleHao, Wen-Rui, Tsung-Yeh Yang, Chun-Chao Chen, Kuan-Jie Lin, Chun-Chih Chiu, Yu-Ann Fang, William Jian, Meng-Huan Lei, Hsien-Tang Yeh, Min-Huei Hsu, and et al. 2022. "Influenza Vaccination Reduces the Risk of Liver Cancer in Patients with Chronic Kidney Disease: A Nationwide Population-Based Cohort Study" Vaccines 10, no. 12: 2008. https://doi.org/10.3390/vaccines10122008