Fujiwara K, Yokosuka O, Ehata T, Chuang W L, Imazeki F, Saisho H, Omata M
First Department of Medicine, Chiba University School of Medicine, Chiba City, Japan.
Dig Dis Sci. 1998 Feb;43(2):368-76. doi: 10.1023/a:1018870709286.
During the course of hepatitis B virus (HBV) infection, there exists a long period of normal liver function tests with different states of HBeAg/Ab. As the state of HBV in asymptomatic carriers was not well characterized, we quantitatively and qualitatively examined HBV in both HBeAg-positive and anti-HBe-positive asymptomatic carriers. Sera from 10 HBeAg-positive and 27 anti-HBe-positive asymptomatic carriers were analyzed. The amount of HBV DNA was determined by dot-blot hybridization and polymerase chain reaction. The mutations in precore and core regions, spanning 636 nucleotides, of hepatitis B virus were examined by directly sequencing the amplified HBV DNA. HBV DNA was detected in all 10 HBeAg-positive cases, whereas it was found in only 7 of 27 (26%) anti-HBe-positive cases by the nested PCR method. The mean amount of HBV DNA in HBeAg-positive cases was 10(9.1 +/- 0.7) copies/ml, while that in anti-HBe-positive cases was 10(1.0 +/- 1.5) copies/ml. There were no missense mutations in the entire precore and core genes of HBV DNA taken from HBeAg-positive asymptomatic carriers. In contrast, many mutations (mean 9.0 +/- 3.3, range 6-14) were detected in the core gene of seven anti-HBe-positive asymptomatic carriers including two cases with increments of the mutations. Analysis of the precore region revealed three wild-type and four mutant-type (including one coexisting with wild-type) cases. These data suggest that HBV exists in quite different ways in "asymptomatic" carriers; in the HBeAg-positive phase HBV probably coexists with the host and remains as the wild type, whereas in the anti-HBe-positive phase a drastically reduced amount of HBV with many mutations remains, probably as a consequence of the long-lasting interaction with the host. Nevertheless, such small amount of virus could cause fulminant hepatic failure. It is important to make further clinical and virological investigations in order to understand the state of asymptomatic carrier.
在乙型肝炎病毒（HBV）感染过程中，存在一段肝功能检查正常但HBeAg/Ab状态不同的较长时期。由于无症状携带者中HBV的状态尚未得到充分表征，我们对HBeAg阳性和抗-HBe阳性无症状携带者的HBV进行了定量和定性检测。分析了10例HBeAg阳性和27例抗-HBe阳性无症状携带者的血清。通过斑点杂交和聚合酶链反应测定HBV DNA的量。通过对扩增的HBV DNA进行直接测序，检测乙型肝炎病毒前核心区和核心区跨度为636个核苷酸的突变。10例HBeAg阳性病例均检测到HBV DNA，而采用巢式PCR方法在27例抗-HBe阳性病例中仅7例（26%）检测到HBV DNA。HBeAg阳性病例中HBV DNA的平均量为10(9.1±0.7)拷贝/ml，而抗-HBe阳性病例中为10(1.0±1.5)拷贝/ml。从HBeAg阳性无症状携带者中获取的HBV DNA的整个前核心基因和核心基因均未发现错义突变。相比之下，在7例抗-HBe阳性无症状携带者的核心基因中检测到许多突变（平均9.0±3.3，范围6 - 14），其中2例突变增加。前核心区分析显示有3例野生型和4例突变型（包括1例与野生型共存）病例。这些数据表明，HBV在“无症状”携带者中以截然不同的方式存在；在HBeAg阳性阶段，HBV可能与宿主共存并保持野生型，而在抗-HBe阳性阶段，HBV数量大幅减少且存在许多突变，这可能是与宿主长期相互作用的结果。然而，如此少量的病毒仍可能导致暴发性肝衰竭。为了解无症状携带者的状态，进一步进行临床和病毒学研究很重要。
