Keiko Katayama

Sex- and Age-Specific Carriers of Hepatitis B and C Viruses in Japan Estimated by the Prevalence in the 3,485,648 First-Time Blood Donors during 1995–2000

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.

Total numbers of undiagnosed carriers of hepatitis C and B viruses in Japan estimated by age- and area-specific prevalence on the national scale.

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.

Minimum infectious dose of hepatitis B virus in chimpanzees and difference in the dynamics of viremia between genotype A and genotype C

BACKGROUND: In planning optimal hepatitis B virus (HBV) blood screening strategies, the minimum infectious dose and early dynamics of HBV need to be determined for defining the window period for HBV DNA as well as for hepatitis B surface antigen (HBsAg).

Titration of hepatitis B virus infectivity in the sera of pre‐acute and late acute phases of HBV infection: Transmission experiments to chimeric mice with human liver repopulated hepatocytes

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 × 106 and 2.8 × 106 copies/ml of HBV DNA, respectively. Three chimeric mice inoculated intravenously with 100 µl of pre‐acute serum (equivalent to 100 copy of HBV DNA) developed an HBV infection. The three chimeric mice that received 100 µl of pre‐acute serum (equivalent to 101 copies of HBV DNA), developed high levels of serum HBV DNA. None of the three chimeric mice inoculated with 100 µl of 1:104 dilution (equivalent to 101 copies of HBV DNA) of late‐acute serum was infected, while only one of three chimeric mice inoculated with 100 µl of 1:103 dilution (equivalent to 102 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. J. Med. Virol. 80:2064–2068, 2008.

Titration of Hepatitis C Virus in Chimpanzees for Determining the Copy Number Required for Transmission

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.

High incidence of extrahepatic manifestations in an HCV hyperendemic area.

We previously investigated the incidence of extrahepatic manifestations including oral precancerous disease among the inhabitants in a hepatitis C virus (HCV) hyperendemic area in Fukuoka in Japan. The present study design was based on a prospective cohort at the other HCV hyperendemic area. One oral surgeon examined the oral lesions of 59 adult inhabitants (21 men, 38 women; mean age of 70.7 years), of a hyperendemic area of HCV infection. Furthermore, all subjects were interviewed regarding the natural history of extrahepatic manifestations. All sera were examined for antibodies to HCV (anti-HCV), serum HCV RNA, HCV genotype, antinuclear antibody (ANA), rheumatoid factor (RF) activity, and anti-SS-A and-B antibodies. Anti-HCV or HCV RNA was detected in sera from 59 (100%) or 57 (96.7%) of all subjects. Oral lichen planus (OLP), leukoplakia with leukoedema, or only leukoedema was observed in 8 (8.5%), 1 (1.7%), or 2 (3.4%) subjects, respectively. The incidence of all subjects with one or more HCV-related extrahepatic manifestation was 66.1% (39/59). The subjects with dry mouth were 25.4% (15/59). There was no relation among these autoantibodies, symptoms of dry mouth, or prevalence of HCV-associated extrahepatic manifestations. These findings demonstrate that the inhabitants with HCV infection showed various extrahepatic manifestations, and was not always limited to specific HCV areas.

Incidence rates of hepatitis B and C virus infections among blood donors in Hiroshima, Japan, during 10 years from 1994 to 2004.

Objective: Although prevalence rates of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections have kept decreasing in blood donors, there is little information on incidence rates of these hepatitis viruses in Japan. Methods: During 10 years from June 1994 through April 2004, 418,269 inhabitants of Hiroshima, Japan, donated blood (1,409,465 units in total). They were screened for serum markers of HBV and HCV infections, and individuals who developed de novo infections were identified. Results: Infection with HBV occurred at a rate of 2.78 per 100,000 person-years (95% confidence interval: 1.78–4.14/100,000 person-years) and that with HCV at a rate of 1.86 per 100,000 person-years (95% confidence interval: 1.06–3.01/100,000 person-years). Residual risks of transmission by transfusions, based on the relationship risk [window period (estimated at 0.15 and 0.03 years in chimpanzees inoculated with minimum infectious doses for HBV and HCV, respectively) × incidence], were 1/243,000 for HBV and 1/1,960,000 for HCV infections. Conclusion: At present, incidence rates of HBV and HCV infections are extremely low in Japan.

Mother-to-infant transmission occurs more frequently with GB virus C than hepatitis C virus

SummaryA total of 107 hepatitis C virus (HCV)-infected pregnant women were screened for GB virus C (GBV-C) RNA in their sera, and 11 (10.3%) were positive. Among 11 infants born to these HCV/GBV-C co-infected mothers, GBV-C RNA was detected in 7 (63.6%) while HCV RNA was found in 1 (9.1%) within 1 year after birth: this difference was statistically significant (p = 0.023). The mothers of infected infants had significantly higher serum titers of GBV-C RNA than those of uninfected infants: 106.7±0.5 vs 104.0±1.0 copies/ml in average (p=0.001). The baby in whom HCV RNA was found was also positive for GBV-C RNA, and had an elevation in serum transaminase levels, whereas all the other GBV-C infected infants showed no evidence for hepatitis. A family study, performed on 2 of the 7 infected cases, revealed that all the elder siblings of the index infants were also GBV-C RNA-positive. Nucleotide sequence of GBV-C RNA, amplified by PCR from an NS3 region, was completely identical between the mother and the infant within each family, but varied significantly across different families. These results suggest that GBV-C is more easily transmitted from mother to infant than HCV, although hepatitis is not caused thereby.

Seroprevalence, genotypic distribution and potential risk factors of hepatitis B and C virus infections among adults in Siem Reap, Cambodia

We investigated hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among adults in Siem Reap, Cambodia, to consider the prevention strategy in cooperation with the Ministry of Health in Cambodia.

Liver disease in hepatitis C virus carriers identified at blood donation and their outcomes with or without interferon treatment: Study on 1019 carriers followed for 5-10 years.

Aim:  To portray liver disease and project outcomes in carriers of hepatitis C virus (HCV) in the general population.