Clinical and virological features of occult hepatitis B in patients with HBsAg seroclearance post-treatment or spontaneously
Clinical and virological features of occult hepatitis B in patients with HBsAg seroclearance post-treatment or spontaneously
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DOI：
10.1111/liv.12324
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发表时间：
2014-07-01
影响因子：
6.7
通讯作者：
Liu, Chun-Jen
中科院分区：
文献类型：
--
作者：
Cheng, Huei-Ru;Kao, Jia-Horng;Liu, Chun-Jen
背景：B型肝炎表面抗原（HBsAg）血清学清除的患者可能存在隐匿性B型肝炎病毒（HBV）感染（OHB）。目的：我们研究了治疗后HBsAg丢失或自发丢失的OHB患者的临床和病毒学特征。研究方法：我们收集了44例HBsAg血清学清除的患者：15例HBV/丙型肝炎病毒（HCV）双重感染的患者，在聚乙二醇干扰素α-2a（PEG-IFN）联合利巴韦林治疗后HBsAg丢失; 13例HBV单一感染的患者，在各种口服抗病毒治疗后HBsAg丢失; 16例患者，HBsAg自发丢失。OHB定义为在不存在HBsAg的情况下可检测到血清HBV DNA。与OHB相关的病毒突变通过与HBsAg保持阳性的匹配对照进行比较来鉴定，并在体外进一步表征。结果：OHB的发生率为34.1%（15/44），三组间无显著性差异。6例HBsAg血清学清除与表面启动子/聚合酶区C3050 T（preS 1 T68 I）突变有关。该突变不改变聚合酶蛋白的氨基酸序列。与野生型相比，含有C3050 T突变的构建体中的S启动子活性显著降低（P = 0.0008）。然而，在全长HBV基因组的背景下，这种突变不影响HBV的复制、转录和翻译。OHB在HBsAg血清清除患者中并不罕见。结论：一个突变，C3050 T（preS 1 T68 I），降低了S启动子的活性，然而，其他因素可能在这些OHB患者的HBsAg清除中发挥更重要的作用。
Background: Occult hepatitis B virus (HBV) infection (OHB) may exist in patients experiencing hepatitis B surface antigen (HBsAg) seroclearance. Aims: We examined the clinical and virological features of OHB in patients who lost HBsAg post-treatment or spontaneously. Methods: We collected 44 patients with HBsAg seroclearance: 15 patients with dual HBV/hepatitis C virus (HCV) infection who lost HBsAg after peginterferon alfa-2a (PEG-IFN) plus ribavirin therapy; 13 HBV mono-infected patients who lost HBsAg after various oral antiviral therapies; and 16 patients who lost HBsAg spontaneously. OHB was defined as detectable serum HBV DNA in the absence of HBsAg. Viral mutations associated with OHB were identified by comparison with matched controls that remained positive for HBsAg, and further characterized in vitro. Results: The prevalence of OHB was 34.1% (15/44) in all patients, which was not significantly different among three groups. One mutation in surface promoter/polymerase region, C3050T (preS1T68I), was identified to be associated with the seroclearance of HBsAg in six cases. This mutation does not change the amino acid sequence of the polymerase protein. The S promoter activity was significantly lower in the construct containing C3050T mutation as compared with the wild-type (P = 0.0008). However, this mutation did not affect HBV replication, transcription and translation in the context of the full-length HBV genome. OHB was not rare in patients with HBsAg seroclearance. Conclusions: One mutation, C3050T (preS1T68I), decreased S promoter activity; nevertheless, other factors may play more important role in the clearance of HBsAg in these OHB patients.