河南省人群血清中抗—HBs水平及其分布状况研究

为了解人体血清中自然存在的抗—HBs的水平及分布状况,以探讨抗—HBs水平与保护作用之间的关系,1990年3月和1993年3月我们采用固相放射免疫法(SP—RIA)对2122份人群血清标本的抗—HBs进行检测。结果发现,单项抗—HBs阳性(S/N≥10)543例,占25.6％;抗—HBs S/N值在2.1以下的有284人,占13.4%,S/N值在2.1—10之间的1126人,占53.1％,S/N值在10—50之间的688人,占32.4％,S/N值在50以上的仅24人,占1.1％。如果把放免测定的阳性标准定为≥2.1,那么该人群抗—HBs阳性率86.6％,如果把阳性标准定为≥10,那么该人群抗—HBs阳性率仅为33.6 ％。从本研究的结果可以看出,S/N值在2.1—10之间者占整个人群的半数以上(53.1％),而以往把抗—HBs放免测定的标准定为S/N≥2.1,显然是不合适的。根据本研究结果,我们认为用放射免疫法测定人群血清抗—HBs时,应将阳性界值定为S/N≥10是合适的,这对我国人群乙肝疫苗接种策略和方案的制定都具有重要的意义。     

孕期注射乙肝免疫球蛋白阻断HBV宫内感染及对婴儿产生anti-HBs的影响

目的:探讨孕期注射乙肝免疫球蛋白(hepatitis B immunoglobulin,HBIG)对HBV母婴传播的影响及婴儿对乙肝疫苗免疫应答情况。方法:以HBsAg阳性孕妇及其新生儿为研究对象,孕期注射乙肝免疫球蛋白的孕妇300例及新生儿为实验组,未使用者80例为对照组,比较两组新生儿宫内感染率及出生时和7个月抗体产生情况。结果:孕期注射HBIG组与未注射组新生儿宫内感染率分别为5.33%(16/300)和1.25%(1/80),差异无统计学意义(χ2=2.464,P>0.05);孕期注射HBIG组与未注射组新生儿出生时anti-HBs阳性率分别为10.33%(31/300)和1.25%(1/80),差异有统计学意义(χ2=6.757,P<0.05),7个月龄anti-HBs产生率为96.12%(124/129)和95.35%(41/43),差异无统计学意义(χ2=0.049,P>0.05);出生时anti-HBs阳性的新生儿25例,7个月复查均产生anti-HBs,而出生时anti-HBs阴性或弱阳性的147例婴儿,7个月复查有7例婴儿anti-HBs仍为阴性或弱阳性,但差异无统计学意义(χ2=0.321,P>0.05)。结论:孕期注射HBIG不能降低HBV宫内感染率,可提高新生儿出生时anti-HBs阳性率,但对7个月anti-HBs产生率无影响。     

Quantitative evaluation of the effect of the hepatitis B vaccine based on the HBsAg- and anti-HBs-positive rates in the Chinese population over the last 33 years

Objective

The purpose of the study was to quantitatively evaluate the effect of the hepatitis B vaccine based on 33 years of data published on the HBsAg- and anti-HBs-positive rates.

Methods

All data were obtained from studies in published Chinese scientific journals from 1977 to 2009. The HBsAg- or anti-HBs-positive rate over a certain observation period was presented.

Results

When the anti-HBs-positive rate was low, the ability of anti-HBs to control the HBsAg-positive rate is not apparent. When the anti-HBs level is high, the ability of anti-HBs to control the HBsAg-positive rate increases gradually, and a linear relationship was observed between the HBsAg-positive rate and the anti-HBs-positive rate. However, the rate of decrease of HBsAg positivity was markedly higher than the theoretical rate.

Conclusion

The effect of other known or unknown factors, in addition to the vaccination campaign, could have contributed to the decrease in the prevalence of HBV infection.     

孕期注射乙肝免疫球蛋白对婴儿anti-HBs产生的影响

目的探讨孕期注射乙肝免疫球蛋白的孕妇分娩的婴儿对乙肝疫苗免疫应答情况。方法以HBsAg阳性孕妇及其新生儿为研究对象,孕期母亲注射乙肝免疫球蛋白的300例新生儿为实验组,未使用者80例为对照组,比较两组新生儿出生时及联合免疫后7个月anti-HBs产生情况。结果实验组与对照组婴儿出生时anti-HBs阳性率分别为10.3%（31/300）和1.25%（1/80）,差异有统计学意义;7个月龄实验组anti-HBs产生率为96.1%（124/129）,对照组anti-HBs产生率95.3%（41/43）,差异无统计学意义;出生时anti-HBs阳性的新生儿25例,7个月龄均产生anti-HBs,出生时anti-HBs阴性或弱阳性的147例婴儿中有7例婴儿anti-HBs仍为阴性或弱阳性,差异有统计学意义。结论孕期使用乙肝免疫球蛋白可提高新生儿出生时anti-HBs产生率,但对7个月anti-HBs产生率无影响。     

慢性乙型肝炎病毒感染者HBsAg和抗-HBs共存的不同血清学模式及其意义分析

目的探讨慢性HBV感染者HBsAg和抗-HBs共存的不同血清学模式及其意义。方法在3042例慢性HBV感染者中筛选出HBsAg和抗-HBs共存患者93例,分析其临床特征、HBsAg和抗-HBs相对滴度模式、HBeAg状态和HBV DNA水平。结果根据HBsAg和抗-HBs水平的高（H）或低（L）,将HBsAg＋/抗-HBs＋血清学模式分为H/L、H/H、L/L和L/H四型,分别占43.0%、14.0%、35.5%和7.5%;其HBeAg＋比例依次为H/L（55.0%）〉H/H（38.5%）〉L/L（18.2%）〉L/H（14.3%）;H/L与L/L型患者HBV DNA水平之间差别显著（P=0.016）,而在H/L与H/H（P=0.569）以及H/H与L/L之间（P=0.095）均无显著性差别。结论在HBsAg和抗-HBs共存患者,HBsAg水平越低和抗-HBs水平越高,则HBeAg阳性率和HBV DNA水平越低。     

Occult HBV infection in anti-HBs-positive young adults after neonatal HB vaccination

Previous follow-up on our neonatal HB vaccination cohorts with 80,000 individuals in Qidong, China, showed significant protective efficacy of immunization against HBV infection in childhood. However, some vaccinees were found to be HBsAg negative, but anti-HBs positive and anti-HBc positive at age 10–11 years. To study this phenomenon, 2919 vaccinees at age 19–21 years were sampled from the cohort. HBsAg(−), anti-HBs(+) and anti-HBc(+) were found in 124/2919 (4.2%) of the vaccinees. HBV DNA was detectable in 81/106 sample sera by using nested PCR. The PreS-S regions of HBV were sequenced in 41 randomly sampled sera. All the HBV isolates were HBV genotype C. Twenty one isolates (21/41, 51.2%) were identical to an HBV isolated in this area (GU434374). Only 4/41 (9.8%) showed mutations at the “a” epitope and three of them were G145A. The other mutations were found outside of the “a” epitope. Most of the sera contained <10,000 HBV copies/ml. Occult HBV infection happened in the young adults with HBsAg(−), anti-HBs(+) and anti-HBc(+) status, who received neonatal vaccination in Qidong.     

HBsAb/HBeAb/HBcAb阳性多发性骨髓瘤化疗后HBV再激活1例并文献复习

乙肝再激活通常发生在慢性乙型病毒性肝炎感染患者在接受肿瘤化疗或免疫治疗过程中,但发生抗-HBs阳性患者中少见。本文报道1例65岁HBsAb阳性男性患者因诊断“多发性骨髓瘤”长期接受(硼替佐米/阿霉素/地塞米松/雷纳度胺)化疗,既往无肝病病史,化疗前及化疗期间多次查HBV血清标志物提示HBsAg、HBeAg均阴性,HBsAb、HBeAb、HBcAb均阳性,化疗6周期后出现乙肝再激活,HBVDNA回报为2.46×106IU/mL,经护肝、退黄、修复受损肝细胞、人工肝血浆置换等内科综合治疗病情好转出院。     

Correlations of indoleamine 2,3-dioxygenase,interferon-λ3, and anti-HBs antibodies in hemodialysis patients

BackgroundIndoleamine 2,3-dioxygenase (IDO) contributes to maintaining immune homeostasis. Polymorphisms (SNPs) of the IDO encoding gene (IDO1) influence the IDO activity. Interferon (IFN)-λ3 induces IDO expression. We aimed to investigate whether IDO1 variants are associated with anti-HBs production in response to HBV vaccination or infection, interact with IFN-λ3 associated variants of IFNL4, and influence survival of hemodialysis (HD) patients. We also tested circulating IDO concerning IDO1 SNPs and plasma IFN-λ3 and anti-HBs levels.MethodsThe study included HD patients who had established status concerning responsiveness to HBV vaccination (n = 1022) or were exposed to HBV (n = 315). Ability to generate anti-HBs was diagnosed if anti-HBs after vaccination or infection exceeded 10 IU/L. Genotyping of IDO1 (rs3739319 A < G, rs9657182 C < T), IFNL4 rs8099917 G < T and IFNL4 rs12979860 C > T polymorphisms was carried out by high-resolution melting curve analysis. Circulating IDO and IFN-λ3 were measured with ELISA in 57 subjects. Survival probability was analyzed using the Kaplan-Meier method.ResultsIDO1 SNPs did not correlate with the ability to produce anti-HBs after vaccination or infection. Anti-HBs titers, including a frequency of anti-HBs ≥ 1000 IU/l, also did not associate with IDO1 SNPs, but there was an epistatic interaction between rs9657182, rs8099917, and rs12979860 concerning anti-HBs titers (P = 0.028). Significant associations between IDO1 SNPs and circulating IDO were not demonstrated. Anti-HBs titers negatively correlated with plasma IDO (r = −0.358, P = 0.006), and positively with circulating IFN-λ3 (r = 0.498, P = 0.00008). IDO and IFN-λ3 did not correlate. Patients possessing the rs9657182 TT genotype showed higher infection-related mortality, also in multivariate analysis (HR 2.073, 1.221–3.518, P = 0.007).ConclusionsIDO1 rs9657182, IFNL4 rs8099917, and IFNL4 rs12979860 show epistatic interaction concerning anti-HBs titers. Overreacting immune responses to HBsAg occur in patients with lower IDO but simultaneously higher IFN-λ3 levels. The rs9657182 TT genotype associates with infection-related mortality of HD patients.