乙型肝炎血清标志物和HBV-DNA载量相关性分析

目的 探讨乙肝血清标志物与病毒DNA水平之间的相关性.方法 采用实时荧光定量PCR对874例HBV感染者血清中HBV-DNA含量进行检测,同时运用ELISA法检测HBV血清标志物,并统计分析患者乙型肝炎血清标志物、病毒DNA之间的相关性及分布特点.结果 在受检的874例标本中,男性533例,阳性率58.16％ （310/533）;女性341例,阳性率50.44％（172/341）,男性和女性阳性率比较差异有统计学意义（X2=5.01,P＜0.05）,男性和女性HBV-DNA水平差异无统计学意义（t =0.117,P=0.907）.乙肝总阳性率和HBV-DNA水平均随年龄的增长呈下降趋势,不同年龄组间比较差异有统计学意义.同一年龄段的大三阳与小三阳、两头阳和三抗阳之间比较差异有统计学意义;其中男性和女性HBV-DNA水平随年龄增长均呈下降趋势,差异有统计学意义.≤20岁以下人群HBV-DNA阳性率最高达82.86％.结论 HBV-DNA阳性率和HBV-DNA水平都随年龄增长呈下降趋势,其中≤20岁年龄段HBV-DNA阳性率最高达82.86％;男性HBV-DNA的阳性率高于女性.     

1型糖尿病的基因与血清标志物的研究进展

1型糖尿病(type 1 diabetes mellitus,T1DM)需要经过一较长时间的糖尿病前期,在前期预测糖尿病的发生,筛选T1DM病的高危人群.及时进行免疫干预治疗是预防T1DM的关键,因而T1DM的早期诊断指标显得尤为重要.     

海府地区慢性HBV感染不同免疫状态患者基因分型、病毒变异研究

目的 了解海府地区慢性HBV感染不同免疫状态患者基因分型、病毒变异及其相互之间的关联性.方法 入选对象为海府地区慢性HBV感染患者,依照HBV感染自然史分为4组:慢性无症状HBV携带组、HBeAg(+)CHB组、HBsAg-IaC组、HBeAg(-)CHB组,各50例,PCR-RELP、PCR-反向点杂交法检测所有样本基因型、病毒变异.结果 ①4组患者B基因型感染分布比率分别为:60％、56％、62％、60％;C基因为:38％、38％、34％、32％;D基因为:2％、6％、0、6％;B+C基因为:0、0、4％、2％.各型基因在4组患者中感染同比分布差异无统计学意义(P＞0.05).4组之间优势基因均为B、C基因,尤以B基因感染为主.②4组患者均存在PC、BCP区变异,其中HBeAg(-)CHB组患者变异比例最高,其次为HBeAg(+)CHB组,与HBsAg-IaC组相较,差异有统计学意义(x2=24.73、18.32、6.78、3.84;P=6.59E-07、1.87E-05、0.009、0.049).③B、C型基因感染患者均存在PC、BCP区变异.PC、BCP区变异结果中C基因型发生比例较B基因型高,分别为:43.66％比15.97％、33.80％比10.92％,两者相较差异有统计学意义(x2=17.59、14.84,P=2.74E-05、0.000).结论 海府地区慢性HBV感染优势基因为B、C基因,尤以B基因为主,4种免疫状态均存在PC、BCP区变异.C基因型感染患者及HBeAg(-)CHB患者存在高PC、BCP区变异,可能更易引起严重的肝细胞炎症、坏死和纤维化修复、病毒的高复制及流行,因此,对患者基因分型及病毒变异进行有效监控,将为海府地区慢性HBV感染者的管理开辟新的途径,具有很高的临床实用价值.     

血清HBV标志物少见模式的临床意义

乙型肝炎病毒血清学标志物(HBV-M)显示模式及其检测是目前临床分析和判断乙肝患者病情、传染性大小和疗效分析的重要依据之一, 但在实际工作中, 越来越多地遇到一些临床难以解释或认为是不应该出现的反应模式, 给临床的诊断和治疗带来了许多误会和矛盾.为进一步认识HBV-M少见表现模式的临床意义, 我们收集了一年多来本科血清乙肝5项标志物检测资料, 结合当前国内、外分子生物学的研究成果, 进行分析探讨.     

慢性乙肝患者血清HBV DNA载量与HBV-M、ALT、AST含量的关系研究

目的 分析慢性乙型肝炎患者血清HBV DNA与乙肝标志物(HBV-M)、肝功能ALT、AST的关系,以期对慢性乙肝患者的防治提供借鉴.方法 选取在2011年4月至2012年6月入住我院慢性乙肝患者100例为研究对象,搜集乙肝六项、肝功能等资料,探讨HBV DNA载量与HBV-M、ALT、AST含量的关系.结果 各阳性模式的病毒载量比较,大三阳病毒载量高于其他组,差异有统计学意义(P＜0.05),其他各组比较,差异无统计学意义(P＞0.05).阳性率比较,大三阳高于其他组,差异有统计学意义(P＜0.05),其他各组比较,差异无统计学意义(P＞0.05).血清HBV DNA载量与血清HBeAg滴度无相关性(r=0.683,P＞0.05);血清HBV DNA载量与HBsAg含量无相关性(r=-0.483,P＞0.05);血清HBV DNA载量与ALT无相关性(r=-0.157,P＞0.05),血清HBV DNA载量与AST水平也无相关性(r=0.062,P＞0.05).结论 大三阳血清HBV DNA载量、病毒阳性率均高于其他阳性模式;但血清HBV DNA定量值的高低与HBV-M、ALT、AST含量无相关性,所以,HBV DNA可反映HBV在外周血的复制情况,并不能反映肝脏损伤程度及预后.     

Pre-S1、HBV-DNA与乙肝血清标志物阳性关系的探讨

长期以来对病毒性乙型肝炎的诊断和疗效观察、预后判断主要多依靠乙肝两对半的检测,但是HBV基因组易突变,引起HBsAg亚型,或HBsAg阴性,引起HBeAg阴性HBeAb阳性[1],从而导致临床漏诊,目前乙肝前S1抗原(Pre-S1)和乙肝DNA(HBV-DNA)已成为HBV检测常用的新指标,Pre-S1是HBV的前S1基因编码,具有很强的免疫原性,对HBV附着肝细胞诱导特异性免疫反应有重要作用[2]。HBV-DNA直接反映血中HBV含量。本文就Pre-S1与HBV-DNA水平的相关性作一探讨。而Pre-S1测定在基层医疗机构实验室都可进行,完善和补充乙肝病毒血清标志物的检测,对乙肝患者的早期诊断、治疗和愈后,区别患者是否处于感染、病毒复制阶段有很好的参考价值。     

乙型肝炎血清标志物RIA与HBV DNA检测结果的比较

乙型肝炎血清标志物ＲＩＡ与ＨＢＶＤＮＡ检测结果的比较王书奎，时宏珍，傅雷，王自正本文用ＲＩＡ检测了急性乙型肝炎、慢性迁延性肝炎和慢性活动性肝炎患者的部分血清学指标，并与ＰＣＲ对ＨＢＶＤＮＡ的检测结果进行比较，以探讨他们在肝炎诊断中的价值。对象和方法２...     

乙型肝炎异常血清学诊断模式与HBV-DNA载量的相关性研究

目的探讨乙型肝炎异常血清学诊断模式与HBV-DNA的关系.方法对94例慢性HBV携带患者,根据血清学结果,把病例分A、B、C、D四组,分别采用化学发光法(CLIA)定量检测HBV标志物;采用实时荧光定量聚合酶链反应(FQ-PCR)方法检测HBV-DNA载量.结果A组患者HBsAg和HBsAb同时阳性,HBV-DNA阳性率为96.9％ (31/32);B组患者HBeAg和HBeAb同时阳性,HBV-DNA阳性率为90.0％(18/20),两组间比较差异无统计学意义(x2=2.95,P＞0.05).C组患者HBsAg阴性而HBeAg阳性,HBV-DNA阳性率为64.3％(9/14),C组与A、B组比较差异有统计学意义(x2=32.56和23.41,P＜0.05).结论在受检患者各种异常模式中,均存在HBV-DNA不同程度的复制.HBeAg阳性和HBV-DNA检测结果呈正相关.     

HBV-DNA阳性育龄妇女HBV血清标志物、前S1抗原的检测分析

目的：探讨HBV—DNA阳性育龄妇女病毒复制与HBV标志物及前S1抗原的关系。方法：对1643例慢性乙型肝炎育龄妇女采用荧光定量PCR法检测血清HBV—DNA,酶联免疫吸附法（ELISA）检测HBV标志物和前S1抗原。结果：HBV—DNA阳性育龄妇女432例。其中,HBsAg阴性者占19．44％,前S1抗原总阳性率55．09％,且随着HBV—DNA载量增加,前S1抗原阳性率也升高。结论：采用HBV—DNA、HBV标志物、前S1抗原联检,才能更准确提供育龄妇女HBV感染诊疗依据,有效控制HBV感染率。     

慢性乙肝患者血清HBV-DNA和HBeAg定量的相关性分析

目的：研究慢性乙型肝炎病毒（chronic HBV,CHB）患者血清HBV-DNA含量与e抗原定量的相关性。方法：实时荧光定量PCR（FQ-PCR）和化学发光法（CLIA）分别测定1084例CHB患者血清HBV-DNA、HBeAg含量。结果：1084例HBV患者中HBeAg阳性组和阴性组HBV-DNA检出率分别为74.2%和23.8%,平均含量分别为（4.9±1.9）log10（copies/ml）和（3.9±1.0）log10（copies/ml）;HBV-DNA和HBeAg之间的kap-pa系数为0.49;HBV-DNA定量和HBeAg定量之间相关系数（r）为0.659,HBeAg阳性组HBV-DNA定量和HBeAg定量之间r为0.664;不同载量HBV-DNA组,HBeAg量相差显著,HBV-DNA载量高,HBeAg量也高。结论：HBeAg阳性模式的HBV-DNA阳性率及含量进一步证实了HBeAg确实是反映HBV复制活跃的一个可靠指标,但这并不意味HBeAg转阴病毒复制就停止,HBeAg阴性CHB患者血清中仍有部分患者存在乙肝病毒颗粒;HBV-DNA载量与HBeAg量之间有一定的相关性,但相关性一般;同时检测HBV-DNA和HBeAg量对乙肝患者HBV感染、复制、传染性的判断、治疗方案的选择和疗效判断有一定的指导意义。     

Preponderance of hepatitis B virus genotype B contributes to a better prognosis of chronic HBV infection in Okinawa,Japan

The present study was designed to examine the distribution of hepatitis B virus (HBV) genotypes among patients at various stages of chronic liver disease type B in Okinawa Prefecture, Japan, where the prevalence of hepatitis B surface antigen is the highest in Japan despite the lowest mortality rate from primary liver cancer. Serum samples from 227 HBV carriers were determined for HBV genotype by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Five of 227 sera were negative for HBV DNA by nested PCR and were excluded from the genotype analysis. Genotype B was predominant in asymptomatic carriers (45/67, 67%), whereas genotype C was predominant in chronic liver disease: 49% (50/103) in patients with chronic hepatitis, 63% (20/32) in patients with cirrhosis, and 60% (12/20) in patients with hepatocellular carcinoma. The distribution of genotype B decreased with increasing liver disease severity. However, this tendency was seen among patients aged less than 50 years old, whereas the prevalence of genotype B was similar among carriers with various liver diseases who were older than age 50. In conclusion, HBV genotype B was prevalent and less frequent among patients with advanced liver disease, particularly in patients aged less than 50 years. These findings suggest that the preponderance of genotype B is responsible for the low mortality rate of primary liver cancer associated with HBV seen in Okinawa Prefecture, despite having the highest HBV carrier rate in Japanese.     

Leucocyte hepatitis B virus DNA in acute and chronic hepatitis B virus infection

In the present study we have investigated 53 patients with a spectrum of acute and chronic hepatitis B virus (HBV) infection for the presence of leucocyte HBV-DNA with the aid of molecular techniques. HBV-DNA was detected in peripheral blood mononuclear cells of 31 of 45 (69%) of chronic HBsAg carriers and 2 of 8 (25%) patients with acute hepatitis B. Although HBV-DNA was detected more frequently in leucocytes from those HBsAg carriers seropositive for HBeAg (79%), 50% of those with anti-HBe in serum had leucocytes positive for HBV-DNA independent of the presence of serum HBV-DNA. Examination of various leucocyte subpopulations showed the presence of HBV-DNA in polymorphonuclear leucocytes as well as T- and non-T-enriched mononuclear cell fractions. The HBV-DNA identified was predominantly 3.2-kilobase (kb), while higher molecular weight sequences were rarely detected, and lower molecular weight sequences indicative of active viral replication were not observed. These data indicate that although leucocytes do not actively support viral replication, they frequently harbour 3.2-kb HBV-DNA and may act as a reservoir for infection and, more importantly, since leucocytes contaminate several body secretions, may be involved in virus transmission.     

Influence of hepatitis delta virus superinfection on the clearance of hepatitis B virus (HBV) markers in HBV carriers in Japan

To elucidate the influence of hepatitis delta virus (HDV) superinfection on the clearance of hepatitis B virus (HBV) associated antigens in HBV carriers, we examined for antibody to hepatitis delta antigen (anti-HD) serial sera collected from 1,029 HBV carriers in Kure, Japan. Of the 242 HBV carriers with hepatitis B e antigen (HBeAg), 28 became seropositive for anti-HD, of whom 18 (64.3%) cleared HBeAg; 214 did not become seropositive for anti-HD, of whom 70 (32.7%) cleared HBeAg. Thus, HBeAg clearance was observed in a significantly higher proportion of HDV-superinfected carriers as compared with carriers without HDV infection (P less than 0.005). In the 56 HBV carriers who cleared hepatitis B surface antigen (HBsAg), anti-HD was detected in three cases with increased serum alanine aminotransferase activity preceding HBsAg clearance. The duration of anti-HD seropositive state was less than 5 years, and the titer of anti-HD was relatively low in every case. These data suggest that the HDV infection rate in Japan is higher than previously reported, that HDV superinfection can be one of the factors that induce the HBeAg clearance and HBsAg clearance in HBV carriers, and also that the most likely outcome of HDV superinfection in HBV carriers in Japan may be acute self-limited infection.     

Incidence of hepatitis B viraemia, detected using the polymerase chain reaction, after successful therapy of hepatitis B virus carriers with interferon-alpha

Thirty-nine patients (62 sera) who, after interferon-alpha therapy for chronic hepatitis B virus (HBV) infection, were seronegative for HBeAg and HBV-DNA by dot blot hybridisation, were tested using the polymerase chain reaction (PCR) for residual viraemia. Overall, 59% of the HBsAg-positive sera and 43% of the HBsAg-negative sera were positive by PCR. All except one of the HBsAg-negative patients had seroconverted to anti-HBs. Between 13 and 18 months after therapy, 33% of the HBsAg-positive and 20% of the HBsAg-negative patients remained viraemic. Eighteen months after the end of treatment, no patient tested was positive. Twenty-three patients were tested sequentially over periods from 1 to 43 months: Thirteen lost HBV-DNA by PCR, three remained positive, five remained negative, and two patients relapsed. The merits and disadvantages of PCR for assessing interferon treatment of HBV carriers are discussed.     

HBIG联合乙肝疫苗对单个核细胞感染HBV婴儿垂直传播的阻断

目的研究高效价乙肝免疫球蛋白（HBIG）联合乙肝疫苗对单个核细胞（PBMC）感染乙型肝炎病毒（HBV）的新生儿母婴垂直传播的阻断效果。方法选择HBV257例感染产妇，检测新生儿脐血血清和脐血单个核细胞（UBMC）中的HBV—DNA；所有新生儿出生24h内和生后2w分别注射HBIG 200IU，1月时按0、1、6方案注射乙肝疫苗。并在1岁时检测血清HBsAb和HBV—DNA。结果正规注射HBIG和乙肝疫苗后，UBMC中HBVDNA阳性的婴儿1岁时HBsAb阳转率明显低于血清HBV—DNA阳性、UBMC阴性者（50．00％vs．77．78％，P〈0．05）。而且，UBMC阳性组有15．79％的婴儿1岁时血清HBVDNA阳性。结论HBIG联和乙肝疫苗能够阻断PBMC感染HBV新生儿HBV的垂直传播，但存在部分病例的阻断失败。     

Quantitative assessment of hepatitis B virus DNA in chronic hepatitis B: comparison of two solution hybridization assays

We compared two solution hybridization assays, the AffiProbe assay (Orion Corporation) and the Abbott HBV-DNA assay (Abbott), for quantitative measurement of hepatitis B virus (HBV) DNA in serum samples obtained from chronic hepatitis B surface antigen (HBsAg) carriers. Forty transversally collected (group 1) and 83 serially collected (group 2) serum samples from chronic hepatitis B patients were tested with both assays. The serial serum samples were obtained from 6 patients who underwent α-interferon therapy with different outcomes (nonresponse, hepatitis B e antigen [HBeAg] seroconversion, HBeAg and HBsAg seroconversion). In group 1 a good correlation (r = 0.91; P < 0.001) was found between the HBV-DNA results of the two assays. Two samples (5%) were HBV-DNA positive according to the Abbott but negative according to the AffiProbe assay; for all other samples the HBV-DNA status corresponded. In group 2 the assays gave colinear HBV-DNA results during follow-up of 5 of the 6 patients (correlation for the total group: r = 0.90; P < 0.001). Nevertheless, in both groups the AffiProbe assay yielded about 5–10 times higher HBV-DNA levels than the Abbott HBV-DNA assay (P < 0.001). These discordant results were most probably due to standardization differences of the positive control samples of the two test systems. This observation underlines the need for international standardization of HBV-DNA and uniform reference panels. © 1993 Wiley-Liss, Inc.     

Lamivudine therapy for korean children with chronic hepatitis B

PURPOSE: Lamivudine is known to be very effective in suppressing hepatitis B virus replication and virus induced necroinflammation. The aim of this study was to evaluate lamivudine therapy efficacy, predictive factors, breakthrough, prevalence of YMDD mutation, and relapse rate in Korean children with chronic hepatitis B. MATERIALS AND METHODS: Between August 1999 and February 2005, 60 children on lamivudine therapy for chronic hepatitis B were enrolled. Treatment response was defined as alanine aminotransferase (ALT) normalization, and HBeAg and HBV-DNA disappearance. RESULTS: Seroconversion rates of HBeAg and HBV- DNA were 42% and 53%, respectively, and ALT normalization rate was 88%. Seroconversion rates of HBeAg (60.0%) and anti-HBe (60.0%) were higher in patients younger than 6 years. Seroconversion rate of HBV-DNA (68.4%) and normalization rate of serum ALT (94.7%) were highest in patients between 6 and 12 years. Seroconversion rates of all HBV markers were lowest in patients older than 12 years. Predicted 3 year cumulative seroconversion rates, were 70%, 68% for HBeAg, HBV-DNA, respectively. These were calculated by Kaplan-Meier method. Cox proportional hazard regression model showed that pre-treatment ALT was a positive predictive factor for seroconversion of HBeAg and HBV-DNA. Breakthrough phenomenon was noted in 6 patients, and 3 had a YMDD mutation. CONCLUSION: Lamivudine therapy had a significant effect on HBeAg seroconversion and HBV-DNA disappearance, and ALT normalization for Korean children with chronic hepatitis B.     

Characteristics of hepatitis B virus genotype G coinfected with genotype H in chimeric mice carrying human hepatocytes

Accumulated evidence indicated that hepatitis B virus genotype G (HBV/G) is present exclusively in coinfection with other HBV genotypes. In Mexico, HBV/G from 6 men who had sex with men were coinfected with HBV/H. Phylogenetically complete genomes of the 6 Mexican HBV/G strains were closely related to previous ones from the US/Europe. Using uPA/SCID mice with human hepatocytes, monoinfection with HBV/G did not result in detectable HBV DNA in serum, whereas superinfection with HBV/G at week 10 inoculated HBV/H when HBV/H DNA was elevated to >10(7) copies/mL has enhanced the replication of HBV/G. The HBV/G was enhanced in another 3 inoculated with a serum passage containing HBV/G with a trace of HBV/H. Coinfection of mice with HBV/G and H induced fibrosis in the liver. In conclusion, the replication of HBV/G can be enhanced remarkably when it is coinfected with HBV/H. Coinfection with HBV/G may be directly cytopathic in immunosuppressive conditions.     

Prevalence of serologic markers of the hepatitis B virus in pregnant women of Bamako, Mali

A prospective study of the serological markers of hepatitis B virus (HBV) including hepatitis B virus surface antigen (HBsAg) and hepatitis B surface antibody (anti HBs) was conducted over 5 years in Bamako. The aims of this study were to assess the prevalence of HBsAg in pregnant women and to determine the risk of HBV infection for this population. The study involved 829 pregnant women for whom blood samples were collected after the first quarter of pregnancy. HBsAg and anti HBs were detected in all cases by radioimmunoassay. The prevalence of HBsAg and anti HBs in pregnant women was respectively 15.5% and 16.9%. This prevalence of HBsAg, higher than in the general population, points to the fact that pregnant women are a high risk group for hepatitis B infection. In addition, scarification and tattooing practices increase significantly the risk of infection by hepatitis B virus (OR = 2.03; 1.07 < OR < 3.82; chi 2 = 5.62; p: 1%). Thus, we can presumably conclude that infants and new borns in such conditions are largely exposed to hepatitis B virus infection, even though hepatitis B core antibody and hepatitis B e antigen were not investigated for technical reasons. In conclusion, the authors believe that infants and new borns must be systematically immunised against hepatitis B virus infection in Bamako.