Huang Da, Yuan Zhize, Wu Di, Yuan Wei, Chang Jiang, Chen Yuying, Ning Qin, Yan Weiming
Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Med Virol. 2024 Nov;96(11):e70021. doi: 10.1002/jmv.70021.
Little is known for factors associated with virologic breakthrough (VBT) after switching from nucleos(t)ide analogue (NA) to pegylated interferon alpha (Peg-IFN-α) for patients with chronic hepatitis B (CHB). Eighty patients who received 48-week Peg-IFN-ɑ and NA combination therapy followed by Peg-IFN-ɑ monotherapy for additional 48 weeks were included in this study. HBV-related markers including HBV DNA, HBsAg, HBcrAg, HBeAg, cccDNA, and immunological biomarkers were dynamically evaluated. Twelve (15.0%) patients experienced VBT after switching to Peg-IFN-ɑ and exhibited significantly lower rates of HBsAg loss after therapy completion (0% vs. 35.3%, p = 0.014). The patients with HBcrAg≥ 5 logU/mL and HBsAg≥ 100 IU/mL had the highest risk of VBT and failed to achieve subsequent HBsAg clearance. Intrahepatic cccDNA level was significantly higher in patients with HBcrAg≥ 5 logU/mL than those with HBcrAg< 5 logU/mL. Notably, in contrast to patients with HBcrAg< 5 logU/mL or with HBsAg< 100 IU/mL who had obviously restored HBV-specific CD8T cell, Tfh or B cell responses before NA cessation, those with HBcrAg≥ 5 logU/mL or with HBsAg≥ 100 IU/mL exhibited lackluster immunities before NA cessation and notable diminished immune responses thereafter. Monitoring HBcrAg and HBsAg levels, which correlated with poor immune responses during sequential Peg-IFN-ɑ strategy, may help to avoid VBT and improve functional cure of CHB.
对于慢性乙型肝炎（CHB）患者从核苷（酸）类似物（NA）转换为聚乙二醇干扰素α（Peg-IFN-α）后发生病毒学突破（VBT）的相关因素知之甚少。本研究纳入了 80 例接受 48 周 Peg-IFN-α和 NA 联合治疗，随后再接受 48 周 Peg-IFN-α单药治疗的患者。动态评估了 HBV 相关标志物，包括 HBV DNA、HBsAg、HBcrAg、HBeAg、cccDNA 和免疫生物标志物。12 例（15.0%）患者在转换为 Peg-IFN-α后发生 VBT，治疗完成后 HBsAg 丢失率明显较低（0% vs. 35.3%，p=0.014）。HBcrAg≥5logU/mL 和 HBsAg≥100IU/mL 的患者发生 VBT 的风险最高，且无法实现后续 HBsAg 清除。HBcrAg≥5logU/mL 的患者肝内 cccDNA 水平明显高于 HBcrAg<5logU/mL 的患者。值得注意的是，与 HBcrAg<5logU/mL 或 HBsAg<100IU/mL 的患者在停止 NA 治疗前 HBV 特异性 CD8T 细胞、Tfh 或 B 细胞反应明显恢复不同，HBcrAg≥5logU/mL 或 HBsAg≥100IU/mL 的患者在停止 NA 治疗前免疫反应较差，随后免疫反应明显减弱。监测 HBcrAg 和 HBsAg 水平，这些水平与序贯 Peg-IFN-α策略期间的免疫反应不良相关，可能有助于避免 VBT 和提高 CHB 的功能性治愈。
