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乙型肝炎表面抗原和抗-HBs 在与基因型 C 相关的中国慢性乙型肝炎病毒患者中的共存以及 S 和 P 基因逆转录酶区的突变。

Coexistence of hepatitis B surface antigen and anti-HBs in Chinese chronic hepatitis B virus patients relating to genotype C and mutations in the S and P gene reverse transcriptase region.

机构信息

Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China.

出版信息

Arch Virol. 2012 Apr;157(4):627-34. doi: 10.1007/s00705-011-1215-5. Epub 2012 Jan 6.

DOI:10.1007/s00705-011-1215-5
PMID:22222283
Abstract

We aimed to determine the prevalence of the coexistence of HBsAg and anti-HBs and to analyze the clinical and virological features of infection, including amino acid (aa) patterns of the S gene and reverse transcriptase (RT) region in Chinese chronic hepatitis B (CHB) patients. Fifty-four (2.90%) CHB patients who were positive for both HBsAg and anti-HBs were tested, and sequences were obtained from 52 of them as well as 48 patients from a control group. S gene and RT region sequences were amplified and sequenced using in-house protocols. There was no significant difference between patients with and without anti-HBs with regard to age, gender, alanine aminotransferase level, and the proportion positive for HBeAg and HBcAb. The occurrence of genotype C (P = 0.001) and anti-HBeAb positivity (P = 0.027) was significantly higher in HBsAg+/anti-HBs+ individuals. In the S gene, the number of mutated residues in the HBsAg+/anti-HBs+ group was markedly higher than in control patients (1.88 versus 1.02 substitutions per 100 amino acids, P = 0.022). The amino acid exchange occurred mostly within the N-terminal region (2.15 versus 0.87 substitutions per 100 amino acids, P = 0.023) and the "a" determinant (3.61 versus 1.56 substitutions per 100 amino acids, P = 0.049) in the two groups. In the RT region, the mean number of substitution per 100 aa showed a tendency to be significantly higher in HBsAg+/anti-HBs+ patients than in controls (2.34 versus 1.46, P = 0.040). This study showed a prevalence of coexistence of anti-HBs in HBsAg-positive patients and an increased frequency of genotype C and aa variability within both HBsAg and RT involving functionally important regions of those proteins.

摘要

我们旨在确定 HBsAg 和抗-HBs 共存的流行率,并分析感染的临床和病毒学特征,包括中国慢性乙型肝炎 (CHB) 患者 S 基因和逆转录酶 (RT) 区的氨基酸 (aa) 模式。检测了 54 例 HBsAg 和抗-HBs 均阳性的 CHB 患者,其中 52 例获得了序列,48 例来自对照组。使用内部方案扩增和测序 S 基因和 RT 区序列。在年龄、性别、丙氨酸氨基转移酶水平以及 HBeAg 和 HBcAb 阳性比例方面,有抗-HBs 的患者和无抗-HBs 的患者之间没有显著差异。HBsAg+/anti-HBs+个体中基因型 C(P=0.001)和抗-HBeAb 阳性的发生率显著更高。在 S 基因中,HBsAg+/anti-HBs+组的突变残基数明显高于对照组(每 100 个氨基酸 1.88 个与 1.02 个替换,P=0.022)。氨基酸替换主要发生在 N 端区域(2.15 个与 0.87 个替换/每 100 个氨基酸,P=0.023)和“a”决定簇(3.61 个与 1.56 个替换/每 100 个氨基酸,P=0.049)。在 RT 区,每 100 个 aa 的替换平均数在 HBsAg+/anti-HBs+患者中呈显著高于对照组的趋势(2.34 个与 1.46 个,P=0.040)。本研究显示 HBsAg 阳性患者中存在抗-HBs 共存的流行率,并且在 HBsAg 和 RT 中均存在基因型 C 和 aa 变异性的频率增加,涉及这些蛋白的功能重要区域。

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