HCV不同功能区抗体与HCVRNA的关系探讨

探讨HCV不同功能区抗体(抗-C、抗-NS3、抗-NS4及抗-NS5)与HCVRNA的关系。HCV不同功能区抗体测定采用ELISA法,用RT-PCR进行HCV RNA检测。结果显示55例抗HCV阳性血清中有7种抗体阳性组合。抗-NS3、抗-C、抗-NS5及抗-NS4在7种阳性组合中的检出率分别为96．4%、89．1%、58．2%、56．4%。HCVRNA阳性血清中抗-NS3、抗-C、抗-NS5及抗NS4的检出率分别为96．2%,88．5%,57．7%,57．7%。HCV不同功能区抗体ELISA法有很高的敏感性和特异性,与RT-PCR法基本一致。抗-NS3、抗-C在HCV的诊断中有重要的意义,抗-NS5和抗-NS4有诊断的互补作用。     

Knowledge and attitudes about hepatitis C virus (HCV) infection and its treatment in HCV mono‐infected and HCV/HIV co‐infected adults

Hepatitis C virus (HCV) treatment is rapidly changing but little is known about patients' attitudes and knowledge about HCV. This study used a cross‐sectional survey to examine the relationship between HCV knowledge and attitudes towards HCV in patients with HCV mono‐infection and HIV/HCV co‐infection. Subsequently, an education intervention was developed with an abridged version of the cross‐sectional survey administered before and after the education session to assess changes in knowledge and attitudes. 292 people participated in the cross‐sectional survey, and 87 people participated in the education intervention. In the cross‐sectional survey, the mean knowledge score regarding HCV was low (<50% of the total possible score). Mono‐infected and co‐infected individuals shared similar knowledge deficits and attitudes towards HCV despite having distinct demographic differences. Attitudes endorsed by patients included the following: 57% feared the consequences of HCV on their life, 37% felt HCV was not fatal, 27% did not believe they needed HCV medication, 21% felt ashamed of having HCV and 16% felt HCV treatment was not important. Attitudes that reflected indifference and shame towards HCV were associated with lower knowledge scores (HCV knowledge score of 15.1 vs. 17.5, P < 0.01 for indifference and 15.3 vs. 17.2 for shame, P = 0.02). The education intervention improved knowledge scores but did not modify the assessed attitudes. Intervention studies are needed to effectively change attitudes towards HCV infection and treatment.     

Mixing particles from various HCV genotypes increases the HBV‐HCV vaccine ability to elicit broadly cross‐neutralizing antibodies

The development of a safe, effective and affordable prophylactic vaccine against hepatitis C virus (HCV) remains a medical priority. Hepatitis B‐C subviral envelope particles, which could be produced by industrial procedures adapted from those established for the hepatitis B virus vaccine, appear promising for use for this purpose. The prototype HBV‐HCV bivalent vaccine‐bearing genotype 1a HCV envelopes can induce neutralizing antibodies against this genotype, but is less effective against other genotypes. We show here, in a small animal model, that the use of a set of vaccine particles harbouring envelopes from different HCV genotypes in various association strategies can induce broad neutralizing protection or an optimized protection against a particular genotype prevalent in a given region, such as genotype 4 in Egypt. This vaccine could help to control the hepatitis C epidemic worldwide.     

Direct‐acting antivirals and hepatitis B virus (HBV) reactivation in co‐infected HBV/HCV kidney‐transplant recipients

Direct‐acting agents (DAAs) are highly efficient at treating hepatitis C virus (HCV) infections after kidney transplantation. Although drug agencies have recently warned of the risk of hepatitis B virus (HBV) reactivation after patients have received DAAs, reports have discrepant results in HBsAg‐positive and HBsAg‐negative patients. We report on 3 cases of HBV reactivation that were detected after achieving a DAA‐associated sustained virological response in 3 kidney‐transplant recipients initially HBsAg‐negative. In the first case, retrospective virological analysis revealed that HBsAgs had become positive and HBV DNA was detectable before initiating DAA therapy. In the second and third cases, HBV reactivation occurred 2 months and more than 1 year after stopping anti‐HCV therapy. These cases underline the discrepancies and highlight the need for comprehensive information before making definitive conclusions regarding the causal link between DAAs and HBV reactivation.     

HCV genotypes in hepatitis C patients and their clinical significances

ＩＮＴＲＯＤＵＣＴＩＯＮＩｔｈａｓｂｅｅｎｄｉｓｃｏｖｅｒｅｄｔｈａｔｈｅｐａｔｉｔｉｓＣｖｉｒｕｓ（ＨＣＶ）ｐｒｅｓｅｎｔｓｃｏｎｓｉｄｅｒａｂｌｅｎｕｃｌｅｏｔｉｄｅｖａｒｉａｔｉｏｎａｎｄｈａｓｍａｎｙｇｅｎｏｔｙｐｅｓ．Ａｔｌｅａｓｔｔｗｅｌｖｅ,５ｏｆｗｈｉｃｈｐｒｅｖａｌｅｎｔ,ｉ．ｅ．：Ⅰ／１ａ,Ⅱ／１ｂ,Ⅲ／２ａ,Ⅳ／２ｂ,ａｎｄⅤ／３ａｔｙｐｅｓ．ＴｈｅｄｉｆｆｅｒｅｎｔｇｅｎｏｔｙｐｅｓｏｆＨＣＶｍａｙｐｏｓｓｅｓｓｓｏｍｅｒｅｔａｔｉｏｎｓｈｉｐｗｉｔｈｒｅｇｉｏｎａｌｄｉ…     

HCV基因异质性及其宿主基因多态性

丙型肝炎的进展、严重程度、治疗反应性差异不仅与病毒的遗传多样性有关,而且与宿主IL-28B、IP-10、ITPA基因多态性有关。分别介绍了HCV基因多态性和宿主基因单核苷酸多态性的分子流行病学、临床和治疗学方面的研究进展,提出迫切需要可靠的有关病毒及宿主的相关分子流行病学数据,以协助决策HCV筛检等公共卫生问题,降低丙型肝炎全球发病率和病死率。     

Meta‐analysis of the association between anti‐HBc seropositivity and a poor prognosis of chronic HCV infection

Aim: The impact of serological HBsAg? and anti‐HBc+ on the prognosis of chronic hepatitis C virus (HCV) infection is unknown. We conducted a systematic review to analyze whether anti‐HBc positivity imposes any effect on the course of HCV‐related chronic liver disease. Methods: We retrieved references from online databases that included PubMed and EMBASE. Data were gathered with regard to demographic information, disease progression and prognosis, and the results of serological tests. The development of hepatocellular carcinoma (HCC) was the endpoint of follow‐up of all cohort studies. Results: Eighteen references were included in this study, of which four were cohort studies. Twelve studies were retrospective, observational and non‐interventional studies. According to our meta‐analysis, the rate of serological HBsAg? and anti‐HBc+ was higher among HCC patients compared with non‐HCC patients (odds ratio [OR], 1.55; 95% CI, 1.22–1.98). HCV patients that were anti‐HBc+ had a greater chance of developing HCC than their anti‐HBc? counterparts (OR, 2.15; 95% CI, 1.34–3.47). Conclusions: The serological status of HBsAg? and anti‐HBc+ appears to be correlated with a poor prognosis for chronic HCV infection. Though the general quality of these references was low, and multiple confounding factors existed, the likelihood of a poorer outcome of HCV patients that are positive for anti‐HBc should be considered by their physicians.     

The epidemiologic feature of HCV prevalence in Fujian

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.     

HBV/HCV重叠感染的研究进展

HBV是一种嗜肝DNA病毒,HBV DNA和HBV特异P蛋白由核壳包裹成为核心颗粒,再由脂蛋白外膜包裹成完整的病毒颗粒。HCV是黄病毒科病毒,为单股正链RNA。HBV和HCV均由肠道外途径传播,2种病毒常可由相同途径发生感染。归纳了HBV/HCV重叠感染的发病机制、与隐匿性HBV感染和肝细胞癌以及器官移植、HBV疫苗之间的关系,同时介绍了重叠感染的治疗。指出存在于患者体内的HBV和HCV在病毒学方面相互干扰,在病变方面相互叠加。     

Evaluation of clinical usefulness of second‐generation HCV core antigen assay: comparison with COBAS AMPLICOR HCV MONITOR assay version 2.0

Abstract: Background: Hepatitis C virus (HCV) is an important etiologic agent for chronic liver diseases. Methods: The aim of this study was to evaluate the clinical usefulness of second‐generation HCV core antigen assay by comparing the results of the assay with those of the COBAS AMPLICOR HCV MONITOR version 2.0 (COBAS v2.0). Results: HCV core antigen was detectable by this assay in 142/149 (95.3%) of serotype 1 (3821±322 fmol/l; mean±SD), in 56/58 (96.6%) of serotype 2 (2589±449 fmol/l), and in 6/6 (100%) of serotypes 1+2 (1240±548 fmol/l). The HCV core antigen levels measured by this assay correlated well with the HCV RNA levels by COBAS v2.0 (r=0.848, P<0.0001). In relation to the outcome of interferon monotherapy, the pretreatment HCV core antigen levels of sustained and non‐sustained virological responders were 659±189 and 4904±376 fmol/l in serotype 1, 1993±740 and 3145±519 fmol/l in serotype 2. The cutoff values with the best accuracy for HCV core Ag levels to discriminate between sustained and non‐sustained virological response were 699 fmol/l for serotype 1 and 292 fmol/l for serotype 2, respectively, by receiver operating characteristic curve analysis. Conclusion: This new assay was considered to be useful in evaluating the HCV levels in patients with chronic hepatitis C.     

Efficacy of 12 or 18 weeks of elbasvir plus grazoprevir with ribavirin in treatment‐naïve,noncirrhotic HCV genotype 3‐infected patients

Elbasvir (EBR; HCV NS5A inhibitor) and grazoprevir (GZR; HCV NS3/4A protease inhibitor) are approved as a fixed‐dose combination to treat patients chronically infected with HCV genotypes 1 and 4. During the development programme and supported by in vitro potency, the efficacy of EBR+GZR was assessed in HCV GT3‐infected patients. This study's aim was to determine the efficacy and tolerability of 12 or 18 weeks of EBR+GZR with ribavirin (RBV) in treatment‐naïve, noncirrhotic HCV GT3‐infected patients. Randomized patients received open‐label EBR (50 mg once daily) + GZR (100 mg once daily) + RBV. The primary efficacy objective was to evaluate the sustained virologic response rates 12 weeks after the end of all study therapy (SVR12). SVR12 rates (95% confidence interval) were 45.0% (23.1, 68.5) and 57.1% (34.0, 78.2) after treatment with EBR+GZR+RBV for 12 weeks or 18 weeks, respectively. On‐treatment virologic failure was observed in 41% (17 of 41) of patients. At virologic failure, resistance‐associated substitutions (RASs) with a >five‐fold shift in potency occurred in the NS3 region in six (35%) patients and in the NS5A region in 16 (94%) patients. The most common RAS at virologic failure was Y93H in NS5A which was identified in 13 of 17 (76%) patients. The efficacy of EBR+GZR+RBV was suboptimal in HCV GT3‐infected patients due to a high rate of on‐treatment virologic failure and treatment‐emergent RASs which demonstrates an inadequate barrier to the development of GT3 resistance. However, rapid viral clearance demonstrated the antiviral activity of EBR+GZR+RBV in GT3‐infected patients.clinicaltrials.gov: NCT01717326.     

A novel immunocompetent rat model of HCV infection and hepatitis

BACKGROUND & AIMS: Hepatitis C virus (HCV) infects millions of people worldwide. Therapy is limited, and treatment does not produce a sustained response in the majority of patients. Development of new agents has been hampered by the lack of a convenient animal model. The aim of this study was to determine whether an immunocompetent rat, tolerized and transplanted with a human hepatoma cell line (Huh 7 cells), could be used to sustain an HCV infection. METHODS: Fetal rats were tolerized in utero with 10(5) Huh 7 cells. One day after birth, rats were transplanted with 5 x 10(6) Huh 7 cells and, a week later, inoculated with HCV, genotype 1. RESULTS: In tolerized, transplanted, and HCV-infected rats, Huh 7 cells were found in the liver, and HCV viral replication was detected by the presence of negative strand HCV RNA. HCV levels in serum were measured at 11,000 copies/mL at week 4, peaked at 22,500 copies/mL by week 12. In tolerized, transplanted, inoculated rats, but not controls, serum alanine aminotransferase (ALT) values increased to 60 IU/L by week 4 and reached a peak of approximately 120 IU/L by week 13. Histology showed foci of mononuclear infiltrates in portal and central regions. CONCLUSIONS: HCV-inoculated immunocompetent rats tolerized and transplanted with Huh 7 cells support HCV gene expression, viral replication, and develop biochemical and histologic evidence of hepatitis.     

慢性丙型肝炎病毒感染者外周血淋巴细胞增殖反应

目的　观察慢性丙型肝炎患者外周血淋巴细胞对丙型肝炎病毒（ＨＣＶ） 抗原刺激的增殖反应．方法　外周血单个核细胞（ＰＢＭＣ） 与ＨＣＶ 抗原ｃ２２ 、ｃ３３ 、ｃ１００ － ３ 、ＮＳ５ 和植物血凝素（ＰＨＡ） 分别共同孵育,加入胸腺嘧啶核苷（３ ＨＴｄＲ） ,然后收集细胞于液闪仪测定每分钟脉冲数（ｃｐｍ） ．结果　根据对不同ＨＣＶ 抗原的淋巴细胞增殖反应发现,以ｃ２２免疫原性最强,ｃ１００ － ３ 次之：淋巴细胞激活与ＨＣＶ 基因型关系不大;健康对照和慢性乙型肝炎患者对各ＨＣＶ 抗原未能显示有效的淋巴细胞增殖反应;与健康对照比较,慢性丙型肝炎和乙型肝炎患者对ＰＨＡ 刺激的淋巴细胞增殖反应降低．结论　ＨＣＶ 抗原ｃ２２ 免疫原性最强,丙型肝炎患者对ＨＣＶ 抗原的淋巴细胞增殖反应系特异性;慢性丙型肝炎和乙型肝炎患者存在抑制的细胞免疫应答．     

HCV对HIV/HCV共感染患者病情进展的影响

目的探讨HCV对HIV/HCV共感染病情进展的影响。方法研究对象为2012年8月到北京佑安医院随访的HIV/HCV共感染者29例及HIV单独感染者20例。两组患者年龄、性别及HIV感染时间及感染方式、感染的HIV病毒亚型均具有可比性。外周血生化指标检测并采用瞬时弹性扫描仪FibroScan评估肝脏功能及纤维化程度,运用流式细胞技术检测外周血CD4+T、CD8+T细胞绝对计数。两组计量资料比较采用t检验,计数资料比较采用χ2检验。结果 HIV/HCV共感染组ALT、AST及TBil水平分别为(76.16±81.25)U/L、(87.66±71.32)U/L、(14.21±9.56)μmol/L,明显高于HIV单独感染组[(27.74±20.63)U/L、(45.65±16.95)U/L、(10.26±3.22)μmol/L],差异具有统计学意义(P值分别为0.004、0.005及0.046)。与HIV单独感染组相比,HIV/HCV共感染组Stiffness指数有升高的趋势,但差异无统计学意义(t=1.889,P=0.080)。HIV/HCV共感染组HIV病毒载量(拷贝/ml)的对数值为3.66±0.97明显高于HIV单独感染组的3.02±0.90(t=2.251,P=0.030)。HIV/HCV共感染组、HIV单独感染组CD4+T淋巴细胞计数及CD4+T/CD8+T细胞比例分别为(374.25±185.48)/μl及(0.33±0.17)、(496.45±230.98)/μl及(0.46±0.27),HIV/HCV共感染组CD4+T淋巴细胞计数及CD4+T/CD8+T细胞比例低于HIV单独感染组,差异具有统计学意义,P值分别为0.048、0.043。共感染组艾滋病发病率(27.59%)呈现出较HIV单独感染组(5%)高的趋势(P=0.063)。结论HCV促进HIV/HCV共感染者肝脏损伤,增强HIV复制,加剧机体免疫功能损伤,HCV可能加速HIV/HCV共感染者的病情进展。