Modification of the immune response against hepatitis B virus by the human immunodeficiency virus

Summary Hepatitis B virus and the human immunodeficiency virus are similarly transmitted. Individuals with preexisting HIV infection have a higher chance to become HBsAg carriers than do anti-HIV negative persons. Cytotoxic T cells with specificity for HBcAg, that are under the control of HBcAg-specific helper T cells, are responsible for liver injury. There is good evidence that HIV infection lowers inflammatory activity, is associated with milder liver histology, high levels of viral replication and low seroconversion rates. In addition interferon alpha therapy is less effective in anti-HIV positive subjects. The immune response against HBsAg is helper T-cell dependent and vaccination against hepatitis B is of low effectiveness. In addition, vaccination against hepatitis B may activate the HIV disease and is, therefore, presently not to be recommended.     

北京地区人类免疫缺陷病毒感染者合并乙型肝炎病毒感染的流行病学特征及影响因素分析

目的:分析北京市人类免疫缺陷病毒（HIV）感染者/艾滋病（AIDS）患者合并乙型肝炎病毒（HBV）感染的流行病学特征,并探索影响合并感染的相关因素。方法:对北京地区HIV/AIDS定点治疗医院（北京协和医院、北京地坛医院、北京佑安医院）长期随访的接受抗反转录病毒治疗（ART）的13 253例HIV感染者临床资料进行回顾...     

13例HIV/HBV重叠感染患者的实验指标分析

目的了解艾滋病病毒与乙型肝炎病毒（HIV/HBV）重叠感染患者的临床特征,分析HIV与HBV在疾病进展中的相互作用。方法回顾性分析、比较13例HIV/HBV重叠感染组、28例单纯HIV感染组、28例单纯HBV感染组患者,在免疫功能、肝脏功能及血常规方面的差异。结果免疫功能检测：CD4^＋T细胞计数和CD4^＋/CD8^＋T细胞比值表现为HIV/HBV重叠感染组〈单纯HIV组〈单纯HBV组（P〈0.01）;肝脏功能检测：HIV/HBV重叠感染组与单纯HIV感染组各项指标无显著性差异,而单纯HBV组的丙氨酸氨基转移酶（ALT）、天冬氨酸转氨酶（AST）、总胆红素显著高于（P〈0.01）或高于（P〈0.05）另外两组;血常规检测：HIV/HBV重叠感染组和单纯HIV组各指标无显著性差异,但与单纯HBV组比较,则红细胞和血红蛋白显著降低（P〈0.01）,血小板明显升高（P〈0.01）。结论研究结果初步提示,HIV与HBV重叠感染后,可能减轻患者的肝细胞损伤,进一步降低患者的免疫功能。     

人类免疫缺陷病毒-1感染者对重组乙型肝炎疫苗的免疫应答

目的 比较HIV-1感染者与健康者接种乙型肝炎(乙肝)疫苗后免疫应答的差异.方法 健康对照者19例和HIV-1感染者20例分别在0、1、6个月肌内注射重组乙肝疫苗20 μg,并在第1、3次疫苗注射后1个月检测抗-HBs水平,高于10 mIU/mL即为阳性.抗-HBs水平比较采用几何均数进行单因素方差分析,两两比较用Scheffe法,率的比较用Fisher's精确概率检验.结果 健康对照组第1、3次疫苗注射后1个月,抗-HBs阳性血清转换者分别为10例和18例,而HIV-1感染组分别为3例和11例,两组比较差异有统计学意义(P=0.015、0.005).CD4+T淋巴细胞≥200×106/L的HIV-1感染者在第1、3次疫苗注射后1个月,抗-HBs阳性血清转换者分别为2例和6例,而CD4+T淋巴细胞＜200×106/L的分别为1例和4例,两组比较在第1次疫苗注射后1个月差异无统计学意义(P=0.202),在第3次疫苗注射后1个月差异有统计学意义(P=0.005).CD4+T淋巴细胞＜200×106/L组(A组)、CD4+≥200X106/L组(B组)和健康对照组(C组)完成3次疫苗接种后1个月抗-HBs水平分别为(101±210)、(529±704)、(5989±10 704)mIU/mL,三组比较差异有统计学意义(F=18.53,P＜0.001),A组分别与C、B组比较,差异有统计学意义(P＜0.001、＜0.05),B组与C组比较,差异无统计学意义(P=0.353).所有入组者对乙肝疫苗均有良好耐受.结论 HIV-1感染者接种乙肝疫苗后与HIV-1阴性者相比,血清转换率和抗-HBs水平降低,尤其是CD4+T淋巴细胞＜200×106/L组.     

The effect of zinc sulfate on immunologic response to recombinant hepatitis B vaccine in elderly: Zinc sulfate and immunologic response to recombinant hepatitis B vaccine

Background

Hepatitis B is the major cause of chronic hepatitis and cirrhosis in Iran. Sanitation and immunization is one of the most effective measures for prevention of the disease which is now widely used in developing countries. However, the immune response to the vaccine varies by age.

Objectives

To determine the effect of zinc sulfate on immune response to hepatitis-B vaccine in elderly.

Patients and Methods

In a clinical trial on 140 subjects aged ?40 years with a body mass index (BMI) <30 kg/m2, and without any co-morbid disease were recruited. Those who had negative hepatitis B core antibody (102 persons) were randomly allocated to two groups. The trial group received hepatitis B vaccine plus 200 mg zinc sulfate daily for 30 days and the control group received vaccine plus placebo.

Results

52 of 102 people were female (51%). The two studied groups were comparable in terms of age, gender, and smoking habits. The mean antibody production in the intervention and control groups was 116.93 and 157.37 mIU/mL, respectively (p=0.22). No statistical differences were observed between the two groups in terms of proportion of people who were protected after vaccination (26.0% and 36.5% in people with and without zinc, respectively).

Conclusions

This study revealed that zinc sulfate has no effect in level of immunity among elderly.     

慢性丙型肝炎患者混合或重叠感染其他病原体状况分析

目的了解丙型肝炎病毒（HCV）感染者混合或重叠感染乙型肝炎病毒（HBV）、人免疫缺陷病毒（HIV）和梅毒螺旋体（TP）的状况,为HCV感染的防治提供依据。方法采用ELISA法检测乙型肝炎病毒标志物、抗TP和抗HIV;采用化学发光法检测抗HCV;采用蛋白印迹法确认HIV感染。结果在169例HCV感染者中,重叠感染HBV 25例（14.8%）、HIV 4例（2.4%）、TP 9例（5.3%）,重叠感染HBV和TP 2例（1.2%）,重叠感染HBV和HIV 2例（1.2%）;静脉吸毒者重叠感染HIV（6.7%）和TP（11.1%）的比例均明显高于非静脉吸毒者（P〈0.05）;男性患者重叠感染HBV的比例（19.7%）明显高于女性患者（3.8%,P〈0.01）,女性患者重叠感染TP的比例（11.5%）明显高于男性患者（2.6%,P〈0.05）。结论随着感染方式的多元化,慢性丙型肝炎患者重叠感染其他病原体的情况更加常见。     

表达乙型肝炎核心抗原、干扰素γ重组质粒免疫小鼠诱导的免疫应答

本研究通过HBV核心基因DNA重组质粒联合干扰素(IFN)γ基因表达质粒同时免疫动物,了解经联合细胞因子DNA免疫后,免疫小鼠T细胞增殖、自然杀伤(NK)细胞杀伤活性及细胞因子释放等免疫效应.探讨联合IFN γ基因表达质粒用于DNA免疫的应用价值.     

HBV/HIV重叠感染的抗病毒治疗

随着人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染率快速增长,乙型肝炎病毒(hepatitis B virus,HBV)/HIV重叠感染成为一种临床易见疾病.HBV/HIV重叠感染使HBV和HIV的生物学行为发生改变,进而相互影响病情进展,使得HBV/HIV重叠感染患者的抗病毒...     

Hepatitis C virus eradication associated with hepatitis B virus superinfection and development of a hepatitis B virus specific T cell response

BACKGROUND/AIMS: Specific T cell responses during acute hepatitis B and during chronic hepatitis C have been described in detail. However, the T cell responses during the rare setting of acute hepatitis B virus (HBV) infection in the course of chronic hepatitis C that eventually lead to clearance of both viruses are completely unknown. METHODS: We analyzed the virus specific CD4+ and CD8+ T cell response during an acute HBV superinfection in a patient with chronic hepatitis C. RESULTS: The patient eliminated hepatitis C virus (HCV)-RNA and HBV-DNA from serum soon after the clinical onset of acute hepatitis B. The HBV specific T cell response found in this patient corresponds to the typical response that has been described in acute hepatitis B without chronic HCV infection. In contrast the hepatitis C specific immune response was similar to that generally found in chronic hepatitis C despite the fact that the patient also eliminated HCV-RNA. CONCLUSIONS: We hypothesize that the acute HBV infection induced a HBV specific T cell response which was associated with elimination HBV DNA and HCV-RNA, the latter possibly by bystander mechanisms, e.g. via secretion of cytokines. If such a non-specific bystander mechanism which has proven to be effective in the experimental setting and which is formally described here for a single patient can be shown to be a more general phenomenon, it may support the approach with new antiviral strategies, e.g. the induction of non-specific defense mechanisms against HCV.     

Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis

AIM To evaluate hepatitis B virus(HBV) vaccine response and correlation with human leukocyte antigens(HLA) and/or gluten intake in celiac patients at diagnosis.METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania(Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody(anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease.RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0to 5.5 years(48.9%, group A); 16 aged between 5.5 and 9.5 years(30.61%, group B); 9 aged between 9.5 and 17 years(18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups(P 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes(homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences(P 0.05).CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.     

Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico.METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ² and/or Fisher’s exact test.RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05).CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.     

Current therapy for hepatitis C or D or immunodeficiency virus concurrent infection with chronic hepatitis B

Concurrent hepatitis C virus (HCV), hepatitis delta virus (HDV), or human immunodeficiency virus (HIV) infection with chronic hepatitis B virus (HBV) appears to increase the risk of progressive liver disease including liver cirrhosis and hepatocellular carcinoma. There is a 10% prevalence of HCV infection in chronic HBV or HDV infection. Serological evidence of previous exposure to HBV is found in more than 80% of HIV-positive patients in the high risk group. Notably, the most recently acquired virus tends to suppress the pre-existing virus. In chronic HBV infection acquired perinatally or in early childhood, usually HCV is dominant and may suppress or even displace HBV and HDV. Less frequently, HBV or HDV suppresses HCV. It is generally agreed that the dominant virus should be identified in order to make appropriate treatment decisions. Studies with standard interferon (IFN) to treat patients with HCV dominantly dual HBV/HCV infection have showed only limited virological response. But high dose of IFN has been demonstrated with better response rate. Combined ribavirin with standard or pegylated IFN therapy could achieve a sustained HCV clearance rate comparable with those infected with HCV alone. On the contrary, patients with HBV dominantly dual viral infection might indicate more appropriate addition of lamivudine to IFN than ribavirin. Additionally, patients with concurrent infection of HBV and HDV, IFN seems to be the only effective agent. However, the efficacy of IFN is related to the dose. High dose of IFN [9 MU tiw (thrice per week)] and longer treatment duration (at least 2 years) have been shown to achieve adequate virological response. In patients with concurrently infected HBV and HIV, anti-HBV therapy should be considered for all patients with evidence of liver disease, irrespective of the CD4 cell count. In patients not requiring antiretroviral therapy, HBV therapy should be preferentially based on IFN, adefovir, or telbivudine. In contrast, in patients with CD4 cell counts <350 cells/μl or those already on antiretroviral therapy, agents with double anti-HBV and anti-HIV activity are preferred. At present, the evidence of therapeutic efficacy is not sufficient to make a recommendation in treating patients with dual HBV/HCV or HBV/HDV or HBV/HIV infection. Further studies of the well-designed, larger scale are needed to elucidate the role of different regimens or combination in the treatment of dual viral infection.     

重组酵母乙型肝炎疫苗联合干扰素α-1 b治疗慢性乙型肝炎的疗效

目的 探讨重组酵母乙型肝炎疫苗治疗慢性乙型肝炎的疗效,确定合理剂量以用于更大样本的临床研究.方法 多中心、随机、双盲、安慰剂对照的临床试验.选择6个月内未经抗病毒治疗的慢性乙型肝炎患者216例,按1:1:1的比例采用分段随机方法分为90μg组、60μg组、安慰剂组,分别于0、2、6、10、14、18、22周肌内注射重组酵母乙型肝炎疫苗,每次90μg或60μg或安慰剂.所有患者均使用IFNα-1b 50μg,每周3次,治疗24周.停药后观察24周.定期检测患者HBVDNA、HBeAg及肝功能.酶联免疫斑点试验(ELISPOT)法检测部分患者产生IFN-γ的细胞数.结果 治疗24周时高剂量组、低剂量组和安慰剂组患者HBV DNA分别为(6.03±1.79)、(5.52±1.82)和(6.29±1.70)log10拷贝/mL(P=0.458);停药后24周HBV DNA分别为(5.92±1.98)、(5.49±1.99)和(6.16±1.76)log10拷贝/mL(P=0.720);治疗24周时,高剂量组、低剂量组及安慰剂组患者HBV DNA＜1×105拷贝/mL分别占30.4%、39.4%和20.8%,低剂量组与安慰剂组比较差异有统计学意义(P=0.015);停药后24周,ttBV DNA＜1×105拷贝/mL比例以低剂量组最高,但三组与治疗前比较差异无统计学意义(P=0.257).停药后24周,HBV DNA转阴率分别为17.4%、25.4%和6.9%,差异有统计学意义(P=0.012).治疗24周时及停药后24周,ALT复常率和HBeAg血清转换率以低剂量组最高,但三组比较差异无统计学意义.治疗24周时及停药后24周行ELISPOT试验显示,高剂量组、低剂量组ELISPOT阳性率比安慰剂组明显升高,差异有统计学意义(P＜0.05).三组不良事件发生率相近,无一例发生药物相关的严重不良反应.结论 重组酵母乙型肝炎疫苗治疗对HBV有一定的抑制作用,合理剂量是60 μg.     

小鼠对乙肝病毒小基因嵌合DNA疫苗免疫应答

目的:探讨含CD80的乙肝病毒小基因嵌合DNA疫苗的免疫应答.方法:以乙肝病毒小基因嵌合DNA疫苗pcHBV-CD80(含CMV启动子、HBV-preS2片段、HBV-C片段和CD80)、pcHBV(含CMV启动子、HBV-preS2片段、HBV-C片段),以及质粒pcDNA-CD80、pcDNA3.1和生理盐水,im免疫小鼠2次(间隔2 wk),末次接种后2 wk时检测特异性抗体、γ-IFN水平和淋巴细胞转化率.结果:质粒pcHBV-CD80和pcHBV免疫后均可检测到特异性的抗体,抗-preS2在pcHBV-CD80组和DcHBV组分别为1 5125.52 nkat/L和14463.56 nkat/L;抗-HB c在pcHBV-CD80组和DcHBV组分别为7607.35 nkat/L和7711.21 nkat/L,两组间无明显差异;但p cHBV-CD80更能增加γ-IFN的产生(1266.7 ng/L vs 986.3 ng/L,P＜0.01),并增强免疫小鼠的激淋巴细胞转化.结论:含CD80的乙肝病毒小基因嵌合DNA疫苗可诱导特异性的体液免疫和细胞免疫应答.     

重叠感染SEN病毒影响拉米夫定抗乙型肝炎病毒疗效

目的 通过检测慢性乙型肝炎(CHB)患者在拉米夫定治疗过程中SEN病毒(SENV)感染情况,了解SENV感染对拉米夫定抗乙型肝炎病毒(HBV)疗效的影响。 方法 采用套式聚合酶链反应检测45例CHB患者经拉米夫定治疗12个月时血清中的SENV DNA,并采用基因芯片技术对HBV DNA阳性的患者进行拉米夫定耐药相关基因YMDD基序(酪氨酸-蛋氨酸-天冬氨酸-天冬氨酸)变异检测。 结果SENV在拉米夫定治疗12个月时CHB患者中的感染率为11.1％(5/45),5例SENV DNA阳性的CHB中4例为HBV DNA阳性,其中2例出现YMDD变异,1例为HBV DNA阴性;40例SENV DNA阴性患者中10例HBV DNA为阳性,30例为阴性,SENV感染组与无感染组之间HBV DNA对拉米夫定的应答率差异有显著性,x2-3.97,P<0.05。 结论 CHB患者在治疗过程中重叠SENV感染可能会使HBV DNA对拉米夫定的应答率下降。     

厦门市乙型肝炎病毒亚基因型分布的初步研究

目的探讨厦门地区乙型肝炎患者血清乙型肝炎病毒（HBV）基因型的分布情况。方法应用混合性型特异性引物聚合酶链反应法结合琼脂糖电泳，根据PCR产物片段大小直接判定HBV基因型；应用PCR扩增全S基因序列-DNA测序-生物信息学分析方法确定部分样本的亚基因型，并探讨前前S区编码的流行情况。结果在217例可以通过混合性型特异性引物聚合酶链反应法确定基因型的感染者中，B型83例（38．2％）、C型71例（32．7％），B／C混合型63例（29．0％）。HBeAg阳性患者中感染B基因型占50％，B／C型混合感染占22％；抗-HBe阳性患者中B／C型混合感染36％，B型38％；在慢性乙型肝炎患者中，以B基因型多见（46％），在肝硬化和肝癌患者中，以C（41％和42％）或B／C混合基因型（38％和33％）感染为主；20例患者血清经过DNA测序-生物信息学分析方法确定了亚基因型，其中B2亚型2例，C2亚型18例，其中混合性型特异性引物聚合酶链反应判断为B型的4例经过测序分析为C2亚型。B2亚型不编码前前S区，18例C2亚型均编码前前S区。结论本研究提示厦门地区乙型肝炎患者群的HBV基因型B、C型的感染率大致相同，亚基因型分析提示C2亚基因型占90％，可能是B／C基因型重组的结果。C2亚基因型病毒株均编码前前S区，提示前前S区的编码可能具有亚基因型特异性。     

慢性乙型肝炎患者HBV基因型和哑型分布调查

目的研究慢性乙型肝炎患者HBV基因型和亚型流行情况。方法应用HBV基因型和亚型特异性引物PCR法对北京、长春、大连、西安、石家庄、郑州和合肥7个城市660份HBV DNA阳性慢性乙型肝炎患者血清进行基因型和亚型分析。结果在660份HBV DNA阳性血清中,B基因型、C基因型和B／C混合感染分别为16．67％（110／660）、74．54％（492／660）和8．79％（58／660）;在C基因型中,C1亚型6例（1．22％）、C2亚型473例（96．14％）、C1／C2混合基因亚型13例（2．64％）;B基因型均为Ba亚型,B基因型和C基因型混合感染者均为Ba与C2亚型混合感染,未发现其他基因型和基因亚型;不同基因型感染患者HBeAg阳性率差异无统计学意义（P=0．153）;B基因型和C基因型患者之间血清HBV DNA水平差异无统计学意义（6．37±1．62lg copies／ml对6．29±1．76lg copies／ml）,但均高于B和C基因型混合感染患者（5．25±1．65lg copies／ml）。结论这7个城市慢性乙型肝炎患者以B基因型和C基因型感染为主,有部分B／C基因型混合感染。HBV亚型以Ba和C2亚型占优势。     

Co-infection of hepatitis B and hepatitis C virus in human immunodeficiency virus-infected patients in New York City,United States

AIM： To study the prevalence and risk factors associated with triple infection with human immunodeficiency virus （HIV）/hepatitis B virus （HBV）/hepatitis C virus （HCV） in an urban clinic population. METHODS： Retrospective chart review of 5639 patients followed at St. Luke＇s-Roosevelt Hospital HIV Clinic （Center for Comprehensive Care） in New York City, USA from January 1999 to May 2007. The following demographic characteristics were analyzed： age, sex, race and HIV risk factors. A multiple logistic regression analysis was performed to evaluate the influence of demographic factors on acquisition of these viruses. RESULTS： HIV/HBV, HIV/HCV and HIV/HBV/HCV infections were detected in 252/5639 （4.47%）, 1411/5639 （25.02%） and 89/5639 （1.58%） patients, respectively. HIV/HBV co-infections were associated with male gender （OR 1.711; P = 0.005）, black race （OR 2.091, P 〈 0.001）, men having sex with men （MSM） （OR 1.747, P = 0.001）, intravenous drug use （IDU） （OR 0.114, P 〈 0.001）, IDU and heterosexual activity （OR 0.247; P = 0.018）, or unknown （OR 1.984, P = 0.004）.HIV/HCV co-infections were associated with male gender （OR 1.241; P = 0.011）, black race （OR 0.788; P = 0.036）, MSM （OR 0.565; P 〈 0.001）, IDU （OR 8.956; P 〈 0.001）, IDU and heterosexual activity （OR 9.106; P 〈 0.001）, IDU and MSM （OR 9.179; P 〈 0.001）, or transfusion （OR 3.224; P 〈 0.001）. HIV/HBV/HCV coinfections were associated with male gender （OR 2.156; P = 0.015）, IDU （OR 6.345; P 〈 0.001）, IDU and heterosexual activity （OR 9.731; P 〈 0.001）, IDU and MSM （OR 9.228; P 〈 0.001）, or unknown （OR 4.219; P = 0.007）. CONCLUSION： Our study demonstrates that coinfection with HBV/HCV/HIV is significantly associated with IDU. These results highlight the need to intensify education and optimal models of integrated care, particularly for populations with IDU, to reduce the risk of viral transmission.