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应用聚合酶链（ＰＣＲ）方法，分别扩增乙型肝炎病毒（ＨＢＶ）标志为ＨＢｓＡｇ（＋）、ＨＢｅＡｇ（＋）、抗ＨＢｃ（＋）的慢性乙型肝炎（ＣＨＢ）１８例（第一组），ＨＢＶ标志为ＨＢｓＡｇ（＋）、抗ＨＢｅ（＋）和抗ＨＢｃ（＋）的慢性乙型肝炎２１例（第二组），以及ＨＢＶ标志与第二组相同的体检健康的正常人１５例（第三组）。其ＰＣＲ的阳性率分别为８３．３％，７１．４％和３３．３％。第二组与第三组相比有显著差异（Ｐ＜０．０５），提示病毒的复制与病情活动有关。对ＰＣＲ扩增后阳性的３０例进行克隆测序分析，发现有５例前核心区基因有变异，均见于第二组病例中。第一组病例无穷变株出现，二组相比有显著差异（Ｐ＜０．０５）。其突变情况为：２例１８９８位Ｇ→Ａ突变，其中１例临床表现为重型肝炎，１例为１９０１位Ｇ→Ａ突变，１例为１８９１位Ｔ→Ｃ突变，另１例为１８３９位Ａ→Ｇ突变。后二种突变形式目前尚未见报道，所有这些均表明ＨＢＶ标志为ＨＢ－ｓＡｇ（＋）、抗ＨＢｅ（＋）和抗ＨＢｃ（＋）的慢乙肝病例，ＨＢＶ前核心区基因变异的发生率较高，可能与病毒迫于机体免疫压力所产生的免疫逃避有关。
18 cases of chronic hepatitis B (CHB) with hepatitis B virus (HBV) markers of HBsAg (+), HBeAg (+) and anti-HBc (+) were amplified by polymerase chain reaction ), 21 cases of chronic hepatitis B (HBsAg (+), anti HBe (+) and anti HBc (+)) in HBV group and 15 healthy subjects (The third group). The positive rates of PCR were 83.3%, 71.4% and 33.3% respectively. There was significant difference between the second group and the third group (P <0.05), suggesting that the virus replication is related to the disease activity. PCR amplification positive 30 cases were cloned and sequenced and found that there are 5 cases of mutations in the core gene, were found in the second group of cases. The first group of cases of infinitive strains appeared, there was significant difference between the two groups (P <0.05). The mutation was as follows: 2 cases of 1898 G → A mutation, 1 case of severe hepatitis, 1 case of 1901 G → A mutation, 1 case of 1891 T → C mutation and the other case of 1839 A → G mutation. The latter two types of mutations have not been reported so far, all of which indicate that the incidence of HBV gene mutation in HBV pre-core region is higher than those in HBsAg-positive, HBeAg-positive and anti-HBc High, may be related to the immune evasion caused by the virus being forced by the body’s immune pressure.