Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B
Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B
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DOI：
10.1016/j.jhep.2020.08.039
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发表时间：
2021-01-15
影响因子：
25.7
通讯作者：
van Boemmel, Florian
中科院分区：
文献类型：
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作者：
Pfefferkorn, Maria;Schott, Tina;van Boemmel, Florian
背景与目的：在慢性乙肝病毒感染的治疗过程中，乙肝表面抗原的丢失或血清转换被认为是一种功能性治疗方法。HBs Ag由大表面蛋白(LHBs)、中表面蛋白(MHBs)和小表面蛋白(SHBs)组成，其相对比例与疾病分期密切相关。我们的目的是评估在治疗过程中，乙肝表面抗原的组成与功能治愈的关系。17/患者在核糖核酸类似物(NA)治疗期间和3/19例患者在聚乙二醇化干扰素-α2a(PEG化干扰素-α)治疗48周后实现了乙肝表面抗原的丢失。对照组为63例无HBs Ag丢失的患者。结果：治疗前，有乙肝表面抗原转阴者的MHBs中位数显著低于无转阴者(p=0.005)。在治疗期间，在HBs Ag丢失的患者中，MHBs和LHBs的比例显示出快速的下降，但在仅有HBe抗原血清转换的患者或没有血清学应答的患者中，MHBs和LHBs的比例没有下降。所有HBs Ag阴转者在NA治疗6个月后均未检出MHBs，平均发生在总HBs阴转率为12.8+/-8.7(0-52)个月。接受者操作特征分析显示，在NA治疗前，MHBs的比例是最好的HBs Ag丢失的早期预测因子(Auc=0.726，p=0.019)。在使用聚乙二醇化干扰素的患者中，MHBs和LHBs的比例呈现相似的动力学变化。结论：HBs Ag蛋白定量有望成为预测早期治疗应答的一种新工具。这些评估可能有助于优化个体化抗病毒治疗，提高慢性乙肝患者的功能治愈率。总结：乙肝表面抗原(HBs)是病毒复制的关键血清标志物。乙肝表面抗原的丧失被认为是稳定的缓解，这可以通过抗病毒治疗实现。我们研究了不同处理过程中不同组分，即大(LHBs)和中(MHBs)HBs Ag的比例是否与HBs Ag丢失有关。我们发现LHBs和MHBs的下降早于总的HBs Ag丢失之前，我们提出了LHBs和MHBs作为预测乙肝病毒感染治愈的新的生物标志物。(C)2020年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background & Aims: During treatment of chronic HBV infections, loss or seroconversion of the HBV surface antigen (HBsAg) is considered a functional cure. HBsAg consists of the large (LHBs), middle (MHBs), and small surface protein (SHBs) and their relative proportions correlate strongly with disease stage. Our aim was to assess the association between HBsAg composition and functional cure during treatment.Methods: A total of 83 patients were retrospectively analyzed. HBsAg loss was achieved by 17/64 patients during nucleos(t)ide analogue (NA) treatment and 3/19 patients following treatment with pegylated interferon-alfa2a (PEG-IFN) for 48 weeks. Sixty-three patients without HBsAg loss were matched as controls. LHBs, MHBs and SHBs were quantified in sera collected before and during treatment.Results: Before treatment, median MHBs levels were significantly lower in patients with subsequent HBsAg loss than in those without (p = 0.005). During treatment, MHBs and LHBs proportions showed a fast decline in patients with HBsAg loss, but not in patients with HBV e antigen seroconversion only or patients without serologic response. MHBs became undetectable by month 6 of NA treatment in all patients with HBsAg loss, which occurred on average 12.8 +/- 8.7 (0-52) months before loss of total HBsAg. Receiver-operating characteristic analyses revealed that the proportion of MHBs was the best early predictor of HBsAg loss before NA treatment (AUC = 0.726, p = 0.019). In patients achieving HBsAg loss with PEG-IFN, the proportions of MHBs and LHBs showed similar kinetics.Conclusion: Quantification of HBsAg proteins shows promise as a novel tool to predict early treatment response. These assessments may help optimize individual antiviral treatment, increasing the rates of functional cure in chronically HBV-infected patients.Lay summary: The hepatitis B surface antigen (HBsAg) is a key serum marker for viral replication. Loss of HBsAg is considered stable remission, which can be achieved with antiviral treatments. We have investigated whether the ratios of the different components of HBsAg, namely the large (LHBs) and medium (MHBs) HBsAg during different treatments are associated with the occurrence of HBsAg loss. We found that LHBs and MHBs decrease earlier than total HBsAg before HBsAg loss and we propose LHBs and MHBs as promising novel biomarker candidates for predicting cure of HBV infection. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.