程序性细胞死亡受体1基因多态性与慢性HCV感染及抗病毒疗效的关系

目的探明程序性细胞死亡受体1(PD-1)基因单核苷酸多态性(SNP)与慢性HCV感染及IFN联合利巴韦林抗HCV疗效的关系。方法选择2010年10月-2012年10月在河北省7家医院住院的慢性丙型肝炎(CHC)患者228例,采用IFN联合利巴韦林个体化方案进行抗病毒治疗,健康体检者81例作为对照组。Taq Man探针法检测PD-1基因多态性,分析患者及对照组PD-1.1及PD-1.3位点等位基因及基因型分布差异,并分析PD-1.1及PD-1.3位点SNP与抗HCV疗效的关系。计数资料组间比较采用χ~2检验。结果 CHC患者组PD-1.1位点T等位基因、TT基因型携带率显著高于对照组(52.41%vs 43.21%,χ~2=4.059,P=0.044;28.51%vs 14.81%,χ~2=6.469,P=0.039);PD-1.1位点等位基因型分布在是否获得完全早期病毒学应答、是否获得持续病毒学应答的患者间差异均无统计学意义(P值均0.05)。PD-1.3位点在CHC患者及对照组均为CC型。结论 PD-1.1位点T等位基因可能与HCV慢性感染有关,TT基因型携带者HCV慢性感染风险可能较高。PD-1.1位点基因多态性与抗HCV治疗病毒学应答无明确关系。     

白细胞介素28B基因多态性与慢性HBV、HCV感染的相关性

HBV、HCV感染具有慢性化的流行特点。白细胞介素(IL)28B基因多态性与HBV、HCV感染慢性化及干扰素(IFN)抗病毒疗效具有相关性。简述了IL-28B生物学功能及特点,述评了IL-28B基因多态性与HCV感染的相关性,并归纳了目前发现的IL-28B基因多态性与HBV感染的相关性的众多研究报道。分析表明,IL-28B基因多态性与丙型肝炎病程转归及IFN抗病毒疗效的相关性研究报道较为一致;而IL-28B基因多态性与乙型肝炎病程转归,HBV感染后肝硬化、肝癌及IFN抗病毒疗效的相关性研究,各方学者均有不同的见解,尚需进一步的研究。     

慢性乙型肝炎重叠HCV,HDV感染80例分析

近几年来，由于免疫学和分子生物学技术的进展，病毒性肝炎病原学诊断逐步得以明确，临床上诊断肝炎病毒混合感染和重叠感染的报道增加．为探讨本地区慢性乙型肝炎重叠丙型肝炎病毒（ＨＣＶ）、丁型肝炎病毒（ＨＤＶ）感染的情况及其临床特点，笔者对我院１９９５０１／１９９８１２所收治的１４５１例各型肝炎中的２４６例慢性肝炎患者的血清标志物检测结果进行分析，其中对８０例慢性乙型肝炎重叠ＨＣＶ，ＨＤＶ感染的患者进行系统的临床观察，并与单纯慢性乙型肝炎８０例进行对比，现将结果报道如下．１　材料和方法１．１　材料　本…     

无干扰素抗HCV方案的研究进展

当前,全球约有1.5亿慢性HCV感染者,其中20%会进展为肝硬化并最终死于终末期肝病和肝癌。干扰素(IFN)长期作为慢性丙型肝炎治疗的基石,在维持持续病毒学应答以及阻止病情进展方面有重要作用,但其疗效有限、不良反应多。近年来,直接抗病毒药物(DAAs)呈现出良好的疗效,在DAAs的基础上,介绍了无IFN抗HCV方案的最新研究进展,认为随着DAAs的出现,无IFN抗HCV方案发展迅速,前景较好。     

滤泡性辅助性T细胞与HCV感染的相关性

目的检测慢性HCV感染者外周血CD4＋T细胞中滤泡性辅助性T细胞（Tfh）所占比例,ICOS及负性调控因子PD-1、Tim-3在Tfh细胞上的表达。方法以31例HCV感染者、9例HCV感染自愈者（SR-HCV患者）及12例健康志愿者作为研究对象,应用流式细胞术分析外周血中CD4＋CXCR5＋Tfh细胞在CD4＋T细胞中所占比率,同时检测其ICOS、PD-1及Tim-3分子表达,通过酶联免疫吸附法测定血浆中白细胞介素（IL）21及HCV抗体水平,实时定量PCR检测HCV RNA滴度;多组数据比较采用单因素方差分析,双变量之间相关性采用Spearman秩相关分析。结果与健康对照组相比,HCV感染者及自愈者外周血CD4＋T细胞比率升高（P〈0.05）;HCV感染者CD4＋CXCR5＋Tfh细胞比率高于自愈及健康对照（P〈0.05）;HCV感染及自愈者CD4＋CX-CR5＋Tfh细胞ICOS、PD-1、Tim-3显著高于健康对照（P〈0.05）;血清IL-21水平HCV感染者与健康对照无统计学差异（P〉0.05）;HCV感染者HCV RNA载量与Tfh细胞比例呈负相关。结论 CD4＋CXCR5＋Tfh可能参与了抗HCV感染免疫应答。     

直接抗病毒药物时代特殊人群HCV感染的管理和治疗

慢性丙型肝炎呈全球性流行,不同性别、年龄、种族、民族人群均易感染HCV。分别阐述了儿童丙型肝炎患者、合并肾损伤患者、肝移植患者、合并肝硬化患者、合并HIV感染者、急性丙型肝炎患者等不同特殊人群HCV感染的管理方法和个体化治疗方案。     

HCV细胞培养系统及其在中草药提取物抗HCV研究中的应用

应用中草药治疗丙型肝炎报道较多,然而这些研究大多采用中药复方制剂进行临床治疗,疗效局限。由于一种中药含有多种活性物质,某些物质之间在体内甚至有相互拮抗的作用,因此,对于治疗结果的作用机理很难阐述清楚。简述了HCV假病毒、复制子和全长细胞培养系统的研究现状,并对应用HCV RNA细胞模型研究中药单体或有效成分进行抗HCV实验研究的相关进展进行了综述,为中药治疗丙型肝炎研究提供新思路。     

血液透析患者动脉粥样硬化与慢性炎症及营养不良的关系

心血管疾病是尿毒症患者的首位死亡原因，而慢性炎症状态、营养不良在尿毒症患者中普遍存在。我们对45例维持性血液透析患者进行了动脉粥样硬化(AS)、炎症指标的测定和营养状况的评估，以探讨尿毒症患者心血管疾病与慢性炎症及营养不良的关系。     

HCV感染者抗病毒治疗前后免疫状态的变化

HCV感染是全球性的公共问题。目前我国主要的抗HCV治疗方案是聚乙二醇干扰素联合利巴韦林,但是该方案的持续病毒学应答率并不理想;直接抗病毒药物(DAA)的出现,在治疗丙型肝炎患者中取得了显著的疗效。简述了抗HCV治疗前后机体免疫状态的变化情况,从固有免疫、适应性免疫以及细胞因子和趋化因子三个方面进行了介绍。分析表明,HCV患者机体的免疫调控十分复杂,不同的研究结果不尽相同。但是总体来看,经过抗病毒治疗后,NK细胞表面受体表达以及其功能有恢复的趋势,甚至可以恢复至正常化;IFN的治疗并不能恢复病毒特异性CD8+T淋巴细胞的功能,而DAA治疗前后细胞毒性T淋巴细胞的变化规律尚未阐明;DAA对细胞因子以及趋化因子的长期的影响仍需要进一步研究。     

慢性丙型肝炎合并自身免疫性肝炎的研究进展

有关慢性丙型肝炎合并自身免疫性肝炎的研究不多,到目前为止,临床针对该类疾病的诊疗仍面临诸多困难。虽然相关的文献给出了一些建议,但目前没有标准指南来指导其诊断和治疗,临床医师常常需根据个人的临床经验治疗这部分患者。就报道的慢性丙型肝炎合并自身免疫性肝炎相关文献进行总结,旨在为临床医师遇到这类临床问题提供帮助。     

Association between chronic hepatitis C virus infection and low muscle mass in US adults

Given that low muscle mass can lead to worse health outcomes in patients with chronic infections, we assessed whether chronic hepatitis C virus (HCV) infection was associated with low muscle mass among US adults. We performed a cross‐sectional study of the National Health Examination and Nutrition Study (1999–2010). Chronic HCV‐infected patients had detectable HCV RNA. Low muscle mass was defined as <10th percentile for mid‐upper arm circumference (MUAC). Multivariable logistic regression was used to determine adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of low muscle mass associated with chronic HCV. Among 18 513 adults, chronic HCV‐infected patients (n = 303) had a higher prevalence of low muscle mass than uninfected persons (13.8% vs 6.7%; aOR, 2.22; 95% CI, 1.39–3.56), and this association remained when analyses were repeated among persons without significant liver fibrosis (aOR, 2.12; 95% CI, 1.30–3.47). This study demonstrates that chronic HCV infection is associated with low muscle mass, as assessed by MUAC measurements, even in the absence of advanced liver disease.     

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.     

Association between dementia and hepatitis B and C virus infection

Several viral infections are known to increase the risk of dementia through brain cell damage and systemic infection. The association between hepatitis B and C virus (HBV and HCV) infections and dementia was evaluated using a national sample cohort from South Korea. Using the national cohort study from the Korean National Health Insurance Service, we extracted data for patients with HBV or HCV infection and for matched control participants. The controls were matched to the patients according to age, sex, income, region of residence, and past medical histories. The incidence of HCV infection was higher in the dementia group (1.0% [113/11,228]) than in the control group (0.8% [364/44,912], P = .043). However, there was no difference in the incidence of HBV infection in the dementia and control groups. The adjusted odds ratio (OR) for HCV infection was 1.25 (95% confidence interval [CI] = 1.01–1.54, P = .043) in the dementia group. According to the subgroup analysis by sex, the adjusted ORs for HCV infection were 1.04 (95% CI = 072–1.49, P = .851) in men and 1.38 (95% CI = 1.06–1.79, P = .016) in women. We concluded that the incidence of HCV infection was higher (with a higher OR) in women with dementia than in matched control participants in South Korea.     

Association of hepatitis C infection and acute coronary syndrome: A case-control study

Infections with hepatitis C virus (HCV) represent a substantial national and international public health burden. HCV has been associated with numerous extrahepatic conditions and can lead to metabolic derangements that are associated with atherosclerosis and cardiovascular disease. We investigated whether HCV infection is associated with an increased number of acute coronary syndrome (ACS) events among hospitalized patients in an inner-city tertiary hospital.We performed a matched (age, sex, and race/ethnicity) case-control study on patients at least 18 years old admitted to inpatient medical and cardiac services at the University of Maryland Medical Center from 2015 through 2018. The primary outcome was ACS and the primary exposure was HCV infection. Covariates of interest included: alcohol use, tobacco use, illicit drug use, hypertension, diabetes mellitus, human immunodeficiency virus infection, body mass index, dyslipidemia, and family history of coronary heart disease. Covariates with significant associations with both exposure and outcome in bivariate analyses were included in the multivariable analyses of the final adjusted model.There were 1555 cases and 3110 controls included in the final sample. Almost 2% of cases and 2.4% of controls were HCV infected. In adjusted models, there was no significant association found between experiencing an ACS event in those with HCV infection compared to those without HCV infection (odds ratio 0.71, 95% confidence interval 0.45–1.11).We found no significant association between HCV infection and ACS in our study population. However, given the mixed existing literature, the association between HCV and ACS warrants further investigation in future prospective cohort and/or interventional studies.     

白细胞介素与HBV感染的关系

HBV进入宿主体内后,多种免疫细胞及其分泌的细胞因子参与了机体的免疫应答。白细胞介素是一类对免疫应答各个环节都有重要调节作用的细胞因子,介绍了几种在乙型肝炎发生、发展及转归中作用较大的白细胞介素及其与HBV感染的相关性,分析表明对白细胞介素免疫调节机制的深入研究可为各种类型乙型肝炎的诊断和治疗提供新的依据和方法。     

CXCL10血清水平及单核苷酸多态性与慢性丙型肝炎患者发生甲状腺功能异常的相关性研究

目的：研究CXCL10血清水平及单核苷酸多态性（single nucleotide polymorphisms, SNPs）与未接受干扰素（interferon, IFN）α治疗的慢性丙型肝炎（chronic hepatitis C, CHC）患者发生甲状腺功能异常的相关性。方法在前期已经进行甲状腺功能检测的312例未接受IFNα治疗的CHC患者中,筛选出与发生甲状腺功能异常的39例患者（甲状腺功能异常组）匹配的甲状腺功能正常患者39例（甲状腺功能正常组）。采用ELISA分别检测2组血清CXCL10水平;采用QIAamp DNA Blood Mini Kit提取2组患者基因组DNA,分别对CXCL10-135和CXCL10-1447基因片段进行PCR扩增和直接序列测定,应用BioEdit软件对样本序列进行分析。结果甲状腺功能异常组和正常组的血清CXCL10水平分别为（472.11±274.91） pg/ml和（516.39±272.40） pg/ml,2组比较差异无统计学意义。甲状腺功能异常组CXCL10-135的G、T等位基因频率分别为95.0%和5.0%,甲状腺功能正常组的G、T等位基因频率分别为96.2%和3.8%,2组比较差异无统计学意义。甲状腺功能异常组CXCL10-1447的A、G等位基因频率分别为41.7%和58.3%,甲状腺功能正常组的A、G等位基因频率分别为47.4%和52.6%,2组比较差异无统计学意义。甲状腺功能异常组CXCL10-135的GG、GT、TT基因型频率分别为93.4%、3.3%和3.3%,甲状腺功能正常组的GG、GT、TT基因型频率分别为92.3%、7.7%和0%,2组比较差异无统计学意义。甲状腺功能异常组CXCL10-1447的AA、AG、GG基因型频率分别为16.7%、50.0%和33.3%,甲状腺功能正常组的AA、AG、GG基因型频率分别为20.5%、53.9%和25.6%,2组比较差异无统计学意义。结论未接受IFNα治疗的CHC患者发生甲状腺功能异常与CXCL10血清水平和基因多态性位点-135、-1447无相关性。     

New infection with heterotypic hepatitis C virus in a patient with long-term hepatitis C virus eradication

BACKGROUND: Experimental hepatitis C virus infection in chimpanzees has shown that natural hepatitis C virus infection does not induce protective immunity and reinfection can occur in seroconverted animals. AIM: To study the clinical, virological and histological outcome of a new infection sustained by a different hepatitis C virus strain after a primary infection with eradication of the original virus. PATIENTS AND METHODS: A young Italian man with chronic hepatitis C virus type 4 hepatitis was treated with Interferon therapy and achieved a sustained biochemical and virological response. After long follow-up, an asymptomatic flare-up of alanine transaminase occurred. This alanine transaminase increase was associated with serum hepatitis C virus RNA positivity and a low viral load, and the infecting hepatitis C virus genotype was type 3. The clinical and virological course of this new infection is described. RESULTS AND CONCLUSIONS: This report shows that there is no protective immunity against hepatitis C virus type 3 after infection by hepatitis C virus type 4 strain.     

Association between human leukocytes antigen alleles and chronic hepatitis C virus infection in the Korean population.

BACKGROUND/AIM: Recent data have shown that the clinical outcome of hepatitis C virus (HCV) infection may be influenced by the host genetic factor. The aim of this study was to investigate whether particular human leukocytes antigen (HLA) molecules are associated with the susceptibility to HCV infection in the Korean population. METHODS: One hundred and thirty-seven patients with chronic HCV infection and 206 normal individuals were examined for HLA class I and II molecules. RESULTS: In class I antigens, the frequencies of HLA-A3 (relative risk (RR)=3.5, P<0.04), HLA-B35 (RR=2.0, P<0.03), and HLA-B46 (RR=2.5, P<0.02) significantly increased in chronic HCV carriers compared with the controls. The frequencies of DRB1*0803, DQB1*0601 and DQB1*0604 were significantly higher in chronic HCV carriers than in controls (RR=2.5, P<0.005; RR=1.8, P<0.05; RR=1.9, P<0.04, respectively). On the other hand, the frequencies of DRB1*0301, DQA1*0501 and DQB1*0201 were significantly lower in chronic HCV carriers than in normal controls (RR=0.2, P<0.03; RR=0.4, P<0.004; RR=0.5, P<0.02, respectively). The haplotype DRB1*0803-DQB1*0601 significantly increased (RR=2.5, P<0.02) while the DQA1*0501-DQB1*0201 significantly decreased (RR=0.2, P<0.03) in chronic HCV carriers compared with normal controls. In stratification analysis to investigate the interrelationships among the associated alleles, DRB1*0803 and DQB1*0601 were associated with HLA-B46, particularly in patients with chronic HCV carriers. CONCLUSIONS: These results suggest that particular HLA alleles may have an influence on chronic HCV infection as a host genetic factor in the Korean population.