Robust antiviral responses in severe hepatitis flare persist after early retreatment cessation and lead toward hepatitis B surface antigen loss: A proof-of-concept study

Ming Ling Chang, Rong Nan Chien, Yun Fan Liaw*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

3 Scopus citations

Abstract

Aim: Hepatitis B flare has been interpreted as result of immune response against upsurging hepatitis B virus (HBV) and its antigen(s) that may lead to HBV decline/clearance spontaneously. It has been speculated that antiviral therapy could halt the effective immune response with viral persistent as a consequence. A proof-of-concept study was conducted to investigate this issue. Methods: Serial biochemical, quantitative hepatitis B surface antigen (HBsAg), interferon-γ (IFN-γ) and tumor-necrosis factor-α (TNF-α) assays were performed in four patients with severe hepatitis flare who had achieved precipitous HBsAg decline within 4 weeks of antiviral therapy. Results: TNF-α and IFN-γ were found to be elevated in parallel to upsurging HBV DNA and HBsAg levels in all patients. Higher levels of TNF-α and IFN-γ and levels relative to qHBsAg were observed during and after early termination of therapy within 4 weeks in two patients and were followed by further HBsAg decline to <5 IU/ml and even achieved HBsAg loss in one patient. The patient who had stopped therapy on day 44 showed minimal HBsAg decline afterward and the patient who continued therapy showed a 10-fold rebound of qHBsAg from its nadir. The subsequent IFN-γ and TNF-α activity of these two patients was minimal. Conclusions: The results suggest that patients with severe hepatitis flare who achieved precipitous HBsAg decline may have robust immune response to clear the virus, and early termination of antiviral therapy may allow the protective immune response to continue and accelerate HBV decline toward HBsAg loss.

Original languageEnglish
Pages (from-to)817-823
Number of pages7
JournalHepatology Research
Volume52
Issue number10
DOIs
StatePublished - 10 2022

Bibliographical note

Publisher Copyright:
© 2022 Japan Society of Hepatology.

Keywords

  • HBeAg-negative chronic hepatitis
  • host-dominating flare
  • interferon-γ(INF-γ)
  • nucleos(t)ide analog
  • quantitative HBsAg
  • tumor necrosis factor-α(TNF-α)
  • virus-dominating flare

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