丙型肝炎病毒实验室诊断的现状与存在的问题

实验室诊断方法对丙型肝炎病毒(HCV)感染的确认和治疗的监测起着关键作用.自从1989年HCV被鉴定至今的近20年间,随着分子生物学检测技术的发展,HCV的实验室诊断也取得了长足进步,但同时也有很多问题需要研究和解决.HCV抗体检测操作简便,耗时少,但对处于窗口期的标本容易漏检,且不能判别是活动性感染还是感染已被清除.HCV RNA检测有较高的敏感度和特异度,定量检测还可以用于抗病毒治疗监测;国际上,RNA检测的发展趋势为全自动化.目前RNA检测亟待解决的两个问题是标准化和高成本问题.近5年HCV抗原检测和抗原抗体联合检测试剂盒也已问世,但其敏感度尚不及RNA的检测.HCV基因分型主要基于核酸杂交或直接测序原理,均有相应的商品化试剂盒,但高成本限制了其在临床实验室的广泛应用.     

MicroRNA对脓毒症炎症因子的调控

在过去的几十年里关于脓毒症的研究取得了巨大的进展,但是脓毒症休克发生后尽管给予很多治疗,其死亡率仍然保持在50%左右.脓毒症的发生机制极其复杂,近年的研究显示其与调节失控的炎症反应有密切的关系.已经证实MicroRNA可以在转录后水平调节生物蛋白质的表达.近年研究发现MicroRNA可以通过转录后水平下调炎症因子以及炎症因子信号通路的受体来控制失衡的炎症反应,有望成为治疗脓毒症的一条更合适的途径.本文就MicroRNA 在脓毒症炎症因子调节失衡中作用的研究近况做一综述.     

The comparison of chronic hepatitis C treatment outcome between intravenous drug users and non-intravenous drug users

Despite the fact that the majority of prevalent and incident cases of HCV are associated with intravenous drug use (IVDU), these patients have largely been excluded from HCV care. The aim of this study was to examine the treatment outcome of chronic hepatitis C in IVDUs compared to non-IVDUs.     

慢性丙型肝炎患者第一高变区抗体的交叉反应性与抗病毒治疗早期病毒应答的关系

目的 探讨慢性丙型肝炎患者血清第一高变区( HVR1)抗体的交叉反应性与抗病毒治疗早期病毒应答(EVR)的关系.方法 用ELISA丙型肝炎病毒(HCV)HVR1抗体交叉反应性矩阵试剂检测抗HCV高变区抗体差异性,16条高变区抗原与患者血清交叉反应性比较采用Fisher精确概率检验.同时对2009年1月至12月首都医科大学附属北京佑安医院46例慢性丙型肝炎患者抗病毒治疗前基线血清标本进行分析.用荧光定量逆转录(RT)-PCR检测46例患者在治疗前、聚乙二醇干扰素联合利巴韦林治疗12周、48周的血清HCV RNA水平,并进行基因分型.结果 46例慢性丙型肝炎患者中,HCV2a型16例,1b型30例;治疗12周及结束时分别检测HCV RNA,其中,EVR组33例,非EVR组13例;2a型EVR发生率[93.8％ (15/16)]高于1b型[60.0％( 18/30),x2=4.316,P＜0.05].HCV 1b型慢性丙型肝炎患者中,EVR组平均多靶点HVR1抗原阳性反应数目为(12±4)个,明显高于非EVR组[(7±5)个,t=2.797,P＜0.01].经Fisher精确概率法检验,HVR1抗原编号分别为001、003、009、013、016的5条抗原在EVR组患者基线血清的反应阳性率明显高于非EVR组(P均＜0.05).结论 HVR1抗体的交叉反应性可能是一项抗病毒治疗疗效的预测指标.     

HCV核心抗原动态监测抗HCV疗效的临床研究(英文)

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.     

Lymphotropism of hepatitis B and C viruses: an update and a newcomer

International Journal of Clinical and Laboratory Research - The mechanisms of viral persistence are complex and include infection of the lymphoid cells. In the case of hepatitis B virus, early...     

维持性血液透析患者并发病毒性肝炎的临床研究

目的 了解维持性血液透析患病毒性肝炎的感染率及其有关因素。方法 用酶联免疫法(ELISA)检测53例乙型肝炎病毒(HBV)标志物、丙型肝炎病毒(HCV)抗体，逆转录一套式PCR法检测HCV—RNA。回顾分析53例维持性血液透析患的临床资料。结果 53例维持性血液透析患肝炎病毒感染率分别为乙型肝炎病毒(HBV)22．6％、丙型肝炎病毒(HCV)41．5％、HBV／HCV总感染率49．1％，HCV感染组、非感染组在输血次数、透析年限的差异有显性，而HBV感染组、非感染组在输血次数、透析年限的差异无显性。结论 病毒性肝炎仍是血液透析(HD)的主要并发症之一，其中以HCV的发生率最高。严格消毒措施，血源筛选，减少输血，对减少透析中肝炎感染至关重要。     

Drug-induced liver injury by glecaprevir/pibrentasvir treatment for chronic hepatitis C infection: a systematic review and meta-analysis

Background: Glecaprevir/pibrentasvir (G/P; 300 mg/120 mg) is a new direct-acting antiviral (DAA) that exhibits anti-hepatitis C virus (HCV) pan-genotype (GT) activity for 8, 12, or 16 weeks. However, the U.S. Food and Drug Administration have received reports that using G/P causes moderate to severe liver impairment. In some cases, isolated hyperbilirubinemia and jaundice have been reported without concomitant evidence of increased transaminase levels or other hepatic decompensation events. Objective: This study aimed to analyze the incidence of drug-induced liver injury of G/P for chronic hepatitis C virus.Materials and methods: We searched databases from the inception of each database until March 2021. Data were pooled using a random-effects model. The Cochrane Risk of Bias Tool (RoB 2.0) and the OpenMeta [Analyst] software were performed for quality assessment and quantitative studies, respectively. The primary outcome was grade 3 level of drug-induced liver injury (DILI). Results: The nine studies included in the meta-analysis involved a total of 7,650 participants, and the overall sustained virologic response rate was above 95%. The most frequent drug-related laboratory abnormalities in DILI involved total bilirubin, alanine aminotransferase, aspartate aminotransferase, and hemoglobin, but these abnormalities were minimal. The cirrhosis–without cirrhosis incidence risk ratio (IRR) was 2.724 (95% confidence interval: 1.182–6.276) in the grade 3 hyperbilirubinemia subgroup analysis. No significant differences were found within the other subgroups, in HCV GTs, and in treatment duration.Conclusions: DILI was found to occur frequently with G/P treatment. Hyperbilirubinemia occurred most frequently, especially, in patients with cirrhosis. However, G/P is still the primary therapy of choice for CKD and end-stage renal disease (ESRD) patients due to a superior safety rate.     

丙型肝炎病毒核心抗原检测试剂的研制及初步应用

目的　研制丙型肝炎病毒核心抗原 (HCV cAg)ELISA检测试剂 ,用于诊断早期丙型肝炎。方法　用基因工程表达的HCV cAg ,免疫Balb/c小鼠 ,制备抗HCV cAg单克隆抗体 ,建立检测HCV cAg双抗体夹心酶联免疫吸附试验 (ELISA) ;以此检测 12 5份抗 HCV、抗 HIV、抗 TP阴性 ,但单项ALT高的献血者血浆。结果　 12 5份单项ALT高的献血者血浆中检出 9份HCV cAg阳性。结论　HCV cAg双抗体夹心ELISA试剂 ,有望用于早期丙型肝炎诊断。     

中国和部分省份网络直报中丙型病毒性肝炎重复报告和诊断情况评价

目的评价现有丙型病毒性肝炎(丙肝)报告病例的重复报告和诊断报告情况,为进一步规范和提高丙肝疫情监测工作提供参考依据。方法下载《疾病监测信息报告管理系统》网络直报中2009—2011年中国丙肝报告卡,计算中国及部分省份2009—2011年年度内和年度间重复报告率。收集天津、吉林、浙江、河南和广东5省(直辖市)2011年诊断并报告过丙肝实验室诊断病例的医疗机构的核酸检测资质情况,以及上述5省部分"有丙肝核酸检测资质"医疗机构的丙肝实验室诊断病例的医学信息,了解实验室诊断病例诊断报告情况。使用SPSS18.0和Excel 2010软件对数据进行统计分析。χ2检验中检验水准α取0.05。结果 2009—2011年年度内重复报告率全国平均3.8%,天津1.2%、吉林2.7%、浙江1.4%、河南4.4%、广东2.9%;剔除各年年度内重复报告病例后,该3年年度间重复报告率全国6.9%,天津2.9%、吉林6.1%、浙江4.5%、河南7.7%、广东5.6%。2011年全国报告154 122例实验室诊断病例共来自8680家报告单位,在5省份调查的517家医疗机构中,48.4%"无丙肝核酸检测资质";核查的857例实验室诊断病例中,32.8%符合报告标准。结论重复报告对于丙肝疫情的准确判断有一定影响。应加强网络直报的实名制管理,提高病例的可查重性。强化丙肝临床诊断和报告管理规范,提高实验室诊断能力。加强培训督导,提高丙肝疫情监测和管理能力。加强健康宣教,提高公众对丙肝的预防、就诊意识。     

Antiviral treatment of hepatitis C: present status and future prospects

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis. A substantial proportion of patients with chronic hepatitis C eventually develop hepatocellular carcinoma (HCC), which is one of the leading causes of death worldwide. Therefore, efficient antiviral treatments for HCV have long been needed. A recently developed combination therapy of pegylated interferon and ribavirin has dramatically improved the outcome of antiviral therapy for HCV infection. In genotype 1b HCV infection, 48 weeks of the combination therapy achieved eradication of the virus in 50% of patients, and in genotype 2 HCV infection, 24 weeks of the therapy resulted in viral eradication in 80%–90% of patients. By this eradication, an improvement in the hepatic fibrosis, an inhibition of HCC development, and an improvement in life expectancy were attained. Patients who did not respond to the combination therapy may be treated with long-term interferon monotherapy, which is not intended to eradicate HCV, but will lower the serum alanine aminotransferase (ALT) level. Thus, the treatment for HCV infection has progressed significantly, but therapies with new modalities, such as inhibitors of viral protease or RNA polymerase, are still being awaited.     

肝脂肪变性促进慢性丙型肝炎病程进展的研究

目的 研究脂肪变性在慢性丙型肝炎疾病进程中的作用.方法 收集治疗前行肝穿刺病理检查的慢性丙型肝炎患者159例,按照感染HCV基因亚型分为基因1b型组、基因2a型组和其他基因型组,荧光定量PCR法检测所有病例血清HCV载量,组织学评估各组穿刺肝组织炎症坏死、纤维化和肝细胞脂肪变性程度.结果 HCV基因1b型和2a型感染患者占总病例的65.41%,63.52%(101/159)的慢性丙型肝炎患者发生肝细胞脂肪变性,不同基因型组间脂肪变性程度无统计学差异.不同基因型组HCV慢性感染者间炎症活动度、纤维化程度和脂肪变性程度无统计学差异(P均>0.05).肝脂肪变性与肝纤维化和炎症活动度均密切相关(r值分别为0.34和0.29,P均<0.01),但HCV感染病毒量与脂肪变性、肝纤维化和炎症活动度间无明显相关性.结论 脂肪变性促进慢性丙型肝炎病程进展.     

HIV and hepatitis C co-infection

HIV/HCV co-infection is emerging as a major cause of morbidity and mortality in the 21st century. This editorial reviews the prevalence of co-infection, the factors involved in acquisition of HCV, and the influence of co-infection on disease progression. We examine the results of the major co-infection trials including APRICOT, ACTG 5071 and RIBAVIC. These trials, in association with emerging evidence for future therapies currently undergoing investigation, have led to increased hope of treatment success in co-infected individuals.     

丙型肝炎IgM抗体检测及其临床意义

为探讨丙型肝炎ＩｇＭ抗体的临床意义，建立了间接酶联免疫吸附法（ＥＬＩＳＡ），该方法重复性好、特异性强、操作简便。检测２２例急性丙型肝炎和５０例慢性丙型肝炎患者的血清，结果单独使用核心区抗原检测ＩｇＭ抗体的阳性率大于用核心区和非结构区３抗原共同检测。抗－丙型肝炎病毒（ＨＣＶ）ＩｇＭ在急性丙型肝炎患者中检出率为８６％，慢性丙型肝炎中检出率为６６％，但急性组中５０％患者ＩｇＭ出现（约于输血后７．０±３．７周即可在血清中测出）早于ＩｇＧ，而慢性组中无一例如此，两组间差异有非常显著意义（Ｐ＜０．００５）。急性组血清丙氨酸转氨酶显著升高患者中８０％可测出ＩｇＭ；慢性组中６７％可测出ＩｇＭ。ＨＣＶＩｇＭ对急性丙型肝炎的诊断是一个有价值的指标，同时与疾病的活动性有一定相关性。     

Current status and emerging challenges in the treatment of hepatitis C virus genotypes 4 to 6

Hepatitis C virus(HCV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endpoints. Response rates to a 48-wk combined peginterferon/ribavirin treatment range to 40%-69% for HCV 4, 55%-60% for HCV 5 and 60%-90% for HCV 6. Response-guided schedules are recommended to optimize the outcomes of peginterferon/ribavirin treatment in HCV 4 and, in form of preliminarydata, for HCV 6, but no data are yet available to support such an individualization of therapy for HCV 5. Recently, the direct-acting antivirals(DAAs) with pan-genotypic activities simeprevir, sofosbuvir and daclatasvir have been recommended in triple regimens with peginterferon/ribavirin for the treatment of HCV genotypes 4 to 6 infections. In the future, DAA-based interferon-free therapies are awaited to drastically improve treatment outcomes in HCV. However, efforts to improve treatment outcomes with peginterferon/ribavirin should continue, as the HCV 4-6 infected population is mainly based in resource-limited settings with restricted access to the costly DAAs.     

三种不同检测方法对婴幼儿丙型肝炎病毒感染的诊断价值

目的探讨不同检测方法对婴幼儿丙型肝炎病毒感染诊断结果的影响。方法对66例ELISA法检测抗HCV阳性孕妇所生婴幼儿血清,分别用ELISA法检测抗HCV和HCV-cAg,用荧光定量PCR法检测HCV-RNA,并对结果对比分析。结果 66例婴幼儿血清中,61例抗HCV阳性,阳性率92.4%;9例HCV-cAg阳性,阳性率13.6%;11例HCV-RNA阳性,阳性率16.6%。结论抗HCV检测阳性率过高,且有可能漏诊。建议采用HCV-RNA检测和HCV-cAg综合诊断婴幼儿HCV感染。     

2006-2015年山西省太原市丙型病毒性肝炎流行特征分析

目的 了解2006-2015年太原市丙型病毒性肝炎（丙肝）的流行特征,为防治工作提供理论依据。方法 采用描述流行病学方法对太原市2006-2015年丙肝流行特征进行分析。结果 2006-2015年太原市累计报告丙肝病例 14 841例,年发病率38.56/10万,10年间平均增长速度约为11.64%。太原市2006-2015年丙肝报告发病率总体呈逐年上升趋势。丙肝占甲乙丙类传染病总发病数的比例、占肝炎比例和占血液及性传播疾病比例逐年增加。全年各月均有发病,无明显季节性;中心城区发病率高于远郊县;发病以青壮年为主,无性别差异;职业分布以家务待业、离退休人员、工人和农民为主,占75.14%。吸毒者丙肝阳性检出率明显高于暗娼、男男性行为者、性病门诊男性就诊者和无偿献血者。结论 近年来,太原市丙肝发病率呈快速上升趋势,应尽快开展相应的现场流行病学调查和制定预防控制措施以控制丙肝流行。     

Prevalence of hepatitis C virus infection among men who have sex with men with human immunodeficiency virus-1 infection between 2010 and 2020 in Japan: A single-center retrospective cohort study

IntroductionThe high prevalence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) is an important health issue. The purpose of this study is to investigate the actual prevalence of HCV infection among HIV-positive MSM in Japan.MethodsThis study is a single-center retrospective cohort study. We collected data of HIV-infected MSM who visited our hospital from January 2010 to December 2020, and evaluated HCV prevalence, course of HCV infection, and direct-acting antiviral (DAA) treatment efficacy in HIV-infected MSM.ResultsOverall, 1135 HIV-infected MSM had HCV antibody (Ab) tests during the observation period. The first anti-HCV Ab positive rate in HIV-infected MSM was 4% (45/1135), and the seroconversion rate of HCV antibody was 3.6% (39/1090). Treponema pallidum hemagglutination antigen positivity (odds ratio [OR], 5.28; 95% confidence interval [CI], 2.9 to 10.5) and intravenous drug injection (OR, 19; 95% CI, 3.4 to 149) were identified as factors associated with HCV Ab positivity. Spontaneous elimination of HCV infection was observed in 17.9% (7/39) of patients. DAA treatment was performed in 43 cases, and the overall sustained virologic response 12 (SVR12) rate for DAA treatment was 93% (40/43).ConclusionA high HCV infection rate among HIV-infected MSM was observed in Japan. The DAA treatment response rate in patients with HIV/HCV co-infection was the high response rate.     

Safety of oral direct acting antiviral regimens for chronic hepatitis C in real life conditions

Objectives: Direct acting antivirals (DAA) are extremely effective to treat chronic hepatitis C. The aim of this study was to evaluate, by using objective variables, the safety of DAA combinations under clinical practice conditions.

Methods: A retrospective study was carried out in mono-infected patients with chronic hepatitis C treated with DAA between January and December 2015 in our centre. Discontinuations, treatment modifications, deaths and laboratory parameters were studied (liver function tests, hemoglobin, creatinine and lipid profile at baseline, weeks 4, 8 and post 12). Temporal variation of laboratory parameters was analyzed by t-test for paired data, and comparison between groups was made by t-test for independent samples and ANOVA.

Results: 227 patients were included (40.5% cirrhotic). Sustained virological response (SVR) was achieved in 97.3% of patients. In only one case was the antiviral medication suspended due to toxicity, and there were no voluntary treatment discontinuations. The use of ribavirin (RBV) was associated with mild transient hyperbilirubinemia (41.2%) and anemia (32.6%, with RBV dose reduction in 7.9% of cases). There was an elevation in total cholesterol and LDL-cholesterol (LDL-C) during and after treatment: mean increase of 23 mg/dL (0.59 mmol/L) and 22 mg/dL (0.57 mmol/L), respectively in post 12 (p < .0001). An increment of 20% of patients with cholesterol levels over optimal figures was observed after DAA completion.

Conclusion: DAA have an optimum safety profile in real life conditions, with infrequent discontinuation and minor laboratory alterations.     

Viral hepatitis: A brief introduction,review of management,advances and challenges

Viral hepatitis represents a major public health hazard and is associated with significant global mortality. Over the last decade, there have been significant developments in the prevention and treatment of viral hepatitis. These changes have led to a situation whereby global elimination has become a realistic goal, fully endorsed by the World Health Organization (WHO). By 2030, the WHO aims to reduce viral hepatitis mortality by 65% and reduce new infections by 90% by 2030. These are ambitious targets and will only be met through a sustained programme. This will require expertise from hepatologists and virologists and the fields of public health and primary care. In this article, we review the causes of viral hepatitis, its management through prevention and treatments, and the most pressing challenges and recent advances.