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抗病毒治疗后乙型肝炎表面抗原早期清除与乙型肝炎病毒再激活患者的缓解。

Early Hepatitis B Surface Antigen Seroclearance Following Antiviral Treatment in Patients with Reactivation of Resolved Hepatitis B.

机构信息

Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea.

出版信息

Dig Dis Sci. 2019 Oct;64(10):2992-3000. doi: 10.1007/s10620-019-05614-6. Epub 2019 Apr 13.

Abstract

BACKGROUND AND AIMS

Long-term results on hepatitis B virus (HBV) reactivation in patients with resolved infection during anti-cancer therapy are unknown. This study investigated long-term risk and therapeutic endpoints including hepatitis B surface antigen (HBsAg) seroclearance following antiviral therapy in patients developing reactivation of resolved HBV.

METHODS

The study included 528 consecutive HBsAg-negative/hepatitis B core antibody-positive patients who underwent rituximab treatment or hematopoietic stem cell transplantation (HSCT) between 2006 and 2016. Long-term outcomes of patients with reactivation after antiviral therapy were examined in comparison with 37 HBsAg-positive chronic carriers under the same medical settings.

RESULTS

The 7-year cumulative rate of HBV reactivation was 10.8% and 57.9% in patients receiving rituximab treatment and HSCT, respectively. After antiviral initiation, patients with reactivation of resolved HBV showed significantly higher 1-year cumulative rates of hepatitis B e antigen seroconversion (69.2% vs. 22.6%, P = 0.008) and HBsAg seroclearance (61.8% vs. 3.3%, P < 0.001) than chronic HBsAg carriers. Reactivation of resolved HBV was independently predictive of HBsAg seroclearance in a combined group of reactivated patients and chronic HBsAg carriers. Low viral load at reactivation was predictive of HBsAg seroclearance in reactivated patients. The majority of patients with HBsAg seroclearance developed anti-HBs. None of the reactivated patients who achieved HBsAg seroclearance relapsed after cessation of antiviral therapy.

CONCLUSIONS

HBsAg seroclearance rapidly occurs following antiviral therapy for reactivation of resolved HBV infection, suggesting distinct clinical phenotypes as well as shorter duration of HBV infection associated with this particular disease setting-HBV reactivation.

摘要

背景和目的

在抗肿瘤治疗期间,已清除感染的患者乙型肝炎病毒(HBV)再激活的长期结果尚不清楚。本研究调查了接受抗病毒治疗后再激活已清除 HBV 患者的长期风险和治疗终点,包括乙型肝炎表面抗原(HBsAg)血清学清除。

方法

该研究纳入了 528 例连续的 HBsAg 阴性/乙型肝炎核心抗体阳性患者,他们在 2006 年至 2016 年期间接受了利妥昔单抗治疗或造血干细胞移植(HSCT)。在相同的医疗环境下,将接受抗病毒治疗后发生再激活的患者与 37 例 HBsAg 阳性慢性携带者的长期结局进行了比较。

结果

接受利妥昔单抗治疗和 HSCT 的患者,HBV 再激活的 7 年累积发生率分别为 10.8%和 57.9%。在开始抗病毒治疗后,与慢性 HBsAg 携带者相比,HBV 再激活的已清除感染患者在 1 年时的乙型肝炎 e 抗原血清学转换(69.2% vs. 22.6%,P=0.008)和 HBsAg 血清学清除(61.8% vs. 3.3%,P<0.001)的 1 年累积发生率显著更高。在再激活患者和慢性 HBsAg 携带者的综合组中,HBV 再激活是 HBsAg 血清学清除的独立预测因素。再激活时低病毒载量可预测 HBsAg 血清学清除。HBsAg 血清学清除的大多数患者产生了抗-HBs。在停止抗病毒治疗后,未再发生乙型肝炎表面抗原血清学清除的再激活患者复发。

结论

抗病毒治疗可迅速清除乙型肝炎表面抗原,提示与特定疾病背景(HBV 再激活)相关的临床表型和乙型肝炎病毒感染时间更短。

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