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Serum HBV RNA and HBeAg are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients

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

Background

Treatment for chronic hepatitis B has improved drastically with the use of nucleot(s)ide analogues (NAs). However, NA therapy typically fails to eliminate Hepatitis B virus (HBV) completely, and it is difficult to discontinue these therapies. We previously demonstrated that NA therapy induced immature viral particles, including HBV RNA in sera of chronic hepatitis B patients. In the study reported here, we analyzed the association between HBV RNA titer and the recurrence rate of hepatitis after discontinuation of NA therapy.

Methods

The study cohort comprised 36 patients who had discontinued NA therapy. Serum HBV DNA or DNA plus RNA levels were measured by real time PCR and statistical analyses were performed using clinical data and HBV markers.

Results

At 24 weeks after discontinuation of NA therapy, HBV DNA rebound was observed in 19 of the 36 patients (52.8 %), and alanine aminotransferase (ALT) rebound was observed in 12 of 36 patients (33.3 %). Multivariate statistical analysis was used to identify factors predictive of HBV DNA rebound. The HBV DNA + RNA titer following 3 months of treatment was significantly associated with HBV DNA rebound [P = 0.043, odds ratio (OR) 9.474, 95 % confidence interval (CI) 1.069–83.957)]. Absence of hepatitis B e antigen (HBeAg) at the end of treatment was significantly associated with ALT rebound (P = 0.003, OR 13.500, 95 % CI 2.473–73.705). In HBeAg-positive patients, the HBV DNA + RNA titer after 3 months of treatment was marginally associated with ALT rebound (P = 0.050, OR 8.032, 95 % CI 0.997–64.683).

Conclusions

Monitoring of serum HBV DNA + RNA levels may be a useful method for predicting re-activation of chronic hepatitis B after discontinuation of NA therapy.

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Abbreviations

ADV:

Adefovir dipivoxil

ETV:

Entecavir

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

LMV:

Lamivudine

NA:

Nucleot(s)ide analogue

RT:

Reverse transcriptase

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Acknowledgments

This study was supported in part by a Grant-in-aid from the Ministry of Health, Labor and Welfare of Japan and was carried out at the Research Center for Molecular Medicine, Faculty of Medicine, Hiroshima University and the Analysis Center of Life Science, Hiroshima University. The authors thank Rie Akiyama for technical assistance and Aya Furukawa for clerical assistance.

Conflict of interest

None to declare.

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Masataka Tsuge, Eisuke Murakami, Michio Imamura, Hiromi Abe, Daiki Miki, Nobuhiko Hiraga, Shoichi Takahashi, Hidenori Ochi, C. Nelson Hayes & Kazuaki Chayama

  2. Liver Research Project Center, Hiroshima University, Hiroshima, Japan

    Masataka Tsuge, Eisuke Murakami, Michio Imamura, Hiromi Abe, Daiki Miki, Nobuhiko Hiraga, Shoichi Takahashi, Hidenori Ochi, C. Nelson Hayes & Kazuaki Chayama

  3. Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan

    Masataka Tsuge

  4. Virology/Microbiology Group, Molecular Diagnostics Marketing Department, Marketing Division, In Vitro Diagnostics Business Unit, Roche Diagnostics K.K, Tokyo, Japan

    Hiroyuki Ginba & Kazuhiro Matsuyama

  5. Kawakami Clinic, Hiroshima, Japan

    Hiroiku Kawakami

  6. Division of Frontier Medical Science, Department of Medical and Molecular Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan

    Kazuaki Chayama

Authors
  1. Masataka Tsuge
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  2. Eisuke Murakami
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  9. C. Nelson Hayes
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  10. Hiroyuki Ginba
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  11. Kazuhiro Matsuyama
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  13. Kazuaki Chayama
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Corresponding author

Correspondence to Kazuaki Chayama.

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Tsuge, M., Murakami, E., Imamura, M. et al. Serum HBV RNA and HBeAg are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients. J Gastroenterol 48, 1188–1204 (2013). https://doi.org/10.1007/s00535-012-0737-2

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  • DOI: https://doi.org/10.1007/s00535-012-0737-2

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