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Hepatitis C virus: Virology, diagnosis and management ofantiviral therapy 被引量:17
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作者 Stéphane Chevaliez Jean-Michel Pawlotsky 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第17期2461-2466,共6页
Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin.... Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti- HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy. 展开更多
关键词 hepatitis c virus serological tests hepatitisc virus genotype hcv RNA quantification Interferon alpha Ri-bavirin-
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Detection of hepatitis C virus core antigen for early diagnosis of hepatitis C virus infection in plasma donor in China 被引量:10
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作者 He-Qiu Zhang Shao-Bo Li +3 位作者 Guo-Hua Wang Kun Chen Xiao-Guo Song Xiao-Yan Feng 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第19期2738-2742,共5页
AIM: To evaluate the efficacy of a new hepatitis C virus (HCV) core antigen assay developed in China. METHODS: After the determination of HCV infection, 49 serial samples were selected from II regular plasma donor... AIM: To evaluate the efficacy of a new hepatitis C virus (HCV) core antigen assay developed in China. METHODS: After the determination of HCV infection, 49 serial samples were selected from II regular plasma donors in 5 different plasma stations. To compare the performance of HCV core antigen detection and HCV PCR, these samples were genotyped, and each specimen was analyzed by ELISA for the detection of HCV core antigen and by qualitative HCV PCR. RESULTS: Among all of the sequential samples, the original 23 specimens were HCV RNA-negative, and 36 samples were HCV RNA-positive. Twenty-seven samples (75%) were HCV core antigen-positive from these HCV RNA-positive specimens. Conversely, 27 samples (93.2%) were found HCV RNA-positive in HCV core antigen- positive samples. Intervals between HCV RNA and HCV core antigen-positive, as well as between HCV core antigen-positive and HCV antibody-positive were 36.0 and 32.8 d, respectively. CONCLUSION: This HCV core antigen assay, developed in China, is able to detect much of anti-HCV-negative, HCV RNA-positive preseroconversion window period (PWP) plasma donations. 展开更多
关键词 hepatitis c virus core antigen ANTI-hcv hcv RNA
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Coinfection of hepatitis B and hepatitis C virus in HIV-infectedpatients in south India 被引量:6
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作者 Shanmugam Saravanan Vijayakumar Velu +5 位作者 Nagalingeswaran Kumarasamy Subhadra Nandakumar Kailapuri Gangatharan Murugavel Pachamuthu Balakrishnan Solomon Suniti Sadras Panchatcharam Thyagarajan 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第37期5015-5020,共6页
AIM: To screen for the co-infection of hepatitis B (HBV) and hepatitis C virus (HCV) in human immunodeficiency virus (HIV) infected patients in southern India. METHODS: Five hundred consecutive HIV infected patients w... AIM: To screen for the co-infection of hepatitis B (HBV) and hepatitis C virus (HCV) in human immunodeficiency virus (HIV) infected patients in southern India. METHODS: Five hundred consecutive HIV infected patients were screened for Hepatitis B Virus (HBsAg and HBV-DNA) and Hepatitis C virus (anti-HCV and HCV-RNA) using commercially available ELISA kits; HBsAg, HBeAg/ anti-HBe (Biorad laboratories, USA) and anti-HCV (Murex Diagnostics, UK). The HBV-DNA PCR was performed to detect the surface antigen region (pre S-S). HCV-RNA was detected by RT-PCR for the detection of the constant 5' putative non-coding region of HCV. RESULTS: HBV co-infection was detected in 45/500 (9%) patients and HCV co-infection in 11/500 (2.2%) subjects. Among the 45 co-infected patients only 40 patients could be studied, where the detection rates of HBe was 55% (22/40), antiHBe was 45% (18/40) and HBV-DNA was 56% (23/40). Among 11 HCV co-infected subjects, 6 (54.5%) were anti-HCV and HCV RNA positive, while 3 (27.2%) were positive for anti-HCV alone and 2 (18%) were positive for HCV RNA alone. CONCLUSION: Since the principal routes for HIV transmission are similar to that followed by the hepatotropic viruses, as a consequence, infections with HBV and HCV are expected in HIV infected patients. Therefore, it would be advisable to screen for these viruses in all the HIV infected individuals and their sexual partners at the earliest. 展开更多
关键词 hepatitis B virus hepatitis c virus Humanimmunodeficiency virus cO-INFEcTION hepatotrophicviruses HBV and hcv India HBV and hcv and HIV
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Interleukin-12 as a Genetic Adjuvant Enhances Hepatitis C Virus NS3 DNA Vaccine Immunogenicity 被引量:5
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作者 Malihe Naderi Atefeh Saeedi +4 位作者 Abdolvahab Moradi Mishar Kleshadi Mohammad Reza Zolfaghari Ali Gorji Amir Ghaemi 《Virologica Sinica》 SCIE CAS CSCD 2013年第3期167-173,共7页
Hepatitis C virus (HCV) chronic infection is a worldwide health problem, and numerous efforts have been invested to develop novel vaccines. An efficient vaccine requires broad immune response induction against viral p... Hepatitis C virus (HCV) chronic infection is a worldwide health problem, and numerous efforts have been invested to develop novel vaccines. An efficient vaccine requires broad immune response induction against viral proteins. To achieve this goal, we constructed a DNA vaccine expressing nonstructural 3 (NS3) gene (pcDNA3.1-HCV-NS3) and assessed the immune response in C57BL/6 mice. In this study, the NS3 gene was amplified with a nested-reverse transcriptase-polymerase chain reaction (RT-PCR) method using sera of HCV-infected patients with genotype 1a. The resulting NS3 gene was subcloned into a pcDNA3.1 eukaryotic expression vector, and gene expression was detected by western blot. The resultant DNA vaccine was co-administered with interleukin-12 (IL-12) as an adjuvant to female C57BL/6 mice. After the final immunizations, lymphocyte proliferation, cytotoxicity, and cytokine levels were assessed to measure immune responses. Our data suggest that co-administration of HCV NS3 DNA vaccine with IL-12 induces production of significant levels of both IL-4 and interferon (IFN)-γ (p<0.05). Cytotoxicity and lymphocyte proliferation responses of vaccinated mice were significantly increased compared to control (p<0.05). Collectively, our results demonstrated that co-administration of HCV NS3 and IL-12 displayed strong immunogenicity in a murine model. 展开更多
关键词 hepatitis c virus hcv NS3 INTERLEUKIN-12 DNA vaccine
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Occult persistence and lymphotropism of hepatitis C virus infection 被引量:3
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作者 Tram NQ Pham Tomasz I Michalak 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第18期2789-2793,共5页
Recent discovery of occult hepatitis C virus (HCV) infection persisting after spontaneous or antiviral therapy-induced resolution of hepatitis C was made possible by the introduction of nucleic acid amplification assa... Recent discovery of occult hepatitis C virus (HCV) infection persisting after spontaneous or antiviral therapy-induced resolution of hepatitis C was made possible by the introduction of nucleic acid amplification assays capable of detecting HCV RNA at sensitivities superseding those offered by clinical tests. Although individuals with this seemingly silent HCV infection are usually anti-HCV antibody reactive and have normal liver function tests, occult HCV infection has also been reported in anti-HCV-negative individuals with persistently elevated liver enzymes of unknown etiology. Studies have shown that HCV RNA can persist for years in serum, lymphomononuclear cells and liver in the absence of clinical symptoms, although histological evidence of a mild inflammatory liver injury can be occasionally encountered. Furthermore, while HCV RNA can be detected in circulating lymphoid cells in approximately 30% of cases, a short-term culture under stimulatory conditions augments HCV replication in these cells allowing detection of virus in otherwise HCV-negative cases. HCV infects different immune cell subsets, including CD4+ and CD8+ T lymphocytes, B cells and monocytes. Studies employing clonal sequencing and single-stranded conformational polymorphism analyses have revealed unique HCV variants residing in immune cells, further strengthening the notion of HCV lymphotropism. Overall, the data accumulated suggest that occult HCV infection is a common consequence of resolution of symptomatic hepatitis C and that examination of the cells of the immune system is an effective approach to diagnosis of HCV infection and its long-term persistence. Further work is required to fully realize pathogenic and epidemiological consequences of occult HCV persistence. 展开更多
关键词 hepatitis c virus chronic hepatitis c Occul tviral persistence hcv lymphotropism consequences of occult hcv persistence
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Regulation of Hepatitis C Virus Replication and Gene Expression by the MAPK-ERK Pathway 被引量:2
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作者 Rongjuan Pei Xiaoyong Zhang +4 位作者 Song Xu Zhongji Meng Michael Roggendorf Mengji Lu Xinwen Chen 《Virologica Sinica》 SCIE CAS CSCD 2012年第5期278-285,共8页
The mitogen activated protein kinases-extracellular signal regulated kinases (MAPK-ERK) pathway is involved in regulation of multiple cellular processes including the cell cycle. In the present study using a Huh7 ce... The mitogen activated protein kinases-extracellular signal regulated kinases (MAPK-ERK) pathway is involved in regulation of multiple cellular processes including the cell cycle. In the present study using a Huh7 cell line Conl with an HCV replicon, we have shown that the MAPK-ERK pathway plays a significant role in the modulation of HCV replication and protein expression and might influence IFN-a signalling. Epithelial growth factor (EGF) was able to stimulate ERK activation and decreased HCV RNA load while a MAPK-ERK pathway inhibitor U0126 led to an elevated HCV RNA load and higher NS5A protein amounts in Conl cells. It could be further demonstrated that the inhibition of the MAPK-ERK pathway facilitated the translation directed by the HCV internal ribosome entry site. Consistently, a U0126 treatment enhanced activity of the HCV reporter replicon in transient transfeetion assays. Thus, the MAPK-ERK pathway plays an important role in the regulation of HCV gene expression and replication. In addition, cyclin-dependent kinases (CDKs) downstream of ERK may also be involved in the modulation of HCV replication since roscovitine, an inhibitor of CDKs had a similar effect to that of U0126. Modulation of the cell cycle progression by cell cycle inhibitor or RNAi resulted consistently in changes of HCV RNA levels. Further, the replication of HCV replicon in Conl cells was inhibited by IFN-~z. The inhibitory effect of IFN-CZ could be partly reversed by pre-incubation of Con-1 cells with inhibitors of the MAPK-ERK pathway and CDKs. It could be shown that the MAPK-ERK inhibitors are able to partially modulate the expression of interferon-stimulated genes. 展开更多
关键词 hepatitis c virus hcv Mitogen activated protein ldnases-extracellular signal regulated kinase (MAPK-ERK) cell cycleprogression
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Efficacy and Safety of Glecaprevir/Pibrentasvir in Combination Therapy in Chronic Hemodialysis Patients with Genotype 2 Hepatitis C Virus Infection 被引量:1
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作者 Naoki Hotta 《Open Journal of Gastroenterology》 2019年第1期1-6,共6页
Background: Glecaprevir (nonstructural protein 3/4A protease inhibitor) and Pibrentasvir (nonstructural protein 5A inhibitor) (G/P), a coformulated once-daily, all oral, ribavirin (RBV)-free, direct-antiviral regimen,... Background: Glecaprevir (nonstructural protein 3/4A protease inhibitor) and Pibrentasvir (nonstructural protein 5A inhibitor) (G/P), a coformulated once-daily, all oral, ribavirin (RBV)-free, direct-antiviral regimen, was evaluated for safety and efficacy in chronic hemodialysis patients with genotype 2 hepatitis C virus infection. Methods: In this prospective, observational, single-center study at Masuko Memorial Hospital, between November 2017 and December 2018, a total of 8 HD patients with an HCV infection genotype 2 received G/P combination therapy. Age was an average of 67.1 (61 - 75) years and there were four men and two women. It was FIB4 INDX an average of 2.67 (1.5 - 3.34) before the start of therapy. It was quantity of HCV RNA an average of 4.43 (2.1 - 6.5). HCV RNA levels were measured by real-time RCR-based method (COBAS AmpiPrep/COBAS TaqMan HCV Test. 4 cases 12 weeks were 2 cases eight weeks for dosing period. Patients were excluded if they had evidence of hepatocellular carcinoma. This study was approved by the ethics committee of our hospital, while we obtained written consent from the participants after providing a thorough explanation of the contents and methods of this study. Results: 6 patients were available for total dose internal use. As for the HCV RNA of the fourth week, (100%) HCV RNA became negative after administration start of therapy. Rapid virologic response (RVR) achieved all cases. 5 patients achieved 12-week sustained virologic response (SVR12) and were following up the 1 patient. The itching appeared in two cases (33%), but there was symptom improvement in nalfurafine hydrochloride use treatment, and treatment continuation was possible. Conclusion: It is thought that G/P can be given to the HD patients’ safety, but we will accumulate a case in future, and it is thought to be necessary to examine utility and safety. 展开更多
关键词 hcv RNA hepatitis c virus Infection cHRONIc HEMODIALYSIS PATIENTS
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Cladogynos orientalis Zipp. extracts inhibit cell culture-derived hepatitis C virus genotype 2a replication in Huh-7 cells through NS5B inhibition
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作者 Piyanoot Thongsri Khanit Sa-ngiamsuntorn +2 位作者 Pongtip Sithisarn Mullika T. Chomnawang Krit Thirapanmethee 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2019年第8期346-352,共7页
Objective: To evaluate the potential anti-hepatitis C virus (HCV) activities of Cladogynos orientalis Zipp. ex Span and to investigate the molecular mode of action. Methods: Ethanolic and water extracts from various p... Objective: To evaluate the potential anti-hepatitis C virus (HCV) activities of Cladogynos orientalis Zipp. ex Span and to investigate the molecular mode of action. Methods: Ethanolic and water extracts from various parts of Cladogynos orientalis were examined for cytotoxicity by MTT assay. Sub-cytotoxic concentrations of the extracts were used for further determining anti-HCV activity using cell culture-derived HCV genotype 2a propagated in HepaRG cell line. Immunofluorescence assay was performed to observe the effect on viruses at the pre-entry step. Mode of action at the post-entry step was investigated for the viral RNA and protein expressions by real time RT-PCR and Western blotting assays, respectively. Results: Although Cladogynos orientalis water extracts exhibited lower cytotoxicity than ethanolic extracts, all ethanolic extracts from roots, stems, and leaves of Cladogynos orientalis exhibited higher anti-HCV activities than water extracts. The highest anti-HCV activity was observed in infected cells treated with the extracts 5 h after absorption. No extracts showed pre-viral entry effect. At the post-viral entry step, only leaf ethanolic extracts inhibited NS5B expression, while all extracts did not inhibit HCV NS3 expression. Conclusions: Cladogynos orientalis ethanolic extracts could be further studied and the major active compound needs to be identified as a promising source for anti-HCV agents. 展开更多
关键词 cladogynos ORIENTALIS hepatitis c virus cell culture-derived hcv GENOTYPE 2a
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In vitro inhibitory analysis of consensus siRNAs against NS3 gene of hepatitis C virus 1a genotype
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作者 Imran Shahid Waleed Hassan Al Malki +6 位作者 Mohammed Wanees Al Rabia Mohammed Hasan Mukhtar Shaia Saleh R.Almalki Saad Ahmed Alkahtani Sami S.Ashgar Hani S.Faidah Muhammad Hassan Hafeez 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2017年第7期763-770,共8页
Objective: To explore inhibitory effects of genome-specific, chemically synthesized siRNAs(small interference RNA) against NS3 gene of hepatitis C virus(HCV) 1a genotype in stable Huh-7(human hepatoma) cells as well a... Objective: To explore inhibitory effects of genome-specific, chemically synthesized siRNAs(small interference RNA) against NS3 gene of hepatitis C virus(HCV) 1a genotype in stable Huh-7(human hepatoma) cells as well as against viral replication in serum-inoculated Huh-7 cells. Methods: Stable Huh-7 cells persistently expressing NS3 gene were produced under antibiotic gentamycin(G418) selection. The cell clones resistant to 1 000 μg antibiotic concentration(G418) were picked as stable cell clones. The NS3 gene expression in stable cell clone was confirmed by RT-PCR and Western blotting. siRNA cell cytotoxicity was determined by MTT cell proliferation assay. Stable cell lines were transfected with sequence specific siRNAs and their inhibitory effects were determined by RT-PCR, real-time PCR and Western blotting. The viral replication inhibition by siRNAs in serum inoculated Huh-7 cells was determined by real-time PCR. Results: RT-PCR and Western blot analysis confirmed NS3 gene and protein expression in stable cell lines on day 10, 20 and 30 post transfection. MTT cell proliferation assay revealed that at most concentrated dose tested(50 nmol/L), siRNA had no cytotoxic effects on Huh-7 cells and cell proliferation remained unaffected. As demonstrated by the siRNA time-dependent inhibitory analysis, siRNA NS3-is44 showed maximum inhibition of NS3 gene in stable Huh-7 cell clones at 24(80%, P=0.013) and 48 h(75%, P=0.002) post transfection. The impact of siRNAs on virus replication in serum inoculated Huh-7 cells also demonstrated significant decrease in viral copy number, where siRNA NS3-is44 exhibited 70%(P<0.05) viral RNA reduction as compared to NS3-is33, which showed a 64%(P<0.05) decrease in viral copy number. siRNA synergism(NS3-is33 + NS3-is44) decreased viral load by 84%(P<0.05) as compared to individual inhibition by each siRNA(i.e., 64%–70%(P<0.05) in serum-inoculated cells. Synthetic siRNAs mixture(NS5Bis88 + NS3-is33) targeting different region of HCV genome(NS5B and NS3) also decreased HCV viral load by 85%(P< 0.05) as compared to siRNA inhibitory effects alone(70% and 64% respectively, P<0.05). Conclusions: siRNAs directed against NS3 gene significantly decreased m RNA and protein expression in stable cell clones. Viral replication was also vividly decreased in serum infected Huh-7 cells. Stable Huh-7 cells expressing NS3 gene is helpful to develop anti-hepatitis C drug screening assays. siRNA therapeutic potential along with other anti-HCV agents can be considered against hepatitis C. 展开更多
关键词 hepatitis c virus NS3 protein Stable Huh-7 cell culture system RNA interference NS5B hcv therapeutics
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Expression of core gene cDNA of Chinese hepatitis C virus in HepG2 cell line
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作者 姜荣龙 卢桥生 +3 位作者 侯金林 骆抗先 章廉 王燕军 《Journal of Medical Colleges of PLA(China)》 CAS 1997年第4期313-316,共4页
Objective: To clone core gene cDNA of Chinese hepatitis C virus (HCV) into eukaryotic expression vector pTM3 and to express HCV core antigen in HepG2 cells. Methods: Core gene cDNA of HCV was introduced into eukaryoti... Objective: To clone core gene cDNA of Chinese hepatitis C virus (HCV) into eukaryotic expression vector pTM3 and to express HCV core antigen in HepG2 cells. Methods: Core gene cDNA of HCV was introduced into eukaryotic expression vector pTM3. Using vaccinia virus/bacteriophage T7 hybrid expression system, HepG2cells were trans feeted with the recombinant plasmid pTM3-Q534 by lipofectin. Results: From the transfected bacteria Top10F, 2pTM3-Q534 clones containing the recombinant plasmid were identified from randomly selected 10ampicillin-resistant colonies. By indirect immunofluorescence technique HCV core protein was identified in HepG2cells trans feeted with the recombinant plasmid. Conclusion: The construction of a recombinant plasmid and the expression of core gene cDNA of HCV in HepG2 were successful. 展开更多
关键词 hepatitis c virus (hcv)/core gene cDNA cosmid vector cLONAL EXPRESSION
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Challenge of managing hepatitis B virus and hepatitis C virus infections in resource-limited settings
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作者 Zeinab Nabil Ahmed Said Manal Hamdy El-Sayed 《World Journal of Hepatology》 2022年第7期1333-1343,共11页
The global burden of hepatitis B virus(HBV)and hepatitis C virus(HCV)infections and coinfection represents a major public health concern,particularly in resource-limited settings.Elimination of HCV by 2030 has become ... The global burden of hepatitis B virus(HBV)and hepatitis C virus(HCV)infections and coinfection represents a major public health concern,particularly in resource-limited settings.Elimination of HCV by 2030 has become foreseeable,with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries(LMICs).However,access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices.Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal.Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection,and with improved access to medications,the most significant barrier remains access to affordable diagnostics and preventive strategies.The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs,albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage.This review underpins the HBV and HCV management challenges in resource-limited settings,highlighting the current status and suggested future elimination strategies in some of these countries.Global efforts should continue to improve awareness and political commitment.Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal. 展开更多
关键词 hepatitis B virus/hepatitis c virus chronic hepatitis Resource-limited settings HBV and hcv elimination
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Effect of Hepatitis C Virus Core Protein on Interferon-Induced Antiviral Genes Expression and Its Mechanisms
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作者 Yan-zi CHANG Yan-chang LEI +4 位作者 Wen WU Shan-shan CHEN Han-ju HUANG Dong-liang YANG Meng-ji LU 《中国病毒学》 CSCD 2007年第5期374-379,共6页
Emerging data indicated that HCV subverts the antiviral activity of interferon(IFN);however,whether HCV core protein contributes to the process remains controversial.In the present study,we examined the effect of HCV ... Emerging data indicated that HCV subverts the antiviral activity of interferon(IFN);however,whether HCV core protein contributes to the process remains controversial.In the present study,we examined the effect of HCV core protein on interferon-induced antiviral gene expression and whether the effect is involved in the activation and negative regulation of the Jak/STAT signaling pathway.Our results showed that,following treatment with IFN-α,the transcription of PKR,MxA and 2'-5'OAS were down-regulated in HepG2 cells expressing the core protein.In the presence of HCV core protein,ISRE-dependent luciferase activity also decreased.Further study indicated that the core protein could inhibit the tyrosine phosphorylation of STAT1,whereas the level of STAT1 expression was unchanged.Accordingly,SOCS3,the negative regulator of the Jak/STAT pathway,was induced by HCV core protein.These results suggests that HCV core protein may interfere with the expression of some interferon-induced antiviral genes by inhibiting STAT1 phosphorylation and induction of SOCS3. 展开更多
关键词 丙型肝炎病毒 核心蛋白质 Α-干扰素 抗病毒基因表达 作用机理
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Inhibition of Hepatitis C Virus Genotype 1a Non-Structural Proteins by Small Interference RNA in Human Hepatoma Cell Lines
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作者 Imran Shahid Waleed Hassan AlMalki +3 位作者 Shaia Saleh R. Almalki Ismail Muhammad AlTurkestany Hassan Ali AlGhamdi Saleh Ali AlMenshawi 《Pharmacology & Pharmacy》 2015年第11期502-517,共16页
Hepatitis C virus (HCV) infection and associated liver diseases are still challenging and represent a significant health care burden around the world. Although, the treatment strategies have been improved by the devel... Hepatitis C virus (HCV) infection and associated liver diseases are still challenging and represent a significant health care burden around the world. Although, the treatment strategies have been improved by the development of novel direct-acting antivirals, but such therapeutic options are still expensive and beyond the financial range of the most infected individuals in developing or even in resource replete countries. It demands an urgent need to search novel and improved alternate treatment strategies to treat the infection. The present study was aimed to develop an in vitro stable cell culture system, persistently expressing HCV genotype 1a non-structural genes and to characterize the inhibitory effects of synthetic siRNAs (short interference RNA) directed against the most conserved regions of nonstructural genes in an in vitro cell culture model. The continuous expression of nonstructural genes for more than 30 days post transfection was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis in stable human hepatoma cell line (Huh-7). The gene expression studies revealed significantly reduced gene expression of HCV nonstructural genes (i.e., NS2, NS4A and NS5A) both at mRNA and protein levels when treated against genome specific synthetic siRNAs in stable cell lines (51%, 47% and 54% respectively, p < 0.05). Similarly, a vivid decrease in HCV viral titer was exhibited by synthetic siRNAs in an in vitro viral replicate cell culture model (58%, 48% and 50%, respectively, p < 0.05) determined by quantitative Real-Time PCR (qPCR). Our data indicate that siRNA mediated gene silencing may be considered a promising alternate treatment strategy against HCV in combination with other effective therapeutic regimens in future. 展开更多
关键词 hepatitis c virus NON-STRUcTURAL PROTEINS Stable cell Line ANTI-hcv DRUGS Short Interference RNA
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Treatment of chronic hepatitis C in patients with HIV/HCV coinfection 被引量:3
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作者 Nicola Coppola Salvatore Martini +3 位作者 Mariantonietta Pisaturo Caterina Sagnelli Pietro Filippini Evangelista Sagnelli 《World Journal of Virology》 2015年第1期1-12,共12页
Hepatitis C virus(HCV) infection is one of the mostfrequent causes of comorbidity and mortality in the human immunodeficiency virus(HIV) population, and liver-related mortality is now the second highest cause of death... Hepatitis C virus(HCV) infection is one of the mostfrequent causes of comorbidity and mortality in the human immunodeficiency virus(HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals(DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa(Peg-IFN) + ribavirin(RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCVgenotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence. 展开更多
关键词 hepatitis c virus INFEcTION Human immunodeficiency virus INFEcTION Anti-hepatitis c virus TREATMENT Directly acting antivirals HIV/hcv cOINFEcTION chronic hepatitis c
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CHANGES OF ANTIBODIES AGAINST ANTIGENS ENCODED BY DIFFERENT REGIONS OF HCV GENOME IN CHRONIC HEPATITIS C PATIENTS TREATED WITH INTERFERON
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作者 蔺淑梅 张树林 +1 位作者 狄鹏超 梁雪松 《Journal of Pharmaceutical Analysis》 CAS 1997年第1期7-10,26,共5页
Twenty patients with chronic hepatitis c were investigated during the treatment with interferon to explore the changes of antibodies to HCV (anti-RCV). Anti-HCV was tested with recombinant immunoblot assay (RIBA) by u... Twenty patients with chronic hepatitis c were investigated during the treatment with interferon to explore the changes of antibodies to HCV (anti-RCV). Anti-HCV was tested with recombinant immunoblot assay (RIBA) by using three antigens (C22, C33c, and C100-3) encoded by different regions of HCV genome. The changes of individual anti-HCV and ALT were compared with the change of HCV RNA. The results showed that persistent disappearance of serum HCV RNA was closely related to the changes of anti-C33c (P<0. 01) and anti-C100-3 (P<0. 005), but there was no relation between persistent ALT normality and HCV viremia clearance (P<0. 05). In conclusion, monitoring anti-C33c and anti-C100-3 could indicate the changes or HCV viremia. The normalization of ALT after interferon treatment did not indicate disappearance of HCV viremia. 展开更多
关键词 hepatitis c hepatitis c virus ribonucleotide acid (hcv RNA) antibody against hcv (Anti-hcv) recombinant immunoblot assay (RIBA)
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Logistic Regression Analysis of Influencing Factors on Serum ALT and HCV RNA Changes in Patients with Chronic Hepatitis C
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作者 Cheng-bao Wang Jian-jie Chen +3 位作者 Hong-ming Nie Feng Gao Hua Lv Hong-ding Li 《国际感染病学(电子版)》 CAS 2012年第2期80-83,共4页
Objective This study was undertaken to investigate the influencing factors on serum ALT level and hepatitis C virus(HCV)RNA titer in chronic hepatitis C(CHC)patients.Methods All patients enrolled into this study were ... Objective This study was undertaken to investigate the influencing factors on serum ALT level and hepatitis C virus(HCV)RNA titer in chronic hepatitis C(CHC)patients.Methods All patients enrolled into this study were anti-HCV positive.Retrospective tracing method was applied to detect serum ALT level and HCV RNA titer and to collect general information of the patients such as genders,age groups,interferon medication history,infection pathways,height and weight.Then the multi-factor analysis was adopted with the application of binominal logistic regression mode.Results The abnormal rate of ALT level was positively correlated to HCV RNA and gender while negatively correlated to interferon medication history and age group,with Wald value of the 4 factors as 39.604,11.823,18.991 and 7.389,respectively.The positive rate of HCV RNA was negatively correlated to interferon medication history and gender while positively correlated to ALT level,with corresponding Wald value of the 3 factors as81.394,7.618 and 27.562,respectively.Conclusions The normal ALT level in HCV infected patients was associated with viral load,age,gender and interferon medication history,while the normal rate of HCV RNA titer was closely associated with gender,interferon medication history and ALT level. 展开更多
关键词 Multi-factor logistic regression analysis hepatitis c virus chronic hepatitis c Serum ALT level hcv RNA
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HCV-RNA与HCV-Ab,HCV-cAg相关性分析研究 被引量:11
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作者 李娅 张赟 +3 位作者 皇海 章迪 苏明权 郭旭昌 《现代检验医学杂志》 CAS 2016年第5期120-122,共3页
目的:探讨丙型肝炎患者中 HCV-RNA与 HCV-Ab,HCV-cAg三种检测指标的相关性和临床应用效果。方法采用酶联免疫法分别检测实时荧光定量 PCR法检测阳性的140例 HCV患者血清中的 HCV-Ab和 HCV-cAg,以了解检测结果及符合率。结果在140例 H... 目的:探讨丙型肝炎患者中 HCV-RNA与 HCV-Ab,HCV-cAg三种检测指标的相关性和临床应用效果。方法采用酶联免疫法分别检测实时荧光定量 PCR法检测阳性的140例 HCV患者血清中的 HCV-Ab和 HCV-cAg,以了解检测结果及符合率。结果在140例 HCV-RNA阳性血清中,HCV-cAg 阳性127例,符合率90.71%;HCV-Ab 阳性110例,符合率78.57%;对不同 HCV-RNA浓度的血清进行 HCV-cAg检测结果其阳性检出率随着 HCV病毒含量的升高而增高;不同 HCV-RNA浓度的血清进行 HCV-Ab检测结果无明显变化。结论通过对 HCV-RNA阳性患者中 HCV-Ag和 HCV-Ab的检测观察分析,HCV-cAg检测与 HCV-RNA的检测结果具有较高的符合率。因此 HCV-cAg检测可作为HCV-Ab的补充检测,为 HCV“窗口期”感染以及免疫低下人群感染的筛查提供简便、廉价方法;同时为不具备 HCV-RNA检测条件的基层医疗单位,作为 HCV感染的快速筛查提供诊断依据。 展开更多
关键词 丙型肝炎病毒 丙型肝炎核酸 丙型肝炎病毒核心抗原 丙型肝炎病毒抗体
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HCV抗原检测与HCV-RNA及HCV抗体检测的比较研究 被引量:11
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作者 肖征 周光 《中国人兽共患病学报》 CAS CSCD 北大核心 2009年第6期539-540,共2页
目的评价HCV抗原检测在临床的应用价值。方法用HCV抗原酶联法检测试剂盒对临床送检HCV-RNA及HCV抗体的血标本进行检测,并分析结果。结果39例HCV-RNA阳性标本中,HCV抗原阳性28例(71.8%);116例HCV-RNA阴性标本中,HCV抗原阳性1例(0.86%);96... 目的评价HCV抗原检测在临床的应用价值。方法用HCV抗原酶联法检测试剂盒对临床送检HCV-RNA及HCV抗体的血标本进行检测,并分析结果。结果39例HCV-RNA阳性标本中,HCV抗原阳性28例(71.8%);116例HCV-RNA阴性标本中,HCV抗原阳性1例(0.86%);96例HCV抗体阳性标本中HCV抗原阳性47例(48.96%),HCV抗体阴性106例中,HCV抗原均为阴性。结论现有HCV抗原检测试剂盒尚不适合作临床丙型肝炎的筛选,但可作为HCV抗体检测的进一步验证,部分程度地替代HCV-RNA检测。 展开更多
关键词 hcv 抗原 酶联免疫吸附试验 抗体 核酸
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慢性丙型肝炎患者HCV-RNA载量与抗-HCV及肝功指标的相关性研究 被引量:10
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作者 方伟 吴虹 《中国继续医学教育》 2015年第31期40-42,共3页
目的探讨慢性丙型肝炎患者血清HCV-RNA水平与肝功指标的相互关系。方法收集104例慢性丙型肝炎患者血清,应用荧光定量聚合酶链反应(FQ-PCR)检测HCV-RNA的水平,用酶免疫吸附试验法(ELISA)检测抗-HCV,全自动生化分析仪检测ALT、AST、GGT、... 目的探讨慢性丙型肝炎患者血清HCV-RNA水平与肝功指标的相互关系。方法收集104例慢性丙型肝炎患者血清,应用荧光定量聚合酶链反应(FQ-PCR)检测HCV-RNA的水平,用酶免疫吸附试验法(ELISA)检测抗-HCV,全自动生化分析仪检测ALT、AST、GGT、ALB等肝功指标。结果 104例慢性丙型肝炎患者,抗-HCV均为阳性,其中83例HCV-RNA大于临界值。与100例健康对照组比较,慢性丙型肝炎患者的AST、ALT、GGT升高,而ALB减低;而其HCV-RNA载量与AST、ALT的异常率呈正相关,与AST、ALT、ALB、GGT的水平无相关性。结论联合检测HCV-RNA载量与抗-HCV及肝功指标对指导临床用药及疗效观察有指导意义。 展开更多
关键词 慢性丙型肝炎 hcv—RNA 慢性丙型肝炎抗体 肝功能
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HCV抗体血清学检测联合HCV-RNA检测的应用价值:附2例病例分析 被引量:8
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作者 马淑青 宋宇 +7 位作者 毕艳妮 姚继承 邵淑丽 耿建利 王晓伟 鞠毅 黄忠义 王明义 《实用检验医师杂志》 2019年第2期122-124,共3页
丙型肝炎(丙肝)为常见传染病,丙肝病毒(HCV)抗体血清学检测是HCV感染筛查的主要方式,常用的方法为化学发光法。但感染HCV后,抗体的血清学转换可延迟至数月后。HCV-RNA检测可直接检测病毒复制量,感染HCV后1~2周即可在血清中检测到病毒,是... 丙型肝炎(丙肝)为常见传染病,丙肝病毒(HCV)抗体血清学检测是HCV感染筛查的主要方式,常用的方法为化学发光法。但感染HCV后,抗体的血清学转换可延迟至数月后。HCV-RNA检测可直接检测病毒复制量,感染HCV后1~2周即可在血清中检测到病毒,是HCV感染的实验室诊断方法之一。但HCV-RNA检测操作繁琐、成本较高,常规实验室不作为筛选使用。威海市立医院收治2例疑诊病毒性肝炎患者,经核酸检测确诊后即给予相应治疗,患者肝功能好转。说明在实验室常规开展HCV-RNA检测提高了HCV感染检出的准确性。 展开更多
关键词 丙型肝炎 丙型肝炎病毒 抗体血清学检测 核酸检测
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