Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Department of Medical Microbiology and Parasitology, School of Medical Sciences, Fudan University, Shanghai, China.
Front Cell Infect Microbiol. 2023 Feb 24;13:1120300. doi: 10.3389/fcimb.2023.1120300. eCollection 2023.
Hepatitis B surface antigen (HBsAg) loss, namely, the functional cure, can be achieved through the pegylated interferon (PEG-IFN)-based therapy. However, it is an unignorable fact that a small proportion of patients who achieved functional cure develop HBsAg reversion (HRV) and the related factors are not well described.
A total of 112 patients who achieved PEG-IFN-induced HBsAg loss were recruited. HBV biomarkers and biochemical parameters were examined dynamically. HBV RNA levels were assessed in the cross-sectional analysis. The primary endpoint was HRV, defined as the reappearance of HBsAg after PEG-IFN discontinuation.
HRV occurred in 17 patients during the follow-up period. Univariable analysis indicated that hepatitis B e antigen (HBeAg) status, different levels of hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) at the end of PEG-IFN treatment (EOT) were significantly associated with the incidence of HRV through using the log-rank test. Additionally, time-dependent receiver operating characteristic (ROC) analysis showed that the anti-HBs was superior to anti-HBc in predictive power for the incidence of HRV during the follow-up period. Multivariable Cox proportional hazard analysis found that anti-HBs ≥1.3 logIU/L (hazard ratio (HR), 0.148; 95% confidence interval (CI), 0.044-0.502) and HBeAg negativity (HR, 0.183; 95% CI, 0.052-0.639) at EOT were independently associated with lower incidence of HRV. Cross-sectional analysis indicated that the HBV RNA levels were significantly correlated with the HBsAg levels in patients with HRV (r=0.86, p=0.003).
EOT HBeAg negativity and anti-HBs ≥1.3 logIU/L identify the low risk of HRV after PEG-IFN discontinuation.
乙肝表面抗原（HBsAg）丢失，即功能性治愈，可以通过聚乙二醇干扰素（PEG-IFN）治疗实现。然而，一个不可忽视的事实是，一小部分实现功能性治愈的患者会出现 HBsAg 逆转（HRV），并且相关因素尚未得到很好的描述。
共招募了 112 例接受 PEG-IFN 诱导 HBsAg 丢失的患者。动态检测 HBV 标志物和生化参数。在横断面分析中评估 HBV RNA 水平。主要终点是 HRV，定义为 PEG-IFN 停药后 HBsAg 的再次出现。
在随访期间，17 例患者发生 HRV。单变量分析表明，乙肝 e 抗原（HBeAg）状态、PEG-IFN 治疗结束（EOT）时不同水平的乙肝表面抗体（抗-HBs）和乙肝核心抗体（抗-HBc）与 HRV 的发生率显著相关，通过使用对数秩检验。此外，时间依赖性接收器操作特征（ROC）分析表明，在随访期间，抗-HBs 优于抗-HBc 对 HRV 发生率的预测能力。多变量 Cox 比例风险分析发现，EOT 时抗-HBs≥1.3 logIU/L（风险比（HR），0.148；95%置信区间（CI），0.044-0.502）和 HBeAg 阴性（HR，0.183；95%CI，0.052-0.639）与 HRV 发生率较低独立相关。横断面分析表明，HBV RNA 水平与 HRV 患者的 HBsAg 水平显著相关（r=0.86，p=0.003）。
EOT HBeAg 阴性和抗-HBs≥1.3 logIU/L 可识别 PEG-IFN 停药后 HRV 的低风险。
