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…     

定位检测HCV不同编码区抗体的临床意义

第三代试剂盒虽然提高了ＨＣＶ抗体检出率，但仍存在假阳性及假阴性．我们采用合成肽及基因重组抗原对相应的核壳蛋白和非结构区抗体进行检测，为丙肝的诊治提供依据．１　材料和方法１．１　材料　根据１９９５年北京全国传染病与寄生虫病学术会议修订的《病毒性肝炎防治方案》［１］诊断标准，病例选自我院１９９２０５／１９９８０５传染科住院患者，抗ＨＣＶ阳性或伴ＨＣＶＲＮＡ阳性结合流行病学资料及临床表现确诊的丙型肝炎７５例，男５０例，女２５例．年龄１０岁～６８岁，平均４４岁．其中急性肝炎３３例，慢性肝炎轻度１６…     

甲状腺自身免疫性抗体与丙型肝炎病毒感染的相关性分析

目的 探讨自身免疫性甲状腺病、甲状腺自身抗体与HCV感染的相关性.方法 选取甲状腺过氧化物酶抗体(TPOAb)和(或)甲状腺球蛋白抗体(TgAb)阳性者462例,分别选取年龄和性别匹配的TPOAb和TgAb阴性者380例作为对照,检测血清抗-HCV,阳性者进一步作HCVRNA定性检测.同时,选取临床诊断的195例丙型肝炎患者作病例组,并选取年龄和性别匹配的150名健康人和150例乙型肝炎患者作对照组,行甲状腺相关指标的测定.采用独立样本t检验和X2检验.结果 甲状腺自身抗体阳性组462例患者中,HCV感染阳性率为1.30%,阴性组380例中HCV感染阳性率为0.53%,差异无统计学意义(X2=1.322,P>0.05).丙型肝炎患者的TPOAb阳性率为30.8%,TgAb阳性率为30.8%,均显著高于乙型肝炎患者和健康人(X2=21.496,X2=30.454; P<0.01).结论 甲状腺自身免疫异常者未见HCV感染率增高,而丙型肝炎患者甲状腺自身抗体阳性率增高,提示丙型肝炎患者应注意检测甲状腺相关指标.     

急性丙型肝炎的丙氨酸转氨酶(ALT)类型与慢性化的关系

54例丙型肝炎抗体阳性的急性丙型肝炎病人的临床和血清学动态观察证实:ALT峰越多,其慢性化率越高;ALT、AST值越高,慢性化的可能性越大。50例病程6个月以上病人的抗-HCV动态观察表明:单峰型组中3例抗-HCV消失,部分抗-HCV滴度渐渐减弱,部分仍持续强阳性;而双峰型、多蜂型组的抗-HCV持续强阳性。提示HCV的持续存在是丙型肝炎慢性化的重要原因。     

天津地区慢性丙型肝炎患者自身抗体的检测结果及临床分析

目的分析天津地区慢性丙型肝炎（CHC）患者血清中自身抗体阳性率及其临床意义。方法选择天津地区98例CHC患者,检测自身抗体（ANA、ASA、AMA、RF、LKM-I）阳性率,并比较自身抗体（＋）及自身抗体（-）群年龄、性别及病毒复制状况。结果 CHC患者血清中自身抗体至少一种阳性的32例,阳性率32.7%。ANA阳性率最高,为26.5%;其次为RF阳性率（8.1%）,再次为AMA阳性率（2.0%）,LC-1及LKM-1阳性率为1.0%。另外,自身抗体阳性组和阴性组有关因素比较发现,阳性组年龄较大（57.1岁vs 46.8岁）,女性多见（65.6%vs 47.0%）。肝脏功能差,免疫功能异常,病毒复制活跃。结论丙型肝炎病毒（HCV）感染者存在自身免疫反应。HCV感染使感染者体内产生多种自身抗体,自身抗体检出率与年龄关系密切且与病毒的复制有关。自身抗体可能是HCV感染后肝组织损伤的重要因素。     

丙型肝炎疫苗的研究现状

丙型肝炎在全世界广泛流行,全球有2～3亿的慢性HCV感染者,亟待研制有效的丙肝疫苗。然而,丙肝疫苗的研制尚面临诸多困难。本文就丙型肝炎疫苗的研究现状及相关的免疫学进展作一综述。 1 HCV与机体免疫应答体液免疫应答在保护机体免受病毒的攻击中发挥着重要作用,包括与HCV同属的黄热病毒、登革热病毒、tickbone脑炎病毒等的疫苗设计均着力于诱生机体的中和抗体,接种后机体均能产生具有中和作用的包膜抗体,并能抵抗随后相应病毒的攻击,然对HCV而言,目前尚不能确定其中和抗体表位。有研究表明,HCV-E_2区的高变区(HVR1)含有具有中和作用的B细胞表位,并发现HCV-E_2蛋白能与细胞上的CD81分子结合(CD81被认为是感染肝细胞的HCV受体)。     

对《丙型肝炎防治指南》中有关“实验室诊断”抗体和核酸检测内容的思考

2004年3月由中华医学会肝病学分会和中华医学会传染病与寄生虫病学分会联合制定发布了《丙型肝炎防治指南》,随着对HCV感染检测研究的进展,人们对有关检验项目的理解更多更深,指南修改在即,现提出几点建议。     

抗─HCV阳性患者自身抗体的意义

抗＿ＨＣＶ阳性患者自身抗体的意义靳淑玲李彩王北宁北京军区总医院检验科北京市１００７０主题词肝炎，丙型／免疫学抗体，病毒／分析自身抗体／分析荧光抗体技术ＳｕｂｊｅｃｔｈｅａｄｉｎｇｓｈｅｐａｔｉｔｉｓＣ／ｉｍｍｕｎｏｌｏｇｙａｕｔｉｂｏｄｉｅｓ，ｖ...     

48例原发性肝癌患者血清丙型肝炎抗体检测

为探讨PHC与丙型肝炎的关系,采用ELISA方法检测48例PHC及106例非肝病患者的扰HCV抗体及HBV-M。结果显示PHC组中抗HCV抗体阳性21例(43.8％),对照组14例(13.2％,P<0.01);HBV-M阳性45例(93.8％),对照组50例(47.2％,P<0.01)。HBV-M阳性PHC病人中,HBsAg、HBeAb及HBcAb三项阳性21例(46.7％),HBsAg、HBeAg及HBcAb三项阳性7例(15.6％),HBsAg及HBcAb二项阳性5例(11.1％)。HBV-M阴性PHC患者中,抗HCV抗体阳性2/3例(66.7％),HBV-M阳性PHC病人中,抗HCV抗体阳性19/45例(42.2％,P<0.05);HBsAg阳性PHC病人中,抗HCV抗体阳性14/38例(36.8％);HBsAg阴性病人中,抗HCV抗体阳性7/10例(70.0％,P<0.05)。在抗HCV抗体阳性PHC患者中,3个月前有明确输血史8例(38.1％)。以上结果提示在我国,PHC与丙型肝炎有关,在HBV-M阳性患者中。HBsAg、HBeAb及HBcAb三项阳性患者发生PHC可能性最大。     

慢性丙型肝炎的诊疗现状

慢性丙型肝炎的诊疗现状张树林蔺淑梅李义方西安医科大学第一临床医学院肝炎研究室陕西省西安市７１００６１主题词肝炎，丙型／诊断肝炎，丙型／治疗肝炎抗体／分析肝炎病毒组，丙型／遗传学ＲＮＡ，病毒／分析Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｈｅｐａｔｉｔｉｓ，Ｃ...     

Low prevalence of hepatitis C virus infection in patients with auto-immune hepatitis type 1

Hepatitis C virus (HCV) antibodies were measured in 28 patients with auto-immune hepatitis type 1 using six different assay kits, three for C100–3 antibody and three for second generation HCV antibody, and two confirmatory tests to determine the prevalence of HCV infection in auto-immune hepatitis. These patients were confirmed to have human leucocyte antigen DR 4 or 2 which is susceptible to auto-immune hepatitis in Japanese. Of the 28 patients, four (14.3%) were positive for HCV antibody in all assays and reacted positively in at least one of the two confirmatory tests, indicating a true positive finding. Eight were positive for HCV antibody only by the Ortho ELISA kit and were negative in both confirmatory tests. The cut-off level for these results was low and became negative soon after the patients received corticosteroid treatment. Thus, these eight patients are presumed to be false-positive reactors. Hepatitis C virus RNA was detected in the serum of two of the four patients with HCV antibody and in none of 24 patients without HCV antibody. No significant difference was observed between the patients with and without HCV antibody in terms of clinical background, liver function tests and auto-antibodies. Our results showed that the prevalence of a past or present HCV infection in patients with auto-immune hepatitis in Japan is low; thus, auto-immune hepatitis is thought to be distinct from hepatitis type C. However, it is also suggested that HCV infection can potentially trigger auto-immune hepatitis.     

A possible role of hypervariable region 1 quasispecies in escape of hepatitis C virus particles from neutralization

We examined serial changes in the hypervariable region 1(HVR1) quasispecies both in immune and nonimmune complexed hepatitis C virus (HCV) particles from 12 patients with chronic hepatitis C to elucidate the mechanism by which genetic diversification of HCV during the course of infection allows escape of virus from the humoural immune response. Immune and nonimmune complexes were separated by differential flotation centrifugation and immunoprecipitation, and their HVR1 quasispecies were determined by subcloning and sequencing. The presence of a specific antibody against a specific viral clone in serum was examined in two patients by Western blotting of the corresponding recombinant HVR1 protein. The distribution of HVR1 quasispecies in both immune and nonimmune complexes conspicuously changed over time in most of the patients studied. In seven patients, various HCV clones serially shifted from nonimmune complexes to immune complexes. In four of them, a group of clones with similar HVR1 sequences to each other remained predominant in nonimmune complexes, whereas minor clones with sequences considerably divergent from the predominant clones shifted from nonimmune complexes to immune complexes. These results suggest a mechanism for persistent infection of HCV, in which major HCV clones escape from neutralization by anti-HVR1 antibodies by generating considerably divergent minor 'decoy' clones which may be preferentially neutralized.     

输血后丙型肝炎病毒感染的血清病毒定量研究

目的 研究血清丙型肝炎病毒（ＨＣＶ）含量与ＨＣＶ致病的关系及ＨＣＶ含量与抗－ＨＣＶ和丙氨酸转氨酶（ＡＬＴ）的相关性。方法 以逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）法对ＨＣＶ感染的受血及相关供血系列血清进行ＨＣＶ ＲＮＡ定量分析,同时检测ＡＬＴ与抗－ＨＣＶ。结果 致输血后ＨＣＶ感染的供血中,ＨＣＶ ＲＮＡ平均含量为１０＾８．６拷贝／Ｌ,抗－ＨＣＶ及ＡＬＴ的异常检出率随ＨＣＶ ＲＮＡ滴度升高而增加。结论     

丙型肝炎病毒高变区1抗体的交叉反应性分析

目的探索检测丙型肝炎病毒（HCVJ高变区1（HVR1）抗体交叉反应性的意义。方法采用16种重组的HVRI抗原包被,酶联免疫吸附检测不同病程及不同干扰素治疗效果HCV感染者血清中HVR1抗体的情况,分析其高变区抗体交叉反应性。结果在慢性丙型肝炎、肝硬化和肝细胞癌这三组患者血清中HVR1抗体交叉反应阳性数目分别为10．93±4．98、12±5．57和10．64±4．83,三组间差异无统计学意义（P〉0．05）;对干扰素治疗效果好的患者HVR1抗体交叉反应阳性数为13．85±2．85,治疗效果差的患者为7±5．27,前者显著高于后者（P〈0．05）。但两者治疗前HCV病毒载量差异无统计学意义（P〉0．05）。结论HVRI抗体的交叉反应性与HCV感染的严重程度无明显关系,但可能成为一项干扰素疗效的辅助预测指标。     

Hepatitis C virus RNA detection in serum and peripheral blood mononuclear cells of patients with hepatitis C

ＨｅｐａｔｉｔｉｓＣｖｉｒｕｓＲＮＡｄｅｔｅｃｔｉｏｎｉｎｓｅｒｕｍａｎｄｐｅｒｉｐｈｅｒａｌｂｌｏｏｄｍｏｎｏｎｕｃｌｅａｒｃｅｌｓｏｆｐａｔｉｅｎｔｓｗｉｔｈｈｅｐａｔｉｔｉｓＣＺＨＯＵＰｉｎｇ，ＣＡＩＱｉｎｇ，ＣＨＥＮＹｏｕＣｈｕｎ，ＺＨＡ...     

Rapid virological response in peripheral blood mononuclear cells with an increase of hepatitis C virus-specific interferon-gamma production predisposes to sustained virological response in patients with chronic hepatitis C genotype 1 undergoing treatment with pegylated-interferon alpha 2a plus ribavirin

Abstract

Objective. Viral load evaluation in plasma, after 1 month of treatment, represents one of the most important parameters to predict treatment response during interferon (IFN) treatment in chronic hepatitis C (CHC). It has been proven that hepatitis C virus (HCV) RNA may be present in peripheral blood mononuclear cells (PBMCs) but few studies have investigated the viral load in PBMCs during treatment. The aim of this study was to evaluate HCV RNA in PBMCs during therapy with pegylated-IFN-α2a plus ribavirin and whether its clearance in PBMCs may induce a treatment response. Furthermore, we also analyzed the IFN-γ and interleukin (IL)-4 responses of PBMCs during therapy. Material and methods. We studied 35 patients with CHC genotype 1 undergoing antiviral treatment with pegylated IFN-α2a 180 μg weekly plus ribavirin 1000 mg/daily. In these patients we evaluated HCV-RNA in plasma and PBMCs, IFN-γ and IL-4 before treatment, after 1, 3 and 12 months of treatment and 6 months after the end of treatment. Results. We found that rapid virological clearance of HCV-RNA in PBMCs with a restored and improved HCV-specific IFN-γ response was statistically significantly higher in those with a sustained virological response (SVR). Conclusion. Patients having a rapid virological response in PBMCs with an improved Th1 network achieve a complete SVR, whereas those having viral clearance only in plasma without a restored Th1 network have a relapse.     

Hepatitis C virus antibodies, viral RNA and genotypes in sera from patients on maintenance haemodialysis

SUMMARY. Patients on maintenance haemodialysis in four dialysis centres were tested for markers of hepatitis C virus (HCV) infection. Antibody to HCV (anti-HCV) was detected by the second-generation enzyme immunoassay in 142 (26%) of the 543 patients and HCV RNA in 117 (22%) of whom four were without detectable anti-HCV in serum. Seventy-seven (66%) were infected with HCV of genotype II/1b, 31 (27%) with genotype III/2a and eight (7%) with genotype IV/2b. in a distribution similar to that in blood donors who carried HCV asymptomatically. Haemodialysis patients had high HCV RNA titres comparable to those of patients with chronic hepatitis C. HCV RNA was detected in 96 (26%) of the 365 patients with a history of transfusion more frequently than in 21 (12%) of the 178 without previous transfusion ( P <0.001). In transfused patients, frequencies of anti-HCV and HCV RNA increased in parallel with the duration of haemodialysis. The frequency of anti-HCV in non-transfused patients, however, did not change appreciably with the duration of haemodialysis up to 22 years. The patients with anti-HCV had a higher frequency of HCV RNA in serum than symptom-free blood donors with anti-HCV (113/142 or 80% vs 109/166 or 66% P <0.01) and the patients with HCV RNA had a lower frequency of elevated aminotransferase levels than blood donors with HCV RNA (5/113 or 4% vs 27/109 or 25%, P <0.00l). These results indicate that transfusion is a significant cause of HCV infection in patients on maintenance haemodialysis, and that these patients are prone to establish the HCV carrier state after infection.     

Preparation and application of monoclonal antibodies against hepatitis C virus nonstructural proteins

ＰｒｅｐａｒａｔｉｏｎａｎｄａｐｐｌｉｃａｔｉｏｎｏｆｍｏｎｏｃｌｏｎａｌａｎｔｉｂｏｄｉｅｓａｇａｉｎｓｔｈｅｐａｔｉｔｉｓＣｖｉｒｕｓｎｏｎｓｔｒｕｃｔｕｒａｌｐｒｏｔｅｉｎｓＧＡＯＪｉａｎＥｎ，ＴＡＯＱｉＭｉｎ，ＧＵＯＪｉａｎＰｉｎ...     

丙型肝炎肝组织中HCV RNA和HCV NS5抗原表达及意义

目的研究丙型肝炎肝组织中ＨＣＶＲＮＡ与ＨＣＶＮＳ５抗原分布及其与肝组织损伤的关系．方法应用原位杂交和免疫组化方法检测３４例丙型肝炎病毒（ＨＣＶ）感染者肝组织中ＨＣＶＲＮＡ和ＨＣＶＮＳ５抗原表达状况,采用Ｋｎｏｄｅｌ方法评价肝组织病理损伤程度．结果分别有２１例（６１８％）和２４例（７０６％）患者肝组织中检出ＨＣＶＲＮＡ和ＨＣＶＮＳ５抗原．ＨＣＶＲＮＡ阳性信号主要位于肝细胞浆中,在胆管上皮细胞和炎性浸润细胞中也可检出,其分布与肝组织炎症坏死无固定解剖学关系．ＨＣＶＲＮＡ与肝组织中ＨＣＶＮＳ５抗原表达正相关,但二者在肝组织中的分布存在一定差异．多因素分析显示ＨＣＶＮＳ５抗原的表达与肝组织损伤相关．结论丙型肝炎肝组织中ＨＣＶＲＮＡ和ＨＣＶＮＳ５抗原表达相关,病毒在肝组织中的活跃程度与肝损伤有关