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  • 作者: Wu Nan Rao Hui-Ying Yang Wei-Bo Gao Zhi-Liang Yang Rui-Feng Fei Ran Gao Ying-Hui Jin Qian Wei Lai
  • 学科: 医药卫生 >
  • 创建时间:2020-08-10
  • 出处:《中华医学杂志(英文版)》 2020年第03期
  • 机构:Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Beijing 100044, China,Department of Infectious Diseases, The First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan 650032, China,Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, China,Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease, Beijing 100044, China; Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Institute for Precision Medicine, Tsinghua University, Beijing 102218, China.
  • 简介:AbstractBackground:Hepatitis C virus (HCV) genotype 3, particularly subtype 3b, is increasing in prevalence and distribution in China. This study evaluated the prevalence, regional distribution, clinical characteristics, host factors, treatment outcomes, and disease progression of patients with HCV genotype 3 in China.Methods:A 5-year follow-up was preceded by a cross-sectional study. Treatment choices were at the discretion of treating physicians. Estimated infection time to overall-disease-progression (defined by ≥1 of: newly diagnosed cirrhosis; cirrhosis at baseline, Child-Turcotte-Pugh score increased 2 points or more; progression from compensated cirrhosis to decompensated cirrhosis; hepatocellular carcinoma; liver transplantation; or death) was calculated using the Kaplan-Meier method. Cox regression analyses were conducted to evaluate the risk factors for disease progression.Results:The cross-sectional study enrolled 997 patients, including 91 with HCV genotype 3 infection. Among them, subtype 3b (57.1%) was more dominant than subtype 3a (38.5%). Five hundred and twelve patients were included into the follow-up phase. Among patients analyzed for estimated infection time to overall-disease-progression, 52/304 (17.1%) patients with HCV genotype 1 and 4/41 (9.8%) with HCV genotype 3 (4/26 with genotype 3b, 0/13 with genotype 3a, and 0/2 with undefined subtype of genotype 3) experienced overall-disease-progression. Patients with HCV genotype 3 were younger than those with genotype 1 (mean age: 39.5 ± 8.7 vs. 46.9 ± 13.6 years) and demonstrated more rapid disease progression (mean estimated infection time to overall-disease-progression 27.1 vs. 35.6 years).Conclusions:HCV genotype 3, specifically subtype 3b, is associated with more rapid progression of liver disease. Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions.Trial registration:NCT01293279, https://clinicaltrials.gov/ct2/show/NCT01293279; NCT01594554, https://clinicaltrials.gov/ct2/show/NCT01594554.

  • 标签: Hepatitis C virus genotype 3 Chronic hepatitis C Disease progression
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  • 简介:ThepurposeofthisstudywastoconstructaneukaryoticDNAvectorencodingamultipleepitopeantigen(MFC)ofhepatitisCvirus(HCV)andahepatitisBsurfaceantigen(HBsAg),andexploretheeffectofHBsAggeneontheimmunityofHCVmultiple-epitopeDNAconstructinvitroandinvivoinmice.AnHCVDNAvector(pVAX1-HBs-MFC)wasconstructedbyfusingHBsAggenetotheNterminalofanHCVmultiple-epitopeantigengene.ThepVAX1-HBs-MFCwastransfectedintoHEK293TcellsanditsexpressionwasmeasuredbyELISAandWesternblotting.BALB/cmicewereintramuscularlyimmunizedwiththepVAX1-HBs-MFC,andanELISAapproachwasappliedtodeterminethespecificantibodytitersandsubtypesinthemouseserum.Thecross-reactivityoftheantibodieswasalsocheckedwithtwosynthesizedHCVhypervariableregion1(HVR1)peptides.TheIFN-γproductionandcellproliferationofthemousespleencellswereevaluatedbyELISAandMTS(3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium,innersalt)assays,respectively.TheexpressionofpVAX1-HBs-MFCwasdetectableinthetransfectedHEK293Tcells.TheserumantibodyresponsewaseffectivelyelicitedinBALB/cmiceinjectedwithpVAX1-HBs-MFC.ThehighesttiterofantibodyagainstHCV(MFC)was1:1280,andtheratioofIgG2a/IgG1was1.50±0.12atthefifthweekafterfirstimmunization.Moreover,thecollectedmouseserumantibodyhadtheabilitytocross-reactwiththetwosynthesizedHCVHVR1peptides.ThestimulationindexofthemousesplenocytestoMFCwas1.79±0.07,andtheIFN-γlevelwas287±6pg/mlatweek21afterfirstimmunization.ThehighesttiteroftheantibodyincontrolBALB/cmiceimmunizedwithpVAX1-MFCwas1:320,andtheratioofIgG2a/IgG1was1.33±0.11atweek5post-immunization.Furthermore,thestimulationindexofthemousesplenocytescellstoMFCwas1.52+0.06,andtheIFN-γlevelwas225±9.3pg/mlatweek21post-immunization.TheHBsAggenecanenhancetheeffectsofanHCVmultiple-epitope

  • 标签: 乙型肝炎病毒 丙型肝炎病毒 免疫反应 DNA 抗原决定基
  • 简介:瞄准:把在病人之间的标准肝炎B(HBV)种痘的反应与长期的丙肝作比较病毒(HCV)感染和健康个人。方法:这是未来的盒子控制研究。有长期的HCV感染和40健康控制的38个病人的一个总数被包括。种痘被20大杯recombinantHBsAg的注射在瞬间0,1和6点执行进三角肌肌肉。Anti-HBs集中是在最后剂量以后决定了3瞬间并且在二个组之间比较了。反应模式是被描绘(1)高反应当anti-HBs抗体效价是>时100IU/L,(2)低反应当效价是10-100IU/L时并且(3)没有反应当效价是<时10IU/L。结果:在耐心的组,有10/38(26.3%)非应答者,8/38(21.1%)低应答者并且20/38(52.6%)高应答者。在控制组的相应价值是2/40(5.0%),7/40(17.5%)和31/40(77.5%)分别地。反应模式在二个组之间是统计上不同的。在里面多变量分析,吸烟是重要confounder,当HCV感染与更低的抗体反应失去了它的重要关联时。结论:有长期的HCV感染的病人趋于与健康个人相比对HBV种痘微弱地作出回应,尽管这关联不是独立的根据多变量分析。

  • 标签: 乙型肝炎 病毒 疫苗 免疫原性
  • 简介:瞄准:为了学习流行和风险因素,与人的免疫不全与三倍的感染联系了在一张城市的诊所人口的病毒(HIV)/hepatitisB(HBV)/hepatitisC病毒(HCV)。方法:5639个病人的回顾的图表评论在纽约城市里在圣卢凯斯鲁塞韦尔特医院HIV诊所(全面照顾的中心)列在后面,从1999年1月的美国到2007年5月。下列人口统计的特征被分析:年龄,性别,种族和HIV冒因素的风险。多重逻辑回归分析被执行在这些病毒的获得上评估人口统计的因素的影响。结果:HIV/HBV,HIV/HCV和HIV/HBV/HCV感染在252/5639(4.47%)被检测,1411/5639(25.02%)和89/5639(1.58%)病人分别地。HIV/HBV合作感染与男性被联系(或1.711;P=0.005),黑色跑(或2.091;P<0.001),人与\O性交人(MSM)(或1.747;P=0.001),静脉内的药使用(IDU)(或0.114;P<0.001),IDU和异性爱的活动(或0.247;P=0.018),或未知(或1.984;P=0.004)。HIV/HCV合作感染与男性被联系(或1.241;P=0.011),黑色跑(或0.788;P=0.036),MSM(或0.565;P<0.001),IDU(或8.956;P<0.001),IDU和异性爱的活动(或9.106;P<0.001),IDU和MSM(或9.179;P<0.001),或输送(或3.224;P<0.001)。HIV/HBV/HCV合作感染与男性被联系(或2.156;P=0.015),IDU(或6.345;P<0.001),IDU和异性爱的活动(或9.731;P<0.001),IDU和MSM(或9.228;P<0.001),或未知(或4.219;P=0.007)。结论:我们的学习证明有HBV/HCV/HIV的合作感染显著地与IDU被联系。这些结果加亮需要加强教育和综合照顾的最佳的模型,特别地为有IDU的人口,到减少病毒的传播的风险。

  • 标签: 人体免疫缺陷病毒 人口统计学 乙肝 丙肝
  • 简介:瞄准:为了在病人调查胰岛素抵抗和糖尿病的临床的参数的流行,由长期的丙肝(CHC)或长期的肝炎B(CHB)影响了。方法:我们回顾地评估了经历了肝活体检视的852个连续病人(726CHC和126CHB)。我们记录了年龄,性别,中高音,类型2糖尿病或新陈代谢的症候群(MS),身体团索引(BMI),和明显的疾病持续时间(增加)。结果:年龄,增加,BMI,在有温和/中等的肝纤维变性的病人的MS和糖尿病的流行在CHC是显著地更高的。然而,脂肪变性的度和在肝活体检视评估的肝纤维变性没在CHC和CHB病人之间不同。在多变量分析,年龄,性别,BMI,中高音和糖尿病是为在CHC的肝纤维变性的独立风险因素,而仅仅年龄与在CHB的肝纤维变性有关。我们也评估了在重要脂肪变性之间的协会(>30%)并且年龄,性别,BMI,糖尿病,MS和肝纤维变性。糖尿病,BMI和肝纤维变性与脂肪变性>被联系30%在CHC,而仅仅年龄和BMI与在CHB的脂肪变性有关。结论:这些数据可以显示丙肝病毒感染是为胰岛素抵抗的一个风险因素。

  • 标签: 糖尿病 胰岛素 临床 抵抗力 肝炎
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  • 简介:INTRODUCTIONMolecularbiologyhasmadeatremendousimpactonthediagnosisandtreatmentofliverdiseases.Inparticular,advancesinmolecularbiologymadepossiblethediscovery

  • 标签: HEPATITIS C molecular BIOLOGY VIRAL HEPATITIS
  • 简介:流行病学的研究为长期的肝炎B的一个原因的角色提供了压到优势的证据在hepatocellular癌(HCC)的发展的病毒(HBV)感染。然而,HBV感染的致病和联系HBV的HCC的carcinogenesis仍然是逃犯的。这评论将在涉及HBV相关的肝carcinogenesis的机制上总结当前的知识。在肿瘤形成的HBV的角色出现到复杂,并且可以包含直接、间接的机制。进主人染色体的HBVDNA的集成发生在同种细胞的肿瘤的早步扩大,和它被显示了提高主人chromosomal不稳定性,导致大转换复制,删除和chromosomaltranslocations。chromosomal改变的率在HBV相关的肿瘤显著地被增加,这被显示出。病毒的规章的HBVx蛋白质的延长表示可以贡献调整表明小径的细胞的抄写,蛋白质降级,增长,和apoptotic,并且它在hepatocellular癌的发展起一个关键作用。

  • 标签: 病毒感染 肝癌 染色体易位 宿主基因组 蛋白质降解 风险
  • 简介:ThechronicinfectionofhepatitisBvirus(HBV)iscloselyrelatedtotheoccurrenceanddevelopmentofhepatocellularcarcinoma(HCC).AccumulatedevidencehasshownthatHBVXprotein(HBxprotein)isamultifunctionalregulatorwithacrucialroleinhepatocarcinogenesis.However,informationonthemechanismbywhichHBVinducesHCCislacking.ThisreviewfocusesonthepathologicalfunctionsofHBxinHBV-inducedhepatocarcinogenesis.Asatransactivator,HBxcanmodulatenuclearfactorkappa-light-chain-enhancerofactivatedBcells(NF-κB)andtranscriptionfactorAP-2.Moreover,HBxcanaffectregulatorynon-codingRNAs(ncRNAs)includingmicroRNAsandlongncRNAs(lncRNAs),suchasmiRNA-205andhighlyupregulatedinlivercancer(HULC),respectively.HBxisalsoinvolvedinepigeneticmodification,includingmethylationandacetylation.HBxinteractswithvarioussignal-transductionpathways,suchasproteinkinaseB/Akt,Wnt/β-catenin,signaltransducerandactivatoroftranscription,andNF-κBpathways.Moreover,HBxaffectscellularfatebyshiftingthebalancetowardcellsurvival.HBxmayleadtothelossofapoptoticfunctionsordirectlycontributestooncogenesisbyachievingtransformingfunctions,whichinducehepatocarcinogenesis.Additionally,HBxcanmodulateapoptosisandimmuneresponsebydirectorindirectinteractionwithhostfactors.WeconcludethatHBxhastensthedevelopmentofhepatoma.

  • 标签: 乙型肝炎病毒 蛋白质 肝癌 非编码RNA 信号转导途径 核因子KAPPA
  • 简介:AbstractChronic hepatitis B virus (HBV) infection due to vertical transmission remains a critical concern with regards to eliminating HBV infection. Implementation of hepatitis B vaccine, the foundation to prevent perinatal and horizontal transmission, has reduced the prevalence of HBV by >80%. In countries where the hepatitis B immune globulin (HBIG) is available, such as China and the United States, the administration of HBIG and hepatitis B vaccine to the infants of mothers who are positive for hepatitis B surface antigen has become a standard practice and is effective in preventing vertical transmission. Accumulating evidence on the efficacy and safety of antiviral prophylaxis during pregnancy indicates the probability of attaining the goal of the World Health Organization to eliminate hepatitis by 2030. In this review, we discuss the transmission routes, diagnostic criteria, and preventive strategies for vertical transmission. A preventive program that includes screening before pregnancy, antiviral prophylaxis during pregnancy, and postpartum immunoprophylaxis provides "perfect strategies" to eliminate vertical transmission. However, there is still a notable gap between "perfect strategies" and real-world application, including insufficient coverage of timely birth dose vaccine and the efficacy and necessity of HBIG, especially in mothers who are negative for hepatitis B envelope antigen. In particular, there is a clear need for a comprehensive long-term safety profile of antiviral prophylaxis. Therefore, feasible and cost-effective preventive strategies need to be determined across regions. Access also needs to be scaled up to meet the demands for prophylaxis and prevalence targets.

  • 标签: Hepatitis B virus Vertical transmission Immunoprophylaxis Antiviral prophylaxis
  • 简介:肝炎B病毒(HBV)感染与传染virions和非传染的空表面抗原粒子的版本首先在hepatocytes发生在肝进血液。HBV复制是non-cytopathic。短暂感染运用几个月,和长期的感染的一堂功课经常是终生的。长期的感染能与肝硬化和hepatocellular癌导致肝失败。抵销anti-HBs抗体由在感染的主人包含感染的传播并且便于病毒的粒子的移动和破坏从HBV感染在恢复起一个关键作用,这通常被接受。然而,对病毒的抗原的T房间反应开始的有免疫力的反应在HBVinfection.The为病毒的清理和疾病致病也是重要的病毒的蛋白质,HBsAg,微粒HBcAg,和nonparticulateHBeAg的三种结构的形式,可以优先地得到不同Th房间子集。在不同HBV感染地位的anti-HBs,anti-HBc,和anti-HBe的不同IgG亚纲侧面被揭示。而且,在长期的搬运人的不同IgG亚纲侧面没随着不同中高音和著名计算机生产厂商层次变化并且可以反映刺激抗原之间的差别,有免疫力的反应,并且病毒的疾病的阶段并且在人的HBV感染的高风险为个人为疫苗和预防处理的使用提供基础。这评论阐明在短暂、坚持的感染期间导致的有免疫力的回答的详细理解,和在有HBV感染的病人的免疫疗法和immunodiagnosis的发展,和减少肝的可能的工具损坏。

  • 标签: 抗原疗法 免疫疗法 乙型肝炎病毒 病理机制
  • 简介:AbstractBackground:Antiretroviral therapy (ART) has reduced mortality among people living with HIV (PLWH) in China, but co-infections of hepatitis B virus (HBV) and hepatitis C virus (HCV) may individually or jointly reduce the effect of ART. This study aimed to evaluate the impacts of HBV/HCV coinfections on treatment drop-out and mortality among PLWH on ART.Methods:A retrospective cohort study analysis of 58,239 people living with HIV (PLWH) who initiated antiretroviral therapy (ART) during 2010-2018 was conducted in Guangxi Province, China. Data were from the observational database of the National Free Antiretroviral Treatment Program. Cox proportional hazard models were fitted to evaluate the effects of baseline infection of HBV or HCV or both on death and treatment attrition among PLWH.Results:Our study showed high prevalence of HBV (11.5%), HCV (6.6%) and HBV-HCV (1.5%) co-infections. The overall mortality rate and treatment attrition rate was 2.95 [95% confidence interval (CI): 2.88-3.02] and 5.92 (95% CI: 5.82-6.01) per 100 person-years, respectively. Compared with HIV-only patients, HBV-co-infected patients had 42% higher mortality [adjusted hazard ratio (aHR)=1.42; 95% CI 1.32-1.54], HCV-co-infected patients had 65% higher mortality (aHR=1.65; 95% CI: 1.47-1.86), and patients with both HCV and HBV co-infections had 123% higher mortality (aHR=2.23; 95% CI:1.87-2.66).Conclusions:HBV and HCV coinfection may have an additive effect on increasing the risk of all-cause death among PLWH who are on ART. It is suggested that there is need for primary prevention and access to effective hepatitis treatment for PLWH.

  • 标签: Hepatitis C virus Hepatitis B virus HIV Antiretroviral therapy Mortality Retrospective cohort
  • 简介:AbstractChronic hepatitis B virus (HBV) infection is a serious health issue because of its severe sequelae. Prevention of mother-to-child transmission (MTCT) of HBV is critical to eliminate chronic HBV infection. Here, we reviewed the progress toward the elimination of HBV infection in children in China in the recent decade. A universal hepatitis B vaccination program started from 2002 has been intensified, with the coverage of timely birth dose >95% of all newborn infants from 2012. Since 2011, China has taken a nationwide program to administer hepatitis B immunoglobulin (HBIG) with free of charge in all neonates of HBV-infected mothers, leading to a significant increment of timely use of HBIG. The prevalence of hepatitis B surface antigen (HBsAg) was declined from around 10% among children in 1980s to <0.5% among children born after 2011. Administration of oral antiviral agents in HBV-infected pregnant women with HBV DNA >2 × 105 U/mL during the third trimester is increasing, which will further reduce MTCT of HBV. However, there are some challenges in the elimination of HBV infection in children, which need to overcome by the concerted efforts. Nevertheless, it is anticipated that China will achieve the goal set by the World Health Organization that the prevalence of HBsAg in children aged <5 years is ≤0.1% by 2030.

  • 标签: Hepatitis B virus Mother-to-child transmission Immunoprophylaxis HBsAg prevalence Children China
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