The Two Different States of Hepatitis B Virus DNA in Asymptomatic Carriers (HBe-Antigen-Positive versus Anti-HBe-Positive Asymptomatic Carriers)

During the course of hepatitis B virus (HBV)infection, there exists a long period of normal liverfunction tests with different states of HBeAg/Ab. As thestate of HBV in asymptomatic carriers was not well characterized, we quantitatively andqualitatively examined HBV in both HBeAg-positive andanti-HBe-positive asymptomatic carriers. Sera from 10HBeAg-positive and 27 anti-HBe-positive asymptomatic carriers were analyzed. The amount of HBV DNAwas determined by dot-blot hybridization and polymerasechain reaction. The mutations in precore and coreregions, spanning 636 nucleotides, of hepatitis B virus were examined by directly sequencing theamplified 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 inHBeAg-positive cases was 109.1±0.7copies/ml, while that in anti-HBe-positive cases was101.0±1.5 copies/ml. There were no 0.7missense mutations in the entire precore and core genes of HBV DNA taken fromHBeAg-positive asymptomatic carriers. In contrast, manymutations (mean 9.0 ± 3.3, range 6-14) weredetected in the core gene of seven anti-HBe-positiveasymptomatic carriers including two cases with increments of themutations. Analysis of the precore region revealed threewild-type and four mutant-type (including one coexistingwith 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 andremains as the wild type, whereas in theanti-HBe-positive phase a drastically reduced amount of HBV with many mutationsremains, probably as a consequence of the long-lastinginteraction with the host. Nevertheless, such smallamount of virus could cause fulminant hepatic failure. It is important to make further clinical andvirological investigations in order to understand thestate of asymptomatic carrier.