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Hepatitis B virus strains of subgenotype A2 with an identical sequence spreading rapidly from the capital region to all over Japan in patients with acute hepatitis B
  1. Yoko Tamada1,2,
  2. Hiroshi Yatsuhashi1,2,
  3. Naohiko Masaki3,
  4. Makoto Nakamuta4,
  5. Eiji Mita5,
  6. Tatsuji Komatsu6,
  7. Yukio Watanabe7,
  8. Toyokichi Muro8,
  9. Masaaki Shimada9,
  10. Taizo Hijioka10,
  11. Takeaki Satoh11,
  12. Yutaka Mano12,
  13. Toshiki Komeda13,
  14. Masahiko Takahashi14,
  15. Hiroshi Kohno15,
  16. Hajime Ota16,
  17. Shigeki Hayashi17,
  18. Yuzo Miyakawa18,
  19. Seigo Abiru1,2,
  20. Hiromi Ishibashi1,2
  1. 1Clinical Research Center, NHO Nagasaki Medical Center, Nagasaki, Japan
  2. 2Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  3. 3National Center for Global Health and Medicine, Tokyo, Japan
  4. 4NHO Kyushu Medical Center, Fukuoka, Japan
  5. 5NHO Osaka National Hospital, Osaka, Japan
  6. 6NHO Yokohama Medical Center, Kanagawa, Japan
  7. 7NHO Sagamihara Hospital, Kanagawa, Japan
  8. 8NHO Oita Medical Center, Oita, Japan
  9. 9NHO Nagoya Medical Center, Aichi, Japan
  10. 10NHO Osaka-Minami Medical Center, Osaka, Japan
  11. 11NHO Kokura Medical Center, Fukuoka, Japan
  12. 12NHO Sendai Medical Center, Miyagi, Japan
  13. 13NHO Kyoto Medical Center, Kyoto, Japan
  14. 14NHO Tokyo Medical Center, Tokyo, Japan
  15. 15NHO Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan
  16. 16NHO Kanazawa Medical Center, Ishikawa, Japan
  17. 17NHO National Disaster Medical Center, Tokyo, Japan
  18. 18Miyakawa Memorial Research Foundation, Tokyo, Japan
  1. Correspondence to Professor Hiroshi Yatsuhashi, Clinical Research Center, NHO National Nagasaki Medical Center and Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Address: 2-1001-1 Kubara, Omura, Nagasaki 856-8562, Japan; yatsuhashi{at}


Objective To examine recent trends of acute infection with hepatitis B virus (HBV) in Japan by nationwide surveillance and phylogenetic analyses.

Methods During 1991 through 2009, a sentinel surveillance was conducted in 28 national hospitals in a prospective cohort study. Genotypes of HBV were determined in 547 patients with acute hepatitis B. Nucleotide sequences in the preS1/S2/S gene of genotype A and B isolates were determined for phylogenetic analyses.

Results HBV genotype A was detected in 137 (25% (accompanied by genotype G in one)) patients, B in 48 (9%), C in 359 (66%), and other genotypes in the remaining three (0.5%). HBV persisted in five with genotype A including the one accompanied by genotype G; another was co-infected with HIV type 1. The genotype was A in 4.8% of patients during 1991–1996, 29.3% during 1997–2002, and 50.0% during 2003–2008 in the capital region, as against 6.5%, 8.5% and 33.1%, respectively, in other regions. Of the 114 genotype A isolates, 13 (11.4%) were subgenotype A1, and 101 (88.6%) were A2, whereas of the 43 genotype B isolates, 10 (23.3%) were subgenotype B1, 28 (65.1%) were B2, two (4.7%) were B3, and three (7.0%) were B4. Sequences of 65 (64%) isolates of A2 were identical, as were three (23%) of A1, and five (18%) of B2, but none of the B1, B3 and B4 isolates shared a sequence.

Conclusions Acute infection with HBV of genotype A, subgenotype A2 in particular, appear to be increasing, mainly through sexual contact, and spreading from the capital region to other regions in Japan nationwide. Infection persisted in 4% of the patients with genotype A, and HBV strains with an identical sequence prevailed in subgenotype A2 infections. This study indicates the need for universal vaccination of young people to prevent increases in HBV infection in Japan.

  • Hepatitis B virus
  • acute hepatitis B
  • genotypes
  • Japan
  • molecular epidemiology
  • acute hepatitis
  • genotype
  • hepatitis
  • hepatitis B
  • hepatitis C
  • acute hepatitis
  • hepatoma
  • autoimmune hepatitis
  • primary biliary cirrhosis
  • autoimmune disease
  • autoimmune biliary disease
  • autoimmune liver disease
  • autoimmunity

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  • Funding This study was supported by a grant-in-aid from the National Hospital Organization (grant number H21-NHO(Kan)-03).

  • Competing interests None.

  • Ethics approval Approved by the ethics committee of each institution.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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