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目的探讨乙型肝炎病毒表面抗原(HBsAg)和抗HBsAg抗体(抗HBs)同时阳性的HBV感染者的流行病学及分子病毒学特征。方法分析52 070例医院就诊人群HBV血清学标志物检测结果,以HBsAg和抗HBs双阳性患者为实验组,HBsAg阳性、抗HBs阴性患者为对照组,比较2组患者的流行病学特征。半巢氏PCR扩增2组患者HBV S蛋白编码区并测序,比较2组间在不同基因区、基因型及临床诊断时的统计学差异。结果医院检测人群HBsAg阳性率为20.40%(10 621/52 070),其中HBsAg、抗HBs双阳性率为2.48%(263/10 621)。HBsAg、抗HBs双阳性在0~9岁和≥80岁人群流行率较高,而HBsAg阳性、抗HBs阴性则相反。实验组S蛋白氨基酸突变率显著高于对照组(1.52%vs 0.81%,P<0.01),差异主要存在于主要亲水区(MHR)(1.68%vs 0.57%,P<0.01)。实验组中除肝癌(HCC)患者外(1.97%vs 2.21%,P>0.05),乙肝携带者、慢性乙型肝炎(CHB)患者和肝硬化(LC)患者的S蛋白突变率均显著高于对照组同疾病患者(分别为1.47%vs 0.65%,1.28%vs0.84%,2.21%vs 0.44%,P均<0.05)。结论 HBsAg、抗HBs双阳性以0~9岁和≥80岁HBsAg阳性人群更多见。HBV感染者血清HBsAg和抗HBs共存可能与S蛋白(主要为MHR)的突变造成的免疫逃逸有关。HBsAg、抗HBs双阳性和HBsAg阳性、抗HBs阴性患者之间S蛋白的突变率差异与患者肝脏疾病所处的阶段有关。
Objective To investigate the epidemiological and molecular virological characteristics of HBV infected patients with positive HBsAg and anti-HBsAg antibodies (anti-HBs). Methods The HBV serological markers of 5270 hospitalized patients were analyzed. HBsAg and anti-HBs double positive patients were used as experimental group, HBsAg positive and anti-HBs negative patients as control group, and the epidemiological characteristics of two groups were compared. The HBV S protein coding region of two groups was amplified by semi-nested PCR and sequenced. The differences between the two groups in different gene regions, genotypes and clinical diagnosis were compared. Results The positive rate of HBsAg in hospital was 20.40% (10 621/52 070). The double positive rate of HBsAg and anti-HBs was 2.48% (263/10 621). HBsAg, anti-HBs double positive in 0 to 9 years old and ≥ 80-year-old population higher prevalence, while HBsAg-positive, anti-HBs-negative on the contrary. The amino acid mutation rate of S protein in experimental group was significantly higher than that in control group (1.52% vs 0.81%, P <0.01). The difference was mainly in MHR (1.68% vs 0.57%, P <0.01). In the experimental group, the mutation rates of S protein in patients with hepatitis B, chronic hepatitis B (CHB) and patients with cirrhosis (LC) were significantly higher than those without HCC (1.97% vs 2.21%, P> 0.05) Patients in the control group with the same disease (1.47% vs 0.65%, 1.28% vs 0.84%, 2.21% vs 0.44%, P <0.05 respectively). Conclusion HBsAg, anti-HBs double positive in 0 to 9 years old and ≥ 80 years old HBsAg positive population more common. The coexistence of serum HBsAg and anti-HBs in HBV-infected patients may be related to the immune escape caused by the mutation of S protein (mainly MHR). The mutation rate of S protein between HBsAg-positive, HBsAg-positive and anti-HBs-negative patients is related to the stage of liver disease.