皖北地区丙型肝炎流行病学及临床疗效

目的 探讨本地区丙型肝炎的流行特征和基因型分布,探索提高丙型肝炎疗效的方法.方法 调查了解丙型肝炎传播途径,对丙型肝炎病毒(HCV)进行测序分型,根据患者具体情况分别采用普通干扰素(IFN)联合利巴韦林(RBV)和聚乙二醇干扰素(PEG-IFN)联合RBV治疗,根据病毒基因型及应答情况等决定疗程,总疗程24～72周,对治疗过程中出现的不良反应进行适当处理.结果 本地区HCV基因型有1a、1b、2a、3a、3b、6k型.1b型最多,占56.3％,其次为2a型占21.3％,1b和2a混合型占5.3％,3b型占9.6％,3a型占4.3％,1a型占2.1％,6k型占1％.传播途径中通过静脉吸毒感染35.8％(102/285),输血及血制品感染31.2％(89/285).基因1b型和非1b型两组早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)、持续病毒学应答(SVR)分别为12(46.1％)、16(61.5％)、15(57.7％)和17(81.0％)、19(90.4％)、19(90.4％),差异均有统计学意义(P＜0.05).采取个体化治疗,能大幅提高丙型肝炎的应答率,减少不良反应,但因各个病例差异较大,无法进行统计学处理.结论 皖北地区丙型肝炎的主要传播方式是静脉吸毒及输血;基因型以1b型为主,占56.3％,其次为2a型,并可见混合型及6k型.治疗上基因1b型疗效远不如非1b型.个体化治疗能明显提高SVR.     

323例慢性丙型肝炎患者流行病学及临床特点分析

目的 了解慢性丙型肝炎患者的流行病学及临床特点.方法 对323例确诊为慢性丙型肝炎患者的临床资料进行系统分析,研究该组人群感染HCV的传播途径,临床表现及病毒学特征,并分析39例行肝组织活检患者的肝脏组织学改变.两组之间比较采用t检验.结果 323例慢性丙型肝炎患者经输血或使用血制品感染者135例,占41.8%;有手术等有创操作史者67例,占20.7%,其中接受过针灸治疗者19例,占5.9%,有血液透析史者18例,占5.6%;母婴传播2例,占0.6%;有静脉注射毒品史者21例,占6.5%;性传播者2例,占0.6%;其他不明原因者78例,占24.1%;合并HBV感染者14例,占4.3%.222例患者中,HCV基因型1b型和2a型分别为145例和21例,分别占65.3%和9.5%,283例患者血清HCV RNA病毒载量为1×105和1×106IU/mL者分别为74例和103例,分别占26.1%和36.4%.临床表现有明显肝炎症状和体征者23例,占7.1%.行肝组织活检的39例慢性丙型肝炎患者中,肝脏炎症活动指数(HAI)≥4有14例,占35.9%;纤维化评分(F)≥3的患者6例,占15.4%;HAI≥4同时 F≥3的患者4例,占10.3%.结论 我国慢性丙型肝炎患者感染途径多为输血或使用血制品,经手术等有创操作感染也不容忽视,而除输血外,静脉注射毒品、血液透析及针灸疗法等感染途径亦增加.感染HCV常见的病毒基因型为1b和2a型,病毒复制水平较高,大多数患者发病隐匿,无明显肝炎症状和体征,但肝组织活检显示多数患者肝脏有组织学改变.     

丙型肝炎核心抗原检测在丙型肝炎诊断中的意义

目的了解丙型肝炎核心抗原（HCV-cAg）检测方法的敏感性及特异性,确定具有临床意义的S/CO值,探讨其在丙型肝炎诊断中的意义。方法使用ELASA方法检测丙型肝炎核心抗原,RT-PCR检测HCV RNA定量,观察不同S/CO值所对应的HCV RNA定量之间的关系,以HCV RNA为诊断金标准,列四格表做诊断实验。结果 HCV-cAg抗原检测的敏感性为87.05%,特异性为76.67%,阳性预测值为96.53%,阴性预测值为44.23%。结论 （1）随着HCV-cAg的S/CO值逐渐增大,其与HCV RNA阳性符合率明显增高,随着HCV-cAg的S/CO值减小,其与HCV RNA阴性符合率明显增高;（2）S/CO值=2可以作为临床判断HCV感染病毒血症存在的一个标准;（3）本实验的敏感性和特异性较好,检测方法简单,可以作为丙型肝炎临床诊断的补充试验及筛查。     

136例丙型肝炎患者的5年随访研究

目的 探讨慢性丙型肝炎患者的临床转归及干扰素干预对临床转归的影响.方法 采用回顾性调查与前瞻性研究相结合的方法,对136例慢性丙型肝炎患者进行定群随访,采用SPSS16.0统计软件包进行x2检验及多元logistic回归分析.结果 136例患者以输血及血制品感染为主,诊断时间主要集中在2000-2005年,其中,98例用干扰素联合利巴韦林抗病毒治疗,余38例患者未行干扰素治疗;136例患者中,5年来新增12例肝硬化或肝癌患者,占8.8％;76例经干扰素治疗有效患者,5年来,46例复发,占60.5％.5年随访肝癌及肝硬化发生率:136例患者中,年龄＜40岁的患者发生率为0;40～60岁的患者发生率为12.5％ (7/56);年龄≥60岁的患者发生率为35.7％ (10/28),多元logistic回归分析,差异有统计学意义(B=0.111,Wald=4.324,P=0.038).AST水平正常或2倍正常值上限以内为0,2～4倍为43.5％(10/23),4倍以上为58.3％ (7/12),多元logistic回归分析,差异有统计学意义(B=2.184,Wald=5.443,P=0.02).患者经聚乙二醇干扰素治疗后复发率为29.7％(11/37),普通干扰素治疗复发率为89.7％ (35/39),两者比较差异有统计学意义(Logistic回归分析B=-2.077,Wald=4.352,P=0.037).而总疗程＜24周的患者,复发率为100％(15/15);总疗程在24 ～ 48周的患者,复发率为76.2％ (16/21);疗程≥48周的患者,复发率为37.5％ (15/40),差异有统计学意义(Logistic回归分析B=-1.632,Wald=6.651,P=0.01).46例复发患者中42例再次接受干扰素治疗,HCV RNA均可转阴.结论 丙型肝炎病毒感染增加肝硬化、肝癌的风险,干扰素干预能有效抑制病毒,改善预后.通过使用聚乙二醇干扰素替代普通干扰素及延长疗程治疗可降低复发率.     

丙型肝炎防治指南(2015年更新版)

为规范丙型肝炎的预防、诊断和抗病毒治疗,中华医学会肝病学分会和感染病学分会根据丙型肝炎病毒(HCV)感染的特点、国内外最新的循证医学证据和药物的可及性,于 2015 年组织国内有关专家修订了《丙型肝炎防治指南》.完善的病毒学检测是慢性 HCV 感染筛查、监测、诊断和治疗的基础.根据我国社会和经济发展情况,还需要积极发展适宜于资源有限地区HCV RNA 定量和 HCV 基因分型的检测试剂.政府、社会组织、学术团体、制药企业共同努力,以达到新型抗病毒治疗的可及和可负担.     

丙型肝炎的免疫学研究热点

目前,长效α干扰素和利巴韦林联合应用作为丙型肝炎治疗的"标准方案",其持久病毒学应答率只有500%,而且不良反应大,费用昂贵,停止治疗后仍有很高的复发率[1].     

沈阳地区650例慢性丙型肝炎病毒感染者的病毒基因型分析

HCV感染呈全球分布,不同基因型和亚型的地理分布,可能与抗HCV治疗的疗程及效果相关.本研究以核酸序列分析法对650例患者进行HCV基因型检测分析,以探讨沈阳地区感染人群中HCV的基因型特征. 一、资料与方法     

湘南地区住院患者丙型肝炎病毒感染方式的特征分析

目的 了解湖南地区住院患者中HCV疑似感染方式分布的规律特征,为HCV感染的防治提供参考.方法 应用电子病历查询法对住院患者中诊断有丙型肝炎者进行回顾性分析.化学发光法检测抗HCV抗体,实时荧光定量PCR法检测HCV RNA定量.结果 肾内科患者主要经血液透析感染(80.0％),妇产科患者主要经手术感染(64.7％),感染科患者主要为输血感染(39.0％)和静脉吸毒感染(28.6％),其他科室患者也主要为输血感染(40.7％)和静脉吸毒感染(37.0％),不同科室住院患者的HCV疑似感染方式构成比存在明显差异(P＜0.01).年龄≤40岁患者主要经静脉吸毒感染( 38.2％),而年龄＞40岁患者主要经输血感染(49.3％),不同年龄患者HCV疑似感染方式构成比存在明显差异(P＜0.01).男性患者主要经静脉吸毒(35.0％)和输血感染( 32.5％),而女性患者主要经手术(32.7％)和输血( 26.9％)感染,不同性别患者HCV疑似感染方式构成比存在明显差异(P＜0.01).结论 HCV的感染方式已呈现明显的多样化,静脉吸毒将成为越来越重要的感染因素.     

隐匿性丙型肝炎病毒感染与慢性丙型肝炎的比较分析

目的:比较隐匿性丙型肝炎病毒(HCV)感染者与慢性丙型肝炎(CHC)患者的特点.方法:选择51例隐匿性HCV感染者和52例未经治疗的CHC患者,两组患者的年龄、性别、肝功能异常的持续时间相匹配,分别比较两组患者的肝功能指标和外周血单个核细胞(PBMCs)中的丙型肝炎病毒核酸(HCV RNA)含量.结果:CHC患者的天门冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、甲胎蛋白(AFP)显著高于隐匿性HCV感染者(P<0.01),而胆固醇(Ch)和甘油三酯(TG)则显著低于后者(P<0.01),γ谷氨酰转肽酶(GGT)在两组感染者中差异无显著性意义(P>0.05);CHC患者的PBMCs中HCV RNA平均含量显著高于隐匿性HCV感染者(P<0.01).结论:隐匿性HCV感染者病情严重程度不如CHC患者,这可能与其PBMCs中的病毒载量高低相关.     

慢性丙型肝炎患者病毒血清抗体的分型

不同地区分离的ＨＣＶ分属不同的基因型，对治疗的反应有较大的差异，检测病毒类型应对丙肝的临床预后有较大的帮助．但基因分型方法复杂，技术要求高，价格昂贵，不便于临床应用．血清抗体分型方法简便，能部分地反映ＨＣＶ的分型情况．我们对８３例ＣＨＣ患者进行了ＨＣＶ血清抗体的检测，旨在了解在ＣＨＣ中不同血清型的分布，及与患者预后的关系．１　材料和方法１．１　材料　１９９４０４／１９９７０８我院收治的ＣＨＣ８３例，男５３例，女３０例，平均年龄４５岁±１２岁．按１９９５年北京会议病毒性肝炎诊断标准，其中轻度３…     

Cross-sectional epidemiology of hepatitis C virus detection and treatment in HIV-infected patients

Background

Sustained virologic response to peginterferon plus ribavirin reduces liver-related complications and mortality in patients co-infected with HIV and hepatitis C virus. Therefore, the presence of any barriers to start hepatitis C virus therapy should be identified and eliminated in order to recruit all eligible patients.

Methods

Cross-sectional study. In a HIV referral clinic we assessed the proportion of patients eligible for hepatitis C virus evaluation and treatment according to consensus guidelines.

Results

We identified 134 patients with hepatitis C virus and HIV co-infection. Twenty-one patients were excluded from the analysis due to never attending the HIV clinic (n = 12) or having hepatitis C virus RNA not detectable (n = 9). In the remaining 113 patients, only 61% had identification of hepatitis C virus genotype and quantification of hepatitis C viral load. Thirty-six patients started peginterferon plus ribavirin, and 16 (44%) achieved sustained virologic response. Seventy-seven patients did not receive treatment for hepatitis C virus due to the presence of medical contraindications (n = 22), provider barriers (n = 15), or patient barriers (n = 40). Multivariate analysis identified lower education degree (odds ratio: 4.53; 95% confidence intervals: 1.36-15.16, p = 0.014) and patient civil status single, separated or widower (odds ratio: 4.81; 95% confidence intervals: 1.54-14.99, p = 0.007) as the independent determinants associated to not initiating therapy for hepatitis C virus infection in patients with barriers.

Conclusion

A minor proportion of HIV-infected patients received appropriate assessment and treatment for hepatitis C virus infection. Social disadvantages require multidisciplinary models of health care to improve hepatitis C virus treatment initiation and success.     

合并乙型肝炎病毒感染对丙型肝炎病毒核心抗原检测的影响

目的 探讨合并HBV感染对慢性HCV感染者血清丙型肝炎病毒核心抗原(HCVcAg)检出情况的影响. 方法 收集2005年12月-2009年10月慢性丙型肝炎患者和HBV/HCV合并感染者资料,检测血清HCVcAg和HCV RNA,对后者血清进行HBV DNA、HBeAg检测,分析HCVcAg检出率与HBeAg、HBV DNA定量检测的关系.用独立两组多分类的X2检验方法进行统计学分析. 结果 共收集88例慢性丙型肝炎患者和62例HBV/HCV合并感染者资料,血清HCVcAg的检出率分别为72.7％(64/88)和38.7％ (24/62),两者比较,x2= 17.358,P＜0.01,差异有统计学意义.HCV RNA检出率分别为81.8％ (72/88)和53.2％ (33/62),两者比较,x2=20.110,P＜0.01,差异有统计学意义.62例HBV/HCV合并感染者血清中,HBeAg阳性和HBeAg阴性感染者HCVcAg检出率分别为28.6％ (12/42)和60.0％ (12/20),两者比较,x2=5.641,P=0.011,差异有统计学意义.HCV RNA阳性率分别为42.9％ (18/42)和80.0％ (16/20),两者比较,X2=7.547,P＜ 0.01,差异有统计学意义.HBV DNA阳性和阴性时HCVcAg检出率分别为39.1％ (18/46)和37.5％ (6/16),两者比较,P＞0.05,差异无统计学意义.与单纯HCV感染者血清HCVcAg检出率72.7％ (64/88)比较,HBeAg阴性合并感染者为60.0％ (12/20),x2=1.266,P=0.261,差异无统计学意义;HBV DNA阴性合并感染者为37.5％ (6/16),x2=7.635,P＜0.01,差异有统计学意义.结论 HBV/HCV合并感染时HCVcAg检出率较低,可能是由于HBeAg抑制HCV的复制,从而减少HCVcAg的表达所致.     

肝组织中丙型肝炎病毒抗原的表达及其临床意义

目的研究肝炎患者肝组织中丙型肝炎病毒抗原的表达及其临床意义。     

慢性丙型肝炎患者HCV基因型分析

目的研究慢性丙型肝炎患者HCV基因型概况。方法采用基因芯片法检测HCV基因分型;采用PCR法测定HCV RNA定量。结果在570例患者中,HCV RNA阳性552例（95%）,其中1b型400例（72.4%）,2a型63例（11.4%）,3a型20例（3.6%）,3b型20例（3.6%）,1b＋2a型12例（2.1%）,1a型2例（0.4%）,6型7例（1.26%）,1b＋3a型1例（0.18%）,2a＋1b型3例（0.5%）,未定型24例（4.3%）;不同HCV基因型感染者血清HCVRNA水平无统计学差异（P〉0.05）。结论本组患者HCV基因型以1b型为主,2a型次之,多种混合型的出现提示HCV基因型呈现多样化趋势。     

肝特异性自身抗体与丙型肝炎病毒感染的关系

本研究探讨了HCV感染时体内产生免疫应答并出现多种自身抗体的特点,试图通过检测分析HCV感染与自身抗体的相关性,对丙型肝炎的诊断及治疗提供一些实验数据.     

Post-translational modifications of hepatitis C viral proteins and their biological significance

Replication of hepatitis C virus(HCV)depends on the interaction of viral proteins with various host cellular proteins and signalling pathways.Similar to cellular proteins,post-translational modifications(PTMs)of HCV proteins are essential for proper protein function and regulation,thus,directly affecting viral life cycle and the generation of infectious virus particles.Cleavage of the HCV polyprotein by cellular and viral proteases into more than 10 proteins represents an early protein modification step after translation of the HCV positivestranded RNA genome.The key modifications include the regulated intramembranous proteolytic cleavage of core protein,disulfide bond formation of core,glycosylation of HCV envelope proteins E1 and E2,methylation of nonstructural protein 3(NS3),biotinylation of NS4A,ubiquitination of NS5B and phosphorylation of core and NS5B.Other modifications like ubiquitination of core and palmitoylation of core and NS4B proteins have been reported as well.For some modifications such as phosphorylation of NS3 and NS5A and acetylation of NS3,we have limited understanding of their effects on HCV replication and pathogenesis while the impact of other modifications is far from clear.In this review,we summarize the available information on PTMs of HCV proteins and discuss their relevance to HCV replication and pathogenesis.     

Global epidemiology of hepatitis C virus infection: an up-date of the distribution and circulation of hepatitis C virus genotypes

AIM To review Hepatitis C virus(HCV) prevalence and genotypes distribution worldwide.METHODS We conducted a systematic study which represents one of the most comprehensive effort to quantify global HCV epidemiology,using the best available published data between 2000 and 2015 from 138 countries(about 90% of the global population),grouped in 20 geographical areas(with the exclusion of Oceania),as defined by the Global Burden of Diseases project(GBD). Countries for which we were unable to obtain HCV genotype prevalence data were excluded from calculations of regional proportions,although their populations were included in the total population size of each region when generating regional genotype prevalence estimates.RESULTS Total global HCV prevalence is estimated at 2.5%(177.5 million of HCV infected adults),ranging from 2.9% in Africa and 1.3% in Americas,with a global viraemic rate of 67%(118.9 million of HCV RNA positive cases),varying from 64.4% in Asia to 74.8% in Australasia. HCV genotype 1 is the most prevalent worldwide(49.1%),followed by genotype 3(17.9%),4(16.8%) and 2(11.0%). Genotypes 5 and 6 are responsible for the remaining 5%. While genotypes 1 and 3 are common worldwide,the largest proportion of genotypes 4 and 5 is in lower-income countries. Although HCV genotypes 1 and 3 infections are the most prevalent globally(67.0% if considered together),other genotypes are found more commonly in lowerincome countries where still account for a significant proportion of HCV cases.CONCLUSION A more precise knowledge of HCV genotype distribution will be helpful to best inform national healthcare models to improve access to new treatments.     

Status of hepatitis C virus vaccination:Recent update

Hepatitis C virus(HCV) infection is still a major public health problem worldwide since its first identification in 1989. At the start, HCV infection was post-transfusion viral infection, particularly in developing countries. Recently, due to iv drug abuse, HCV infection became number one health problem in well-developed countries as well. Following acute HCV infection, the innateimmune response is triggered in the form of activated coordinated interaction of NK cells, dendritic cells and interferon α. The acquired immune response is then developed in the form of the antibody-mediated immune response(ABIR) and the cell-mediated immune response(CMIR). Both are responsible for clearance of HCV infection in about 15% of infected patients. However, HCV has several mechanisms to evade these antivirus immune reactions. The current review gives an overview of HCV structure, immune response and viral evasion mechanisms. It also evaluates the available preventive and therapeutic vaccines that induce innate, ABIR, CMIR. Moreover, this review highlights the progress in recent HCV vaccination studies either in preclinical or clinical phases. The unsatisfactory identification of HCV infection by the current screening system and the limitations of currently available treatments, including the ineligibility of some chronic HCV patients to such antiviral agents, mandate the development of an effective HCV vaccine.     

慢性肝病者乙型和丙型肝炎病毒重叠感染的研究

对２１３例老年慢性肝病患者的乙型肝炎病毒（ＨＢＶ）和丙型肝炎病毒（ＨＣＶ）血清标志物检测发现：ＨＢＶ感染占７３．２４％、ＨＢＶ和ＨＣＶ重叠感染占重叠感染点１５．４９％、ＨＣＶ感染占７．０４％、其它占４．２６％；ＨＢＶ阴性者ＨＣＶ检出率高于ＨＢＶ阳性者，肝癌和肝硬化患者较慢性肝炎患者高；ＨＢＶ和ＨＣＶ重叠感染患者的血清血蛋白下降显著，γ－球蛋白升高明显，肝硬化并腹水和上消化道出血者了多。结果表明，老