简介:AbstractBackground:Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.Methods:One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.Results:HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log10 U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log10 U/mL P= 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P= 0.025), and Ishak fibrosis score (r= -0.292, P= 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = -0.263, P = 0.014) and HBeAg-negative patients (r= -0.291, P= 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r= 0.366, P= 0.001; r= 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log10 U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005).Conclusions:HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy.Trial registration:Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1
简介:AbstractChronic hepatitis B virus (HBV) infection remains a global health burden. Timely and effective antiviral therapy is beneficial for patients with HBV infection. With existing antiviral drugs, including nucleos(t)ide analogs and interferon-alfa, patients can achieve viral suppression with improved prognosis. However, the rate of hepatitis B surface antigen loss is low. To achieve a functional cure and even complete cure in chronic hepatitis B patients, new antivirals need to be developed. In this review, we summarized the advantages and disadvantages of existing antiviral drugs and focused on new antivirals including direct-acting antiviral drugs and immunotherapeutic approaches.
简介:在这篇文章,我们在场有浸透的发生的一个肝炎B流行模型。确定、随机的系统的动态行为被学习。到这个目的,我们首先建立确定的模型的平衡的本地、全球的稳定性条件。由构造合适的随机的Lyapunov功能,第二,为肝炎B的各态历经的静止分发以及扑灭的存在的足够的条件被获得。
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。
简介:Inordertoinvestigatetheimmtmogenicityofthecontrolled-releasemicroencapsulatedhepatitisBvaccineinmice,polyethyleneglycol-poly-dl-lactide(PELA)microsphereswithentrappedHSsAgwerepreparedbydoubleemulsionW/O/Wbasedonsolventextractionmethods.BALB/cmicewereimmunizedwiththeencapsulatedvaccinebyoralfeedingorinjection.Bloodsampleswerecollectedat8^th,10^th,14^thand24^thweeks,respectively,andthelevelsofantibodyresponseweredetectedbyEI.ISA.Itwasfoundthatthescanningelectronmicroscopyshowedthepreparedmicrosphereshadsmoothandsphericalsurface,suitableforvaccinedelivery.Twogroupsofmiceorallyfedwiththeencapsulatedorconventionalrecombinantvaccines,respectively,theresereshowednoobviousdifferenceintheIgGlevels.At14^thweek,thegroupinjectedwithasingledoseofencapsulatedvaccinehadasimilarlevelofIgGresponsetothegroupinjectedwithtwodosesoftherecombinationvaccine.At24^thweek,theIgGlevelsofthegroupinjectedwithtwodosesofencapsulatedvaccinewerehigherthanthoseofthegroupinjectedwithtwodosesoftherecombinationvaccine.ItconcludesthatControlled-releasemicroencapsulatedhepatitisBvaccinepossessesthefeatureofslowlyreleasinginv/voandlongtimesimmtmogenicity.
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简介:AbstractMother-to-child transmission (MTCT) of hepatitis B virus (HBV) is the main cause of chronic hepatitis B. The prevention of MTCT plays a critical role in control chronic hepatitis B. The main purpose of the present clinical guidelines is to aid healthcare providers in managing pregnant women with positive HBsAg and in preventing MTCT of HBV. We recommend: (1) all pregnant women require prenatal screen for hepatitis B serological markers; (2) newborn infants of mothers with negative hepatitis B surface (HBsAg) require administration of hepatitis B vaccine on a 0, 1, and 6 month-schedule; (3) newborn infants of mothers with positive HBsAg need hepatitis B immunoglobulin (HBIG) and birth dose vaccine within 12 hours (the sooner the better) after birth, followed by injection of the second and third dose of hepatitis B vaccine at the age of one and six months respectively; (4) in preterm neonates or neonates with poor health conditions born to HBsAg-positive mothers, the immunoprophylaxis measures should be appropriately taken; (5) to further reduce MTCT of HBV, pregnant women with HBV DNA levels >2×105 IU/mL or positive hepatitis B e antigen may receive oral antivirals, starting from 28 to 32 weeks of gestation and discontinuing the drug on the delivery day; (6) cesarean section is not recommended to reduce MTCT of HBV; (7) breastfeeding is recommended in infants of HBsAg-positive mothers, regardless of maternally positive hepatitis B e antigen, maternal nipple injury or bleeding, oral mucosal injury in neonates or infants; (8) breastfeeding is recommended in infants born to HBsAg-positive mothers who require continuation of antiviral therapy after delivery, and the infants should be followed up to observe whether adverse effects develop; and (9) the infants born to HBsAg-positive mothers should be tested for hepatitis B serological markers at the age of 7-12 months, and those who are negative for HBsAg and anti-HBs should receive three doses of hepatitis B vaccine on the 0, 1, and 6 month-schedule as soon as possible.
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。
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.
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.
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。
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.
简介:HepatitisBvaccine,asthefirsthigh-effectiverecombinantcommercialvaccine,wassuccessfullydevelopedintheearly1980s.Sincethen,differentopinionshaveoccurredonthequalityofvaccineswithrapiddevelopmentoftargetgeneselecting,antigenexpressionsystem,andqualityevaluation.DifferentantigensofhepatitisBvaccinesarederivedfromdifferentexpressionsystem,andtherearealsosomedifferencesonmanufactureprocedureorglycosylateddegreeofantigen.
简介:Objective:TostudytheeffectofmoxibustiononhyperbilirubinemiainhepatitisBcirrhosispatients.Methods:56casesofinpatientswithhepatitisBcirrhosisweredividedintotreatmentgroup(n=27)andcontrolgroup(n=29)randomly.Allthepatientsofthesetwogroupsweregivenwithroutineexpectanttreatmentincludingadministrationofmedicines(Bifendate,Eessentiale,Potenline,etc)forprotectingliverfunctions,reducingthelevelofalanineaminotransferase(ALT),etc.,andinthemeantime,patientsofthetreatmentgroupwereAfter4weeksoftreatment,ofthe27and29casesoftreatmentandcontrolgroup,23and10patientshadimprovementinclinicalsymptoms,4and19failed,withthetotaleffectiveratesbeing85.18%and34.48%respectively.Serumtotalbilirubin(Tbil)contentsoftreatmentandcontrolgroupsdecreasedsignificantly,andthelevelofTbilinthetreatmentgroupwassignificantlylowerthanthatinthecontrolgroup(P<0.01).Conclusion:MoxibustionisaneffectiveremedyinrelievinghyperbilirubinemiaandimprovingclinicalsymptomsinthetreatmentofhepatitisBcirrhosispatients.
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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
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。