乙型肝炎患者免疫球蛋白检测的作用分析

目的 探讨乙型肝炎患者免疫球蛋白检测的临床意义.方法 128例乙肝患者分为急性乙肝组、慢性乙肝组和慢性重型乙肝组,另随机选取同期我院体检健康者40名作为对照组.4组受试者均晨起取空腹静脉血,测定血清免疫球蛋白（IgG、IgA、IgM）.结果乙肝患者IgG、IgM、IgA水平明显高于对照组,差异有统计学意义（P＜0.05）.结论 免疫球蛋白的增多提示患者肝脏细胞的受损加重,在一定程度上也可辅助判定患者肝脏损伤的程度和病情的进展阶段.     

Anti-idiotypes to Oxidized LDL Antibodies in Intravenous Immunoglobulin Preparations--Possible Immunomodulation of Atherosclerosis

Objective : The aim of this study was to examine whether intravenous immunoglobulin (IVIg) preparations contain anti-oxLDL and anti-anti-oxLDL antibodies. Background : Oxidized low-density lipoprotein (oxLDL) is one of the major players in atherogenesis. IVIg can reduce atherosclerosis in experimental animal models. Methods : Six commercial IVIg preparations were tested for the presence of anti-oxLDL antibodies by EIA. Inhibition studies were performed with the different IVIg preparations and IgGs purified from a pool of sera from patients with high anti-oxLDL antibody levels. Absorption assays were carried out to evaluate the presence of anti-idiotypes against anti-oxLDL antibodies in IVIg preparations. Results : IVIg preparations tested had various degrees of reactivity towards oxLDL. Absorption experiments suggested that the reactivity was specific because it could be effectively absorbed by oxLDL and not by an irrelevant antigen PPD. The reactivity was smaller than that observed with the IgG from the pool with high anti-oxLDL antibody levels. Inhibition studies with IVIg demonstrated 20-45% inhibition of anti-oxLDL binding to oxLDL, compared to 76% inhibition by the pool with high anti-oxLDL levels. To investigate the presence of anti-idiotypes against anti-oxLDL antibodies within IVIg, F(ab') 2 fragments of IVIg IgG were used to absorb IgG F(ab') 2 fragments from the pool of sera with high anti-oxLDL levels. The decreased binding to oxLDL of the absorbed supernatants shows that IgG F(ab') 2 fragments of the IVIg preparations had high inhibitory capacities ranging from 65 to 90%. Conclusions : IVIg preparations contain both anti-oxLDL and anti-anti-oxLDL activity. This finding may explain the immunomodulating effect of IVIg in atherosclerosis.     

Assay Sensitivity Difference Can Induce Anti-Hepatitis A Virus IgM Non-Reactive But Total (IgM and IgG) Reactive Results in Early Acute Hepatitis A

Although anti-hepatitis A virus (HAV) IgM non-reactive and anti-HAV total (immunoglobulin [Ig] M and IgG) reactive results are generally interpreted as immunity to HAV, some early acute hepatitis A patients show the same results. We compared IgM detection sensitivity between anti-HAV IgM and anti-HAV total assays. Acute hepatitis A patients’ samples were serially diluted and tested with Elecsys anti-HAV IgM and total assay (Roche Diagnostics). This resulted in anti-HAV IgM non-reactive but anti-HAV total reactive results. Samples of two hepatitis A patients showing false-negative anti-HAV IgM at initial presentation were analyzed with Elecsys, Atellica (Siemens Healthineers), and Alinity (Abbott Laboratories) HAV assays. Elecsys, Atellica, and Alinity anti-HAV IgM converted reactive on hospital day 3, whereas Elecsys and Atellica anti-HAV total results were reactive from hospital day 1. The anti-HAV total assay had higher sensitivity in detecting IgM antibodies than the anti-HAV IgM assay.     

乙型肝炎病毒基因分型检测试剂临床研究要求探讨

结合体外诊断试剂相关法规和此类试剂临床用途,分析其临床研究的主要要求.对该类试剂的伦理要求、临床试验方案、临床研究单位的选择、临床对象的选择、对比方法的选择、统计学分析、临床试验总结报告撰写等方面进行了详细解析.阐述乙型肝炎病毒基因分型检测类体外诊断试剂的临床研究要点.为从事上市前临床研究的行业人员提供参考.     

慢性乙型肝炎重叠HGV感染对HBV复制的影响

目的观察慢性乙型肝炎重叠ＨＧＶ感染对ＨＢＶ复制的影响．方法采用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）检测患者血清ＨＢＶ－ＤＮＡ．ＨＢＶ－ＤＮＡ定量采用荧光信号引物能量转换法．以单纯慢性乙型肝炎患者作对照研究．结果２３例ＨＧＶ重叠感染的慢性乙型肝炎患者 ＨＢＶ－ＤＮＡ、ＨＢｅＡｇ和抗－ＨＢｅ的阳性率分别为５６．５％、１７．４％和６０．９％而３４例单纯慢性乙型肝炎患者三项指标的阳性率分别为９１．２％、８５．３％和１１．８％．定量分析显示,前组ＨＢＶ－ＤＮＡ量为２．０２、后组为４．１２．经统计学处理,两组各项指标均有显著性差异．结论慢性乙型肝炎重叠ＨＧＶ感染可能会抑制ＨＢＶ的复制．     

乙型肝炎病毒核心基因变异的研究

用聚合酶键反应（ＰＣＲ）对３份肝癌组织及１份乙型肝炎表面抗原阳性但核心抗体（抗－ＨＢｃ）为阴性的无症状携带者血清，扩增及克隆了核心（Ｃ）基因。经核苷酸序列分析，与我国ＨＢＶ克隆株ＰＡＤＲ－１比较，发现无症状携带者的Ｃ基因与ＰＡＤＲ－１的基因差别不大；但自肝癌组织克隆的Ｃ基因平均每例有１５．６个核苷酸变异。结果提示，ＨＢＶ核心基因的变异与疾病的严重程度可能有关。     

HBV基因分型检测试剂性能评估研究要点

依据《体外诊断试剂注册管理办法》和乙型肝炎病毒核酸分型试剂自身特点,提出对HBV基因分型检测试剂性能研究的特殊要求.对该类试剂的参考品和质控品研制、阳性/阴性参考品符合率、最低检测限、分析特异性、精密度、基因混合型研究、携带污染率等方面进行了详细解析.阐述了乙型肝炎病毒基因分型类体外诊断试剂的性能研究要点.为从事该类产品注册申报前性能研究的行业人员提供参考.     

Detection of Occult Hepatitis C and Hepatitis B Virus Infections from Peripheral Blood Mononuclear Cells

Purpose: To investigate the problem of occult HCV & HBV infections in patients with persistently longstanding abnormal liver function test results of unknown etiology and to investigate occult HCV in patients with sustained virological response (SVR). Methods: The study included two groups; first group included 40 patients with persistently longstanding abnormal liver function test, in addition to 62 patients with history of hepatitis C who developed SVR. HCV RNA status was tested in serum by conventional RT-PCR and by real-time PCR in Peripheral Blood Mononuclear Cells (PBMCs). HBV DNA in PBMCs was done in first group only. Results: In first group, PCR in PBMCs was positive for HCV RNA in 4 patients with elevated liver enzymes and HBV DNA was positive in PBMCs in 3 patients. In patients with SVR, 7 patients were positive for HCV RNA in PBMCs. Conclusions: Patients with long-standing abnormal results of liver-function tests with unknown etiology may have HCV RNA or HBV DNA in their PBMCs in the absence of anti-HCV antibodies, HBV markers, serum HBV DNA and serum HCV RNA.In Patients with SVR, HCV RNA in PBMCs is recommended to detect residual infection especially in those with high serum HCV RNA levels before treatment.     

乙型和丙型肝炎病毒感染的免疫学研究进展

世界范围内持续感染乙型肝炎病者（HBV）、丙型肝炎病毒（HCV）的患者已超过5亿。这两种病毒在病原学上有许多共同特点，但在病毒学特点上以及在慢性肝炎的免疫逃逸机制上均有着显著的差别。在早期天然免疫应答方面，HBV感染最初几周并不引起肝脏基因表达的改变，而HCV则会引起许多肝内基因表达改变。在特异性免疫应答方面，HBV和HCV感染后机体清除病毒的途径主要有特异性CTL细胞的杀伤作用、CD4^＋细胞的辅助作用、抗体的中和作用或杀伤作用。相对于HBV来说，HCV在成人更多引起慢性肝炎。     

乙型肝炎核酸疫苗NV—HB／s肌注小鼠后HBsAg的表达和抗 …

目的 研究乙型肝炎核酸疫苗肌注小鼠后在体内的表达及小鼠体液免疫应答的规律,同时观察接种局部组织的病理变化。方法 以乙型肝炎核酸疫苗ＮＶ－ＨＢ／ｓ肌注小鼠,然后定期分批处死,采集肌注局部组织检测ＨＢｓＡｇ（ＡＢＣ免疫组化法）,采集外周血标本检测ＨＢｓＡｇ和抗－ＨＢｓ（ＥＬＩＳＡ法０,并常规病理检查。     

非放射性乙型肝炎病毒核酸探针的制备和应用

非放射性的生物素（Ｂｉｏｔｉｎ）和地高辛（Ｄｉｇｏｘｉｇｅｎｉｎ）标记的乙肝病原基因探针（Ｂｉｏ－ＨＢＶＤＮＡ和Ｄｉｇ－ＨＢＶＤＮＡ探针），特异性强，灵敏度高，最低检出值分别为１ｐｇ和０．５ｐｇ。３２０份血清检测了ＨＢＶＤＮＡ和ＨＢｅＡｇ，并与α－_（３２）Ｐ标记的探针检测结果相比较，它们的特异性分别为９６．５％、９８．１％和８８．９％；灵敏度分别为８１．７％、８６．７％和６１．７％；符合率则为９３．８％、９５．９％和８３．８％。应用Ｄｉｇ－ＨＢＶＤＮＡ探针，作斑点杂交试验，在乙肝患者血清、白细胞、尿、粪、唾液以及旅客列车的桌面、车箱门把手、厕所门把手和水笼头上，均可检得阳性结果。我所研制的非放射性乙型肝炎病原基因诊断试剂，为科学研究和临床检测提供了极为有用的工具。     

我国九个地区丁型肝炎病毒感染状况及其与乙型肝炎病毒复制指标关系的研究

对１５４５例各类乙型肝炎病毒表面抗原（ＨＢｓＡｇ）阳性肝病和无症状ＨＢｓＡｇ携带者的血清进行了乙型肝炎病毒（ＨＢＶ）与丁型肝炎病毒（ＨＤＶ）感染标记物的测定。结果表明，ＨＤＶ感染率为１３．０１％，其中ＨＤＡｇ和抗－ＨＤ阳性率分别为２．９１％和１０．０９％。而且在全国九个地区均有ＨＤＶ感染者存在，说明其分布是较为广泛的。同时还表现出，男性高于女性，慢性肝炎、重型肝炎及原发性肝癌高于急性肝炎和无症状ＨＢｓＡｇ携带者。提示ＨＢＶ与ＨＤＶ合并感染或重叠感染可能导致病情加重和感染的慢性化。本项研究结果还揭示，在ＨＢＶ与ＨＤＶ合并或重叠感染时，可能对ＨＢＶ的复制指标（ＨＢｅＡｇ·ＨＢＶＤＮＡ）有一定的抑制现象。     

从银屑病皮损处鳞屑和组织中检出乙型肝炎病毒成份

应用免疫学及核酸杂交技术和VECTOR、ENZO两公司生产之试剂,从银屑病皮损处鳞屑和组织中检出了乙型肝炎病毒成份。鳞屑中HBsAg和HBV-DNA阳性例数为74/288,占25.6％;组织中HBsAg、HBeAg、HBeAg和HBV-DNA阳性例数为15/75,占20％;有6例在组织中存在两种以上成份。上述成份分布在表皮各层和真皮中,血清HBV感染标志检测结果表明,鳞屑和组织中检出的HBV成份,不是全身感染所致,而是局部存在的。本文首次提出具体病毒和确切定位,并认为乙型肝炎病毒在银屑病发病中可能起主要作用或者是部分病人的发病原因。     

乙型肝炎免疫球蛋白阻断乙型肝炎病毒母婴传播的临床研究

目的探讨乙型肝炎（乙肝）表面抗原（HBsAg）阳性孕妇及其新生儿采用乙肝免疫球蛋白（HBIG）阻断乙型肝炎病毒（HBV）母婴垂直传播的效果。方法将136例HBsAg（＋）的孕妇分为观察组（72例）和对照组（64例）,观察组孕妇于孕28、32与36周分别注射乙型肝炎免疫球蛋白（HBIG）,双阳性注射400IU,单阳性注射200IU;对照组只作随访及常规产检。两组的新生儿在出生6h内、第1、6个月时分别注射乙肝疫苗（HBvac）10μg、5μg、5μg;观察组新生儿在出生6h内臀部肌内注射HBIG 100IU。分别检测两组新生儿及6月龄婴儿血清中HBsAg、乙型肝炎表面抗体（HBsAb）及HBV DNA。结果观察组新生儿HBsAg和HBV DNA阳性率较对照组低,差异有统计学意义（P〈0．05和P〈0．01）。观察组6月龄婴儿HBsAb阳性率较对照组高,而HBV DNA阳性率较对照组低,差异也均有统计学意义（P〈0．01和P〈O．05）。结论HBsAg（＋）的孕妇应用HBIG可有效阻断HBV母婴传播,而新生儿出生时应用HBIG和HBvac联合免疫,可明显提高6月龄婴儿HBsAb阳性率。     

Association of Polymorphism in MicroRNA 604 with Susceptibility to Persistent Hepatitis B Virus Infection and Development of Hepatocellular Carcinoma

MicroRNA polymorphisms may be associated with carcinogenesis or immunopathogenesis of infection. We evaluated whether the mircoRNA-604 (miR-604) polymorphism can affect the persistence of hepatitis B virus (HBV) infection, and the development to hepatocellular carcinoma (HCC) in patients with chronic HBV infection. A total of 1,439 subjects, who have either past or present HBV infection, were enrolled and divided into four groups (spontaneous recovery, chronic HBV carrier without cirrhosis, liver cirrhosis and HCC). We genotyped the precursor miR-604 genome region polymorphism. The CC genotype of miR-604 rs2368392 was most frequently observed and T allele frequency was 0.326 in all study subjects. The HBV persistence after infection was higher in those subjects with miR-604 T allele (P=0.05 in a co-dominant and dominant model), which implied that the patients with miR-604 T allele may have a higher risk for HBV chronicity. In contrast, there was a higher rate of the miR-604 T allele in the chronic carrier without HCC patients, compared to those of the HCC patients (P=0.03 in a co-dominant model, P=0.02 in a recessive model). The T allele at miR-604 rs2368392 may be a risk allele for the chronicity of HBV infection, but may be a protective allele for the progression to HCC in chronic HBV carriers.

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用聚合酶链反应技术研究重型肝炎患者乙型和丙型肝炎病毒的混合感染

采用聚合酶链反应技术（ＰＣＲ）检测了３６例重型肝炎患者血清中乙型肝炎病毒（ＨＢＶ）和丙型肝炎病毒（ＨＣＶ）的复制状况，发现较普遍存在ＨＢＶ复制，阳性率高达７８％；ＨＣＶ复制亦较活跃，为６１％。提示病毒因素仍然是引起肝衰竭的重要原因。临床资料表明，同时感染两种病毒的重肝患者（４１％）预后较差，ＨＢＶ引起的肝坏死较ＨＣＶ引起的更为严重，两者在体内复制有互相抑制作用，但合并感染可造成肝脏的持续损伤。     

重型病毒性肝炎中丁型肝炎病毒的检测

为了探讨丁型肝炎病毒（ＨＤＶ）感染在重型病毒性肝炎中的作用，对北京佑安医院１９８０年至１９８９年收治的５４例急性和亚急性重型肝炎和３８例急性乙肝患者血清，应用国产ＨＤＶＥＬＩＳＡ试剂测定抗－ＨＤ、抗－ＨＤＩｇＭ和ＨＤＡｇ，应用斑点杂交技术测定ＨＤＶＲＮＡ。结果发现重型肝炎组ＨＯＶ－Ｍ检出率明显高于急性乙肝组（２７．８％比５．３％．Ｐ＜０．０５）。单独ＨＢＶ感染和ＨＤＶ／ＨＢＶ混合感染的重型肝炎患者均有较高的病死率。提示ＨＤＶ感染是重型肝炎中重要的病原学因素之一，ＨＤＶ与ＨＢＶ具有协同作用加重肝损害，导致肝衰竭。     

乙型肝炎患者免疫功能的检测及其临床意义

研究乙型肝炎患者外周血T淋巴细胞亚群、NK细胞和血清免疫球蛋白的变化及临床意义.采用流式细胞仪检测150例乙肝患者和30名健康者(对照组)外周血T淋巴细胞亚群(CD3 CD4 、CD3 CD8 )、NK细胞,免疫散射法检测血清免疫球蛋白(IgG、IgM、IgA)变化.结果表明各临床类型乙肝患者NK细胞降低,与对照组比较有显著性差异(P<0.01);慢性乙型肝炎组、慢性重型乙型肝炎组、肝硬化组外周血CD3 CD4 、CD3 CD8 T细胞均下降,其中慢性重型乙型肝炎组外周血CD3 CD8 与对照组比较有显著性差异(P<0.01),急性乙型肝炎组外周血T细胞亚群变化不明显(P>0.05);各临床类型乙型肝炎患者血清免疫球蛋白IgG、IgA随着病情的进展逐渐升高,与对照组比较有显著性差异(P<0.01).因此认为慢性乙肝患者存在细胞免疫和体液免疫功能紊乱,免疫功能的检测对乙肝的诊断、治疗及预后的判断有着一定临床意义.     

乙型肝炎病毒前S1抗原检测的临床意义

探讨乙型肝炎病毒前s1抗原（Pre-S1）检测在乙型肝炎病毒诊断中的临床意义。采用酶联免疫吸附试验（ELISA）和荧光定量聚合酶链反应技术（fluorescenee quantitative PCR,FQ-PCR）对650份HBV-M不同阳性模式及40份HBV—M全阴性模式血清标本进行乙型肝炎病毒Pre-S1、乙肝五项和HBV—DNA检测,并对三种检测结果进行统计学分析。在650份HBV—M不同阳性模式标本中,在119份大三阳标本中Pre—S1阳性检出率92．4％,HBV-DNA阳性检出率100％,在186份小三阳标本中Pre—SI阳性检出率42．5％,HBV—DNA阳性检出率63．4％,在21例HBsAg（＋）和HBcAb（＋）阳性组中Pres1阳性检出率47．6％,HBV．DNA阳性检出率66．7％;在297例HBsAb（＋）标本中Pre—S1阳性检出率0．4％,HBV-DNA阳性检出率0％,在268例HBV—DNA阳性的标本中Pre-S1阳性检出率79．3％。在40份HBV—M全阴模式中Pre-S1阳性检出率0％,HBV-DNA阳性检出率0％。Pre—S1在大三阳、小三阳及HBV-DNA阳性组阳性检出率明显高于阴性组（P〈0．01）,Pre—S1检测可补充和完善乙肝“两对半”检测的不足,尤其对HBeAg阴性或变异的HBV感染者能更好的反映病毒的复制状态和传染性。     

肾小球肾炎肾组织中HBV感染的标志

为了解肾组织中ＨＢＶＤＮＡ与ＨＢＶ抗原存在的关系，探讨肾组织中ＨＢＶ抗原的来源及其与病理变化的关系，我们检测２４６例肾炎肾组织中三种ＨＢＶ抗原。发现除肾小球沉积外，肾小管常有阳性表达。肾小管ＨＢｃＡｇ阳性率达２１．５４％，高于肾小球（１０．９８％）。有１８例肾组织经Ｓｏｕｔｈｅｒｎ印迹杂交检测ＨＢＶＤＮＡ，１５例阳性者中１４例肾组织ＨＢＶ抗原同时阳性，１２例血清感染标志亦阳性。结果提示某些肾炎可能与肾组织感染ＨＢＶ相关，肾组织中出现的ＨＢＶ抗原抗体免疫复合物除来自血循环外，有肾源性──原位形成的可能。