Lengths of hepatitis B viremia and antigenemia in blood donors: preliminary evidence of occult (hepatitis B surface antigen-negative) infection in the acute stage.

BACKGROUND: The Japanese Red Cross (JRC) implemented a fully automated pooling and nucleic acid amplification test (NAT) system for testing seronegative donations. The JRC sample repository and repeat blood donations allowed for lookback and follow-up studies of hepatitis B virus (HBV) DNA-positive donors, who tested negative for hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antigen in the JRC screening system. STUDY DESIGN AND METHODS: From February 1, 2000, to March 31, 2003, 17,314,486 units were tested in 50-sample pools with a semiautomated multiplex assay system (AMPLINAT MPX test, Roche). During this period, 328 HBV DNA-positive donations were found. From 26 of these donors, sequential samples were available at short intervals. This enabled us to examine the dynamics of viral markers in acute HBV infection. The length of detectable periods of plasma viremia and antigenemia were estimated by regression analysis from the results obtained in the quantitative polymerase chain reaction assay (JRC) and HBsAg enzyme immunoassay (Auszyme II, AxSYM, Abbott) and chemiluminescence immunoassay (Abbott). RESULTS: The median length of detectable HBV DNA in individual donation and 20-sample minipool (MP) NAT format was estimated to be 74 and 50 days, respectively, whereas the median length of detectable HBsAg was estimated to be 42 days. Six of the 26 donors were infected with mutant viruses, and 3 of these 6 donors did not develop detectable HBsAg during the entire observation period, despite a moderately high viral load of 10(4) to 10(5) HBV DNA copies per mL. CONCLUSION: Transmission of mutant virus may cause occult HBV infection in the acute stage. HBV NAT, even in MP configuration, is more effective than HBsAg testing and capable of interdicting infected donors in the pre- and post-HBsAg window periods.

Ongoing subclinical infection of hepatitis E virus among blood donors with an elevated alanine aminotransferase level in Japan.

Ongoing subclinical infection of hepatitis E virus (HEV) has not been fully studied. In the present study, serum samples were collected from 6700 voluntary blood donors with an elevated alanine aminotransferase (ALT) level of 61-476 IU/l at a Japanese Red Cross Blood Center, and were tested for the presence of IgG, IgM and IgA classes of antibodies to HEV (anti-HEV) by in-house ELISA and HEV RNA by nested RT-PCR. Overall, 479 blood donors (7.1%) were positive for anti-HEV IgG, including 8 donors with anti-HEV IgM and 7 donors with anti-HEV IgA. Among the nine donors with anti-HEV IgM and/or anti-HEV IgA, six had detectable HEV RNA. The presence of HEV RNA was further tested in 10-sample minipools of sera from the remaining 6691 donors, and three donors including one without anti-HEV IgG were found to be positive for HEV RNA. When stratified by ALT level, the prevalence of HEV RNA was significantly higher among the 109 donors with ALT > or = 201 IU/l than among the 6591 donors with ALT of 61-200 IU/l (2.8% vs. 0.1%, P < 0.0001). The HEV isolates obtained from the nine viremic donors segregated into genotype 3, shared a wide range of identities of 85.6-98.5% and were 87.3-93.9% similar to the Japan-indigenous HEV strain (JRA1), in the 412-nucleotide sequence of open reading frame 2. This study suggests that approximately 3% of Japanese individuals with ALT > or = 201 IU/l have ongoing subclinical infection with various HEV strains.

Characterization of genotype H hepatitis B virus strain identified for the first time from a Japanese blood donor by nucleic acid amplification test.

The Japanese Red Cross has been conducting a nucleic acid amplification test (NAT) screening for hepatitis B virus (HBV), hepatitis C virus and human immunodeficiency virus 1 among blood donors since July 1 1999. The first case of HBV genotype H was found and reported in Japan. Serological markers of HBV were not detected in this NAT-positive donation. It may be that the positive donation was in the serological window period at the early stage of infection. The complete genome of 3215 nt was sequenced, and the sequence had 99.3 % homology with the strain from Los Angeles, USA (LSA2523). Here, a leucine zipper motif was found in the region of the HBV surface antigen conserved through genotypes A-H.