慢性乙型肝炎病毒感染者家族隐匿性乙型肝炎病毒感染的调查

目的 了解慢性HBV感染者家族隐匿性HBV感染的发生率及其与HBV标志物、年龄和性别等的关系.方法 ELISA方法检测慢性HBV感染者家族成员的HBV血清学标志物,套式PCR法检测136例HBsAg阴性家族成员的血清HBV DNA,并将隐匿性HBV感染者和HBsAg、HBV DNA均阴性者分别作为试验组和对照组进行HBV标志物、年龄、性别和生物化学检测结果的比较.两组均数比较采用t检验.率的比较采用χ~2检验或Fisher确切概率法检验.结果 在52个慢性HBV感染者家族中共检测到92例HBsAg阳性者和136例HBsAg阴性者,其中15例为隐匿性HBV感染者,慢性HBV感染者家族HBsAg阳性率和隐匿性HBV感染的发生率分别为40.4%和11.0%,15例隐匿性HBV感染者中有7例抗-HBc阳性(χ~2=5.341,P=0.02),但隐匿性HBV感染的存在与年龄、性别等无关.结论 HBV感染存在家庭聚集现象,且在其家族中存在隐匿性HBV感染,并在抗-HBc阳性者中发生率较高.     

表面抗原和抗体双阳性慢性乙型肝炎病毒感染者病毒S基因的变异分析

目的 了解HBsAg和抗-HBs双阳性慢性HBV感染者的S基因变异情况.方法 分别对8例HBsAg和抗-HBs双阳性(实验组)及9例HBsAg阳性、抗-HBs阴性慢性HBV感染者(对照组)的S基因进行PCR扩增并测序,将测序结果进行对比分析.基因型和血清型分布比较、主要亲水区变异位点数比较采用Fisher'S精确检验,核苷酸和氨基酸序列的同源性比较采用t检验.结果 感染HBV的基因型分布:实验组为B型2例、C型6例,对照组为B型6例、C型3例,两组间差异无统计学意义(P>0.05);血清型分布:实验组为adw 2例、adr 5例、ayr 1例,对照组为adw 6例、adr 3例,两组间差异无统计学意义(P>0.05).实验组和对照组HBV前S1区的核苷酸替换率(2.29%比1.8%)和氨基酸替换率(2.66%比1.59%)差异无统计学意义(t值分别为1.56和1.39,P值均>0.05),前S2区的核苷酸替换率(1.74%比0.91%)差异有统计学意义(t=4.68,P<0.01),氨基酸替换率(3.18%比2.05%)差异无统计学意义(t=1.85,P>0.05);S区的核苷酸替换率(2.13%比0.81%)和氨基酸替换率(4.37%比1.52%)差异有统计学意义(t值分别为6.00和5.32,P值均<0.01).主要亲水区内外均存在氨基酸的替换,"a"决定簇变异相对较高(P<0.05).结论 HBsAg和抗-HBs双阳性慢性HBV感染者的S基因变异率相对较高.     

乙型肝炎病毒感染者血清中双突变X抗原/抗体的检测及意义

目的 探讨HBV慢性感染者血清中野生型及A1762T/G1764A双突变型HBV X抗原/抗体(HBxAg-w、HBxAb-w和HBxAg-m、HBxAb m)与HBV慢性感染者疾病进展的相关性.方法 应用重组抗原创建检测HBxAb的直接ELISA法,应用单克隆抗体和特异性兔多克隆抗体创建检测HBxAg的双抗体夹心ELISA法;对不同临床分期HBV慢性感染者血清中的X抗原/抗体进行检测和比较.数据比较采用∥检验.结果 HBxAg-w和HBxAg-m在慢性无症状HBV携带者、慢性乙型肝炎、乙型肝炎相关性肝硬化和肝细胞癌组血清中的阳性率分别为6.2％(2/32)、10.7％(3/28)、28.6％(6/21)、43.6％(17/39)和3.1％(1/32)、10.7％(3/28)、33.3％(7/21)、48.7％(19/39),HBxAb w和HBxAb-m在慢性无症状HBV携带者、慢性乙型肝炎、乙型肝炎相关性肝硬化和肝细胞癌组血清中的阳性率分别为6.2％(2/32)、21.4％(6/28)、38.1％(8/21)、53.8％(21/39)和6.2％(2/32)、25.0％(7/28)、42.9％(9/21)、61.5％(24/39),每组患者HBxAg w与HBxAg m阳性率的差异(x2值分别为0.871、0.780、0.565、0.317)以及HBxAb-w与HBxAb-m阳性率的差异(x2值分别为0.780、0.709、0.580、0.210)均无统计学意义(均P＞0.05).低病毒载量组(HBVDNA＜1×101拷贝/mL)HBxAgw、HBxAbw、HBxAg-m、HBxAb-m阳性率分别为36.5％(23/63)、44.4％(28/63)、12.9％ (27/63)、54.0％ (34/63),高病毒载量组(HBV DNA≥1×104拷贝/mL)HBxAg w、HBxAb w、HBxAg-m、HBxAb-m阳性率分别为8.8％(5/57)、15.8％ (9/57)、5.3％(3/57)、14.0％(8/57),低病毒载量组HBxAg w、HBxAb-w、HBxAg-m、HBxAb-m阳性率显著高于高病毒载量组(x2值分别为12.869、11.522、22.556、20.976,均P＜0.05);HBeAg阳性组HBxAgw、HBxAb-w、HBxAg m、HBxAb-m阳性率分别为21.7％(18/83)、30.1％(25/83)、22.9％(19/83)、32.5％(27/83),HBeAg阴性组HBxAg w、HBxAb-w、HBxAg-m、HBxAb-m阳性率分别为27.0％(10/37)、32.4％(12/37)、29.7％(11/37)、40.5％ (15/37),HBeAg阳性组与阴性组HBxAg w、HBxAb-w、HBxAg-m、HBxAb-m阳性率的差异均无统计学意义(x2值分别为0.408、0.064、0.638、0.722,均P＞0.05).结论 HBV X基因A1762T/G1764A双突变对HBxAg的抗原性和特异性无明显影响;血清HBxAg和HBxAb随疾病的进展而升高,可能与疾病的发展和乙型肝炎相关性肝细胞癌的形成有关;HBxAg/HBxAb可能具有抑制HBV复制的功能.     

隐匿性慢性乙型肝炎一例

隐匿性慢性乙型肝炎容易出现漏诊,且尚无明确的治疗方案,对于乙型肝炎系列属于抗-HBe阳性、抗-HBc阳性、抗-HBs阳性、HBsAg阴性、HBeAg阴性的患者,应进行进一步的鉴别诊断。本文结合1例隐匿性慢性乙型肝炎患者的临床资料进行分析,探讨其发生机制,并总结经验教训。     

未抗病毒治疗人类免疫缺陷病毒感染者隐匿性乙型肝炎的调查及其临床特点

目的 观察未经抗病毒治疗(ART)的人类免疫缺陷病毒(HIV)感染者和普通人群隐匿性乙型肝炎流行状况,评估HIV感染者合并隐匿性乙型肝炎的临床特点.方法 通过酶联免疫分析法检测未经ART治疗的HIV感染者和普通人群血浆HBsAg、抗-HBs、HBeAg、抗-HBe和抗-HBc水平,筛查出HBsAg阴性的HIV感染者(感染组)249例,健康体检者HBsAg阴性者121例(健康组),再采用罗氏COBASAmpliPrep/COBAS TaqManHBVTest,version2.0试剂盒检测外周血HBV DNA水平.统计分析用STATA 10软件处理本实验各组数据.用Fisher's精确概率检验、秩和检验.结果 感染组HBV DNA阳性者24例,隐匿性乙型肝炎占9.7％;健康组HBV DNA阳性者4例,隐匿性乙型肝炎占3.3％,两组比较,P=0.035,差异有统计学意义.感染组24例HBVDNA阳性者,HBV DNA载量最低者血中能测到,但在检测值水平以下,(即＜20 IU/ml),最高者3.22×105 IU/ml.大于100 IU/ml占37.5％(9/24),20 ～ 99 IU/ml占16.7％ (4/24),＜20IU/ml,但可测出HBV DNA占45.8％ (11/24).HIV感染者抗-HBc(+)/抗-HBs(+)组、抗-HBc(+)/抗-HBs(-)组、抗-HBc(-)/抗-HBs(+)组、抗-HBc(-)/抗-HBs(-)组DNA阳性率分别为7.3％ (8/110),20.8％ (11/53),14.3％ (3/21),3.1％(2/64),抗-HBc(+)/抗-HBs(-)组分别与抗-HBc(+)/抗-HBs(+)组、抗-HBc(-)/抗-HBs(-)组两组比较,P值分别为0.018和0.003,差异有统计学意义.四组间HBV DNA病毒载量比较,P=0.805,差异无统计学意义.感染组HBV DNA(+)组与HBV DNA(-)组比较,CD4计数(Z=1.902,P=0.0586)和ALT水平(Z=1.401,P=0.1611)差异无统计学意义.结论 在未经ART治疗HIV感染者中,隐匿性乙型肝炎高于普通人群,HIV感染者抗-HBc(+)/抗-HBs(-)组隐匿性乙型肝炎最高.     

不同基因型乙型肝炎病毒感染者与其自身抗体的相关性分析

目的 探讨感染不同基因型HBV患者血清中自身抗体的存在状况及其分布特征,以了解HBV感染与自身免疫的关系.方法 采用聚合酶链式反应限制性片段长度多态分析技术对重庆地区252例HBV感染者血清进行HBV基因分型,同时采用间接免疫荧光法或免疫斑点法检测其血清中的抗核抗体、抗线粒体抗体、抗平滑肌抗体、抗肝肾微粒体抗体、抗核糖核蛋白抗体、抗Sm、抗SS-A抗体、抗SS-B抗体、scl-70、抗Jo-1抗体等自身抗体.将患者分为慢性乙型肝炎组、肝硬化组和肝细胞癌组3组,并设立正常对照组,分别就自身抗体分布、性别及年龄等多种指标进行对比分析.计数资料采用x2检验,3组间两两比较P值d校正为0.05/3=0.0176.结果 252例患者血清中检出基因B型170例(67.46％)、C型82例(32.54％),未发现A、D、E、F、G、H基因型存在;其血清中检出多种自身抗体,总检出率为76.98％,与正常对照组(12.0％)比较,差异有统计学意义(x2=44.60,P＜0.05); 170例B基因型患者血清中131例(77.06％)检出自身抗体,82例C型患者血清中63例(76.83％)检出自身抗体,两组比较,差异无统计学意义(P＞0.05).结论 本地区HBV感染者基因型主要为B型和C型,以B型居多;乙型肝炎患者自身抗体阳性率较高,检出率与病程、年龄相关,而与性别、病毒基因的类型等因素无关.     

HBsAg与抗-HBs同时阳性的慢性乙型肝炎患者临床特点分析

目的分析HBsAg与抗-HBs同时阳性的现象及其临床特点,并探讨其产生的原因。方法收集2011年2月-2014年2月东南大学附属第二医院体检者2260例,其中被诊断为慢性乙型肝炎的患者830例。采用化学发光微粒子免疫分析法筛选HBsAg与抗-HBs同时阳性的患者188例,分为HBeAg阳性组(n=101)和HBeAg阴性组(n=87)。同时选取200例HBsAg阳性、抗-HBs阴性者作为对照,其中HBeAg阳性组80例,HBeAg阴性组120例。检测HBV血清学标志物、肝功能、病毒载量并结合临床进行分析。计数资料组间比较采用χ2检验。结果 HBV血清学标志物在HBsAg与抗-HBs双阳性情况下共有5种模式,其中以HBsAg、抗-HBs、HBeAg及抗-HBc阳性,且抗-HBe阴性多见,占47.9%(90/188),肝功能指标总异常率为69.1%(130/188),HBV DNA总阳性率为56.9%(107/188)。HBeAg阳性的2组HBV DNA均存在高水平复制,其中HBsAg与抗-HBs双阳性组HBV DNA阳性率与对照组比较,差异无统计学意义(χ2=2.632,P0.05);HBeAg阴性组中,HBsAg与抗-HBs双阳性组HBV DNA定量1×105IU/ml的比例与对照组比较,差异有统计学意义(χ2=10.740,P0.05)。对HBV S区进行测序分析发现,测序的80例HBsAg与抗-HBs双阳性患者中有27例患者的HBV S区发生变异,突变率33.7%,且S区变异位点主要有P29L、S61L、P62L、I126T/S、Q129N、M133K、F134L、G145R/K、L175S和L186H等。结论 HBsAg与抗-HBs同时阳性者在乙型肝炎患者中有一定比例,其主要原因可能是病毒株变异所致。这种情况并不代表疾病好转,且抗-HBs出现并不一定能完全有效清除HBsAg,病毒DNA往往存在持续复制,需引起重视。     

乙型肝炎病毒感染者血清抗心磷脂抗体检测结果分析

目的了解抗心磷脂抗体（ACA）在乙型肝炎病毒（HBV）感染者血清中的分布及检出情况。方法采用金标法检测158例HBV感染者（HBV感染组）和150名正常对照者（正常对照组）血清ACA。结果HBV感染者的ACA阳性率显著高于正常对照组（P〈0．01）,肝功能异常的HBV感染者ACA阳性率显著高于肝功能正常的HBV感染者（P〈0．01）。结论ACA可在HBV感染者血清中检出,其滴度高低与病情严重程度有一定关系。     

人类免疫缺陷病毒感染者合并隐匿性乙型肝炎病毒感染的现状调查

目的 调查分析上海地区HIV感染者中隐匿性HBV感染的流行现状.方法 对上海市公共卫生临床中心就诊的HIV感染者在尚未接受抗病毒治疗前采集血标本,检测HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc,抗-HCV,CD4+T细胞计数,使用巢式PCR法检测HBV S区.结果 105例(男92例,女13例)HBsAg阴性的HIV感染者中32例(男27例,女5例)HBV DNA阳性;16～30岁年龄组22例,其中5例HBV DNA阳性,31～49岁年龄组44例,其中15例HBV DNA阳性,50～75岁年龄组39例,其中12例HBV DNA阳性;32例中有27例至少一项HBV血清学标志物阳性,5例均阴性.47例合并HCV感染者中有14例HBV DNA阳性,阳性率29.8%;58例未合并HCV感染的HIV感染者中18例HBV DNA阳性,阳性率为31.0%.CD4+T细胞计数平均值145.1个/μ(4～623个/μ1),75例CD4+T细胞<200个/μ1的患者中有26例HBV DNA阳性,约占34.7%,30例CD4+T细胞>200/μ1患者中有6例HBV DNA阳性,阳性率为20.0%.以上各项之间两两相比差异均无统计学意义.结论 HIV感染者中存在隐匿性HBV感染,且与HIV感染者性别、年龄、HBV标志物、是否合并HCV感染及CD4+T细胞计数无明显相关.     

隐匿性乙型肝炎病毒感染

大量研究通过对肝组织和血清乙型肝炎病毒（HBV）DNA或转录体的检测，证实隐匿性HBV感染是所谓“隐源性肝炎”及其它慢性肝病的常见病因。现就其发生率、形成机制、临床意义、诊断、治疗等方面作一综述。     

Genetic variation of occult hepatitis B virus infection

Occult hepatitis B virus infection(OBI), characterized as the persistence of hepatitis B virus(HBV) surface antigen(HBs Ag) seronegativity and low viral load in blood or liver, is a special form of HBV infection. OBI may be related mainly to mutations in the HBV genome, although the underlying mechanism of it remains to be clarified. Mutations especially within the immunodominant "α" determinant of S protein are "hot spots" that could contribute to the occurrence of OBI via affecting antigenicity and immunogenicity of HBs Ag or replication and secretion of virion. Clinical reports account for a large proportion of previous studies on OBI, while functional analyses, especially those based on full-length HBV genome, are rare.     

An overview of occult hepatitis B virus infection

Occult hepatitis B virus (HBV) infection (OBI), alternatively defined as occult hepatitis B (OHB), is a challenging clinical entity. It is recognized by two main characteristics: absence of HBsAg, and low viral replication. The previous two decades have witnessed a remarkable progress in our understanding of OBI and its clinical implications. Appropriate diagnostic techniques must be adopted. Sensitive HBV DNA amplification assay is the gold standard assay for detection of OBI. Viral as well as host factors...     

Diagnostic strategy for occult hepatitis B virus infection

In 2008,the European Association for the study of the liver(EASL) defined occult hepatitis B virus infection (OBI) as thepresence of hepatitis B virus(HBV) DNA in the liver(with detectable or undetectable HBV DNA in the serum) of individuals testing hepatitis B surface antigen(HBsAg) negative by currently available assays.Several aspects of occult HBV infection are still poorly understood,including the definition itself and a standardized approach for laboratory-based detection,which is the purpose of this ...     

Prevalence of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is characterized by the persistence of HBV DNA in the liver tissue in individuals negative for the HBV surface antigen.The prevalence of OBI is quite variable depending on the level of endemic disease in different parts of the world,the different assays utilized in the studies,and the different populations studied.Many studies have been carried out on OBI prevalence in different areas of the world and categories of individuals.The studies show that OBI prevalence...     

Clinical significance of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is defined as the presence of HBV DNA in the liver(with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative.Until recently,the clinical effect of OBI was unclear on the progression of liver disease;on the development of hepatocellular carcinoma;and on the risk for reactivation or transmission of HBV infection.Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease,but its role...     

Long-term clinical impact of occult hepatitis B virus infection in chronic hepatitis B patients

BACKGROUND/AIMS: Long-term clinical outcomes of occult hepatitis B virus (HBV) infection were studied. METHODS: Fifteen chronic hepatitis B patients were monitored for a median of 4.4 years (range 0.9-15.3) after hepatitis B surface antigen (HBsAg) seroclearance. Serum HBV DNA was measured by real-time detection polymerase chain reaction. Thirteen patients underwent liver biopsies at the end of follow-up and liver histology was evaluated by Ishak score. Liver HBV DNA was also measured for 12 patients. RESULTS: At the end of follow-up, HBV viremia was absent in 13 (87%) patients, and antibody titers to hepatitis B core antigen showed an inverse correlation with time from HBsAg seroclearance (r=-0.554; P=0.0040). However, all patients retained liver HBV DNA and tested positive for the covalently closed circular HBV DNA replicative intermediate. The hepatic HBV DNA loads had no relation to liver histology. Paired biopsies from 11 patients disclosed that each necroinflammatory score significantly improved after HBsAg seroclearance. Amelioration of liver fibrosis was also evident in eight (73%) patients (P=0.0391 by signed rank test). CONCLUSIONS: A long-standing but strongly suppressed HBV infection may confer histological amelioration after HBsAg seroclearance.     

Pathogenesis of occult chronic hepatitis B virus infection

Occult hepatitis B infection(OBI) is characterized by hepatitis B virus(HBV) DNA in serum in the absence of hepatitis B surface antigen(HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns.Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays;but more frequently it is due to a strong suppression of viral replication and gene expression.OBI is an entity with world-wide diffusion.The failure to detect HBsAg,despite the persistence of the viral DN...     

Role of occult hepatitis B virus infection in chronic hepatitis C

The development of sensitive assays to detect small amounts of hepatitis B virus(HBV) DNA has favored the identification of occult hepatitis B infection(OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV(HBs Ag) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody(antiHBc) in serum of HBs Ag-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C(CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma(HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC.     

Clinical impact of occult hepatitis B virus infection in immunosuppressed patients

Occult hepatitis B infection(OBI), is characterized by low level hepatitis B virus(HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen(HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI.