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乙型肝炎表面抗原血清学转换对聚乙二醇干扰素 α 治疗诱导功能性治愈的持久性的影响。

The impact of hepatitis B surface antigen seroconversion on the durability of functional cure induced by pegylated interferon alpha treatment.

机构信息

Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.

Department of Infectious Diseases, Ezhou Central Hospital, Ezhou, China.

出版信息

Virol J. 2024 Oct 3;21(1):243. doi: 10.1186/s12985-024-02522-8.

Abstract

BACKGROUND

Hepatitis B surface antigen (HBsAg) loss is regarded as a pivotal criterion for assessing functional cure in patients diagnosed chronic hepatitis B (CHB). We conducted the research to investigate the real-world performance of HBsAg seroconversion in sustaining HBsAg loss.

METHODS

This retrospective analysis confirmed 295 patients who attained HBsAg loss through combination therapy involving nucleos(t)ide analogues (NAs) and pegylated interferon alpha (peg-IFNα). Employing Kaplan-Meier estimates method to conduct survival analysis. The forest plot was used to visualize the results of multivariate Cox regression, and selected variables were included in the nomogram.

RESULTS

HBsAg seroreversion was observed in 45 patients during follow-up periods, with a lower recurrence risk in patients with HBsAg seroconversion at the end of peg-IFNα therapy (EOT) (10.3% vs 37.3% at 96-week, P < 0.0001). Moreover, the sustainability of hepatitis B surface antibody (anti-HBs) in participants continuing therapy after HBsAg seroconversion was superior to those discontinued prematurely (72.5% vs 54.5% at 96 weeks, P = 0.012). Additionally, the former group was also relatively less likely to experience HBsAg reversion during long-term observation (8.4% vs 14.3% at 96 weeks, P = 0.280). Hepatitis B envelope antigen (HBeAg) status, anti-HBs status and consolidation treatment screened by multivariable analysis were utilized to construct a predictive model for HBsAg reversion. The concordance index(C-index = 0.77) and calibration plots indicated satisfactory discrimination and consistency of nomogram.

CONCLUSIONS

HBsAg seroconversion was beneficial for sustaining functional cure in patients treated with peg-IFNα. Continuing consolidation therapy after HBsAg seroconversion also contributed to maintain HBsAg seroconversion and improve the durability of HBsAg loss. The nomogram illustrated its efficacy as a valuable instrument in showcasing survival probability of functional cure.

摘要

背景

乙肝表面抗原(HBsAg)清除被认为是评估慢性乙型肝炎(CHB)患者功能性治愈的关键标准。我们进行了这项研究,以调查 HBsAg 血清转换在维持 HBsAg 清除中的实际表现。

方法

这项回顾性分析确认了 295 例通过核苷(酸)类似物(NAs)和聚乙二醇干扰素α(peg-IFNα)联合治疗实现 HBsAg 清除的患者。采用 Kaplan-Meier 估计法进行生存分析。森林图用于可视化多变量 Cox 回归的结果,并选择有意义的变量纳入列线图。

结果

在随访期间,有 45 例患者出现 HBsAg 血清学转换,在 peg-IFNα 治疗结束时(EOT)HBsAg 血清学转换的患者复发风险较低(96 周时为 10.3% vs 37.3%,P<0.0001)。此外,在 HBsAg 血清学转换后继续治疗的患者中,乙型肝炎表面抗体(抗-HBs)的持续性优于提前停药的患者(96 周时为 72.5% vs 54.5%,P=0.012)。此外,在长期观察中,前者发生 HBsAg 逆转的风险也相对较低(96 周时为 8.4% vs 14.3%,P=0.280)。多变量分析筛选出 HBeAg 状态、抗-HBs 状态和巩固治疗,并将其用于构建 HBsAg 逆转的预测模型。一致性指数(C 指数=0.77)和校准图表明,列线图具有良好的区分度和一致性。

结论

在接受 peg-IFNα 治疗的患者中,HBsAg 血清学转换有利于维持功能性治愈。HBsAg 血清学转换后继续巩固治疗也有助于维持 HBsAg 血清学转换并提高 HBsAg 清除的持久性。该列线图表明其作为一种评估功能性治愈生存概率的有价值工具的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f5a/11448035/93437a0f3ca8/12985_2024_2522_Fig4_HTML.jpg

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