Cheng Huei-Ru, Kao Jia-Horng, Wu Hui-Lin, Chen Ting-Chih, Tseng Tai-Chung, Liu Chen-Hua, Su Tung-Hung, Chen Pei-Jer, Chen Ding-Shinn, Liu Chun-Jen
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Liver Int. 2014 Jul;34(6):e71-9. doi: 10.1111/liv.12324. Epub 2013 Oct 2.
Occult hepatitis B virus (HBV) infection (OHB) may exist in patients experiencing hepatitis B surface antigen (HBsAg) seroclearance.
We examined the clinical and virological features of OHB in patients who lost HBsAg post-treatment or spontaneously.
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.
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.
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.
隐匿性乙型肝炎病毒（HBV）感染（OHB）可能存在于乙肝表面抗原（HBsAg）血清学清除的患者中。
我们研究了治疗后或自发失去HBsAg的患者中OHB的临床和病毒学特征。
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）合并感染患者，在聚乙二醇干扰素α-2a（PEG-IFN）加利巴韦林治疗后失去HBsAg；13例HBV单一感染患者，在接受各种口服抗病毒治疗后失去HBsAg；以及16例自发失去HBsAg的患者。OHB定义为在无HBsAg情况下可检测到血清HBV DNA。通过与仍为HBsAg阳性的匹配对照进行比较，鉴定与OHB相关的病毒突变，并在体外进一步表征。
所有患者中OHB的患病率为34.1%（15/44），三组之间无显著差异。在表面启动子/聚合酶区域发现一个突变C3050T（preS1T68I），在6例患者中与HBsAg的血清学清除相关。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C3050T突变的构建体中S启动子活性显著降低（P = 0.0008）。然而，在全长HBV基因组背景下，该突变不影响HBV复制、转录和翻译。OHB在HBsAg血清学清除的患者中并不罕见。
一种突变C3050T（preS1T68I）降低了S启动子活性；然而，其他因素可能在这些OHB患者的HBsAg清除中起更重要作用。
