剪切HCV RNA的HDV核酶的设计及活性测定

目的：探讨丁型肝炎病毒（Hepatitis D virus,HDV）核酶用于抗丙型肝炎病毒（Hepatitis C virus,HCV）基因治疗的可能性。方法：以HDV基因组核酶的假结样结构为基础,优化其茎IV区,改建基底物结合区,获得3种针对HCV RNA的HDV核酶RzC1、RzC2和RzC3。体外转录获取含HCV RNA5‘－非编码区（5‘-noncoding region,5‘-NCR）及部分C区在内的底物RNA（HCV RNA 5‘－NCR－C）,并进行5‘端放射性标记。在pH7.5、37℃、Mg^2 20mmol/L和去离子甲酰胺2.5mol/L等条件下,将核酶和底物按摩尔比100：1混合,在不同的时间点观察剪切百分率。结论：RzC1、RzC2对底物的剪切百分率随时间延长而递增,90min分别达24.9％、20.3％;未观察到RzC3有剪切活性。结论：经过结构构优化的HDV基因组核酶在合适的位点能够剪切异源性RNA分子HCV RNA。     

丙型肝炎病毒标志物测定的临床应用

目的 :探讨丙型肝炎病毒 (HCV)感染者血清及初乳中该病毒标志物存在状况。　方法 :对 2 44份 HCV感染者、33份对照血清和 35份 HCV特异性 Ig G抗体阳性的产妇、41份健康产妇的初乳进行 HCV四种标志物测定。抗HCV- Ig G、Ig M和 GOR抗体采用间接 EL ISA法 ,HCV C33抗原采用双抗体夹心 EL ISA法。　结果 :抗 HCV- Ig G、抗 HCV- Ig M、HCV C33和抗 GOR抗体四种标志物在慢性活动性丙型肝炎组检出率最高 ,分别为 10 0 .0 %、85 .7%、46 .4%和 6 4.3% ;急性输血后丙型肝炎组检出率为 6 6 .7%、10 0 .0 %、2 2 .9%和 42 .9% ;慢性稳定性丙型肝炎组为 94.1%、2 6 .5 %、17.6 %和 5 2 .9% ;血透患者组为 6 2 .6 %、31.3%、4.8%和 45 .6 %。血清抗 HCV Ig G阳性组初乳为 17.1%、2 .9%、8.5 %和 37.1%。血清和初乳对照组除 1例献血员血清抗 HCV- Ig G阳性外 ,其余均为阴性结果。　结论 :除抗 HCV- Ig G外 ,抗 HCV- Ig M、HCV C33和 GOR抗体三种标志物在 HCV感染的相关疾病组中 ,有一定的阳性检出率 ,均可作为 HCV感染的标志 ,可用于 HCV感染后的实验室诊断。     

Proteomics reveals a global phenotypic shift of NK cells in HCV patients treated with direct-acting antivirals

Chronic hepatitis C virus (HCV) infections compromise natural killer (NK)-cell immunity. Direct-acting antivirals (DAA) effectively eliminate HCV, but the long-term effects on NK cells in cured patients are debated. We conducted a proteomic study on CD56⁺ NK cells of chronic HCV-infected patients before and 1 year after DAA therapy. Donor-variation was observed in NK-cell proteomes of HCV-infected patients, with 46 dysregulated proteins restored after DAA therapy. However, 30% of the CD56⁺ NK-cell proteome remained altered 1 year post-therapy, indicating a phenotypic shift with low donor-variation. NK cells from virus-negative cured patients exhibited global regulation of RNA-processing and pathways related to “stimuli response”, “chemokine signaling”, and “cytotoxicity regulation”. Proteomics identified downregulation of vesicle transport components (CD107a, COPI/II complexes) and altered receptor expression profiles, indicating an inhibited NK-cell phenotype. Yet, activated NK cells from HCV patients before and after therapy effectively upregulated IFN-γ and recruited CD107a. Conversely, reduced surface expression levels of Tim-3 and 2B4 were observed before and after therapy. In conclusion, this study reveals long-term effects on the CD56⁺ NK-cell compartment in convalescent HCV patients 1 year after therapy, with limited abundance of vesicle transport complexes and surface receptors, associated with a responsive NK-cell phenotype.     

大剂量干扰素治疗慢性丙型肝炎50例临床观察

目的：探讨使用大剂量干扰素（ＩＦＮα）治疗慢性丙型肝炎（ＣＡＨ）的效果。方法：使用大剂量ＩＦＮα,每天６００万Ｕ,连续投药３周,以后每周３次间断投药２１周,共计２４周,治疗ＣＡＨ５０例。观察治疗前后血清ＨＣＶＲＮＡ与ＡＬＴ的变化,以此作为ＩＦＮ疗效的判定指标。结果：ＩＦＮ治疗ＣＡＨ有效率为６８％,停药６个月后有３４％复发。结论：ＩＦＮ的疗效与ＣＡＨ的基因亚型有关（Ⅲ型疗效显著,Ⅱ型较差）,与ＩＦＮ的剂量无明显关系。     

吸毒人群丙型肝炎病毒感染危险因素的研究

采用病例对照的研究方法,对广州市５３１名吸毒人员进行丙型肝炎病毒（ＨＣＶ）感染危险因素的调查,资料采用Ｌｏ－ｇｉｓｔｉｃ回归方法分析。结果表明：静脉吸毒（ＯＲ＝６．６８,Ｐ＜０．００１）,非固定婚外性伴侣（ＯＲ＝３．７１,Ｐ＜０．００１）,输液史（ＯＲ＝２．６４,Ｐ＜０．０１）和抗－ＨＢｃ阳性（ＯＲ＝１．７４,Ｐ＜０．０５）是ＨＣＶ感染独立的危险因素,而在性生活中使用避孕套（ＯＲ＝０．３７,Ｐ＜０．００５）是保护因素。提示广州市吸毒人群ＨＣＶ感染的主要途径是血液传播,同时性传播途径也起着重要的作用。     

延边农村地区朝鲜族HBV、HCV、HDV感染状况调查

为摸清延边农村地区朝鲜族人群乙、丙、丁型肝炎病毒(HBV、HCV、HDV)感染状况,用ELISA法对585名朝鲜族成年人进行了HBV、HCV和HDV感染标志物的检测.HBV、HCV标化感染率与HBsAg标化阳性率分别为50.91%、4.85%和8.57%,年龄组间差异无显著性.HBV、HCV双重感染率为2.56%,HBV与HCV的感染相关无显著性.42例HBsAg阳性者中HDV感染率4.76%.HBV感染模式有15种,其中以单项抗-HBs阳性多见,人群中占31.97%.表明人群中HBV、HCV和HDV感染的流行情况不同.     

Impact of hepatitis C virus infection on clinical features, quality of life and survival of patients with lymphoplasmacytoid lymphoma/immunocytoma

Background: The non-Hodgkins lymphoma (NHL) subgroup most frequentlyassociated with hepatitis C virus (HCV) infection is the lymphoplasmacytoidlymphoma/immunocytoma (Lp-Ic). We have assessed the impact of the infectionon the clinical features, quality of life and survival of HCV+ve Lp-Icpatients as compared to its impact in HCV–ve patients.Patients and methods: Seventy patients with Lp-Ic consecutively observedover a six-year period were studied. Clinical, virological andhistopathological features were recorded at diagnosis. Quality of life wasassessed using a scoring system including disease-related symptoms,performance status, working ability, hospital admissions and therapiesrequired.Results: Eighteen patients (26%) with HCV infection wereidentified. Significant differences between those patients and theHCV–ve group included number of symptomatic patients, Hb levels, serumprotein levels, entity of the IgM monoclonal component, number of patientswith cryoglobulins and with organ (liver, kidney) involvement, and entityand pattern of bone marrow infiltration. Survival rates were similar (P =0.8383), but the quality-of-life score was significantly worse for theHCV+ve patients (P = 0.002). All anti-HCV Ab+ve patients tested positive forHCV RNA; genotype 2ac was detected in a significant proportion of cases.Conclusions: This study confirms that HCV infection is present in aboutone-third of patients with Lp-Ic. HCV infection does not seem to affect theoverall survival of patients with Lp-Ic, but it affects the clinicalexpression of the disease, so that the overall quality of life of HCV+vepatients is significantly worse.     

广东地区婴肝患儿的HCV感染

目的探讨广东地区婴儿肝炎综合征中丙型肝炎病毒感染及其传播途径。方法采用酶联免疫吸附法（ELISA法）检测血清中丙型肝炎病毒（HCV）抗体，多聚酶链反应（PCR）检测血清中HCVRNA。结果90例婴肝中有11例HCV标志阳性，阳性率为12．2％（11／90），其中抗HCV以及HCVRNA均阳性4例，单项抗HCV阳性3例，单项HCVRNA阳性4例。母亲抗HCV阳性2例。结论HCV感染是广东地区婴儿肝炎综合征中一个不可忽视的病因，本组11例阳性患者的传播途径主要与输注血制品有关，其次为母婴传播。     

Hepatitis C virus infection and related liver disease in children of mothers with antibodies to the virus

Objective: To evaluate the clinical, biochemical, and virologic features associated with hepatitis C virus (HCV) infection acquired early in life from mothers with antibodies to HCV (anti-HCV).Study design: Multicenter prospective-retrospective study in Italian children.Patients: Two groups of children were investigated. Group 1 included 14 infants, born to mothers with anti-HCV but without human immunodeficiency virus infection, who became seropositive for HCV RNA during the first year of life and were thus considered infected. Group 2 included 16 children with chronic hepatitis C, aged 1 ½ to 14 years, whose mothers were the unique potential source of infection. Both groups were followed for 12 to 48 months.Methods: Alanine transaminase (ALT), anti-HCV, and HCV RNA were investigated by the polymerase chain reaction on entry to the study and during follow-up.Results: All children in group 1 had anti-HCV throughout follow-up, and all had ALT abnormalities, ranging from 1.5 to 10.5 times the normal value during the first 12 months. During further follow-up, 5 of 10 children had HCV RNA with abnormal ALT values, 3 had a return to normal of the ALT values but continued to have viremia, and 2 eventually had normal ALT values and clearance of HCV RNA. Of the 16 children in group 2, all were free of symptoms and 62% had only slight ALT elevations; 7 who underwent liver biopsy had histologic features of minimal or moderate hepatitis.Conclusions: HCV infection acquired early in life from mothers with anti-HCV is usually associated with biochemical features of liver damage during the first 12 months of life. Progression to chronicity seems to occur in the majority of cases, although HCV-associated liver disease is likely to be mild throughout infancy and childhood. (J Pediatr 1997;130:990-3)     

Factors associated with liver biopsy performance in HCV-HIV coinfected injecting drug users with HCV viremia: Results from a five-year longitudinal assessment

The last international consensus conference about hepatitis C virus (HCV) treatment emphasized the importance of treatment for persons coinfected with HCV and human immunodeficiency virus (HIV). As liver biopsy precedes treatment, we aimed to identify factors associated with the performance of liver biopsy among HIV-HCV coinfected drug users during a 5-year follow-up to study their access to HCV treatment. Of the 296 patients followed in the HIV hospital departments of Nice and Marseilles and with retrievable records about HCV diagnosis and care, 166 were eligible for analysis having had detectable HCV RNA at least once during the study period. Overall, 45.2% of patients underwent liver biopsy during follow-up. Using proportional hazard models, predictors of having had a liver biopsy were high social support, complete abstinence from drug injection, and lack of immunosuppression as well as male gender, no history of multiple incarcerations, more recent onset of drug use, and an increase of liver enzyme levels. These results suggest that specific efforts should be devoted to HIV-HCV coinfected drug users to assist with stabilizing these patients to optimize their access to HCV care whenever possible. The MANIF 2000 study group includes C. Boirot, A. D. Bouhnik, M. P. Carrieri, J. P. Cassuto, M. Chesney, P. Dellamonica, P. Dujardin, S. Duran, J. G. Fuzibet, H. Gallais, J. A. Gastaut, G. Lepeu, D. A. Loundou, C. Marimoutou, D. Mechali, J. P. Moatti, J. Moreau, M. Nègre, Y. Obadia, I. Poizot-Martin, C. Pradier, D. Rey, C. Rouzioux, A. Sobel, B. Spire, F. Trémolières, and D. Vlahov.