Table 3.
Clinical significance of hepatitis B surface antigen mutations in chronic hepatitis B
| Ref. | Country | No. of patients | Type of study | Patients with HBsAg mutation, n (%) | Clinical significance |
| Abe et al[103] | Japan | 40 | Case-control | 27/30 (90) in HCC+ | Correlation between preS1-S2 deletion and HCC (P < 0.001) |
| 0/10 (0) in HCC- | |||||
| Bläckberg et al[106] | Sweden | 35 | Case-control | 8/16 (50) in HCC+ | No correlation between Pre-S2 mutations and HCC (P > 0.05) |
| 4/19 (21) in HCC- | |||||
| Cao et al[94] | China | 97 | Case-control | 34/47 (72.3) in HCC+ | Correlation between pre-S deletion or pre-S2 start codon mutation and HCC (P < 0.001) |
| 13/50 (26) in HCC- | |||||
| Chen et al[88] | Taiwan | 152 | Cross-sectional | 26/50 (52.0) in HCC+ | Correlation between pre-S deletion and HCC (P < 0001) |
| 30/102 (29.4) in HCC- | |||||
| Chen et al[95] | Taiwan | 240 | Case-control | Pre-S deletion: 28/80 (35) in HCC+ vs 27/160 (16.9) in HCC- | Correlation between pre-S deletion (P = 0.002), W4P/R (P = 0.021) and M1V/I/A mutations (P = 0.011) and HCC |
| Choi et al[90] | South Korea | 300 | Cross-sectional | W4P/R: 10/80 (12.5) in HCC+ vs 7/160 (4.4) in HCC- M1V/I/A: 23/80 (28.8) in HCC+ vs 24/160 (15) in HCC- | Correlation between pre-S deletion or pre-S2 start codon mutation and HCC (P < 0.001) |
| 31/72 (43.1) in HCC+ | |||||
| Fang et al[93] | China | 66 | Case-control | 51/228 (22.4) in HCC- | Correlation between pre-S deletion and HCC (P < 0.01) |
| 15/33 (45.5) in HCC+ | |||||
| Gao et al[91] | China | 79 | Cross-sectional | 6/33 (18.2) in HCC- | Correlation between pre-S deletion and HCC (P = 0.001) |
| 10/26 (38.5) in HCC+ | |||||
| Huang et al[104] | Taiwan | 38 | Case-control | 3/53 (5.7) in HCC- | Correlation between pre-S deletion and HCC (P = 0.008) |
| 9/19 (47.4) in HCC+ | |||||
| Hung et al[110] | Taiwan | 313 | Cross-sectional | 1/19 (5.3) in HCC- | Correlation between pre-S deletion and HCC (P < 0.001) |
| 41/146 (40) in HCC+ | |||||
| Huy et al[85] | 12 countries | 352 | Cross-sectional | 5/167 (3.0) in HCC- | Correlation between pre-S1/S2 deletion and pre-S2 start codon mutations and HCC (P < 0.05) |
| 17/49 (34.7) in HCC+ | |||||
| 50/303 (16.5) in HCC- | |||||
| Jang et al[96] | South Korea | 119 | Cross-sectional | 17/48 (35.4) in HCC+ | Correlation between pre-S deletion and HCC (P < 0.05) |
| 13/71 (18.3) in HCC- | |||||
| Kao et al[99] | Taiwan | 168 | Case-control | 56/112 (50.0) in HCC+ | Correlation between pre-S deletion and HCC (P < 0.001) |
| 4/56 (7.1) in HCC- | |||||
| Lee et al[98] | South Korea | 270 | Case-control | 28/135 (18.5) in HCC+ | Correlation between pre-S2 deletion and HCC (P < 0.001) |
| 6/135 (4.4) in HCC- | |||||
| Lee et al[107] | South Korea | 247 | Cross-sectional | 19/153 (12.4) in advanced liver disease (LC or HCC) 1/94 (1.1) in non-advanced liver disease | Correlation between W4P/R mutation and HCC or cirrhosis (P < 0.05) |
| Lin et al[89] | Taiwan | 266 | Cross-sectional | 19/64 (29.7) in HCC+ | Correlation between pre-S deletion and HCC (P = 0.02) |
| 25/202 (12.4) in HCC- | |||||
| Mun et al[92] | South Korea | 120 | Cross-sectional | Pre-S1: 13/40 (32.5) in HCC+ vs 11/80 (13.7) in HCC- | Correlation between pre-S1 (P = 0.027) and pre-S1 start codon mutations (P = 0.048) and HCC. Correlation between pre-S2 deletions and cirrhosis (P = 0.001) |
| Pre-S1 start codon: 9/40 (22.5) in HCC+ vs 4/80 (5.0) in HCC- Pre-S2: 8/21 (38.1) in LC+ vs 4/59 (6.8) in LC- | |||||
| Qu et al[102] | China | 193 | Case-control | Pre-S deletion: 28/96 (29.2) vs 11/97 (11.3), Pre-S2 start codon: 17/96 (17.7) vs 7/97 (7.2), T31C: 23/96 (24.0) vs 37/97 (38.1), T53C: 36/96 (37.5) vs 23/97 (23.7), T766A: 13/96 (13.5) vs 14/97 (14.4) in HCC+ vs HCC- | Correlation between pre-S deletion (P = 0.003), pre-S2 start codon (P = 0.027), T31C (P = 0.044), T53C (P = 0.027) but not T766A mutation (P = 0.966) and HCC |
| Raimondo et al[87] | Italy | 110 | Cross-sectional | 16/19 (84.2) in HCC | Correlation between pre-S2 deletion or start codon mutation and HCC (P < 0.02) |
| 40/91 (43.9) in HCC- | |||||
| Sinn et al[100] | South Korea | 195 | Cohort | 13/24 (54.2) in HCC+ | Correlation between pre-S mutation and HCC (P < 0.001) |
| 31/171 (18.1) in HCC- | |||||
| Sugauchi et al[86] | Japan | 160 | Cross-sectional | 20/58 (34.5) in advanced liver disease (LC or HCC) | Correlation between pre-S deletion and HCC or cirrhosis (P < 0.05) |
| 17/102 (16.7) in non-advanced liver disease | |||||
| Sung et al[108] | Hong Kong | 26 | Case-control | T31C: 6/16 (37.5) in HCC+ vs 0/10 (0.0) in HCC- T53C: 6/16 (37.5) in HCC+ vs 1/10 (10.0) in HCC- | Correlation between T31C and T53C mutations and HCC (P < 0.05) |
| Thongbai et al[105] | Thailand | 154 | Cross-sectional | 24/65 (36.9) in HCC+ | No correlation between pre-S1/S2/S deletion or start codon mutation and HCC (P > 0.1) |
| 34/89 (38.2) in HCC- | |||||
| Yeung et al[97] | Taiwan | 192 | Case-control | 28/96 (29.2) in HCC+ | Correlation between pre-S deletion and HCC (P = 0.015) |
| 14/96 (14.6) in HCC- | |||||
| Zhao et al[101] | China | 317 | Case-control | 74/157 (47.1) in HCC+ | Correlation between pre-S deletion and HCC (P < 0.001) |
| 45/160 (28.1) in HCC- | |||||
| Zhu et al[109] | China | 55 | Case-control | 4/20 (20.0) with Pre-S2 start codon, 5/20 (25.0) with T53C and 3/20 with T766A in HCC+ vs 0/20 in HCC- | Correlation between pre-S2 start codon (P = 0.014), T53C (P = 0.004) and T766A mutation (P = 0.043) and HCC |
HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HBsAg: Hepatitis B surface antigen; LC: Liver cirrhosis.