1. HBV DNA International Standard: At present, there is no international standard of HBV-DNA to evaluate the sensitivity and specificity of the HBV-DNA NAT assays. We participated a study organized by NIBSC and WHO (with 24 organizations world wide participating) to develop several HBV-DNA standards for quantitative assays of HBV infections. The results of our collaborative study showed that 3 candidate preparations for international standards of HBV DNA have a mean estimate of 6.42, 6.30, and 5.03 log10 geq/ml respectively (geq=genome equivalent). These standards will be suggested for use to evaluate the sensitivity of commercial HBV NAT assay products. 2. Silent HBV: The uncommon finding of """"""""silent"""""""" hepatitis B virus (HBV), characterized by the presence of HBV DNA in serum or liver tissue in the absence of hepatitis B surface antigen (HBsAg) in serum, is thought to be caused by HBV mutants that produce a very low level of HBsAg, viruses which escape detection by currently available serologic tests. Thus this is an issue of blood transfusion safety. Sera from patients with HCC were assayed for HBsAg and other markers. Sixty-one patients with HCC whose sera were HBsAg-negative were further studied for HBV DNA, including 8 from various areas of the USA, 11 from Vancouver, Canada, 30 from Japan, and 12 from China. HBV DNA was detected by nested PCR in 4 of the 8 HCCs from HBsAg (-) patients from the USA (50%), in 6 of the 11 from Canada (55%), in 22 of the 30 from Japan (73%), and in 12/12 from China (100%). Sequencing of the 241-bp S gene PCR product has been completed thus far for six patients from Canada and four from the USA; each contains the expected S gene sequence with one or more nucleotide variations differing from the consensus sequence and from each other, which rules out the possibility that the positive results could be due to contamination. Four of the 6 HBV DNA-positive HCC patients from Canada were negative for anti-HBc and anti-HBs as well as for HBsAg. Conclusions: HBV DNA was detected in a number of HCCs from HBsAg-seronegative patients from the USA, Canada, Japan and China. Since """"""""silent"""""""" HBV is defined by its ability to escape detection by serologic tests for HBsAg, these findings, though rare, are of interest for blood donor screening, as well as in understanding the development of such complications of chronic HBV infection as HCC.
