HIV/AIDS合并HBV、HCV感染的流行病学研究
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摘要
引言
乙型肝炎病毒、丙型肝炎病毒与人类免疫缺陷病毒具有相似的传播途径,都可以通过血液、性接触及母婴传播,所以HIV感染者常常合并HBV、HCV感染。随着高效抗反转录病毒治疗的广泛应用,肝脏相关性疾病已成为HIV感染者主要的合并症和死亡原因之一。
自1981年美国报告首例AIDS患者以来,全球已有199个国家和地区报告HIV感染者或艾滋病患者。估计全球累计已有7000万以上的人感染了HIV,超过3000万人死于艾滋病。HBV、HCV感染呈世界性流行,据世界卫生组织(WHO)报道,全球约20亿人曾感染过HBV,其中3.5亿人为慢性HBV感染者,全球HCV的感染率约为3%,估计约1.7亿人为慢性丙型肝炎感染者。到2007年底,我国估计现存艾滋病病毒感染者和病人约70万(55万-85万人),全人群感染率为0.05%(0.04%-0.07%),其中艾滋病病人8.5万(8万-9万人)。现在我国HIV感染正处于快速增长期,据估计目前每年大约以30%以上的速度增长。我国属HBV、HCV感染高流行区,一般人群的HBsAg阳性率为9.09%,抗-HCV阳性率为3.2%,我国约有1.3亿慢性HBV感染者和4000万HCV感染者。
HIV、HBV和HCV传播途径相似,因此HIV感染者常常合并HBV、HCV感染。约90%-95%的HIV感染者曾经感染过HBV,其中大约10%-15%为慢性HBV感染者。由于HIV感染者免疫功能不全,不能够完全彻底的清除和抑制HBV,所以HIV感染者常常合并隐匿性HBV感染。国外研究报道HIV感染者合并隐匿性HBV感染率从0%-51.2%不等,甚至在仅抗-HBc阳性的HIV感染者中高达89.5%。约有1/4-1/3的HIV感染者合并HCV感染,据此估计,全球约有近1000万的HIV/HCV重叠感染者。
HIV感染改变HBV、HCV的自然病程,加速肝纤维化、肝硬化及肝细胞癌的进程。HIV感染者由于CD4+T细胞下降,免疫功能受损,导致不能够有效的抑制和清除HBV、HCV,HBV、HCV复制的增加,引起肝脏持续性炎症因子的表达和淋巴单核细胞活化,促进肝纤维化、肝硬化和肝细胞癌的发生。现在肝脏相关性疾病已成为HIV死亡的主要原因之一。另外,HCV基因型对肝病的进程和预后起着重要的作用。其中HCV基因1型感染者的肝脏损伤程度要比其他型严重,对干扰素治疗的效果也更差,特别是合并HIV感染者,由于骨髓抑制,药物的相互作用,HAART的肝脏毒性等原因使HCV的治疗更为困难。
本研究使用PCR等分子生物学的方法,调查上海地区HIV感染者中HBV和/或HCV感染状态、隐匿性HBV感染率及HCV基因型的分布。为我国HIV/AIDS合并HBV、HCV感染的防治提供理论基础。
全文共分三部分:
第一部分:上海地区人类免疫缺陷病毒/艾滋病合并乙型、丙型肝炎病毒感染的临床流行病学研究
第二部分:HIV感染者合并隐匿性乙型肝炎病毒感染的现况调查
第三部分:上海地区201例HIV阳性者合并HCV感染的分子流行病学研究
第一部分:上海地区人类免疫缺陷病毒/艾滋病合并乙型、丙型肝炎病毒感染的临床流行病学研究
目的:了解HIV感染者中HBV和/或HCV感染的流行现状及其特点。方法:对上海市(复旦大学附属)公共卫生临床中心就诊的170例HIV感染者采集血标本,使用微粒子酶联免疫法(MEIA)检测HIV感染者血清的乙肝二对半(HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc),应用酶联免疫法(ELISA)检测丙型肝炎(HCV)抗体。结果:170名HIV感染者中,男性146人,女性24人,最小年龄16岁,最大年龄74岁,平均年龄41±13岁;HBsAg阳性患者19人(11.2%),抗-HBs阳性者87人(51.2%),HBeAg阳性者7人(4.1%),抗-HBe阳性者49人(28.8%),抗-HBc阳性者111人(65.2%);抗-HCV阳性者77人(45.3%)。HIV、HBV和HCV三重感染者9人,约占5.3%。结论:HIV感染者HBsAg阳性率与普通人群相近,但HIV与HCV重叠感染的比例显著高于普通人群。
第二部分:HIV感染者合并隐匿性乙型肝炎病毒感染的现况调查
目的:了解HIV感染者中隐匿性HBV感染状况并对其相关因素进行分析。方法:对上海市(复旦大学附属)公共卫生临床中心就诊的HBsAg阴性的HIV感染者采集血标本,使用微粒子酶联免疫法(MEIA)检测HIV感染者血清的乙肝二对半(HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc),应用酶联免疫法(ELISA)检测丙型肝炎(HCV)抗体,流式细胞仪检测CD4+T细胞记数,使用巢式PCR法检测HBV S区。结果:105名HBsAg阴性的HIV感染者中,男性92人,女性13人。32例HBV DNA阳性,其中27例至少一项HBV血清学标志(HBV M)阳性,5例HBV M均阴性。47例合并丙肝感染者中有14例HBV DNA阳性,阳性率29.8%;58例HBV血清学标志阴性的单纯HIV感染者中18例HBVDNA阳性,阳性率为31.0%,两者相比无显著性差异;CD4+T细胞计数:145.1±158.1/μl,75例CD4+T细胞＜200/μ1的患者中有26例HBV DNA阳性,约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%,两者相比无显著的统计学差异;32例HBV DNA阳性标本中22例无氨基酸序列变异,10例在HBsAg的“a”肽段处有氨基酸序列突变。结论:HIV感染者合并隐匿性HBV感染率较高,免疫功能紊乱及S基因变异可能是隐匿性HBV感染的原因。
第三部分:上海地区201例HIV阳性者合并HCV感染的分子流行病学研究
目的:了解上海地区人类获得性免疫缺陷病毒(HIV)感染者合并丙型肝炎病毒(HCV)感染的流行病学状况及HCV基因型分布特征。方法:对上海市(复旦大学附属)公共卫生临床中心就诊的201例HIV感染者,使用ELISA法检测抗-HCV抗体,反转录聚合酶链反应(RT-PCR)方法扩增,纯化后直接测序检测HCV基因型。结果:201名HlV感染者,女性26(12.9%)人,男性175(87.1%)人,其中88例(43.8%)HCV抗体阳性。对45例合并感染者HCV基因型检测结果:28例(62.2%)基因型为1b亚型,10例(22.2%)基因型为2a亚型,3例(6.7%)基因型为2a/2c亚型,3例(6.7%)患者合并感染1b和2a/2c亚型,1例(2.2%)合并感染1b和2a两种亚型。结论:输血或血制品的HIV感染者合并HCV感染率较高,对于这部分HIV感染者应常规检测HCV抗体。HIV感染者合并感染HCV的主要基因型是1b亚型,其次为2a亚型,并存在多种HCV基因型共感染的现象。
Hepatitis B virus(HBV) and hepatitis C virus(HCV) are common among patients with human immunodeficiency virus(HIV) infection because of shared ways of viral transmission.Since the decline in HIV-related morbidity and mortality after introduction of highly active antiretroviral therapy(HAART),liver disease caused by HBV and/or HCV has become a major cause of morbidity and mortality among HIV-infected patients.
Since the first AIDS case was reported in the United States in 1981, 199 countries/regions had reported HIV infection or AIDS patients around the world.It has been estimated that more than 70 million people have been infected with the HIV,and more than 30 million have died from AIDS globally.Of the 2 billion people who have been infected with the HBV, more than 350 million have chronic infections.An estimated 170 million persons are chronically infected with HCV and 3 to 4 million persons are newly infected each year.By the end of 2007,the estimated results showed approximately 700,000 are now HIV positive(range 550,000-850,000).The HIV infection rate among China' s population is 0.05 per cent(range 0.04%-0.07%).The estimated number of AIDS cases is 85,000(range 80,000-90,000).Now the HIV epidemic in China is at the rapid expansion phase,and it is estimated that it increases by about 30 percent every year.
In China,the HBV and HCV prevalence is high.The HBsAg and anti-HCV positive among the general population is 9.09%and 3.2%,respectively. An estimated 130 million chronic HBV infections and 40 million HCV infections are in China.
Because of shared routes of transmission,coinfection with hepatitis B virus(HBV) and hepatitis C virus(HCV) is common in HIV-infected persons. Serologic evidence of past exposure or current HBV infection is found in 90%to 95%of HIV-infected individuals。Among HIV-infected persons,10% to 15%are chronic carriers of HBV.Occult HBV infections in HIV infected persons are common,because HIV infected patients are immune dysfunction and HBV replication can not be inhibited and cleared.The prevalence of occult HBV in HIV infected patients has been controversial,varied from 0 to 51.2%,and even occult HBV among the HIV infected patients with anti-hbc alone is up to 89.5%.One-quarter to one-third of HIV-seropositve individuals are co-infected with HCV.It is estimated that there are about 10 million cases of HIV-HCV coinfection worldwide.
HIV infection modifies the natural history of HCV infection,which can accelerate the progression to fibrosis,cirrhosis and hepatocellular. HIV-infected individuals show a quantitative depletion of CD4+ T cells and immune dysfunction,which lead to increase the replication of virus of hepatitis,secrete inflammatory cytokines and activate lymphomononuclear cells in the liver,and ultimately result in fibrosis, cirrhosis and hepatocellular carcinoma.Now liver disease has become the leading cause of death of HIV infected patients.In addition,the genotype of HCV plays an important role in the progression of liver disease and can predict the prognosis.HCV genotype 1 may represent a more aggressive strain,which is less respond to interferon treatment than HCV genotype 2 or 3.Treatment of HCV is more complicated in HIV-infected patients due to bone marrow suppression,drug interactions,HAART-related hepatotoxicity and other reasons.
The study used molecular biology techniques to invest the prevalence of HBV and/or HCV,occult HBV and HCV genotype distribution in HIV-infected persons.Provide theoretical basis for prevention and treatment of HBV and/or HCV in HIV infected persons.
The contents of this study are:
(1):Study on HIV/AIDS Subjects co-infected with HBV and/or HCV in Shanghai
(2):The Epidemic Analysis of Occult Hepatitis B Virus in HIV-Infected Patients
(3):Molecular epidemiology of HCV co-infection in 201 HIV patients in Shanghai
Part One:Study on HIV/AIDS Subjects co-infected with HBV and/or HCV in Shanghai
objective:To analyse the epidemiology of HIV/AIDS co-infected with HBV and/or HCV.Methods:Microparticle enzyme immunoassay(MEIA) was used to detect HBV serological immune indicators (HBsAg、anti—HBs、HBeAg、anti—HBe、anti—HBc) and Enzyme linked immuneosorbent assay(ELISA) to HCV antibody in 170 HIV antibody positive subjects.Results:Patients mean age was 41±13 years,and 146(85.8%) were males.A total of 19(11.2%) HIV/AIDS subjects showed HBsAg positive, 87(51.2%) anti-HBs positive,7(4.1%) HBeAg positive,49(28.8%) anti-HBe positive,111(65.2%) anti-HBc positive.There are 45.3%HCV positive in this group,the triple infection rate of HIV,HBV and HCV was 5.3%. Conclusion:HCV infective rate is dramatically higher in the HIV/AIDS infectious patients than the HIV negative population,and the co-infection rate of HBV in HIV/AIDS is similar to the common.
Part two:The Epidemic Analysis of Occult Hepatitis B Virus in HIV-Infected Patients
Objectives:The occult hepatitis B virus(HBV) is defined by the positive of HBV DNA in individuals with undetectable levels of HBV surface antigen(HBsAg).The objective of this study was to assess the prevalence and related factors of occult HBV in hiv-infected patients.Methods:The serum samples were from 105 HBsAg-negative patients with HIV patients hospitalized at Shanghai Public Health Clinical Center.Microparticle enzyme immunoassay(MEIA) was used to detect HBV serologic markers(HBsAg、anti—HBs、HBeAg、anti—HBe、anti—HBc),and enzyme linked immuneosorbent assay(ELISA) to HCV antibody.CD4+ cell count was examined by flow cytometry.Nested polymerase chain reaction(n PCR) was used to amplify surface protein region of HBV.Results:105 HIV/AIDS patients were 92 men (87.6%) and 13(12.4%) women,respectively.32(30.5%) patients were HBV DNA+,5 patients were negative for all HBV serologic markers,and 27 patients detected at least one of anti-HBc,anti-HBe and anti-HBs.14 patients(29.8%) with HBV DNA+ in 47 HIV patients coinfected with HCV,18 patients(31.0%) in 58 HIV-monoinfected patients,The mean CD4+ cell count was 145 cells/μl,26 patients(34.7%) in 75 patients with CD4+ cell＜200 cells/μl,6 patients(20%) in 30 patients with CD4+ cell＞200 cells/μl.No statistical significant association could be established between occult HBV infection and HBV serologic markers,coinfected HCV and CD4+ cell count.Analysis of S gene showed that 1 nucleotide sequence inserted "A" in nt527 and nt539,respectively,and induced the reading frame shift.9aminoacid sequences changed(C124S,I126T,I126V,T131I,L133I, K141N,P142L,S143T and S143P) in the HBV "a" determinant,and the rest of patients had no mutation in the HBV "a" determinant.Conclusions: Occult HBV occurred in a sizable proportion of HIV-infected patients. Immune Dysfunction and S gene variation may be the reason of occult HBV infection.
Part three:Molecular epidemiology of HCV co-infection in 201 HIV patients in Shanghai
Objective:To investigate the molecular epidemic and subtypes of hepatitis C virus(HCV) co-infection in the human immunodeficiency virus patients in Shanghai.Methods:Enzyme linked immuneosorbent assay(ELISA) was used to detect HCV antibody and HCV RNA was extracted and amplified by nested PCR,then purified and directly sequenced in 201 HIV antibody positive subjects,who hospitalized in Shanghai Public Health Clinical Center affiliated to Fudan University. Results:Of 201 HIV infected patients,12.9%(26/201) were female,and 43.8%(88/201) were HCV antibody positive.The possibility of HIV infection transmission:Blood transfusion or blood products were 41.3%(83/201),sexual transmission were 27.4%(55/201),intravenous drug use were 3.0%(6/201),other(tooth extraction two cases,needle-stick injury and transplantation 1 case,respectively) were 2.0%(4/201),but 26.4%(53/201) were unknown.HCV transmission:Blood transfusion or blood products were 85.2%(75/88),sexually transmitted were 4.5%(4/88), intravenous drug use were 3.4%(3/88),unknown reasons were 6.2%(6/88). HCV genotype in 45 HIV/HCV co-infected patients were detected:1b(62.2%, 28/45),2a(22.2%,10/45),2a/2c(6.7%,3/45),1b+2a/2c(6.7%,3/45), 1b+2a(2.2%,1/45).Conclusions:HIV patients,who were infected with HCV major through the transfusion of Blood or blood products,co-infected HCV were higher than others,who should be routinely tested for anti-HCV. Major HCV Subtype is ib in HIV/HCV patients.There are double Subtypes of HCV in HIV/HCV patients.
乙型肝炎病毒、丙型肝炎病毒与人类免疫缺陷病毒具有相似的传播途径,都可以通过血液、性接触及母婴传播,所以HIV感染者常常合并HBV、HCV感染。随着高效抗反转录病毒治疗的广泛应用,肝脏相关性疾病已成为HIV感染者主要的合并症和死亡原因之一。
自1981年美国报告首例AIDS患者以来,全球已有199个国家和地区报告HIV感染者或艾滋病患者。估计全球累计已有7000万以上的人感染了HIV,超过3000万人死于艾滋病。HBV、HCV感染呈世界性流行,据世界卫生组织(WHO)报道,全球约20亿人曾感染过HBV,其中3.5亿人为慢性HBV感染者,全球HCV的感染率约为3%,估计约1.7亿人为慢性丙型肝炎感染者。到2007年底,我国估计现存艾滋病病毒感染者和病人约70万(55万-85万人),全人群感染率为0.05%(0.04%-0.07%),其中艾滋病病人8.5万(8万-9万人)。现在我国HIV感染正处于快速增长期,据估计目前每年大约以30%以上的速度增长。我国属HBV、HCV感染高流行区,一般人群的HBsAg阳性率为9.09%,抗-HCV阳性率为3.2%,我国约有1.3亿慢性HBV感染者和4000万HCV感染者。
HIV、HBV和HCV传播途径相似,因此HIV感染者常常合并HBV、HCV感染。约90%-95%的HIV感染者曾经感染过HBV,其中大约10%-15%为慢性HBV感染者。由于HIV感染者免疫功能不全,不能够完全彻底的清除和抑制HBV,所以HIV感染者常常合并隐匿性HBV感染。国外研究报道HIV感染者合并隐匿性HBV感染率从0%-51.2%不等,甚至在仅抗-HBc阳性的HIV感染者中高达89.5%。约有1/4-1/3的HIV感染者合并HCV感染,据此估计,全球约有近1000万的HIV/HCV重叠感染者。
HIV感染改变HBV、HCV的自然病程,加速肝纤维化、肝硬化及肝细胞癌的进程。HIV感染者由于CD4+T细胞下降,免疫功能受损,导致不能够有效的抑制和清除HBV、HCV,HBV、HCV复制的增加,引起肝脏持续性炎症因子的表达和淋巴单核细胞活化,促进肝纤维化、肝硬化和肝细胞癌的发生。现在肝脏相关性疾病已成为HIV死亡的主要原因之一。另外,HCV基因型对肝病的进程和预后起着重要的作用。其中HCV基因1型感染者的肝脏损伤程度要比其他型严重,对干扰素治疗的效果也更差,特别是合并HIV感染者,由于骨髓抑制,药物的相互作用,HAART的肝脏毒性等原因使HCV的治疗更为困难。
本研究使用PCR等分子生物学的方法,调查上海地区HIV感染者中HBV和/或HCV感染状态、隐匿性HBV感染率及HCV基因型的分布。为我国HIV/AIDS合并HBV、HCV感染的防治提供理论基础。
全文共分三部分:
第一部分:上海地区人类免疫缺陷病毒/艾滋病合并乙型、丙型肝炎病毒感染的临床流行病学研究
第二部分:HIV感染者合并隐匿性乙型肝炎病毒感染的现况调查
第三部分:上海地区201例HIV阳性者合并HCV感染的分子流行病学研究
第一部分:上海地区人类免疫缺陷病毒/艾滋病合并乙型、丙型肝炎病毒感染的临床流行病学研究
目的:了解HIV感染者中HBV和/或HCV感染的流行现状及其特点。方法:对上海市(复旦大学附属)公共卫生临床中心就诊的170例HIV感染者采集血标本,使用微粒子酶联免疫法(MEIA)检测HIV感染者血清的乙肝二对半(HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc),应用酶联免疫法(ELISA)检测丙型肝炎(HCV)抗体。结果:170名HIV感染者中,男性146人,女性24人,最小年龄16岁,最大年龄74岁,平均年龄41±13岁;HBsAg阳性患者19人(11.2%),抗-HBs阳性者87人(51.2%),HBeAg阳性者7人(4.1%),抗-HBe阳性者49人(28.8%),抗-HBc阳性者111人(65.2%);抗-HCV阳性者77人(45.3%)。HIV、HBV和HCV三重感染者9人,约占5.3%。结论:HIV感染者HBsAg阳性率与普通人群相近,但HIV与HCV重叠感染的比例显著高于普通人群。
第二部分:HIV感染者合并隐匿性乙型肝炎病毒感染的现况调查
目的:了解HIV感染者中隐匿性HBV感染状况并对其相关因素进行分析。方法:对上海市(复旦大学附属)公共卫生临床中心就诊的HBsAg阴性的HIV感染者采集血标本,使用微粒子酶联免疫法(MEIA)检测HIV感染者血清的乙肝二对半(HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc),应用酶联免疫法(ELISA)检测丙型肝炎(HCV)抗体,流式细胞仪检测CD4+T细胞记数,使用巢式PCR法检测HBV S区。结果:105名HBsAg阴性的HIV感染者中,男性92人,女性13人。32例HBV DNA阳性,其中27例至少一项HBV血清学标志(HBV M)阳性,5例HBV M均阴性。47例合并丙肝感染者中有14例HBV DNA阳性,阳性率29.8%;58例HBV血清学标志阴性的单纯HIV感染者中18例HBVDNA阳性,阳性率为31.0%,两者相比无显著性差异;CD4+T细胞计数:145.1±158.1/μl,75例CD4+T细胞＜200/μ1的患者中有26例HBV DNA阳性,约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%,两者相比无显著的统计学差异;32例HBV DNA阳性标本中22例无氨基酸序列变异,10例在HBsAg的“a”肽段处有氨基酸序列突变。结论:HIV感染者合并隐匿性HBV感染率较高,免疫功能紊乱及S基因变异可能是隐匿性HBV感染的原因。
第三部分:上海地区201例HIV阳性者合并HCV感染的分子流行病学研究
目的:了解上海地区人类获得性免疫缺陷病毒(HIV)感染者合并丙型肝炎病毒(HCV)感染的流行病学状况及HCV基因型分布特征。方法:对上海市(复旦大学附属)公共卫生临床中心就诊的201例HIV感染者,使用ELISA法检测抗-HCV抗体,反转录聚合酶链反应(RT-PCR)方法扩增,纯化后直接测序检测HCV基因型。结果:201名HlV感染者,女性26(12.9%)人,男性175(87.1%)人,其中88例(43.8%)HCV抗体阳性。对45例合并感染者HCV基因型检测结果:28例(62.2%)基因型为1b亚型,10例(22.2%)基因型为2a亚型,3例(6.7%)基因型为2a/2c亚型,3例(6.7%)患者合并感染1b和2a/2c亚型,1例(2.2%)合并感染1b和2a两种亚型。结论:输血或血制品的HIV感染者合并HCV感染率较高,对于这部分HIV感染者应常规检测HCV抗体。HIV感染者合并感染HCV的主要基因型是1b亚型,其次为2a亚型,并存在多种HCV基因型共感染的现象。
Hepatitis B virus(HBV) and hepatitis C virus(HCV) are common among patients with human immunodeficiency virus(HIV) infection because of shared ways of viral transmission.Since the decline in HIV-related morbidity and mortality after introduction of highly active antiretroviral therapy(HAART),liver disease caused by HBV and/or HCV has become a major cause of morbidity and mortality among HIV-infected patients.
Since the first AIDS case was reported in the United States in 1981, 199 countries/regions had reported HIV infection or AIDS patients around the world.It has been estimated that more than 70 million people have been infected with the HIV,and more than 30 million have died from AIDS globally.Of the 2 billion people who have been infected with the HBV, more than 350 million have chronic infections.An estimated 170 million persons are chronically infected with HCV and 3 to 4 million persons are newly infected each year.By the end of 2007,the estimated results showed approximately 700,000 are now HIV positive(range 550,000-850,000).The HIV infection rate among China' s population is 0.05 per cent(range 0.04%-0.07%).The estimated number of AIDS cases is 85,000(range 80,000-90,000).Now the HIV epidemic in China is at the rapid expansion phase,and it is estimated that it increases by about 30 percent every year.
In China,the HBV and HCV prevalence is high.The HBsAg and anti-HCV positive among the general population is 9.09%and 3.2%,respectively. An estimated 130 million chronic HBV infections and 40 million HCV infections are in China.
Because of shared routes of transmission,coinfection with hepatitis B virus(HBV) and hepatitis C virus(HCV) is common in HIV-infected persons. Serologic evidence of past exposure or current HBV infection is found in 90%to 95%of HIV-infected individuals。Among HIV-infected persons,10% to 15%are chronic carriers of HBV.Occult HBV infections in HIV infected persons are common,because HIV infected patients are immune dysfunction and HBV replication can not be inhibited and cleared.The prevalence of occult HBV in HIV infected patients has been controversial,varied from 0 to 51.2%,and even occult HBV among the HIV infected patients with anti-hbc alone is up to 89.5%.One-quarter to one-third of HIV-seropositve individuals are co-infected with HCV.It is estimated that there are about 10 million cases of HIV-HCV coinfection worldwide.
HIV infection modifies the natural history of HCV infection,which can accelerate the progression to fibrosis,cirrhosis and hepatocellular. HIV-infected individuals show a quantitative depletion of CD4+ T cells and immune dysfunction,which lead to increase the replication of virus of hepatitis,secrete inflammatory cytokines and activate lymphomononuclear cells in the liver,and ultimately result in fibrosis, cirrhosis and hepatocellular carcinoma.Now liver disease has become the leading cause of death of HIV infected patients.In addition,the genotype of HCV plays an important role in the progression of liver disease and can predict the prognosis.HCV genotype 1 may represent a more aggressive strain,which is less respond to interferon treatment than HCV genotype 2 or 3.Treatment of HCV is more complicated in HIV-infected patients due to bone marrow suppression,drug interactions,HAART-related hepatotoxicity and other reasons.
The study used molecular biology techniques to invest the prevalence of HBV and/or HCV,occult HBV and HCV genotype distribution in HIV-infected persons.Provide theoretical basis for prevention and treatment of HBV and/or HCV in HIV infected persons.
The contents of this study are:
(1):Study on HIV/AIDS Subjects co-infected with HBV and/or HCV in Shanghai
(2):The Epidemic Analysis of Occult Hepatitis B Virus in HIV-Infected Patients
(3):Molecular epidemiology of HCV co-infection in 201 HIV patients in Shanghai
Part One:Study on HIV/AIDS Subjects co-infected with HBV and/or HCV in Shanghai
objective:To analyse the epidemiology of HIV/AIDS co-infected with HBV and/or HCV.Methods:Microparticle enzyme immunoassay(MEIA) was used to detect HBV serological immune indicators (HBsAg、anti—HBs、HBeAg、anti—HBe、anti—HBc) and Enzyme linked immuneosorbent assay(ELISA) to HCV antibody in 170 HIV antibody positive subjects.Results:Patients mean age was 41±13 years,and 146(85.8%) were males.A total of 19(11.2%) HIV/AIDS subjects showed HBsAg positive, 87(51.2%) anti-HBs positive,7(4.1%) HBeAg positive,49(28.8%) anti-HBe positive,111(65.2%) anti-HBc positive.There are 45.3%HCV positive in this group,the triple infection rate of HIV,HBV and HCV was 5.3%. Conclusion:HCV infective rate is dramatically higher in the HIV/AIDS infectious patients than the HIV negative population,and the co-infection rate of HBV in HIV/AIDS is similar to the common.
Part two:The Epidemic Analysis of Occult Hepatitis B Virus in HIV-Infected Patients
Objectives:The occult hepatitis B virus(HBV) is defined by the positive of HBV DNA in individuals with undetectable levels of HBV surface antigen(HBsAg).The objective of this study was to assess the prevalence and related factors of occult HBV in hiv-infected patients.Methods:The serum samples were from 105 HBsAg-negative patients with HIV patients hospitalized at Shanghai Public Health Clinical Center.Microparticle enzyme immunoassay(MEIA) was used to detect HBV serologic markers(HBsAg、anti—HBs、HBeAg、anti—HBe、anti—HBc),and enzyme linked immuneosorbent assay(ELISA) to HCV antibody.CD4+ cell count was examined by flow cytometry.Nested polymerase chain reaction(n PCR) was used to amplify surface protein region of HBV.Results:105 HIV/AIDS patients were 92 men (87.6%) and 13(12.4%) women,respectively.32(30.5%) patients were HBV DNA+,5 patients were negative for all HBV serologic markers,and 27 patients detected at least one of anti-HBc,anti-HBe and anti-HBs.14 patients(29.8%) with HBV DNA+ in 47 HIV patients coinfected with HCV,18 patients(31.0%) in 58 HIV-monoinfected patients,The mean CD4+ cell count was 145 cells/μl,26 patients(34.7%) in 75 patients with CD4+ cell＜200 cells/μl,6 patients(20%) in 30 patients with CD4+ cell＞200 cells/μl.No statistical significant association could be established between occult HBV infection and HBV serologic markers,coinfected HCV and CD4+ cell count.Analysis of S gene showed that 1 nucleotide sequence inserted "A" in nt527 and nt539,respectively,and induced the reading frame shift.9aminoacid sequences changed(C124S,I126T,I126V,T131I,L133I, K141N,P142L,S143T and S143P) in the HBV "a" determinant,and the rest of patients had no mutation in the HBV "a" determinant.Conclusions: Occult HBV occurred in a sizable proportion of HIV-infected patients. Immune Dysfunction and S gene variation may be the reason of occult HBV infection.
Part three:Molecular epidemiology of HCV co-infection in 201 HIV patients in Shanghai
Objective:To investigate the molecular epidemic and subtypes of hepatitis C virus(HCV) co-infection in the human immunodeficiency virus patients in Shanghai.Methods:Enzyme linked immuneosorbent assay(ELISA) was used to detect HCV antibody and HCV RNA was extracted and amplified by nested PCR,then purified and directly sequenced in 201 HIV antibody positive subjects,who hospitalized in Shanghai Public Health Clinical Center affiliated to Fudan University. Results:Of 201 HIV infected patients,12.9%(26/201) were female,and 43.8%(88/201) were HCV antibody positive.The possibility of HIV infection transmission:Blood transfusion or blood products were 41.3%(83/201),sexual transmission were 27.4%(55/201),intravenous drug use were 3.0%(6/201),other(tooth extraction two cases,needle-stick injury and transplantation 1 case,respectively) were 2.0%(4/201),but 26.4%(53/201) were unknown.HCV transmission:Blood transfusion or blood products were 85.2%(75/88),sexually transmitted were 4.5%(4/88), intravenous drug use were 3.4%(3/88),unknown reasons were 6.2%(6/88). HCV genotype in 45 HIV/HCV co-infected patients were detected:1b(62.2%, 28/45),2a(22.2%,10/45),2a/2c(6.7%,3/45),1b+2a/2c(6.7%,3/45), 1b+2a(2.2%,1/45).Conclusions:HIV patients,who were infected with HCV major through the transfusion of Blood or blood products,co-infected HCV were higher than others,who should be routinely tested for anti-HCV. Major HCV Subtype is ib in HIV/HCV patients.There are double Subtypes of HCV in HIV/HCV patients.
引文
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17、 Hidenori Toyoda, Kazuhiko Hayashi, Yoshiki Murakami, et al. Prevalence and clinical implications of occult hepatitis B viral infection in hemophilia patients in Japan. J. Med. Virol. 2004.73:195-199.
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34、http://www.who.int/mediacentre/factsheets/fs164/en/
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36、Jurgen Kurt Rockstroh and Ulrich Spengler.HIV and hepatitis C virus co-infection.Lancet Infect Dis 2004:4:437-44
37、Kirsty England,Claire Thorne,Marie-Louise Newell Vertically acquired paediatric coinfection with HIV and hepatitis C virus.Lancet Infect Dis 2006;6:83-90
38、Euge nia Marine-Barjoan,Alain Berre'bi,Vale'rie Giordanengo, et al. HCV/HIV co-infection, HCV viral load and mode of delivery: risk factors for mother-to-child transmission of hepatitis C virus? AIDS 2007, 21:1811 - 1815
39、 Hershow RC, Riester KA, Lew J, et al. Increased vertical transmission of human immunodeficiency virus from hepatitis C virus-coinfected mothers. J Infect Dis 1997; 176: 414-20.
40、 Bonacini M, Govandarajan S, Blatt LM, et al. Patients coinfected with human immunodeficiency virus and hepatitis C virus demonstrate higher levels of hepatic HCV RNA. J Virol Hepatol 1999; 6: 203-8.
41、 AH Mohsen, P Easterbrook, C B Taylor, et al. Hepatitis C and HIV coinfection. Gut 2002;51:601 - 608
42、 LydiaM. Petrovic HIV/HCVco-infection: histopathologic(?)ndings, natural history, (?)brosis, and impactofantiretroviral treatment: a reviewarticle Liver International 2007:598-606
43, Massimo Puoti, Maurizio Bonacini, Angiola Spinetti, et al. Liver fibrosis progression is related to CD4 cell depletion in patients coinfected with hepatitis C virus and human immunodeficiency virus. The Journal of Infectious Diseases 2001; 183:134-137
44、 Anai¨s Vallet-Pichard , Stanislas Pol Natural history and predictors of severity of chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection Journal of Hepatology 44 (2006) S28-S34
45 、 GGreub, B Ledergerber, M Battegay. et al. Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV and hepatitis C virus coinfection: the Swiss HIV Cohort Study Lancet 2000; 356: 1800-05
46、 Eric S. Daar, Henry Lynn, Sharyne Donfield, et al. Hepatitis c virus load is associated with human immunodeficiency virus type 1 disease progression in hemophiliacs The journal of infectious diseases 2001;183:589 -595
47、 Patrick S. Sullivan, Debra L. Hanson, Eyasu H. Teshale, et al. Effect of hepatitis C infection on progression of HIV disease and early response to initial antiretroviral therapy AIDS 2006, 20:1171-1179
48、 Marina Nu＇n～ez Hepatotoxicity of antiretrovirals: Incidence,