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Trends of hepatitis B virus genotype distribution in chronic hepatitis B patients in Japan

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Hepatitis B virus (HBV) is one of the most prevalent chronic viral infections that causes chronic hepatitis B (CHB). In Japan, genotypes B and C account for most of acute and chronic cases of hepatitis. However, previous studies showed that the prevalence of genotype A in CHB gradually increased every 5 years. Therefore, we have conducted a nationwide survey to comprehensively investigate the trends of HBV genotype distribution in CHB patients in Japan.

Methods

4421 CHB patients were recruited between 2015 and 2016. Clinical characteristics and distribution of CHB patients among different age groups and genotypes in 2015–2016 was compared with those in 2000–2001, 2005–2006, and 2010–2011.

Results

The percentages of genotype A, B, C, and D were 4.0, 16.2, 79.1, and 0.7%, respectively. While the overall percentage of CHB patients with genotype A did not change in the past 5 years, CHB with genotype A increased in young adults. On the other hand, the peak distribution of CHB with genotypes B and C, two genotypes with the largest patient population, has shifted to an older age group.

Conclusions

In Japan, the peak distribution for CHB with genotypes B and C advanced to an older age group while CHB with genotype A expanded in a younger age group. Given the universal HBV vaccination launch in Japan in 2016, these pre-vaccination survey data provide important baseline information for comparative studies of the impact of universal vaccination on HBV genotypes.

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Abbreviations

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B surface antigen

AHB:

Acute hepatitis B

HBeAg:

Hepatitis B-e antigen

CHB:

Chronic hepatitis B

HCC:

Hepatocellular carcinoma

CT:

Computerized tomography

MRI:

Magnetic resonance imaging

EIA:

Enzyme immunoassay

HIV:

Human immunodeficiency virus

References

  1. Okamoto H, Tsuda F, Sakugawa H, et al. Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes. J Gen Virol. 1988;69:2575–83.

    Article  CAS  PubMed  Google Scholar 

  2. Norder H, Hammas B, Lofdahl S, et al. Comparison of the amino acid sequences of nine different serotypes of hepatitis B surface antigen and genomic classification of the corresponding hepatitis B virus strains. J Gen Virol. 1992;73:1201–8.

    Article  CAS  PubMed  Google Scholar 

  3. Orito E, Ichida T, Sakugawa H, et al. Geographic distribution of hepatitis B virus (HBV) genotype in patients with chronic HBV infection in Japan. Hepatology. 2001;34:590–4.

    Article  CAS  PubMed  Google Scholar 

  4. Miyakawa Y, Mizokami M. Classifying hepatitis B virus genotypes. Intervirology. 2003;46:329–38.

    Article  CAS  PubMed  Google Scholar 

  5. Norder H, Couroucé AM, Coursaget P, et al. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology. 2004;47:289–309.

    Article  PubMed  Google Scholar 

  6. Kurbanov F, Tanaka Y, Mizokami M. Geographical and genetic diversity of the human hepatitis B virus. Hepatol Res. 2010;40:14–30.

    Article  PubMed  Google Scholar 

  7. Kao JH. Hepatitis B viral genotypes: clinical relevance and molecular characteristics. J Gastroenterol Hepatol. 2002;17:643–50.

    Article  CAS  PubMed  Google Scholar 

  8. Suzuki Y, Kobayashi M, Ikeda K, et al. Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan. J Med Virol. 2005;76:33–9.

    Article  PubMed  Google Scholar 

  9. Ito K, Yotsuyanagi H, Sugiyama M, et al. Geographic distribution and characteristics of genotype A hepatitis B virus infection in acute and chronic hepatitis B patients in Japan. J Gastroenterol Hepatol. 2016;31:180–9.

    Article  PubMed  Google Scholar 

  10. Ito K, Yotsuyanagi H, Yatsuhashi H, et al. Risk factors for long-term persistence of serum hepatitis B surface antigen following acute hepatitis B virus infection in Japanese adults. Hepatology. 2014;59:89–97.

    Article  CAS  PubMed  Google Scholar 

  11. Ito K, Yoneda M, Sakamoto K, et al. Virological and clinical characteristics of hepatitis B virus genotype A. J Gastroenterol. 2018;53:18–26.

    Article  CAS  PubMed  Google Scholar 

  12. Sugiyama M, Tanaka Y, Kato T, et al. Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigens. Hepatology. 2006;44:915–24.

    Article  CAS  PubMed  Google Scholar 

  13. Ito K, Kim KH, Lok AS, et al. Characterization of genotype-specific carboxyl-terminal cleavage sites of hepatitis B virus e antigen precursor and identification of furin as the candidate enzyme. J Virol. 2009;83:3507–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Progress in hepatitis B prevention through universal infant vaccination--China, 1997–2006. MMWR Morbidity and mortality weekly report. 2007;56:441–5.

  15. Matsuura K, Tanaka Y, Hige S, et al. Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A. J Clin Microbiol. 2009;47:1476–83.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Usuda S, Okamoto H, Iwanari H, et al. Serological detection of hepatitis B virus genotypes by ELISA with monoclonal antibodies to type-specific epitopes in the preS2-region product. J Virol Methods. 1999;80:97–112.

    Article  CAS  PubMed  Google Scholar 

  17. Ito K, Tanaka Y, Kato M, et al. Comparison of complete sequences of hepatitis B virus genotype C between inactive carriers and hepatocellular carcinoma patients before and after seroconversion. J Gastroenterol. 2007;42:837–44.

    Article  CAS  PubMed  Google Scholar 

  18. Horai S, Murayama K, Hayasaka K, et al. mtDNA polymorphism in East Asian populations, with special reference to the peopling of Japan. Am J Hum Genet. 1996;59:579–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Michitaka K, Tanaka Y, Horiike N, et al. Tracing the history of hepatitis B virus genotype D in western Japan. J Med Virol. 2006;78:44–52.

    Article  PubMed  Google Scholar 

  20. Ito K. Trends and molecular biological analysis of hepatitis B virus genotype distribution (Japanese). Research result report for Grants-in Aid for Scientific Research. 2018:1–5.

  21. Shiraki K. Vertical Transmission of Hepatitis B Virus and its Prevention in Japan. Tokyo Japan: Springer; 1994.

    Book  Google Scholar 

  22. Noto H, Terao T, Ryou S, et al. Combined passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus carrier state in Shizuoka, Japan during 1980–1994. J Gastroenterol Hepatol. 2003;18:943–9.

    Article  PubMed  Google Scholar 

  23. Koyama T, Matsuda I, Sato S, et al. Prevention of perinatal hepatitis B virus transmission by combined passive-active immunoprophylaxis in Iwate, Japan (1981–1992) and epidemiological evidence for its efficacy. Hepatol Res. 2003;26:287–92.

    Article  PubMed  Google Scholar 

  24. World Health O. Weekly epidemiological record. . [full issue]. 2009;84(40):405–20.

    Google Scholar 

  25. Buster EH, Hansen BE, Lau GK, et al. Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alfa. Gastroenterology. 2009;137:2002–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by “AMED Program on the Innovative Development and the Application of New Drugs for Hepatitis B under Grant Number JP20fk0310118, JP21fk0310118h0005 and JP22fk0310502h0001,” “The Japanese Society of Gastroenterology Grant,” and “JSPS KAKENHI Grant Number JP19K08479”.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Aichi Medical University, 1-1, Yazakokarimata, Nagakute, Aichi, 480-1195, Japan

    Kazumasa Sakamoto, Kiyoaki Ito, Akinori Okumura, Yoshitaka Fukuzawa & Masashi Yoneda

  2. Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Hiroshi Yotsuyanagi

  3. Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Hiroshi Yotsuyanagi

  4. Clinical Research Center, Department of Hepatology, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan

    Hiroshi Yatsuhashi

  5. Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Yasuhito Tanaka

  6. Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo, Japan

    Shuhei Hige

  7. Department of Internal Medicine, Iwate Medical University, Iwate, Japan

    Yasuhiro Takikawa

  8. Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan

    Yoshiyuki Ueno

  9. Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan

    Kazuhide Yamamoto

  10. Safety and Health Organization, Chiba University, Chiba, Japan

    Fumio Imazeki

  11. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Jun Inoue

  12. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan

    Masayuki Kurosaki

  13. Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan

    Takeji Umemura

  14. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan

    Hidenori Toyoda

  15. Department of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka, Japan

    Eiji Mita

  16. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan

    Kojiro Michitaka

  17. Department of Infectious, Respiratory, and Digestive Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan

    Tatsuji Maeshiro

  18. Department of Internal Medicine, Center for Liver Diseases, Seizankai Kiyokawa Hospital, Tokyo, Japan

    Norie Yamada

  19. Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan

    Atsushi Suetsugu

  20. Department of General Internal Medicine2, Kawasaki Medical School, Okayama, Japan

    Miwa Kawanaka

  21. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Yuya Seko

  22. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Kentaro Matsuura

  23. Department of Viral Pathogenesis and Controls, National Center for Global Health and Medicine, Ichikawa, Japan

    Masaya Sugiyama

  24. Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan

    Masashi Mizokami

Authors
  1. Kazumasa Sakamoto
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  2. Kiyoaki Ito
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  3. Hiroshi Yotsuyanagi
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  4. Hiroshi Yatsuhashi
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  5. Yasuhito Tanaka
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  6. Shuhei Hige
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  7. Yasuhiro Takikawa
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  8. Yoshiyuki Ueno
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  9. Kazuhide Yamamoto
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  10. Fumio Imazeki
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Contributions

KS and KI: designed the research study and contributed to the interpretation of data and wrote the manuscript. HY, HY, YT, YK, YT, YU, KY, FI, JI, MK, TU, HT, EM, KM, TM, NY, AS, MK, YS, KM, AO, YF and MS: contributed to data collection. MM and MY: supervised the writing of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kiyoaki Ito.

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Conflict of interest

KI and MY received research funding from AbbVie, Bayer Pharma, EA pharma, Otsuka Pharmaceutical, and Sumitomo Pharmaceutical. JI received research funding from AbbVie. YT received honorariums from FUJIREBIO inc., Gilead Sciences Inc, and GlaxoSmithKline PLC. YT also received research funding from FUJIFILM Corporation, Janssen Pharmaceutical K. K., Gilead Sciences Inc, Board of Trustees of the Leland, Stanford Junior University, GlaxoSmithKline PLC., FUJIREBIO inc., Sysmex Corp. YU received honorariums from Gilead Sciences and AbbVie Inc. YU also received research funding from AbbVie Inc. MK received honorariums from Gilead Sciences, AbbVie, Chugai, Eisai, Bayer, Lilly, and Otsuka. TU received honorariums from AbbVie and also received research funding from AbbVie and Tosoh Corporation. TM received research funding from IQVIA solutions. MY received honorariums from Otsuka pharmaceutical and Sumitomo pharmaceutical.

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Sakamoto, K., Ito, K., Yotsuyanagi, H. et al. Trends of hepatitis B virus genotype distribution in chronic hepatitis B patients in Japan. J Gastroenterol 57, 971–980 (2022). https://doi.org/10.1007/s00535-022-01921-4

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  • DOI: https://doi.org/10.1007/s00535-022-01921-4

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