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Clinical outcome after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients who achieved HBsAg seroclearance

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

Background

We determined the long-term clinical outcome and the durability of treatment cessation after HBsAg seroclearance following nucleos(t)ide analog (NA) therapy in patients with chronic hepatitis B (CHB).

Methods

We analyzed virological relapse (VR), HBsAg reversion, clinical relapse, and changes in HBsAg and HBcrAg levels by iTACT assay after treatment cessation of 90 CHB patients who achieved HBsAg seroclearance by NA treatment.

Results

Median age of patients at treatment cessation was 57 years. Median duration of NA treatment and follow-up from cessation of NA were 9.25 and 5.2 years, respectively. Although VR occurred in 19 of 90 (21.1%) patients, HBV DNA levels of 18 patients had temporal elevations and sustained levels under the detection level thereafter. HBsAg reversion using Architect HBsAg QT assay occurred in six patients (6.7%) after cessation of NA. Five patients had temporal HBsAg level elevations and sustained levels under the detection level thereafter. One patient had virological and clinical relapse at 6 months after cessation of NA, and received NA re-treatment. HBsAg levels by iTACT assay from end of treatment (EOT) gradually decreased and in 18 of 28 (64%) patients reached an undetectable level at 5 years after EOT. In contrast, HBcrAg levels by iTACT assay slowly decreased, and in 8 of 29 patients (28%) reached an undetectable level at 5 years after EOT.

Conclusions

Patients receiving NA treatment who achieved HBsAg seroclearance as determined by HBsAg QT assay rarely experienced virological or clinical relapse after the cessation of treatment.

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Abbreviations

CHB:

Chronic hepatitis B

NA:

Nucleos(t)ide analog

ETV:

Entecavir

TDF:

Tenofovir disoproxil fumarate

TAF:

Tenofovir alafenamide

HBsAg:

Hepatitis B surface antigen

cccDNA:

Covalently closed circular DNA

HBeAg:

Hepatitis B e antigen

HBcrAg:

Hepatitis B core-related antigen

iTACT:

Immunoassay for total antigen including complex via pretreatment anti-HBs antibody to hepatitis B surface antigen

ALT:

Alanine aminotransferase

HBV:

Hepatitis B virus

CLEIA:

Chemiluminescent enzyme immunoassay

VR:

Virological relapse

RR:

Relative risk

CI:

Confidence interval

ROC:

Receiver operating characteristic

IQR:

Interquartile range

EOT:

End of treatment

HBcAg:

Hepatitis B core antigen

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Funding

The study was supported in part by Program for Basic and Clinical Research on Hepatitis, Japan Agency for Medical Research and Development (JP23fk0210084), and by Okinaka Memorial Institute for Medical Research.

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Authors and Affiliations

  1. Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan

    Fumitaka Suzuki, Tetsuya Hosaka, Yoshiyuki Suzuki, Hitomi Sezaki, Norio Akuta, Shunichiro Fujiyama, Yusuke Kawamura, Satoshi Saitoh, Yasuji Arase & Hiromitsu Kumada

  2. Okinaka Memorial Institute for Medical Research, Tokyo, Japan

    Fumitaka Suzuki

  3. Research Institute for Hepatology, Toranomon Branch Hospital, Kawasaki, Japan

    Mariko Kobayashi

Authors
  1. Fumitaka Suzuki
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  2. Tetsuya Hosaka
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Contributions

All authors contributed to the study conception and design, and data collection. Data analyses were performed by FS and TH. The draft of the manuscript was written by FS, and all authors commented on the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Fumitaka Suzuki.

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Conflict of interest

Suzuki F has received lecture fees from Gilead Sciences Inc. Hosaka has received lecture fees from Gilead Sciences Inc. Akuta has received lecture fees from Abbvie GK. Kawamura has received lecture fees from Eisai Co., Ltd. Kumada has received investigator, lecture and consulting fees from Gilead Sciences Inc., Abbvie GK, Eisai Co., Ltd, Chugai Pharmaceutical Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd. The other authors declare that they have no conflict of interest.

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Suzuki, F., Hosaka, T., Suzuki, Y. et al. Clinical outcome after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients who achieved HBsAg seroclearance. J Gastroenterol 59, 34–44 (2024). https://doi.org/10.1007/s00535-023-02046-y

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  • DOI: https://doi.org/10.1007/s00535-023-02046-y

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