Hepatitis B surface antigen particles of subtypes adw and adr, and compound subtype (adwr) in symptom‐free carriers in Japan

Abstract

Of sera from 1,878 Japanese blood donors who carried hepatitis B surface antigen (HBsAg), 420 were subtyped as adw (22.4%) and 1,443 as adr (76.8%); only 15 (0.8%) contained HBsAg of subtype ayw or ayr. Sera with HBsAg/adr had higher HBsAg titres than those with HBsAg/adw (geometric mean of haemagglutination titre: 10.1 +/- 2.4 vs. 9.7 +/- 2.4, p less than 0.01), and a higher prevalence of hepatitis B e antigen (24% vs. 13%, p less than 0.001). Carriers of HBsAg/adr progressively predominated over those of HBsAg/adw with increasing age. Of sera from 1,863 carriers of HBsAg/adw or HBsAg/adr, 182 (9.8%) contained HBsAg particles with both subtypic determinants in the w/r allele. The presence of w and r determinants on the same particles was ascertained by sandwiching them between monoclonal antibody with the specificity for w and that with the specificity for r. HBsAg particles of compound subtype (adwr) were found more often in sera with hepatitis B e antigen than those without it (145/403 [36.0%] vs. 37/1,460 [2.5%], p less than 0.001). Sera with HBsAg/adwr particles had HBsAg titres higher than those without them (12.4 +/- 1.9 vs. 9.7 +/- 2.3, p less than 0.001). HBsAg/adwr particles arise from phenotypic mixing of the S-gene product of wild-type virus and that of mutants with point mutations for subtypic changes. The results obtained indicated that HBV strains of subtype adr have a higher replicative activity than those of adw, and suggested that mutations in the S gene for subtypic changes would be associated with an active replication of hepatitis B virus.

HBV subtype as a marker of the clinical course of chronic HBV infection in Japanese patients

“…Therefore, we speculate that differences in the clinical characteristics of patients with HBV can not be explained by only the HBV genotype and that HBV subtype is also an important factor in determining clinical outcomes. In support of this, past reports demonstrated that subtype adr has a higher replicative activity than subtype adw [Kanagawa et al, 1992], and subtypes may affect the development of chronic liver disease through their relationship with HBeAg/antiHBe status [Shiina et al, 1991]. A recent study describes a correlation between genotype and the clinical course in cirrhotic patients with subtype adw [Tsubota et al, 2001].…”

“…Similar to HBV genotype, the distribution of HBV subtype throughout the world is regionally specific [Courouce et al, 1983]. Furthermore, HBV subtype may affect the development of chronic liver disease through association with HBe Ag/anti-HBe status [Shiina et al, 1991] and may be associated with replicative activity of HBV [Kanagawa et al, 1992]. Therefore, we have investigated the relationship between HBV subtype and the clinical aspects of chronic HBV infection.…”

“…Therefore, the duration of HBV infection is not related to the patients' outcome. Compound subtypes are found rarely (1.5%) in blood donors [Tachibana et al, 1989], but are frequent (36%) in Japanese carriers with actively replicating HBV [Kanagawa et al, 1992]. These compound subtypes might be produced in hepatocytes infected with wildtype HBV of a certain subtype and its mutants with a phenotypic change for another subtype [Okamoto et al, 1987].…”

“…In addition, a recent report on the effects of lamivudine therapy indicates that the HBV adw subtype is associated with a high risk of lamivudine resistance [Zollner et al, 2001]. However, the clinical impact of HBV subtypes on clinical manifestations is not well elucidated [Shiina et al, 1991;Kanagawa et al, 1992;Swenson et al, 2001;Tsubota et al, 2001]. Therefore, we investigated the HBsAg subtype distribution in this area, emphasizing the correlation between HBV subtype and the prognosis of chronic HBV infection.…”

Co-Infection with Hepatitis B Virus Genotype D and Other Genotypes in Western Japan

“…As a result, the present serotyping method may not be sensitive enough to screen patients co-infected with different serotypes. On the other hand, several other reports have described compound serotypes, such as adwr or adywr in infected patients [30][31][32][33] . Further study is needed to determine whether patients with compound subtypes are co-infected with different genotypes.…”