【摘要】 目的 了解河源地区献血人群隐匿性乙型肝炎病毒感染（OBI）检出率高的原因，为制定血液安全防控策略提供依据。方法 以酶联免疫吸附法和核酸扩增技术对2016-2018年河源市中心血站44 598例献血者进行乙型肝炎病毒（HBV）标志物检测，Logistic回归分析OBI检出的影响因素；对确证OBI献血者血液标本进行HBV血清标志物检测和核酸大容量提取，对其BCP/PC区及S区进行巢式PCR扩增及实时荧光定量PCR检测，并对扩增产物进行基因测序及序列分析；对确证OBI献血者进行随访检测；再结合流行病学资料分析OBI检出情况。结果 44598例献血者，共检出OBI 68例，OBI检出率为0.15%。男性OBI检出率高于女性，首次献血者OBI检出率高于重复献血者，本地籍OBI检出率高于外地籍，差异均有统计学意义（χ~2=4.367、5.161、7.382,P均<0.05）；不同年龄组间，18～<27岁乙肝疫苗免疫年龄组OBI检出率最低，47～60岁组OBI检出率最高，差异有统计学意义（χ~2=28.383,P<0.05）。多因素Logistic回归分析显示，性别、年龄、献血史及户籍均为OBI检出的影响因素（P均<0.05）；以女性为参照，男性OBI检出率较高（OR=2.093）；以18～<27岁乙肝疫苗免疫年龄组为参照，47～60岁年龄组OBI检出率最高（OR=7.462）；以重复献血者为参照，首次献血者OBI检出率较高（OR=1.720）；以外地籍献血者为参照，本地籍献血者OBI检出率较高（OR=2.353）。43例可分型OBI标本的HBV S氨基酸序列与参比序列比对分析显示，6例外籍B型序列中未发现显著性突变位点，而本地籍35例OBI序列中共确认11个显著性突变位点（P<0.05），其中72.7%(8/11)为影响血清学检测变异株，另外发现3个免疫逃逸变异株和2个免疫球蛋白治疗失败变异株位点。40例OBI献血者历经3～100个月随访，1例（2.5%）HBV DNA转阴，5例（12.5%）HBsAg转阳，其余34例（85.0%）仍保持OBI状态。结论 当地HBV的高感染基数、特定的献血人群结构、高频显著性S基因突变以及绝大多数OBI献血者临床进程均稳定为OBI，可能是河源地区献血人群OBI检出率偏高的主要原因。更多还原

【Abstract】 Objective To investigate the reasons for the high detection rate of occult hepatitis B virus infection(OBI) among blood donors in Heyuan area, and provide basis for formulating blood safety control strategies. Methods A total of 44 598 blood donors in Heyuan Central Blood Station from 2016 to 2018 were detected for hepatitis B virus(HBV) markers by enzyme-linked immunosorbent assay and nucleic acid amplification technology. Logistic regression was to analyze the influencing factors of OBI detection. The blood samples of blood donors with confirmed OBI were detected for HBV serum markers and nucleic acid high-volume extraction. The BCP/PC region and S region were amplified by nested PCR and realtime fluorescence quantification PCR detection, and the amplified products were subjected to gene sequencing and sequence analysis. The blood donors confirmed as OBI were followed up for detection. The detection of OBI in combination with epidemiological data was analyzed. Results Among 44 598 blood donors, 68 cases of OBI were detected, with a detection rate of 0.15%. The detection rate of OBI was higher in male donors than in female donors, higher in first-time donors than in repeat donors, and higher in local donors than in out-of-town donors,with statistically significant differences （χ~2=4.367, 5.161, 7.382; all P<0.05）. The OBI detection rate was lowest among blood donors aged 18～ <27 who were vaccinated against hepatitis B, and highest among those aged 47-60, with statistically significant differences （χ~2=28.383, P<0.05）. The multivariate Logistic regression analysis showed that gender, age, blood donation history, and residency were all influencing factors for OBI detection(all P<0.05); Compared with females, the OBI detection rate in males was higher(OR=2.093); compared with the age group of 18-<27 years which immunized with hepatitis B vaccine, the OBI detection rate in the age group of 47-60 years was the highest(OR=7.462); compared with repeat blood donors, the OBI detection rate in first-time blood donors was higher(OR=1.720); compared with out-of-town blood donors, the OBI detection rate in local blood donors was higher(OR=2.353). The analysis of the HBV S amino acid sequences of 43 OBI specimens that could be typed showed that no significant mutation sites were found in the 6 foreign B type sequences, while 11 significant mutation sites were confirmed in the 35 local OBI sequences(P<0.05); of which, 72.7%(8/11) were mutations affecting serological detection of variant strains, and 3 immune evasion variant strains and 2 immune failure variant strains were identified. After a followup period ranging from 3 to 100 months for 40 OBI blood donors, 1 case(2.5%) of HBV DNA converted to negative, 5 cases(12.5%) of HBsAg converted to positive, and the remaining 34(85.0%) continued to maintain the OBI state.Conclusion The high infection rate of local HBV, the specific structure of the blood donor, the high-frequency and significant S gene mutation, and the clinical course of most OBI blood donors were stable to OBI, which might be the main reasons for the high detection rate of OBI among blood donors in Heyuan area.更多还原