Chronic Hepatitis B Virus Infection and HLA Variations in a Greek Population
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
4.1. HLA Class I Alleles Associations
4.2. HLA Class II Alleles Associations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
cHBV | chronic hepatitis B |
HLAs | human leukocyte antigens |
PCR-SSP | single-specific primer polymerase chain reaction |
MHC | major histocompatibility complex |
SC | spontaneous clearance |
HBsAg | hepatitis B surface antigen |
anti-HBs | anti-hepatitis B surface antibody |
anti-HBc | anti-hepatitis B core antibody |
OR | odds ratio |
HBV-HCC | hepatitis B-related hepatocellular carcinoma |
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Variables | cHBV Group (n = 107) | SC Group (n = 101) |
---|---|---|
Male, number (%) | 86 (80.4) | 68 (67.3) |
Female, number (%) | 21 (19.62) | 33 (32.7) |
Age (years), mean ± SD | 60.6 ± 5.1 | 60.9 ± 12.0 |
Allele | Patients in the cHBV Group (2N = 214) | Patients in the cHBV Group, % | Patients in the SC Group (2N = 202) | Patients in the SCgroup, % | p Value | OR | 95%CI |
---|---|---|---|---|---|---|---|
HLA–A | |||||||
A*01 | 33 | 16.18 | 22 | 11.11 | 0.15 | 0.65 | [0.35—1.2] |
A*02 | 45 | 22.06 | 56 | 28.28 | 0.17 | 1.39 | [0.86—2.25] |
A*03 | 22 | 10.78 | 13 | 6.57 | 0.16 | 0.58 | [0.26—1.25] |
A*11 | 10 | 4.9 | 17 | 8.59 | 0.16 | 1.82 | [0.76—4.57] |
A*23 | 7 | 3.43 | 4 | 2.02 | 0.54 | 0.58 | [0.12—2.33] |
A*24 | 30 | 14.71 | 31 | 15.66 | 0.89 | 1.08 | [0.6—1.93] |
A*25 | 1 | 0.49 | 2 | 1.01 | 0.62 | 2.07 | [0.11—122.71] |
A*26 | 12 | 5.88 | 9 | 4.55 | 0.66 | 0.76 | [0.28—2.02] |
A*29 | 6 | 2.94 | 3 | 1.52 | 0.5 | 0.51 | [0.08—2.42] |
A*30 | 2 | 0.98 | 3 | 1.52 | 0.68 | 1.55 | [0.18—18.76] |
A*31 | 3 | 1.47 | 6 | 3.03 | 0.33 | 2.09 | [0.44—13.1] |
A*32 | 13 | 6.37 | 13 | 6.57 | 1 | 1.03 | [0.43—2.49] |
A*33 | 5 | 2.45 | 3 | 1.52 | 0.72 | 0.61 | [0.09—3.2] |
A*66 | 1 | 0.49 | 3 | 1.52 | 0.37 | 3.12 | [0.25—164.61] |
A*68 | 11 | 5.39 | 11 | 5.56 | 1 | 1.03 | [0.4—2.7] |
HLA–B | |||||||
B*07 | 6 | 2.94 | 4 | 2.02 | 0.75 | 0.68 | [0.14—2.94] |
B*08 | 17 | 8.33 | 7 | 3.54 | 0.06 | 0.41 | [0.14—1.06] |
B*13 | 4 | 1.96 | 4 | 2.02 | 1 | 1.04 | [0.19—5.65] |
B*14 | 10 | 4.9 | 7 | 3.54 | 0.62 | 0.72 | [0.23—2.13] |
B*15 | 8 | 3.92 | 4 | 2.02 | 0.38 | 0.51 | [0.11—1.94] |
B*18 | 17 | 8.33 | 24 | 12.12 | 0.25 | 1.52 | [0.76—3.13] |
B*27 | 6 | 2.94 | 5 | 2.53 | 1 | 0.86 | [0.2—3.44] |
B*35 | 37 | 18.14 | 31 | 15.66 | 0.59 | 0.84 | [0.48—1.47] |
B*37 | 5 | 2.45 | 2 | 1.01 | 0.45 | 0.41 | [0.04—2.53] |
B*38 | 1 | 0.49 | 5 | 2.53 | 0.12 | 5.27 | [0.58—250.94] |
B*39 | 5 | 2.45 | 5 | 2.53 | 1 | 1.04 | [0.23—4.58] |
B*40 | 9 | 4.41 | 14 | 7.07 | 0.29 | 1.66 | [0.65—4.45] |
B*41 | 4 | 1.96 | 4 | 2.02 | 1 | 1.04 | [0.19—5.65] |
B*44 | 14 | 6.86 | 15 | 7.58 | 0.85 | 1.12 | [0.49—2.58] |
B*49 | 3 | 1.47 | 3 | 1.52 | 1 | 1.04 | [0.14—7.83] |
B*50 | 2 | 0.98 | 5 | 2.53 | 0.28 | 2.62 | [0.42—27.87] |
B*51 | 28 | 13.73 | 30 | 15.15 | 0.67 | 1.13 | [0.62—2.05] |
B*52 | 7 | 3.43 | 10 | 5.05 | 0.46 | 1.5 | [0.5—4.76] |
B*55 | 5 | 2.45 | 4 | 2.02 | 1 | 0.83 | [0.16—3.9] |
B*56 | 2 | 0.98 | 1 | 0.51 | 1 | 0.52 | [0.01—9.99] |
B*57 | 6 | 2.94 | 4 | 2.02 | 0.75 | 0.68 | [0.14—2.94] |
B*58 | 3 | 1.47 | 1 | 0.51 | 0.62 | 0.34 | [0.01—4.31] |
B*73 | 1 | 0.49 | 1 | 0.51 | 1 | 1.04 | [0.01—81.65] |
HLA–C | |||||||
C*01 | 18 | 8.82 | 1 | 0.91 | 0.005 | 0.1 | [0—0.62] |
C*02 | 14 | 6.86 | 6 | 5.45 | 0.81 | 0.78 | [0.24—2.25] |
C*03 | 14 | 6.86 | 8 | 7.27 | 1 | 1.06 | [0.37—2.83] |
C*04 | 36 | 17.65 | 17 | 15.45 | 0.75 | 0.85 | [0.42—1.66] |
C*05 | 7 | 3.43 | 4 | 3.64 | 1 | 1.06 | [0.22—4.29] |
C*06 | 16 | 7.84 | 9 | 8.18 | 1 | 1.05 | [0.39—2.62] |
C*07 | 37 | 18.14 | 18 | 16.36 | 0.76 | 0.88 | [0.45—1.7] |
C*08 | 12 | 5.88 | 5 | 4.55 | 0.8 | 0.76 | [0.2—2.4] |
C*12 | 25 | 12.25 | 17 | 15.45 | 0.49 | 1.31 | [0.63—2.67] |
C*14 | 2 | 0.98 | 2 | 1.82 | 0.61 | 1.87 | [0.13—26.08] |
C*15 | 12 | 5.88 | 14 | 12.73 | 0.05 | 2.33 | [0.96—5.74] |
C*16 | 6 | 2.94 | 6 | 5.45 | 0.36 | 1.9 | [0.49—7.3] |
C*17 | 4 | 1.96 | 2 | 1.82 | 1 | 0.93 | [0.08—6.58] |
HLA–DRB1 | |||||||
DRB1*01 | 21 | 10.29 | 23 | 11.73 | 0.75 | 1.16 | [0.59—2.29] |
DRB1*03 | 21 | 10.29 | 17 | 8.67 | 0.61 | 0.83 | [0.4—1.71] |
DRB1*04 | 12 | 5.88 | 19 | 9.69 | 0.19 | 1.72 | [0.77—3.99] |
DRB1*07 | 13 | 6.37 | 9 | 4.59 | 0.51 | 0.71 | [0.26—1.84] |
DRB1*10 | 2 | 0.98 | 4 | 2.04 | 0.44 | 2.1 | [0.3—23.47] |
DRB1*11 | 61 | 29.9 | 55 | 28.06 | 0.74 | 0.91 | [0.58—1.44] |
DRB1*12 | 2 | 0.98 | 7 | 3.57 | 0.1 | 3.73 | [0.7—37.27] |
DRB1*13 | 15 | 7.35 | 22 | 11.22 | 0.23 | 1.59 | [0.76—3.41] |
DRB1*14 | 14 | 6.86 | 12 | 6.12 | 0.84 | 0.89 | [0.36—2.12] |
DRB1*15 | 13 | 6.37 | 13 | 6.63 | 1 | 1.04 | [0.43—2.52] |
DRB1*16 | 28 | 13.73 | 14 | 7.14 | 0.03 | 0.48 | [0.23—0.99] |
HLA–DQB1 | |||||||
DQB1*02 | 31 | 15.35 | 7 | 11.67 | 0.54 | 0.73 | [0.26—1.82] |
DQB1*03 | 82 | 40.59 | 33 | 55 | 0.05 | 1.78 | [0.96—3.34] |
DQB1*05 | 62 | 30.69 | 16 | 26.67 | 0.63 | 0.82 | [0.4—1.62] |
DQB1*06 | 25 | 12.38 | 4 | 6.67 | 0.25 | 0.51 | [0.12—1.56] |
Allele | Patients in the cHBV Group (2N = 214) | Patients in the cHBV Group, % | Healthy Adults (2N = 29,012) | Healthy Adults, % | p-Value | OR | 95%CI |
---|---|---|---|---|---|---|---|
HLA–A | |||||||
A*01 | 33 | 16.18 | 2814 | 9.7 | 5.21 × 10−10 | 4.33 | [2.77—6.64] |
A*02 | 45 | 22.06 | 7921 | 27.3 | 0.1 | 0.75 | [0.53—1.06] |
A*03 | 22 | 10.78 | 2698 | 9.3 | 0.47 | 1.18 | [0.72—1.84] |
A*11 | 10 | 4.9 | 2002 | 6.9 | 0.33 | 0.7 | [0.33—1.31] |
A*23 | 7 | 3.43 | 928 | 3.2 | 0.84 | 1.08 | [0.43—2.27] |
A*24 | 30 | 14.71 | 4497 | 15.5 | 0.85 | 0.94 | [0.61—1.39] |
A*26 | 12 | 5.88 | 1625 | 5.6 | 0.88 | 1.05 | [0.53—1.89] |
A*32 | 13 | 6.37 | 1770 | 6.1 | 0.88 | 1.05 | [0.55—1.84] |
A*68 | 11 | 5.39 | 1161 | 4 | 0.28 | 1.37 | [0.67—2.51] |
HLA–B | |||||||
B*07 | 6 | 2.94 | 1230 | 4.2 | 0.48 | 0.69 | [0.25—1.54] |
B*08 | 17 | 8.33 | 1259 | 4.3 | 0.009 | 2.02 | [1.15—3.34] |
B*18 | 17 | 8.33 | 3396 | 11.6 | 0.19 | 0.69 | [0.39—1.14] |
B*35 | 37 | 18.14 | 5446 | 18.6 | 0.93 | 0.97 | [0.66—1.39] |
B*38 | 1 | 0.49 | 995 | 3.4 | 0.017 | 0.14 | [0—0.79] |
B*40 | 9 | 4.41 | 966 | 3.3 | 0.33 | 1.35 | [0.61—2.63] |
B*44 | 14 | 6.86 | 2196 | 7.5 | 0.89 | 0.91 | [0.49—1.57] |
B*51 | 28 | 13.73 | 4157 | 14.2 | 0.92 | 0.96 | [0.62—1.44] |
HLA–C | |||||||
C*01 | 18 | 8.82 | 38 | 4.2 | 0.01 | 2.18 | [1.15—4.0] |
C*02 | 14 | 6.86 | 58 | 6.3 | 0.75 | 1.09 | [0.55—2.03] |
C*03 | 14 | 6.86 | 46 | 5.0 | 0.3 | 1.39 | [0.69—2.64] |
C*04 | 36 | 17.65 | 156 | 17.0 | 0.83 | 1.04 | [0.68—1.57] |
C*05 | 7 | 3.43 | 20 | 2.2 | 0.31 | 1.59 | [0.56—3.98] |
C*06 | 16 | 7.84 | 88 | 9.6 | 0.5 | 0.8 | [0.43—1.41] |
C*07 | 37 | 18.14 | 164 | 17.9 | 0.92 | 1.02 | [0.67—1.52] |
C*08 | 12 | 5.88 | 20 | 2.2 | 0.009 | 2.8 | [1.22—6.12] |
C*12 | 25 | 12.25 | 164 | 17.9 | 0.06 | 0.64 | [0.39—1.02] |
C*14 | 2 | 0.98 | 34 | 3.7 | 0.05 | 0.26 | [0.03—1.02] |
C*15 | 12 | 5.88 | 74 | 8.1 | 0.38 | 0.71 | [0.34—1.35] |
C*16 | 6 | 2.94 | 0 | 0.0 | 1 | 60 | [3.37—1069.83] |
C*17 | 4 | 1.96 | 10 | 1.1 | 0.3 | 1.81 | [0.41—6.36] |
C*18 | 1 | 0.49 | 0 | 0 | 1 | 13.5 | [0.55—332.86] |
HLA–DRB1 | |||||||
DRB1*01 | 21 | 10.29 | 1283 | 6.7 | 0.05 | 1.6 | [0.96—2.53] |
DRB1*03 | 21 | 10.29 | 1110 | 5.8 | 0.01 | 1.86 | [1.12—2.95] |
DRB1*04 | 12 | 5.88 | 1838 | 9.6 | 0.07 | 0.59 | [0.3—1.05] |
DRB1*07 | 13 | 6.37 | 1513 | 7.9 | 0.51 | 0.79 | [0.41—1.39] |
DRB1*11 | 61 | 29.9 | 5169 | 27 | 0.34 | 1.15 | [0.84—1.57] |
DRB1*13 | 15 | 7.35 | 1895 | 9.9 | 0.29 | 0.72 | [0.4—1.23] |
DRB1*14 | 14 | 6.86 | 1149 | 6 | 0.55 | 1.15 | [0.62—1.99] |
DRB1*15 | 13 | 6.37 | 1455 | 7.6 | 0.6 | 0.83 | [0.43—1.45] |
DRB1*16 | 28 | 13.73 | 2259 | 11.8 | 0.38 | 1.19 | [0.77—1.78] |
HLA–DQB1 | |||||||
DQB1*02 | 31 | 15.35 | 28 | 11.2 | 0.26 | 1.41 | [0.79—2.54] |
DQB1*03 | 82 | 40.59 | 0 | 0 | 1 | 0 | [0—Inf] |
DQB1*05 | 62 | 30.69 | 54 | 22 | 0.04 | 1.57 | [1.01—2.46] |
DQB1*06 | 25 | 12.38 | 30 | 12.2 | 1 | 1.02 | [0.55—1.86] |
DQB1*07 | 0 | 0 | 71 | 28.8 | 1 | 0 | [0—Inf] |
DQB1*08 | 0 | 0 | 9 | 3.8 | 1 | 0 | [0—Inf] |
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Myserli, E.; Goulis, I.; Fylaktou, A.; Exindari, M.; Minti, F.; Chatzika, G.; Iliopoulou, E.; Agorastou, P.; Papagiouvanni, I.; Oikonomou, T.; et al. Chronic Hepatitis B Virus Infection and HLA Variations in a Greek Population. Viruses 2025, 17, 462. https://doi.org/10.3390/v17040462
Myserli E, Goulis I, Fylaktou A, Exindari M, Minti F, Chatzika G, Iliopoulou E, Agorastou P, Papagiouvanni I, Oikonomou T, et al. Chronic Hepatitis B Virus Infection and HLA Variations in a Greek Population. Viruses. 2025; 17(4):462. https://doi.org/10.3390/v17040462
Chicago/Turabian StyleMyserli, Evangelia, Ioannis Goulis, Asimina Fylaktou, Maria Exindari, Fani Minti, Georgia Chatzika, Eleni Iliopoulou, Polyxeni Agorastou, Ioanna Papagiouvanni, Theodora Oikonomou, and et al. 2025. "Chronic Hepatitis B Virus Infection and HLA Variations in a Greek Population" Viruses 17, no. 4: 462. https://doi.org/10.3390/v17040462
APA StyleMyserli, E., Goulis, I., Fylaktou, A., Exindari, M., Minti, F., Chatzika, G., Iliopoulou, E., Agorastou, P., Papagiouvanni, I., Oikonomou, T., & Gioula, G. (2025). Chronic Hepatitis B Virus Infection and HLA Variations in a Greek Population. Viruses, 17(4), 462. https://doi.org/10.3390/v17040462