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©The Author(s) 2020.
World J Gastroenterol. Sep 21, 2020; 26(35): 5314-5327
Published online Sep 21, 2020. doi: 10.3748/wjg.v26.i35.5314
Published online Sep 21, 2020. doi: 10.3748/wjg.v26.i35.5314
Table 1 Summary of immune escape-associated mutations in the major hydrophilic region of hepatitis B surface antigen
| Region in major hydrophilic region | Mutation pattern |
| Upstream “a” determinant (aa 99-123) | sY100S, sQ101H/K/R, sM103I/T, sL109I/P/R, sP111L/Q/S, sG112K/R, sS114A/L/T, sT115A/N, sT116N, sS117G/N/R, sT118A/K/M/R/S/V, sG119E/R/T, sP120A/L/Q/S/T, sC121R/S, sK122R, sT123A/I/N/S/V |
| Within “a” determinant (aa 124-147) | sC124R/Y, sT125A/M, sI/T126A/N/P/S, sP127H/L/S/T, sA128T/V, sQ129N/H/P/R, sG130A/K/N/R/S, sT131A/I/K/N, sS132F/P, sM133I/L/T, sF/Y134H/L/R/S/V, sS136F/P/Y, sC137W/Y, sC139R/S/Y, sT140I, sK141E/R, sP142L, sD144A/E, sG145A/R, sC147R/Y |
| Downstream “a” determinant (aa 148-169) | sS154P, sA159G/V, sV168A |
Table 2 Analysis of immune escape-associated mutations in the major hydrophilic region in patients with and without resistance mutations
| Clinical features | Resistance mutation (+), n = 6982 | Resistance mutation (-), n = 12458 | P value | The MHR Mutation occurrence [(+) vs (-)] |
| Age in year | 44.01 ± 11.73 | 39.01 ± 13.08 | < 0.05 | |
| Gender, male | 5709 (81.77%) | 9982 (80.13%) | < 0.05 | |
| HBV genotype, C%/B% | 86.79/12.52 | 83.00/16.05 | < 0.05 | |
| HBV DNA as log10 IU/mL | 4.62 (3.17, 6.47) | 4.24 (2.83, 6.16) | < 0.05 | |
| sY100S | 20 (0.29%) | 29 (0.23%) | NS | |
| sQ101H/K/R | 298 (4.27%) | 229 (1.84%) | < 0.05 | ↑ |
| sM103I/T | 8 (0.11%) | 14 (0.11%) | NS | |
| sL109I/P/R | 12 (0.17%) | 24 (0.19%) | NS | |
| sP111L/Q/S | 10 (0.14%) | 21 (0.17%) | NS | |
| sG112K/R | 4 (0.06%) | 9 (0.07%) | NS | |
| sS114A/L/T | 117 (1.68%) | 137 (1.10%) | < 0.05 | ↑ |
| sT115A/N | 2 (0.03%) | 8 (0.06%) | NS | |
| sT116N | 6 (0.09%) | 32 (0.26%) | < 0.05 | ↑ |
| sS117G/N/R | 5 (0.07%) | 19 (0.15%) | NS | |
| sT118A/K/M/R/S/V | 31 (0.44%) | 32 (0.26%) | < 0.05 | ↑ |
| sG119E/R/T | 6 (0.09%) | 10 (0.08%) | NS | |
| sP120A/L/Q/S/T | 107 (1.53%) | 35 (0.28%) | < 0.05 | ↑ |
| sC121R/S | 1 (0.01%) | 1 (0.01%) | NS | |
| sK122R | 154 (2.21%) | 315 (2.53%) | NS | |
| sT123A/I/N/S/V | 56 (0.80%) | 91 (0.73%) | NS | |
| sC124R/Y | 4 (0.06%) | 9 (0.07%) | NS | |
| sT125A/M | 8 (0.11%) | 21 (0.17%) | NS | |
| sT/I126A/N/P/S | 366 (5.24%) | 534 (4.29%) | < 0.05 | ↑ |
| sP127H/L/S/T | 91 (1.30%) | 165 (1.32%) | NS | |
| sA128T/V | 7 (0.10%) | 15 (0.12%) | NS | |
| sQ129N/H/P/R | 90 (1.29%) | 129 (1.04%) | NS | |
| sG130A/K/N/R/S | 65 (0.93%) | 85 (0.68%) | NS | |
| sT131A/I/K/N | 133 (1.90%) | 219 (1.76%) | NS | |
| sS132F/P | 2 (0.03%) | 9 (0.07%) | NS | |
| sM133I/L/T | 196 (2.81%) | 277 (2.22%) | < 0.05 | ↑ |
| sF/Y134H/L/R/S/V | 65 (0.93%) | 51 (0.41%) | NS | |
| sS136F/P/Y | 6 (0.09%) | 4 (0.03%) | NS | |
| sC137W/Y | 9 (0.13%) | 5 (0.04%) | < 0.05 | ↑ |
| sC139R/S/Y | 3 (0.04%) | 9 (0.07%) | NS | |
| sT140I | 39 (0.56%) | 61 (0.49%) | NS | |
| sK141E/R | 3 (0.04%) | 4 (0.03%) | NS | |
| sP142L | 11 (0.16%) | 9 (0.07%) | NS | |
| sD144A/E | 17 (0.24%) | 26 (0.21%) | NS | |
| sG145A/R | 123 (1.76%) | 163 (1.31%) | < 0.05 | ↑ |
| sC147R/Y | 0 | 0 | NS | |
| sS154P | 1 (0.01%) | 2 (0.02%) | NS | |
| sA159G/V | 223 (3.19%) | 319 (2.56%) | < 0.05 | ↑ |
| sV168A | 143 (2.05%) | 234 (1.88%) | NS | |
| Average number/patient | 0.35 | 0.27 | < 0.05 | ↑ |
| Patient percentage with the MHR mutation(s) | 23.32% (1628/ 6982) | 18.51% (2306/12458) | < 0.05 | ↑ |
Table 3 Analysis of clinical features of sA159V-positive and sA159V-negative patients
| Clinical features | sA159V-positive, | sA159V-negative, | Univariate, | Univariate, | Multivariate, | Multivariate , P |
| Age in year | 46.67 ± 12.19 | 40.72 ± 12.83 | 0.00 | < 0.05 | 0.00 | < 0.05 |
| Gender, male | 214 (79.26%) | 15477 (80.74%) | 0.54 | > 0.05 | 0.97 | > 0.05 |
| Genotype, C%/B% | 90.00/10.00 | 84.31/14.82 | 0.03 | < 0.05 | 0.40 | > 0.05 |
| HBV DNA as log10 IU/mL | 4.54 (3.18, 6.55) | 4.37(2.95, 6.27) | 0.09 | > 0.05 | 0.40 | > 0.05 |
| ALT in U/L | 42 (25, 87) | 42 (26, 82) | 0.67 | > 0.05 | 0.32 | > 0.05 |
| AST in U/L | 41 (28, 83) | 38 (26,71) | 0.33 | > 0.05 | 0.61 | > 0.05 |
| TBIL in μmol/L | 16.10 (10.95, 25.45) | 14.30 (10.40, 22.10) | 0.13 | > 0.05 | 0.58 | > 0.05 |
| CHE in U/L | 5940 (3114, 8091) | 6764 (4276, 8469) | 0.11 | > 0.05 | 0.87 | > 0.05 |
| HBsAg, COI | 4987.83 ± 3128.43 | 5064.50 ± 2931.79 | 0.05 | > 0.05 | 0.15 | > 0.05 |
| Coexistent with ADV-r mutation | 41 (15.19%) | 1663 (8.68%) | 0.00 | < 0.05 | 0.00 | < 0.05 |
| Coexistent with LAM-r mutation | 97 (35.93%) | 5316 (27.73%) | 0.00 | < 0.05 | 0.01 | < 0.05 |
| Coexistent with ETV-r mutation | 20 (7.41%) | 868 (4.53%) | 0.04 | < 0.05 | 0.40 | > 0.05 |
- Citation: Huang BX, Liu Y, Fan ZP, Si LL, Chen RJ, Wang J, Luo D, Wang FS, Xu DP, Liu XG. Investigation of immune escape-associated mutations of hepatitis B virus in patients harboring hepatitis B virus drug-resistance mutations. World J Gastroenterol 2020; 26(35): 5314-5327
- URL: https://www.wjgnet.com/1007-9327/full/v26/i35/5314.htm
- DOI: https://dx.doi.org/10.3748/wjg.v26.i35.5314