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Defining Virologic Relapse in Chronic Hepatitis B

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Abstract

Background and Aims

Different definitions of virologic relapse (VR) are being used. One way of defining VR is “reappearance of HBV DNA in the serum,” while another definition is an “increase in HBV DNA level greater than 1 log in two determinations at least 4 weeks apart.” The aim of this study was to see the effectiveness of these two definitions

Methods

Forty-five HBeAg-positive chronic hepatitis B patients with a virologic response [negative PCR (<12 IU/ml)] who had discontinued therapy were analyzed retrospectively for VR, HBeAg reversion and biochemical flare.

Results

HBV DNA reappeared in the serum (≥12 IU/ml) of all 45 patients (100%). An increase in HBV DNA level greater than 1 log in two determinations at least 4 weeks apart was identified in 20 of 25 patients (80%). Biochemical flare and HBeAg reversion were observed in 18 (40%) and 14 (31%) patients, respectively. Peak off-therapy HBV DNA level was significantly associated with biochemical flare (r = 0.758, P < 0.001) and HBeAg reversion (r = 0.645, P < 0.001). Two patients with high initial off-therapy HBV DNA levels (≥4.0 log10 IU/ml) were reassessed at 4 weeks, and both experienced a biochemical flare and HBeAg reversion. Two patients had an increase in HBV DNA level greater than 1 log at a very low level (1 log to 2 or 3 log), but did not experience biochemical flare or HBeAg reversion during follow-up.

Conclusions

Reappearance of HBV DNA was universal when sensitive HBV DNA assay was used. Waiting 4 weeks to confirm VR may be harmful for patients with a high HBV DNA level, and was ineffective to indicate re-therapy for patients with increase in HBV DNA at a very low level. There is a need for improved and standardized definitions of VR.

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Abbreviations

CHB:

Chronic hepatitis B

NA:

Nucleoside/nucleotide analogues

HBV:

Hepatitis B virus

PCR:

Polymerase chain reaction

ALT:

Alanine aminotransferase

HBeAg:

Hepatitis B e-antigen

VR:

Virologic relapse

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Authors and Affiliations

  1. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea

    Kyung Hee Kim, Won Kyoung Yun, Hyun Chin Cho, Yun Young Lee, Geum-Youn Gwak, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Byung Chul Yoo & Seung Woon Paik

  2. Department of Medicine, Armed Forces Capital Hospital, Seongnam, Korea

    Dong Hyun Sinn

Authors
  1. Kyung Hee Kim
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  2. Dong Hyun Sinn
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  3. Won Kyoung Yun
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  4. Hyun Chin Cho
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  5. Yun Young Lee
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  6. Geum-Youn Gwak
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  7. Moon Seok Choi
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  8. Joon Hyeok Lee
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  9. Kwang Cheol Koh
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  10. Byung Chul Yoo
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  11. Seung Woon Paik
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Corresponding author

Correspondence to Seung Woon Paik.

Additional information

Kyung Hee Kim and Dong Hyun Sinn contributed equally to this study.

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Kim, K.H., Sinn, D.H., Yun, W.K. et al. Defining Virologic Relapse in Chronic Hepatitis B. Dig Dis Sci 56, 2432–2438 (2011). https://doi.org/10.1007/s10620-011-1597-y

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  • DOI: https://doi.org/10.1007/s10620-011-1597-y

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