慢性乙型肝炎的功能性治療與HBsAg /抗HBs免疫複合物與ALT並發

StephenW

FUNCTIONAL CURE OF CHRONIC HEPATITIS B IS ASSOCIATED WITH CO-OCCURRENCE OF HBsAg/anti-HBsIMMUNE COMPLEXES WITH ALT FLARES, AND SEROCONVERSION TO NEUTRALISING anti-HBs

AASLD 2020 Nov 11-16
Reported by Jules Levin

Hui Xu1, Stephen Locarnini1, Darren Wong2, Renae Walsh1, Sally Soppe1, Danni Colledge1, Rachel Hammond1, Alexander Thompson3, Peter Revill4, Patrick Marcellin5, Anuj Gaggar6 and Nadia Warner1, (1)Victorian Infectious Diseases Reference Laboratories, (2)Gastroenterology, Gastroenterology, (3) Medicine, University of Melbourne, (4)Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, (5)Department of Hepatology, AP-HP Hôpital Beaujon, 92110 Clichy, France, (6)Gilead Sciences, Inc, Foster City, CA, USA

Background: HBsAg specific antibody responses during chronic hepatitis B infection are poorly defined due to lack of standardised detection methodologies. The aim of this study was to investigate the nature of the anti-HBs responses in chronically infected HBV patients during the process of functional cure.

Methods: Longitudinal samples from 25 patients undergoing nucleos(t)ide analogue (NA) treatment were examined, 14 patients achieved functional cure while 11 patients remained infected. HBsAg/anti-HBs Immune complexes (HBs-IC) were quantified using an optimized quantification assay. Epitope-specific anti-HBs responses were detected using a 19-plex assay and neutralization efficacy of anti-HBs was measured using an in vitro HBV infection model.

Results: HBs-IC was detected in all patient’s serum samples with a fluctuating profile of peaks and troughs. In the 14 patients who achieved functional cure, 10 had an ALT flare immediately prior to HBsAg loss and seroconversion and of these 10 patients, nine had co-occurring HBs-IC peaks . Patients who did not clear the virus had lower anti- HBs responses compared to those functional cured patients. Anti-HBs derived from functionally cured patients after seroconversion was more potent in neutralizing HBV infection in vitro, and recognised more anti-HBs epitopes compared to anti-HBs from vaccinee controls.

Conclusion: Anti-HBs responses are present and fluctuate during chronic hepatitis B infection and are important for achieving functional cure. Functional cure in the analysed cohort was associated with co-occurring HBs-IC peak and ALT flare prior to clearance, and was followed by the production of anti-HBs that recognize broad epitopes on HBsAg which potently neutralize HBV infection. Failure of virus clearance was associated with inadequate anti-HBs responses in the early phase of NA treatment. These results further demonstrate the importance of anti-HBs responses in clearing HBV infection.

StephenW

慢性乙型肝炎的功能性治療與HBsAg /抗HBs免疫複合物與ALT並發並血清轉化為中性抗HBs有關

AASLD 2020年11月11日至16日
朱爾斯·萊文報導

許輝1，斯蒂芬Locarnini1，Darren Wong 2，Renae Walsh1，Sally Soppe1，Danni Colledge1，Rachel Hammond1，Alexander Thompson3，Peter Revill4，Patrick Marcellin5，Anuj Gaggar6和Nadia Warner1，（1）維多利亞州傳染病參考實驗室，（2）胃腸病學胃腸病學，（3）墨爾本大學醫學，（4）皇家墨爾本醫院維多利亞傳染病參考實驗室，（5）AP-HPHôpitalBeaujon肝病科，92110克利希，法國，（6）Gilead Sciences，Inc，美國加利福尼亞州福斯特城

背景：由於缺乏標準化的檢測方法，慢性乙型肝炎感染期間HBsAg特異性抗體反應的定義不明確。這項研究的目的是調查功能性治愈過程中慢性感染的HBV患者的抗HBs反應的性質。

方法：檢查25例接受核苷酸類似物（NA）治療的患者的縱向樣本，其中14例獲得了功能性治愈，而11例仍然感染。 HBsAg /抗HBs免疫複合物（HBs-IC）使用優化的定量分析進行定量。使用19-plex分析檢測抗原決定簇特異性的抗HBs反應，並使用體外HBV感染模型測量抗HBs的中和效果。

結果：在所有患者的血清樣本中均檢測到HBs-IC，且其波峰和波谷波動較大。在完成功能性治癒的14例患者中，有10例在HBsAg喪失和血清轉化之前即刻出現ALT發作，在這10例患者中，有9例同時出現HBs-IC高峰。與那些功能治癒的患者相比，未清除病毒的患者抗HBs反應較低。血清轉化後，來自功能治癒的患者的抗HBs在體外中和HBV感染方面更有效，並且與來自疫苗接種者對照的抗HBs相比，可識別更多的抗HBs表位。

結論：在慢性乙型肝炎感染期間，抗-HBs反應存在且波動，對於實現功能性治愈很重要。在所分析的隊列中，功能性治愈與清除前同時出現的HBs-IC峰和ALT爆發有關，然後產生可識別HBsAg廣泛表位的抗HBs，該表位可有效中和HBV感染。在NA治療的早期，病毒清除失敗與抗HBs反應不足有關。這些結果進一步證明了抗HBs​​應答在清除HBV感染中的重要性。