Journal
HEPATOLOGY RESEARCH
Volume 52, Issue 10, Pages 817-823Publisher
WILEY
DOI: 10.1111/hepr.13804
Keywords
HBeAg-negative chronic hepatitis; host-dominating flare; interferon-gamma(INF-gamma); nucleos(t)ide analog; quantitative HBsAg; tumor necrosis factor-alpha(TNF-alpha); virus-dominating flare
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Funding
- Prosperous Foundation, Taipei, Taiwan
- Chang Gung Medical Research Fund [CMRPG1K0101-3, CMRPG1K0111-3]
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The study suggests that severe hepatitis flare patients who experience precipitous HBsAg decline may have a strong immune response that can clear the virus. Early termination of antiviral therapy allows the protective immune response to continue and accelerate HBV decline towards HBsAg loss.
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-gamma (IFN-gamma) and tumor-necrosis factor-alpha (TNF-alpha) assays were performed in four patients with severe hepatitis flare who had achieved precipitous HBsAg decline within 4 weeks of antiviral therapy. Results: TNF-alpha and IFN-gamma were found to be elevated in parallel to upsurging HBV DNA and HBsAg levels in all patients. Higher levels of TNF-alpha and IFN-gamma 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-gamma and TNF-alpha 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 dear the virus, and early termination of antiviral therapy may allow the protective immune response to continue and accelerate HBV decline toward HBsAg loss.
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