Hepatitis: Yoshizawa H

Miyakawa Y, Yoshizawa H. · Miyakawa Memorial Research Foundation, Minami-Aoyama 2-19-8, Minato-Ku, Tokyo 107-0062, Japan. · Hepatol Res. · Pubmed #17092770 No free full text.

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Yugi H, Mizui M, Tanaka J, Yoshizawa H. · Department of NAT, Central Blood Institute, Japanese Red Cross Society Tokyo, Japan. · J Clin Virol. · Pubmed #16831695 No free full text.

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Yoshizawa H, Tanaka J. · Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Science, Hiroshima University. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #16180669 No free full text.

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Tanaka J, Kumagai J, Komiya Y, Yoshizawa H. · Department of Epidemiology, Infectious Disease Control and Prevention, Hiroshima University Graduate School of Biomedical Sciences. · Nippon Rinsho. · Pubmed #15359802 No free full text.

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Katayama K, Tanaka J, Komiya Y, Kumagai J, Yoshizawa H. · Department of Epidemiology, Infectious Disease Control and Prevention, Hiroshima University Graduate School of Biomedical Sciences. · Nippon Rinsho. · Pubmed #15359801 No free full text.

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Miyakawa Y, Yoshizawa H. · Miyakawa Memorial Research Foundation, Tokyo 107-0062, Japan. · Indian J Gastroenterol. · Pubmed #11293191 No free full text.

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Matsubara N, Kusano O, Sugamata Y, Itoh T, Mizuii M, Tanaka J, Yoshizawa H. · R&D Division, Advanced Life Science Institute, Inc., Saitama, Japan. · Transfusion. · Pubmed #19192255 No free full text.

Abstract: BACKGROUND: The aim was to considerably enhance the sensitivity of hepatitis B virus (HBV) surface antigen (HBsAg) detection and investigate whether the window period for HBV detection could be reduced. STUDY DESIGN AND METHODS: A high-sensitivity chemiluminescent enzyme immunoassay (CLEIA) was developed for quantitative HBsAg detection by a combination of monoclonal antibodies, each one for a specific epitope of HBsAg, and by improving the conjugation technique. The sensitivity of the assay was compared with that of the existing chemiluminescent immunoassay (CLIA). Commercially available seroconversion panels and samples of HBV-infected chimpanzees were tested with the developed prototype to assess whether the window period for HBsAg detection could be reduced to that for DNA detection. RESULTS: Compared to the existing CLIA, the CLEIA prototype detected HBsAg with approximately 230-fold higher sensitivity and showed a reduced window period. HBsAg detection by the CLEIA prototype and HBV DNA detection by polymerase chain reaction (PCR) occurred simultaneously. The mean time for the CLEIA prototype to first detect HBsAg was approximately 17.4 days less than that for the existing systems. Further, CLEIA prototype enabled HBsAg detection even in anti-HBs-positive seroconversion samples. In the inoculated chimpanzees the HBsAg and HBV DNA became detectable simultaneously and concentrations increased in parallel, whereas HBsAg remained detectable longer than HBV DNA in the declining phase of viremia. CONCLUSION: The CLEIA prototype yielded results comparable with those of HBV DNA PCR. This novel high-sensitivity assay may be useful for early detection of HBV infection and monitoring patients with a history of infection.

Tabuchi A, Tanaka J, Katayama K, Mizui M, Matsukura H, Yugi H, Shimada T, Miyakawa Y, Yoshizawa H. · Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. · J Med Virol. · Pubmed #19040280 No free full text.

Abstract: 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.

Tanaka J, Mizui M, Nagakami H, Katayama K, Tabuchi A, Komiya Y, Miyakawa Y, Yoshizawa H. · Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. · Intervirology. · Pubmed #18309247 No free full text.

Abstract: 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) x 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.

Komiya Y, Katayama K, Yugi H, Mizui M, Matsukura H, Tomoguri T, Miyakawa Y, Tabuchi A, Tanaka J, Yoshizawa H. · Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. · Transfusion. · Pubmed #18028278 No free full text.

Abstract: 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). STUDY DESIGN AND METHODS: Pairs of chimpanzees were inoculated with preacute-phase inocula containing HBV of genotype A or genotype C to determine the minimum infectious dose, and two pairs of chimps infected with the lowest infectious dose of genotypes A and C were followed for HBV markers. RESULTS: The minimum 50 percent chimpanzee infectious dose (CID50) was estimated to be approximately 10 copies for genotype A and for genotype C. In the two chimps inoculated with the lowest infectious dose, the HBV DNA window was 55 to 76 days for genotype A and 35 to 50 days for genotype C, respectively. The HBsAg window was 69 to 97 days for genotype A and 50 to 64 days for genotype C, respectively. The doubling times of HBV DNA were 3.4 days (95% confidence interval [CI], 2.6-4.9 days) for genotype A and 1.9 days (95% CI, 1.6-2.3 days) for genotype C. When comparing the replication velocity of HBV DNA between the two genotypes, the doubling time of genotype C was significantly shorter than that of HBV genotype A (p < 0.01). CONCLUSION: 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.

Nagao Y, Myoken Y, Katayama K, Tanaka J, Yoshizawa H, Sata M. · Department of Digestive Disease Information and Research, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. · Oncol Rep. · Pubmed #17914569 No free full text.

Abstract: The objective of our study was to evaluate the natural history of oral lichen planus (OLP) and other extrahepatic manifestations in the inhabitants of an area in Japan that is hyperendemic for hepatitis C virus (HCV) infection. Over 4 years, 224 adult inhabitants with HCV infection were examined for OLP by a single oral surgeon. All subjects were interviewed regarding the natural history of other extrahepatic manifestations they had developed. The antibodies to HCV (anti-HCV) and serum HCV RNA were determined. Anti-HCV were detected in sera from 224 subjects (100%); HCV RNA in 210 (93.8%). Of the 224, 88 had at least 1 oral examination for OLP during the 4-year period. In 2000, 2001, 2002 and 2003, OLP was observed in 8.5 (5/59), 14.8 (8/54), 20 (11/55) and 21.4% (12/56) of subjects, respectively. OLP prevalence increased as the subjects grew older. The incidence of OLP over the 4 years among all subjects with HCV infection was 17.0% (15/88, 2 men and 13 women). None experienced natural healing or the development of malignant transformations. Between 2000 and 2003, there was an increase in the prevalence of type 2 diabetes mellitus (DM), thyroid dysfunction, skin disease, renal disease and hypertension. Screening for extrahepatic manifestations should be conducted in patients with risk factors for HCV infection.

Mizui M, Tanaka J, Katayama K, Nakanishi T, Obayashi M, Aimitsu S, Yoshida T, Inoue J, Yokoyama T, Tsuji K, Arataki K, Yamaguchi S, Miura T, Kitamoto M, Takezaki E, Orimen S, Sakata T, Kamada K, Maruhashi A, Tamura T, Nakamura T, Ishida K, Teramen K, Miyakawa Y, Yoshizawa H. · Department of Laboratory Medicine, Japanese Red Cross, Hiroshima Blood Center, Hiroshima, Japan. · Hepatol Res. · Pubmed #17627620 No free full text.

Abstract: Aim: To portray liver disease and project outcomes in carriers of hepatitis C virus (HCV) in the general population. Methods: Liver disease was evaluated in 1019 individuals who were found with HCV infection at blood donation, and they were followed for 5-10 years with or without receiving interferon (IFN). Results: At baseline, chronic hepatitis was detected in 529 (51.9%) HCV carriers and more frequently in men than in women (62.6% [299/478]vs 42.5% [230/541], P < 0.01); cirrhosis was diagnosed in five (0.5% [three men included]) and hepatocellular carcinoma (HCC) in one (0.1% [man]). Of the carriers who were followed for 5 years or longer, loss of HCV-RNA from serum was achieved in 61 (31.0%) of the 197 treated with interferon (IFN) and only one of the 211 (0.5%) without IFN (P < 0.0001). HCC developed in 14 carriers including six ofthe 211 (2.8%) without IFN and eight of the 197 (4.1%) with IFN (six non-responders included). Follow ups of the 949 carriers identified age (P < 0.002), male gender (P < 0.01) and cirrhosis at the baseline (P < 0.0001) as factors contributing to the development of HCC. Cumulative incidence rates of HCC during 10 years among carriers found with chronic hepatitis increased in parallel with the age at the baseline. Conclusion: Identification of HCV carriers in the general population and treating those indicated with IFN would help decrease the development of HCC and lift its medical, as well as economic, burdens off society.

Kato H, Fujiwara K, Gish RG, Sakugawa H, Yoshizawa H, Sugauchi F, Orito E, Ueda R, Tanaka Y, Kato T, Miyakawa Y, Mizokami M. · Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. · World J Gastroenterol. · Pubmed #16419158 links to  free full text

Abstract: AIM: To explore the propriety of providing hepatitis B virus (HBV) genotypes F and H with two distinct genotypes. METHODS: Eleven HBV isolates of genotype F (HBV/F) were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carried out among them along with HBV isolates previously reported. RESULTS: Seven of them clustered with reported HBV/F isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by > 13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked genomic divergence, falling just short of > 8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes (A-E and G), two clusters separated by distinct genetic distances emerged. CONCLUSION: Based on these analyses, classifying HBV/F isolates into two subtypes (F1 and F2) would be more appropriate than providing them with two distinct genotypes (F and H).

Yoshizawa H, Tanaka J, Miyakawa Y. · Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan. · Intervirology. · Pubmed #16166783 No free full text.

Abstract: During the past 30 years, hepatocellular carcinoma (HCC) in Japan has kept linearly increasing from 10 to 30 per 100,000 population per year and is expected to grow further. The increment is attributed to infection with hepatitis C virus (HCV). Hence, there is a pressing need to find subjects with persistent HCV infection in the general population of Japan and take necessary measures to prevent HCC developing in them. As a first approach toward this goal, the sex- and age-specific prevalence of ongoing HCV infection was surveyed in 3,485,648 first-time blood donors during 1995-2000. Taking into account the size of subpopulations with different sex and age in Japan registered at the Census 2000, there are an estimated 884,954 HCV carriers aged from 16 to 69 years, and 759,316 (86%) of them are older than 40 years, with an increased risk for HCC; they are hidden in the society, without overt liver disease. The national 5-year project searching for HCV carriers in the general population was started in April 2002. Subjects are examinees of health check-ups, which they receive every 5 years when reaching the age of 40, as well as those at increased risk for HCV infection. The project detected HCV RNA in 14,672 of the 1,298,746 (1.1%) health check examinees and in 16,721 of the 624,734 (2.7%) high-risk individuals during the first fiscal year. Subjects found with HCV RNA have been referred to clinics and hospitals with expert hepatologists. Hopefully, this project will decrease HCC development in HCV carriers in Japan and be considered in other countries where increases in HCC are predicted from the current age-specific prevalence of anti-HCV.

Kumagai J, Komiya Y, Tanaka J, Katayama K, Tatsukawa Y, Yorioka N, Miyakawa Y, Yoshizawa H. · Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. · J Med Virol. · Pubmed #15977246 No free full text.

Abstract: Patients on maintenance hemodialysis (HD) are at increased risk of infection with hepatitis C virus (HCV). A prospective follow-up study on HCV infection from November 1999 to February 2003 was conducted in nine hemodialysis (HD) units in Hiroshima. A total of 2,744 HD patients were surveyed regularly for HCV RNA in serum. The prevalence of HCV RNA decreased from 15.7% (262/1,664) on the first survey to 12.9% (242/1,882) in the last one (P<0.05). This decrease may be attributed to the inclusion of patients with a lower prevalence of HCV RNA compared to patients leaving dialysis centers (111/1,080 [10.3%] vs. 132/862 [15.3%], P<0.01). During the 40 months of this study, 16 de novo HCV infections were documented in the nine HD units corresponding to an incidence of 0.33% per year. These cases included eight new HCV infections, three re-infections, and five infections that presumably occured in the window period when tested during the first survey. Our study shows that the annual incidence of de novo HCV infection during HD was 0.33%, and emphasizes the need for frequent serum HCV RNA testing and for stringent disinfection procedures in order to prevent the transmission of HCV in these settings.

Tanaka J, Katayama K, Kumagai J, Komiya Y, Yugi H, Kishimoto S, Mizui M, Tomoguri T, Miyakawa Y, Yoshizawa H. · Department of Epidemiology, Infectious Disease Control and Prevention, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. · Intervirology. · Pubmed #15812184 No free full text.

Abstract: Two chimpanzees were inoculated with hepatitis C virus (HCV) and followed on a daily basis for 12 days. HCV RNA became detectable in their sera on day 5 by polymerase chain reaction with the detection limit of 10(2) copies/ml. Based on an exponential growth observed until 8 or 9 days after inoculation in their sera, the doubling time of HCV in the circulation was estimated at 6.3-8.6 h and log time (time required to grow 10-fold) at 31.3- 42.9 h. The exact doubling time of HCV determined in them would help plan an efficient strategy for screening out blood donors in the window period of infection between the exposure and the development of antibody to HCV in serum.

Tanaka Y, Hanada K, Orito E, Akahane Y, Chayama K, Yoshizawa H, Sata M, Ohta N, Miyakawa Y, Gojobori T, Mizokami M. · Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya 467-8601, Japan. · J Hepatol. · Pubmed #15629506 No free full text.

Abstract: BACKGROUND/AIMS: The mortality due to hepatocellular carcinoma (HCC) has ranged widely in various areas of Japan since 30 years ago and the incidence was particularly high in once Schistosoma japonicum (Sj)-endemic areas. Our aim was to estimate the spread time of hepatitis C virus (HCV) infection in the past with possible relevance to a higher incidence of HCC in once Sj-endemic than Sj-nonendemic areas. METHODS: During 2001, 131 strains of HCV-1b were obtained from patients in three previously Sj-endemic areas, as well as Sj-nonendemic areas in Japan and a cross-sectional study was conducted on them with molecular evolutionary analyses. RESULTS: A phylogenetic tree reconstructed on HCV-1b sequences in the NS5B region disclosed 2 independent clusters for Sj-positive and -negative groups with a high bootstrap value. The estimated effective number of HCV-infections indicated a transition from quiescence to rapid exponential growth in the 1920s among patients with schistosomiasis, which is 20 years earlier than that among patients without schistosomiasis. CONCLUSIONS: The estimated spread time in previously Sj-endemic areas in Japan coincides with injection treatment for Sj since 1921. A high incidence of HCC there would be attributed to a long duration of HCV infection since 1920s.

Tanaka J, Yoshizawa H. · Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima City, Hiroshima 734-8551, Japan. · Gan To Kagaku Ryoho. · Pubmed #15222102 No free full text.

Abstract: Annual incidence of hepatocellular carcinoma (HCC) keeps increasing during the past 30 years in Japan, most of which represents the end-stage disease of persistent infection with hepatitis C virus (HCV). To cope with this dire situation, a 5-year national project was launched since April 2002 for the management of viral hepatitis toward eventual prevention of HCC in Japan. This project is based on robust data on the epidemiology of chronic hepatitis and HCC induced by persistent HCV infection that have gained in the past 10 years by untiring efforts. It has been thrust by rapid advancement in diagnosis and treatment of HCC, and is targeted on the Japanese aged 40 years or older who are at increased risk of developing HCC. Further efforts are required to arouse concerns and attract commitment in the public, for an increased compliance to screening. At the same time, the national system has to be worked out for following up HCV carriers for immediate treatment of those who are found with liver disease.

Agha S, Tanaka Y, Saudy N, Kurbanov F, Abo-Zeid M, El-Malky M, Khalaf M, Ohta N, Yoshizawa H, Mizokami M. · Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. · J Med Virol. · Pubmed #15122795 No free full text.

Abstract: Nucleic acid amplification-based methods are used for confirmation of viremia in antibody to hepatitis C virus (anti-HCV)-positive patients. However, this technology is labor intensive, time consuming, requires complex laboratory conditions, and expensive. The aim of this study was to evaluate the sensitivity and specificity of the HCV core antigen (HCVcAg) assay as an alternative approach for confirmation of viremia in HCV-infected subjects with HCV genotype 1-4. Two hundred forty-six asymptomatic HCV RNA- positive donors were enrolled in this study, consisting of 122 blood donors from Egypt (116 with genotype 4, 4 with genotype 1, and 2 with 1 + 4 genotypes), 109 from Japan (85 with genotype 1, and 24 with genotype 2), and 15 from Uzbekistan (all with genotype 3). A total of 234 (95.1%) of 246 RNA-positive specimens were detected by the HCVcAg assay; the sensitivity of HCVcAg assay consisted 93.4, 100, 100, and 94.8% for genotypes 1, 2, 3, and 4, respectively in comparison with RT-PCR assay. The specificity of the assay was confirmed in the absence of the false-positive results among 53 anti-HCV-negative, but anti-Schistosoma mansoni (anti-Sm) positive donors from Egypt. A positive correlation between HCVcAg and HCV RNA concentration levels (r = 0.671, P < 0.05) was observed among specimens with HCV genotype 4. The mean HCVcAg level was significantly lower in specimens with genotype 4 (2,935 fmol/L) comparing to genotypes 1, 2, and 3 (5,034, 4,962, and 4,740 fmol/L, respectively). No specific mutation was found in the core-encoding region of the studied specimens. In conclusion, HCVcAg is shown to be specific, sensitive, and informative qualitative index for HCV viremia in asymptomatic carriers.

Katayama K, Kumagai J, Komiya Y, Mizui M, Yugi H, Kishimoto S, Yamanaka R, Tamatsukuri S, Tomoguri T, Miyakawa Y, Tanaka J, Yoshizawa H. · Department of Infectious Disease and Control, Hiroshima University Graduate School of Biomedical Sciences, Kasumi, Hiroshima, Japan. · Intervirology. · Pubmed #15044837 No free full text.

Abstract: 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 x 10(6) 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 x 10(1) 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.

Tanaka J, Kumagai J, Katayama K, Komiya Y, Mizui M, Yamanaka R, Suzuki K, Miyakawa Y, Yoshizawa H. · Department of Epidemiology and Control of Infectious Diseases, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. · Intervirology. · Pubmed #15044834 No free full text.

Abstract: 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.

Hiraoka T, Katayama K, Tanaka J, Ohno N, Joko K, Komiya Y, Kumagai J, Mizui M, Hino K, Miyakawa Y, Yoshizawa H. · Department of Epidemiology and Control of Infectious Diseases, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. · Intervirology. · Pubmed #12867755 No free full text.

Abstract: OBJECTIVE: The role of resolved hepatitis B virus (HBV) infection in promoting hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) in Japan was evaluated by epidemiological surveys. METHODS: Antibody to hepatitis B core (anti-HBc) was determined in age-matched blood donors, and the frequency was compared with that in patients with HCV-associated HCC in Japan. RESULTS: Anti-HBc was detected significantly more frequently in the blood donors with than without antibody to HCV (anti-HCV; 76/135 or 56.3% vs. 65/255 or 25.5%, p < 0.001). In the patients with HCV-associated HCC, anti-HBc was detected in 109 of 202 (54.0%), which was comparable to the frequency in anti-HCV-positive blood donors (56.3%). Among the blood donors with anti-HCV, the prevalence of anti-HBc was no different between those with and without HCV RNA in serum (40/77 or 51.9% vs. 36/58 or 62.1%). CONCLUSIONS: The individuals of an age with high cancer frequency (>or=40 years) in Japan would have been exposed to HBV frequently (>50%), whether or not they have developed HCV-associated HCC. Despite repeated assertions in the literature, no epidemiological evidence was obtained for a role of past HBV infection in hepatocarcinogenesis in patients infected with HCV in Japan.

Noto H, Terao T, Ryou S, Hirose Y, Yoshida T, Ookubo H, Mito H, Yoshizawa H, Anonymous00344. · Department of Obstetrics, Hamamatsu Medical College, Shizuoka, Japan. · J Gastroenterol Hepatol. · Pubmed #12859724 No free full text.

Abstract: BACKGROUND: Efficacy and limits in preventing perinatal infection with hepatitis B virus (HBV) have been examined in a model area in Japan. METHODS: In Shizuoka (population of 3.6 million), immunoprophylaxis of perinatal HBV infection was started in 1980 in four institutions (Hamamatsu Medical College, Shimada City Hospital, Shizuoka Kodomo Hospital and Numazu City Hospital). Babies born to carrier mothers with hepatitis B e antigen (HBeAg) in serum received hepatitis B immune globulins at birth and 2 months thereafter and vaccines at 2, 3 and 5 months after birth. RESULTS: Overall, 980 of the 1030 babies born to HBeAg-positive carrier mothers were protected by the immunoprophylaxis during the 15 years from 1980 to 1994 with an efficacy of 95.1%. From 1986 to 1994 while the national immunoprophylaxis was conducted, 329,674 of the 346,637 (95.1%) expectant mothers were tested, and 2081 (0.63%) of them were positive for hepatitis B surface antigen (HBsAg). The immunoprophylaxis was given only to babies born to 764 (36.7%) of the 2081 mothers who tested positive for HBeAg. Of the 494 babies receiving immunoprophylaxis, in whom HBsAg was followed monthly after birth, 462 (93.5%) were protected. The HBV carrier state developed in the remaining 32 (6.5%) babies, 10 of whom (31.3% of the 32) turned positive for HBsAg within 1 month after birth, most likely owing to infection in utero. CONCLUSIONS: Passive-active immunoprophylasxis of high-risk babies was highly efficacious in preventing perinatal transmission of the HBV carrier state. Most failures (approximately 70%) occurred in the high-risk babies who were exposed to HBV after birth, and would have been avoided by careful and extensive execution of the immunoprophylaxis.

Tanaka J, Kumada H, Ikeda K, Chayama K, Mizui M, Hino K, Katayama K, Kumagai J, Komiya Y, Miyakawa Y, Yoshizawa H. · The Department of Infectious Disease and Control, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. · J Med Virol. · Pubmed #12767000 No free full text.

Abstract: The Markov model was introduced to simulate natural histories of hepatitis C virus (HCV) infection in men and women. The data set was constructed on 942 HCV carriers who were examined at least once a year without receiving antiviral therapies. Based on 2,251 patient-year data, the probabilities of transition between any two of the four clinical states, i.e., asymptomatic carrier state, chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in 1 year were calculated. Hepatocellular carcinoma was defined as the absorbing state from where no transitions occur. Probability matrices thus obtained on six each subsets of HCV infection (asymptomatic carrier state, chronic hepatitis and liver cirrhosis in men and women) in their forties, fifties, and sixties, were used to simulate long-term outcomes of HCV infection. Male asymptomatic carriers aged 40 years were expected to retain the asymptomatic carrier state in 2.6%, evolve into chronic hepatitis in 48.4%, liver cirrhosis in 14.6% and hepatocellular carcinoma in 34.4% after 30 years when they reached 70 years of age, in contrast to 1.9%, 45.3%, 32.8% and 20.0%, respectively, of female asymptomatic carriers. Likewise, male patients with chronic hepatitis aged 40 years were expected to remain with chronic hepatitis in 43.8%, evolve into liver cirrhosis in 15.0% and hepatocellular carcinoma in 41.1%, contrasting with 38.9%, 32.7% and 22.0%, respectively, of female patients during 30 years. The Markov model could simulate the outcomes of 153 HCV carriers identified among blood donors after 5 years. The Markov simulation would help in assessing the long-term outcome of HCV infection and making decisions in the management of HCV carriers toward prevention of hepatocellular carcinoma.

Fujiwara S, Sharp GB, Cologne JB, Kusumi S, Akahoshi M, Kodama K, Suzuki G, Yoshizawa H. · Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan. · Radiat Res. · Pubmed #12751961 No free full text.

Abstract: The aim of this study was to determine whether the prevalence of hepatitis B virus (HBV) carriers increased with atomic bomb radiation dose, and whether radiation decreased the ability to clear HBV among the atomic bomb survivors. The study subjects were 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. After adjustment for age, sex, city and potential confounders, the rates of seropositivity for hepatitis B surface antigen (HBsAg), indicating current HBV infections, and anti-hepatitis B core antibody, indicating either cured or current infections, increased with radiation dose. However, no relationship was observed between radiation and anti-hepatitis B surface antibody (indicating cured infection). The proportion of persons who were unable to clear the virus, as the proportion of HBsAg-positive persons among those ever infected by HBV (positive for HBsAg or surface or core hepatitis B antibody), increased significantly with radiation dose among those receiving blood transfusions. This proportion was not related to dose among those who reported no such transfusions. The findings may suggest a lower likelihood of clearance after HBV infection among those who were more likely to have been infected with HBV as adults after atomic bomb irradiation rather than as infants or adults prior to irradiation.