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Journal of Clinical Microbiology, May 2009, p. 1476-1483, Vol. 47, No. 5
0095-1137/09/$08.00+0     doi:10.1128/JCM.02081-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Distribution of Hepatitis B Virus Genotypes among Patients with Chronic Infection in Japan Shifting toward an Increase of Genotype A{triangledown}

Kentaro Matsuura,1,2 Yasuhito Tanaka,1* Shuhei Hige,3 Gotaro Yamada,4 Yoshikazu Murawaki,5 Masafumi Komatsu,6 Tomoyuki Kuramitsu,7 Sumio Kawata,8 Eiji Tanaka,9 Namiki Izumi,10 Chiaki Okuse,11 Shinichi Kakumu,12 Takeshi Okanoue,13 Keisuke Hino,14 Yoichi Hiasa,15 Michio Sata,16 Tatsuji Maeshiro,17 Fuminaka Sugauchi,2 Shunsuke Nojiri,2 Takashi Joh,2 Yuzo Miyakawa,18 and Masashi Mizokami1,19

Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan,1 Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan,2 Department of Internal Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan,3 Department of Basic Laboratory Sciences, Kawasaki Medical School, Kawasaki Hospital, Okayama, Japan,4 Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, Tottori, Japan,5 Department of Gastroenterology, Akita City Hospital, Akita, Japan,6 Kuramitsu Clinic, Akita, Japan,7 Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan,8 Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan,9 Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan,10 Department of Internal Medicine, Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan,11 Department of Gastroenterology, Aichi Medical University School of Medicine, Aichi, Japan,12 Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan,13 Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan,14 Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan,15 Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan,16 First Department of Internal Medicine, University Hospital, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan,17 Miyakawa Memorial Research Foundation, Tokyo, Japan,18 Research Center for Hepatitis and Immunology, Kohnodai Hospital International Medical Center of Japan, Ichikawa, Japan,19

Received 29 October 2008/ Returned for modification 17 December 2008/ Accepted 2 March 2009

Acute hepatitis B virus (HBV) infection has been increasing through promiscuous sexual contacts, and HBV genotype A (HBV/A) is frequent in patients with acute hepatitis B (AHB) in Japan. To compare the geographic distribution of HBV genotypes in patients with chronic hepatitis B (CHB) in Japan between 2005 and 2006 and between 2000 and 2001, with special attention to changes in the proportion of HBV/A, a cohort study was performed to survey changes in genotypes of CHB patients at 16 hospitals throughout Japan. Furthermore, we investigated the clinical characteristics of each genotype and examined the genomic characteristics of HBV/A isolates by molecular evolutionary analyses. Of the 1,271 patients, 3.5%, 14.1%, and 82.3% were infected with HBV/A, -B, and -C, respectively. In comparison with our previous survey during 2000 and 2001, HBV/A was twice as frequent (3.5% versus 1.7%; P = 0.02). The mean age was lower in the patients with HBV/A than in those with HBV/B or -C. Based on phylogenetic analyses of 11 full-length genomes and 29 pre-S2/S region sequences from patients, HBV/A isolates were imported from Europe and the United States, as well as the Philippines and India. They clustered with HBV/A from AHB patients and have spread throughout Japan. HBV/A has been increasing in CHB patients in Japan as a consequence of AHB spreading in the younger generation through promiscuous sexual contacts, aided by a tendency of HBV/A to induce chronic hepatitis. The spread of HBV/A infection in Japan should be prevented by universal vaccination programs.

* Corresponding author. Mailing address: Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya 467-8601, Japan. Phone: 81-52-853-8292. Fax: 81-52-842-0021. E-mail: ytanaka{at}med.nagoya-cu.ac.jp

{triangledown} Published ahead of print on 18 March 2009.

Journal of Clinical Microbiology, May 2009, p. 1476-1483, Vol. 47, No. 5
0095-1137/09/$08.00+0     doi:10.1128/JCM.02081-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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