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要重视血液透析患者感染丙型病毒性肝炎的防治
丙型病毒性肝炎(hepatitis.C virus,HEV)已经呈全球性流行,维持性血液透析患者由于机体免疫功能低下、反复输血和其它各种医源性因素,而成为HCV感染的高危人群.透析患者感染HCV后,不仅影响生活质量,也是增加并发症、死亡率和移植肾失功的重要原因之一.因此,我们必须重视血液透析患者的HCV感染问题,下面讨论有关血液透析患者感染HCV防治中几个需要重视的问题.
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应重视维持性血液透析患者乙、丙型肝炎病毒感染的防治
维持性血液透析是慢性肾衰竭尿毒症患者维持生命的基本治疗手段.血液透析通过40余年的发展,至今在许多城市和地区已经普及和成熟,成功挽救了许多尿毒症患者,使部分患者能长期存活.但是作为一种治疗手段,血液透析技术仍有其局限性,患者仍有较多的短期和长期并发症.在接受血液透析治疗的尿毒症患者中,乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)的感染率远高于一般人群,已成为维持性血液透析患者主要并发症之一,是影响血液透析患者长期存活率、生活质量及肾移植术后存活率的主要因素.维持性血液透析患者肝炎病毒感染的防治应该引起广大从事血液净化工作的医务人员的高度重视.
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HCV核心抗原动态监测抗HCV疗效的临床研究
Objective To evaluate the performance of Hepatitis C virus (HCV) core antigen and HCV RNA PCR in the determining of the efficacy of HCV antiviral therapy in patients infected with HCV. Methods HCV core antigen and HCV RNA were measured in sera of 35 chronic HCV infected Chinese patients. Concentrations of HCV core antigen and HCV RNA were analyzed at 5 time points before, during and at the end of antiviral therapy. Results This study showed that the HCV core antigen and HCV RNA concentrations in 35 HCV patients were significantly correlated. Decrease of HCV core antigen and HCV RNA concentrations at the 4th, 12th,24th and 48th week were observed during the antiviral therapy. However,HCV core antigen levels at week 12 and 24 of therapy were significantly lower than those at week 4 (P < 0. 05 ). In contrast,no further decrease was observed in HCV RNA concentrations at weeks 12 and 24 (P >0. 05). HCV core antigen testing may be advantageous in some cases,in particular,the low levels of HCV core antigen at week 4 may be predictive of satisfactory outcome of treatment. Conclusions HCV core antigen represents a stable and sensitive marker of viral replication and could be used to monitor the clinical efficacy of HCV antiviral therapy.
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丙型肝炎抗病毒治疗药物研究进展
我国丙型肝炎病毒(HCV)感染发病率较高,一般人群抗HCV阳性率为3.2%,总数超过4000万,多数演变成慢性感染者,目前对.HCV感染尚无有效疫苗预防[1].HCV属于黄病毒科,基因组为单股正链RNA,易变异,分为6个基因型及58个不同亚型[2],我国以1b型HCV感染常见[3].HCV感染后,病毒血症持续6个月仍未清除者为慢性感染.
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迎接慢性丙型肝炎治疗的春天——DAAs时代的到来
对于慢性丙型肝炎(chronic hepatitis C, CHC)的抗病毒治疗,直接抗病毒药物(direct-acting antiviral agents, DAAs)无疑是主角和焦点.DAAs自2011年问世以来,使CHC的治疗领域发生了翻天覆地的变化.人们用里程碑、新时代和革命性等词语来评价和期待DAAs对CHC治疗即将带来的影响.是的,就像HAART使AIDS不再是令人绝望的致死性疾病一样,DAAs的应用使得CHC的治愈变得触手可及,给CHC患者带来了确确实实的治愈希望.2015年世界肝病三大学会及我国中华医学会均对CHC防治指南进行了更新,重点内容就是CHC的抗病毒治疗,而其中核心内容就是DAAs的临床应用.治疗方案的更新体现在从过去的单一聚乙二醇干扰素(Peg-IFN)α联合利巴韦林(ribavirin)(P/R)方案到现在P/R/DAAs"三联"方案,以及无IFN的DAAs单独或联合方案;还体现在从控制病毒到治愈丙型肝炎,从治疗疾病到以治为防,从个体化治疗到全口服、泛基因型、短疗程全治愈等的变化.
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丙型肝炎防治指南
丙型肝炎是一种主要经血液传播的疾病,丙型肝炎病毒(HCV)慢性感染可导致肝脏慢性炎症坏死和纤维化,部分患者可发展为肝硬化甚至肝细胞癌(HCC),对患者的健康和生命危害极大,已成为严重的社会和公共卫生问题.在卫生部和中华医学会有关领导的支持下,中华医学会肝病学分会和传染病与寄生虫病学分会组织国内有关专家,按照循证医学的原则,并参照国内外新研究成果,制订了我国丙型肝炎防治指南.必须指出,临床医学的精髓在于根据患者的具体情况及现有的医疗资源,采取合理的诊疗措施.因此,任何临床诊疗指南都不应看作为一成不变的金科玉律.现代医学的发展日新月异,新理论、新观点、新的诊断技术和新的防治方法会不断出现,本指南将根据新的临床医学证据定期进行修改和更新.
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趋化因子与慢性丙型肝炎
越来越多的实验证实,慢性丙型肝炎(chronic hepatitis C,CHC)患者肝脏局部炎症产生的趋化因子(chemokines,CK)在淋巴细胞的迁移和募集中起着至关重要的作用,他不仅与肝细胞损伤程度密切相关,可能是肝病加重的潜在预兆,而且与干扰素治疗后的应答反应密切相关.因此,本文就趋化因子的分类、分泌细胞、趋化细胞的类型,趋化因子与慢性HCV感染肝脏炎症程度的关系以及趋化因子对曼性HCV感染干扰素治疗应答的影响等进行了简要的综述.
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慢性丙型肝炎的规范性抗病毒治疗及研究进展
0引言丙型肝炎是由丙型肝炎病毒(HCV)引起的一种以肝脏为靶器官的传染性疾病.我国肝炎患者为数众多,据1992-1995年全国病毒性肝炎血清流行病学调查表明,我国抗HCV阳性者占3.2%,约4 200万人,其中约70-80%的感染者将发展为慢性,即HCV感染后持续6 mo以上可以检测到HCV RNA.慢性患者由于进行性的肝纤维化将导致在20 a内约有12.5%的人发展为肝硬化,部分发展为肝癌,严重影响了人们的生活质量.由于目前尚缺乏合适、有效的疫苗,远期危害更大.抗病毒治疗是慢性丙型肝炎(CHC)治疗的关键,其目的是根除或长期抑制病毒的复制,减轻肝内炎症和纤维化程度,从而抑制可能出现的肝硬化和肝癌的发生和发展.
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丙型肝炎的实验室诊断和临床意义
0引言丙型肝炎病毒(hepatitis C virus,HCV)感染的实验室诊断是丙型肝炎诊断的重要依据,主要包括特异性抗体(抗-HCV)的检查、HCV基因和HCV核心抗原的检测以及肝细胞损害的检查.抗-HCV阳性是感染的标记,感染的间接证据;而病毒基因和抗原检测阳性是病毒存在的直接证据.
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输血后HCV感染血清病毒含量及基因型与临床转归的关系
目的:了解我国输血后HCV感染病毒含量及基因型与疾病转归的关系.方法:对河北省某农村314例单采浆献血员HCV感染后的现状调查,包括临床表现、血清肝酶、病毒学标志检测以及B型超声检查,其中,HCV RNA的测定采用荧光定量PCR方法,HCV基因分型采用5'端非编码区限制性酶切长度多态性分析.结果:本调查组HCV感染的慢性化率为57.6%,自然阴转率为42.4%.314例感染者目前几乎均无症状,总的ALT的异常率为40.2%.HCV RNA含量变化与ALT水平高低呈正相关性(r=0.346,P<0.001).HCV基因Ⅱ型感染者HCV RNA含量和血清ALT均显著高于HCV基因Ⅲ型感染者(P<0.001).男性感染者的慢性化率高于女性感染者(66.7%vs50.4%).结论:本组输血后HCV感染自然阴转率较高,慢性HCV感染表现隐匿,肝酶学检查指标大多轻度到中度异常.HCV基因Ⅱ型感染者HCV RNA含量和血清ALT均显著高于HCV基因Ⅲ型感染者.男性感染者的慢性化率高于女性感染者.
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AIM To investigate the epidemiological features of HCV prevalence, a seroepidemiological survey on HCVinfection has been carried out in Fujian since 1992.METHODS Using stratified multistage random cluster sampling, 3809 serum samples collected from 1237families in the diseases surveillance points were tested by UBI HCV EIA kit.RESULTS The results showed that the prevalence rate was 3.99%. The rate in male and female was3.63% and 4.25%, and in urban and rural 3.12% and 4.6% respectively (P>0.05). There was lower ratein children aged under 10 years. The highest rate was in 20 - 24 years old. The rates in different areas wereranged from 1.39% to 6.08% (P<0.05). The intrafamilial transmission was not important, indicating nointrafamilial aggregation. The superinfection of HCV with HAV, HBV and HEV were existed. The HCVinfection was slightly correlated with the history of hepatitis and transfusion.CONCLUSION It suggests that the HCV transmission among the population in Fujian is mainly sporadicinfection.
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AIM To study the long-term efficiency of therapy with Interferon alpha (IFN-a) in patients with HCVRNA positive chronic hepatitis C.METHODS Ten patients were enrolled in the study, whose age 31 -62 years (mean 53 years), course 6- 72months (mean 24 months), of whom, 6 patients with mild CHC, 4 moderate CHC. All patients receivedIFN-a 3 MU three times weekly for six to twelve months, and then followed up for seven years after the endof treatment. The results of hepatic functions and HCV RNA at the end of treatment and follow-up period inall patients were observed.RESULTS ( At the end of treatment, clinical symptoms recovered obviously in all patients, virologicalresponse (defined as HCV RNA loss) occurred in 5 of 7 (71.4%) patients (<60 years old) and in 1 of 3(33.3%) patients ( >60 years old). At the end of follow-up, the rates of HCV RNA loss were 42.9% (3/7)and 33.3% (1/3), respectively, in these group. Virological sustained response (defined as HCV RNA loss atthe end of treatment and follow-up) occurred in 3 of 6 (50%) patients (6 - 12 month-course) and in 1 of 4(25%) patients (> 12 month-course). A sustained HCV RNA response was observed in 2 of 7 (28.6%)patients with IFN-a therapy for 6m and in 2 of 3 (66.7%) patients with IFN-a therapy for more than 6 m. Ofall patients, 4 patients with sustained HCV RNA response were mild CHC, 4 patients with sustained HCVRNA positive were mild CHC (2 patients), moderate CHC (2 patients), respectively; other 2 patients withHCV RNA loss at the end of treatment but recurred at the end of follow-up, were moderate CHC. ②Biochemically sustained response (defined as ALT normalization at the end of treatment and follow-up) wasobserved in 5 out of 10 (50%) patients, and these 5 patients were mild CHC, of whom, 4 patients with HCVRNA sustained negative, 1 patient with HCV RNA loss and then recurred again. Two patients with ALTnormalization at the end of follow-up were one mild CHC, one moderate CHC, respectively. Other 3patients with no response were moderate CHC, of whom, 2 patients with HCV RNA sustained positive, 1patient with HCV RNA loss then recurred, and in these 3 patients, the lower limits of ALT were more than121 U/L- 148 U/L. ③ Of 10 patients, 3 moderate CHC patients were far from satisfactory to IFN-αtherapy, of whom, 2 coinfected with HBV, t with post-hepatitis cirrhosis.CONCLUSION The CHC patients with younger age, shorted course, and lighter liver changes in biopsy(mild CHC) have better response to IFN-α therapy, and the efficiency of therapy with IFN-α for 12 m aremore satisfactory than those for 6 m. The patients with coinfected HCV and HBV have a response to IFN-αtherapy worse than the others.
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Molecular biology has made a tremendous impact on the diagnosis and treatment of liver diseases[1,2]. In particular, advances in molecular biology made possible the discovery of the virus that causes hepatitis C. In this review, we use hepatitis C as an example of the impact that molecular biology has made in the area of liver disorders. We emphasize how our growing understanding of the hepatitis C virus (HCV) has lead to the identification of targets for development of new treatments.
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慢性丙型肝炎铁代谢异常的研究进展
铁是人体所必须的微量元素,主要存在于血液中,其次是肝脏。在血液中其通过转铁蛋白转运,并以铁蛋白形式贮存于肝脏,血清中仅含有少量铁蛋白。铁的生理作用主要包括:参与氧的储存和运输、参与机体新陈代谢、提高免疫功能、防止上皮组织受损、维持正常造血功能[1,2]。铁代谢异常不仅可引起缺铁性贫血或铁沉积症,而且还与心血管疾病以及慢性肝炎等消化系统疾病有关。丙型肝炎病毒(hepatitis C virus,HCV)是导致慢性肝炎、并进一步发展为肝硬化和肝癌等晚期肝病的一个主要致病因子[3]。丙型肝炎是散在于世界各地的一种疾病,据世界卫生组织统计,在全球丙型肝炎病毒慢性感染的人数大约为1.7亿,占世界人口的3%,每年新发丙型肝炎例数大约为3.5万[4]。而有关调查显示30%~40%的慢性丙型肝炎(chronic hepatitis C ,CHC)患者血清铁、转铁蛋白饱和度及铁蛋白水平高于正常值[5]。近年来随着铁代谢研究的深入,对CHC发生肝铁蓄积以及铁对CHC治疗的影响有了更多的认识。
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丙型肝炎病毒感染与肝脏脂肪变性研究进展
1 肝脏脂肪变性在慢性丙型肝炎患者中的发病情况据文献报道,全世界1.7 亿慢性丙型肝炎(chronic hepatitis C,CHC )患者中,大约一半的患者伴有肝细胞脂肪变,10% 的儿童CHC 患者并发非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH ).在排除肥胖、糖尿病、高脂血症及嗜酒之后,仍有30% 左右的CHC 患者存在肝细胞脂肪变性[1] .西方国家CHC 患者肝脏脂肪变性的发生率是40%~86% (平均约55% ),而普通人群肝脏脂肪变性的发生率仅为20%~30%[2,3] .我国有学者针对159 例CHC 患者的研究发现,82.39% 的CHC 患者并发不同程度和病理类型的肝脏脂肪变性[1] .
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中国慢性丙型肝炎抗病毒治疗DAA时代与PegIFN/RBV标准治疗
慢性丙型肝炎(chronic hepatitis C,CHC)是导致肝脏疾病进展、肝硬化和肝细胞癌发生主要因素之一,而阻断慢性丙型肝炎病毒(HCV)感染相关肝脏疾病进展的重要手段是抗病毒治疗。有效的抗病毒治疗可达到病毒的清除,从而给患者带来长期良好的临床结局、提高生活质量和延长生存期。由于利巴韦林(ribavirin,RBV)的使用和聚乙二醇化干扰素(PegIFN)的开放使得持续病毒学应答(sustained viral response,SVR)率与普通干扰素/RBV联合治疗相比较,有显著的提高,使PegIFN/RBV治疗从2002年起成为CHC标准治疗。然而在欧洲和美国,特别是HCV G1患者的SVR仍仅有41%~66%,且标准方案的治疗期长、不良反应多,往往使患者难以完成治疗。为了进一步提高SVR和缩短疗程、降低药物的不良反应,在欧美开发出了抗-HCV的直接抗病毒药物(directly acting antivirals, DAAs),且于2011年得到临床的广泛使用,治疗12~24周,使HCV G1患者的SVR率达到98%以上,抗-HCV治疗进入DAA时代。由于诸多的因素,DAA仍未在中国上市,且因中国患者与欧美患者可能存在的差异,与PegIFN/RBV标准治疗相比较,DAA尚难解决中国患者的临床问题。
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IL-28B基因多态性在丙型病毒性肝炎中的临床意义
丙型肝炎(hepatitis C)作为一种世界范围内广泛流行的传染性疾病,其主要传播方式为血液传播,此外针刺、吸毒等也是其常见的感染途径。据统计,全球目前有约1.8亿人曾感染过HCV病毒,约占人口总数的3%[1],其中仅不足1/3的急性感染者体内会出现病毒的自发清除(spontaneous clearance,SC),大多数患者逐渐发展至慢性丙型肝炎(chronic hepatitis C, CHC)。若不能得到正规有效的治疗干预,约1/3的慢性丙型肝炎患者将终进展至肝硬化、肝功能衰竭等晚期病变[2]。多年来,干扰素联合利巴韦林的治疗方式一直是治疗丙型肝炎的标准方案(standard of care, SOC)[3],近年随着各类新型药物的研发与使用,丙型肝炎的抗病毒治疗方案得以不断改进与完善,对于难治性丙型肝炎的患者,在原有标准基础上联合采用以蛋白酶抑制剂(protease inhibitors,PIs)为代表的直接抗病毒药物(direct-acting antiviral drugs, DAAs),已获得了较既往单用SOC更佳的抗病毒疗效。然而哪些患者更容易获得较高的病毒学应答,应答发生的具体作用机制是什么,诸如此类的问题依旧是临床医师在制定与实施抗病毒治疗方案中所面对的主要困难。目前的诸多研究提示,丙型病毒性肝炎预后转归、接受抗病毒治疗的疗效与宿主IL-28B基因多态性、HCV基因型、基线病毒RNA水平(baseline viral load)和肝纤维化程度等密切相关[4]。作为近年来丙型肝炎防治研究领域内的热点问题,IL-28B基因单核苷酸多态性(single nucleotide polymorphism, SNP)在丙型肝炎的发展、演变中的影响与地位越发引起人们的瞩目。本文将近年来丙型肝炎与IL-28B基因单核苷酸多态性相关性研究总结如下。
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HOMA-IR评分系统及其在慢性丙型肝炎患者中的应用
慢性丙型肝炎(chronic hepatitis C,CHC)患者常并发脂肪肝和糖尿病(diabetes metlitus,DM),胰岛素抵抗(insulin resistance,IR)是联系三者关系的一个重要枢纽.临床上常用稳态模型评估方法(homeostasis model assessment,HOMA)来判定机体是否存在IR以及IR的程度.
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日本慢性肝炎治疗指南中有关丙型肝炎的建议
为了补充、修订2004年版的慢性肝炎治疗标准化指南,进行了针对乙型及丙型肝炎病毒感染者治疗标准化临床研究的实况调查,该调查由日本国家公务员共济组合联合会虎门医院熊田博光副院长主持,有山口大学等13家单位参加.其综述研究报告书发表于2006年3月,现将调查报告中有关慢性丙型肝炎部分摘译以飨国内相关专业人士.
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2007亚太区肝病年会丙型肝炎诊治专家共识
一、HCV感染的实验室检测丙型肝炎病毒(HCV)既往感染的检测,使用多的方法是酶免疫分析法(EIA)检测抗-HCV.抗-HCV阳性提示既往HCV感染,但不能说明是急性、慢性感染及感染是否已清除,抗-HCV检测阴性通常说明没有HCV感染.