Objective: Carriers of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Japan were estimated on a national basis. Methods: Sera from the first-time blood donors aged 16–64 years in eight jurisdictions of the Japanese Red Cross Blood Center during 1995–2000 were tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV). Viremia with HCV was estimated to be present in 70% of donors with anti-HCV. Results: HBsAg was detected in 22,018 of 3,485,648 (0.63%) blood donors including 12,990 of 1,780,149 (0.73%) men and 9,028 of 1,705,499 (0.53%) women, and anti-HCV in 17,010 (0.49%) including 8,504 (0.48%) men and 8,506 (0.50%) women. Multiplying the carrier rate by the population registered in the Census 2000, the total HBV carriers aged 15–65 years were estimated at 967,753 (95% confidence interval 806,760–1,128,745), of whom 571,210 (479,267–663,152) were men and 396,543 (327,494–465,593) were women. Likewise, the total HCV carriers were estimated at 884,954 (95% confidence interval 725,082–1,044,826), of whom 464,363 (377,927–550,799) were men and 420,591 (347,156–494,027) were women. Conclusion: Estimated numbers of HBV and HCV carriers would help plan to prevent the development of hepatocellular carcinoma in Japan.

Objective: To estimate total numbers of undiagnosed carriers of hepatitis C virus (HCV) and hepatitis B virus (HBV) in Japan. Methods: Area- and age-specific prevalence of HCV as well as HBV was determined in the first-time blood donors [20–39 years (n = 2,429,364)] and examinees of periodical health check-ups [40–74 years (6,204,968 for HCV and 6,228,967 for HBV)] in Japan. Prevalence in adolescents [5–19 years (79,256 for HCV and 68,792 for HBV)] was determined in a single prefecture, and that of HCV in the elderly (≧75 years) was estimated by the exponential model. HBV infection was determined by the detection of hepatitis B surface antigen, and HCV infection by either the algorithm or assuming persistent infection in 70% of the individuals with antibody to HCV. Results: Of the total population of 127,285,653 in 2005, 807,903 (95% CI 679,886–974,292) were estimated to be infected with HCV at a carrier rate of 0.63%, and 903,145 (837,189–969,572) with HBV at that of 0.71%. Conclusion: Accurate estimation of undiagnosed HCV and HBV carriers in the general population would help to predict the future burden of liver disease, and take appropriate measures for improving healthcare.

Although the CID50 of approximately 10 copies was similar for the two HBV genotypes, the doubling time and pre-HBV nucleic acid amplification technology (<100 copies/mL) window period in chimps infected with the lowest infectious dose seemed to be shorter for genotype C than for genotype A.

Studies of hepatitis B virus (HBV) infection in non-human primates such as chimpanzees are no longer possible due to ethical considerations and the endangered status of chimpanzees since April 2007 in Japan. A human hepatocyte transplanted chimeric mouse was used to characterize HBV infectivity in serial stages of acute infection. Chimeric mice were inoculated intravenously with serum samples obtained from an experimentally infected chimpanzee with HBV. Sera from the pre-acute phases (i.e., rump-up viremia prior to anti-HBc) and late acute phases (i.e., declining phase of HBsAg and anti-HBcAb positive) were collected from the chimpanzees 57 and 244 days after inoculation. These sera contained 2.6 x 10(6) and 2.8 x 10(6) copies/ml of HBV DNA, respectively. Three chimeric mice inoculated intravenously with 100 microl of pre-acute serum (equivalent to 10(0) copy of HBV DNA) developed an HBV infection. The three chimeric mice that received 100 microl of pre-acute serum (equivalent to 10(1) copies of HBV DNA), developed high levels of serum HBV DNA. None of the three chimeric mice inoculated with 100 microl of 1:10(4) dilution (equivalent to 10(1) copies of HBV DNA) of late-acute serum was infected, while only one of three chimeric mice inoculated with 100 microl of 1:10(3) dilution (equivalent to 10(2) copies of HBV DNA) of late-acute serum developed an HBV infection. Based on these results, chimeric mice can be used as animal models for the study of HBV infectivity, pathogenesis and control. The results show that pre-acute phase HBV serum is about 100-times more infectious than late acute phase serum.

Objective: To determine the copy number of hepatitis C virus (HCV) RNA, determined by nucleic acid amplification test (NAT) for screening blood units in Japan, that can transmit infection to chimpanzees. Methods: Fresh-frozen plasma with markers of HCV infection, as well as inocula pedigreed from 1 of them, were evaluated for the infectious activity in chimpanzees. Results: One unit each (273–282 ml) of fresh-frozen plasma from 2 blood donors or a pool from 13 donors to make a unit, which contained high-titered antibody to HCV but without HCV RNA detectable by NAT, did not infect any of 3 chimpanzees. Two chimpanzees were infected, however, when they were inoculated with 1 ml of serum from a blood donor in the ‘window period’ of HCV infection and containing 7.0 × 10⁶ copies/ml of HCV RNA. The preacute phase serum from 1 of them harvested 7 weeks after the inoculation was titrated in 2 chimpanzees, and an inoculum containing approximately 2 × 10¹ copies of HCV RNA could transmit infection to both of them. Conclusion: Approximately 20 copies of HCV can transmit infection to recipients, which needs to be taken into consideration in planning the screening of blood units for HCV RNA by NAT. Although the sensitivity of present NAT could be improved further, there would be a limit of it in detecting a low-level HCV RNA in the window period of donors with the infectious capacity in recipients.

Our results showed that operation and blood transfusion were potential risk factors for HBV and HCV infection, respectively, and supposed that horizontal HBV transmission may be frequent in adults in Cambodia. Hence, for reducing HBV and HCV infections, it is necessary to improve the safety of blood and medical treatment.

In Binh Thuan, prevalences of HBV and HCV infections are high, HBV genotype B and HCV genotype 6a are predominant, and horizontal HBV transmission may still occur. Therefore, raising the coverage of a universal HBV vaccination program may be an effective liver cancer control in Vietnam.

RESULTS.In AH patients and HBV-inoculated chimpanzees with HBsAg loss, CXCL9, CXCL10, CXCL11, CXCL13, and IL-21 were elevated at hepatitis with subsequent decline of HBsAg. Interestingly, IL-21 elevation was observed only in resolving AH patients but not in nonresolvers. CXCL13 and IL-21 elevation was not observed in CH patients who failed to attain HBsAg loss, even at hepatic flare. A concomitant increase of CXCL13 and IL-21 was significant in CH patients who attained HBsAg seroconversion with a sequential therapy. CONCLUSION.Elevation of serum CXCL9, CXCL10, CXCL11, CXCL13, and IL-21 might be a hallmark of functional cure of AH or CH patients.