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1.
Molecules ; 26(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652639

RESUMO

Hepatitis C is affecting millions of people around the globe annually, which leads to death in very high numbers. After many years of research, hepatitis C virus (HCV) remains a serious threat to the human population and needs proper management. The in silico approach in the drug discovery process is an efficient method in identifying inhibitors for various diseases. In our study, the interaction between Epigallocatechin-3-gallate, a component of green tea, and envelope glycoprotein E2 of HCV is evaluated. Epigallocatechin-3-gallate is the most promising polyphenol approved through cell culture analysis that can inhibit the entry of HCV. Therefore, various in silico techniques have been employed to find out other potential inhibitors that can behave as EGCG. Thus, the homology modelling of E2 protein was performed. The potential lead molecules were predicted using ligand-based as well as structure-based virtual screening methods. The compounds obtained were then screened through PyRx. The drugs obtained were ranked based on their binding affinities. Furthermore, the docking of the topmost drugs was performed by AutoDock Vina, while its 2D interactions were plotted in LigPlot+. The lead compound mms02387687 (2-[[5-[(4-ethylphenoxy) methyl]-4-prop-2-enyl-1,2,4-triazol-3-yl] sulfanyl]-N-[3(trifluoromethyl) phenyl] acetamide) was ranked on top, and we believe it can serve as a drug against HCV in the future, owing to experimental validation.


Assuntos
Catequina/análogos & derivados , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Proteínas do Envelope Viral/genética , Antivirais/química , Antivirais/farmacologia , Catequina/química , Catequina/farmacologia , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C/virologia , Humanos , Ligantes , Simulação de Acoplamento Molecular , Polifenóis/química , Polifenóis/farmacologia , Chá/química , Proteínas do Envelope Viral/antagonistas & inibidores , Internalização do Vírus/efeitos dos fármacos
2.
BMC Bioinformatics ; 22(1): 132, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33736614

RESUMO

BACKGROUND: Historical and updated information provided by time-course data collected during an entire treatment period proves to be more useful than information provided by single-point data. Accurate predictions made using time-course data on multiple biomarkers that indicate a patient's response to therapy contribute positively to the decision-making process associated with designing effective treatment programs for various diseases. Therefore, the development of prediction methods incorporating time-course data on multiple markers is necessary. RESULTS: We proposed new methods that may be used for prediction and gene selection via time-course gene expression profiles. Our prediction method consolidated multiple probabilities calculated using gene expression profiles collected over a series of time points to predict therapy response. Using two data sets collected from patients with hepatitis C virus (HCV) infection and multiple sclerosis (MS), we performed numerical experiments that predicted response to therapy and evaluated their accuracies. Our methods were more accurate than conventional methods and successfully selected genes, the functions of which were associated with the pathology of HCV infection and MS. CONCLUSIONS: The proposed method accurately predicted response to therapy using data at multiple time points. It showed higher accuracies at early time points compared to those of conventional methods. Furthermore, this method successfully selected genes that were directly associated with diseases.


Assuntos
Hepatite C , Esclerose Múltipla , Teorema de Bayes , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/genética , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética , Transcriptoma
3.
Drugs Today (Barc) ; 57(3): 199-208, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33729217

RESUMO

Effective oral combination regimens have been approved for treatment of hepatitis C virus (HCV) infection and demonstrated high cure rates in different HCV genotypes. These direct-acting agents target a variety of HCV proteins, including HCV-NS5A (nonstructural protein 5A). Ravidasvir hydrochloride, a potent pan-genotypic HCV-NS5A inhibitor approved in Egypt for treatment of HCV genotype 4 (G4), demonstrated impressive efficacy, safety profiles and a high barrier to resistance in multiple clinical trials when used as a key component in combination with other direct-acting agents in treating patients with HCV-G1.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Farmacorresistência Viral/genética , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Valina/análogos & derivados , Proteínas não Estruturais Virais
4.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33704042

RESUMO

At present, the available point of care (POC) molecular assays for hepatitis C are not considered as true POC due to sample collection and processing requiring minimal laboratory infrastructure. A new POC Xpert HCV VL Fingerstick (Xpert FS) precludes such requirements where specimen collected by simple fingerstick can be loaded directly into the test cartridge with results available within 60 min. The present study compared the performance of this assay for HCV RNA quantitation using both capillary whole blood (CWB) and venous whole blood (VWB) with plasma HCV RNA performed on Abbott Real Time HCV PCR. CWB via fingerstick and VWB via venipuncture collected from serologically confirmed HCV-infected participants were loaded into Xpert HCV VL WB for viral load estimation. Simultaneously Abbott Real Time HCV PCR assay was also performed using plasma (reference method). Among the enrolled participants (n=157), the mean age was 46.22±14.79 years and 63 % were male. HCV RNA was detected in 100 cases (63.7 %), median 5.69 (IQR: 5.00-6.32)log10IU ml-1 on the reference method. Xpert FS showed 100 % sensitivity and specificity using both CWB and VWB. The median viral loads detected in CWB and VWB were 5.52 (IQR: 4.59-6.15) and 5.48 (IQR: 4.61-6.07)log10IU ml-1, respectively. Xpert FS offers potential as true POC enabling accurate diagnosis in a single patient visit to the health-care facility, hence may reduce the number of dropouts with a confirmed diagnosis. However, further real-time studies with larger sample size are warranted.


Assuntos
Coleta de Amostras Sanguíneas/métodos , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Testes Imediatos , Adulto , Feminino , Hepacivirus/genética , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/normas , Testes Imediatos/normas , RNA Viral/sangue , RNA Viral/genética , Sensibilidade e Especificidade , Fatores de Tempo , Carga Viral
5.
Z Gastroenterol ; 59(3): 241-249, 2021 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-33684956

RESUMO

BACKGROUND: Hepatitis C virus (HCV) genotype (GT) 1 is the most common HCV GT in Western and Central Europe. The main focus of this present work is to analyze the change of baseline characteristics of 17 093 HCV-patients with genotype 1a/1b with antiviral therapy in Germany between 2004 and 2018. We analyzed five periods: (i) 2004-2007, (ii) 2008-2010, (iii) 2010-2013, (iv) 2014-2016, (v) 2017-2018. METHODS: The present analysis is based on five German non-interventional registry studies and comprises data on 17 093 HCV-GT1 patients documented between 2004 and 2018 [ML17071, ML19464, ML21645, ML25724 (Peginterferon alfa-2a® non-interventional study [PAN]) and the German Hepatitis C-Registry (DHC-R). FINDINGS: Overall, 7662 patients were infected with HCV GT1a and 9431 patients with HCV GT1b. GT1a patients were younger (46.5 years vs. 51.2 years) and more often male (70 % vs. 52 %). Previous or ongoing drug abuse was documented more frequently for GT1a patients throughout the study periods with highest frequencies in the most recent period (2017-2018; 44 % for GT1a and 10.3 % for GT1b). Metabolic comorbidities, such as those who are overweight and those with diabetes mellitus, were associated with HCV GT1b-infected women. The GT1a ratio increased from 33.6 % (2004-2007) to 50 % (2017-2018). A relevant change in the GT1a/1b ratio was observed over time in men (2004-2007: 38 %/63 %; 2017-2018: 59 %/41 %). In contrast, only 30 % of women had GT1a infection throughout all study periods without relevant changes. There were no regional differences within Germany in HCV GT1a/1b distribution despite a higher proportion of GT1b-infected women in East Germany in 2004-2007 (86 %). CONCLUSION: A marked increase of GT1a infection associated with drug use was observed in men, but not women, in Germany between 2004 and 2018. The present data show a fundamental change in HCV epidemiology, which has an impact on therapy management and general care of hepatitis C patients in Germany.


Assuntos
Hepacivirus/genética , Hepatite C Crônica/epidemiologia , Sistema de Registros , Antivirais/uso terapêutico , Quimioterapia Combinada , Europa (Continente) , Feminino , Genótipo , Alemanha/epidemiologia , Hepacivirus/classificação , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino
6.
Zhonghua Gan Zang Bing Za Zhi ; 29(2): 102-107, 2021 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-33685075

RESUMO

Hepatitis C is the first chronic viral infection that can be cured, and it has taken only 30 years from the discovery of the hepatitis C virus genome to the ability to eliminate the public health threat posed by hepatitis C virus. In the past ten years, the etiological detection of hepatitis C has experienced the development from sensitive and quantitative to rapid, convenient, automatic and point of care testing. With the continuous introduction of direct antiviral drugs, all types of hepatitis C patients, including special populations, can be safely and effectively cured by short courses of all-oral drugs. Progress in the diagnosis and treatment of hepatitis C is an important basis for eliminating the public health threat of hepatitis C. China has published the Planning of prevent and treatment for viral hepatitis in China (2017-2020). We look forward to achieving WHO's goal of eliminating viral hepatitis as a public health threat at an early date through effective screening, diagnosis and treatment.


Assuntos
Hepatite C Crônica , Hepatite C , Hepatite Viral Humana , Antivirais/uso terapêutico , China , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos
7.
Klin Lab Diagn ; 66(2): 122-128, 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33734647

RESUMO

Globally, about 70 million people are infected with the hepatitis C virus (HCV), and about 400 thousand people die annually from chronic hepatitis C complications. The management of patients with chronic hepatitis C may require HCV genotyping, since the efficiency of some widely used antiviral drugs strongly depend on the viral genotype and/or subtype. The most prevalent HCV circulating recombinant form, RF1_2k/1b, is misclassified as genotype 2 by many commercial HCV genotyping kits, based on the RT-PCR analysis of the 5' untranslated region of the HCV genome. This leads to inappropriate patient treatment, since the accepted treatment schemes for HCV genotype 2 are ineffective for the RF1_2k/1b. Here we describe a method for detecting the RNA HCV RF1_2k/1b in blood samples by RT-PCR analysis of two regions in HCV genome (5'UTR and NS5b). The method was tested on 240 blood serum samples from HCV infected patients, in which HCV genotype was defined as 2 or mixed (2+1 or 2+3) by the two commercial genotyping kits "OT-Hepatogen-C genotype" ("DNA-Technology", Moscow) and "RealBest RNA HCV-1/2/3" ("Vector- Best ", Novosibirsk). 50 (20.8%) RF1_2k/1b cases were revealed, including three mixed infections: RF1_2k/1b + 1a, RF1_2k/1b + 3a, RF1_2k/1b + 1b. In all cases, the accuracy of HCV typing by the proposed method was confirmed by Sanger sequencing and phylogenetic analysis. The method is easy to implement into clinical practice and may be used in clinical settings equipped for RT-PCR analysis to correctly identify the recombinant variant RF1_2k/1b.


Assuntos
Hepacivirus , Hepatite C , Genótipo , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/genética , Humanos , Moscou , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Soro
8.
Zhonghua Gan Zang Bing Za Zhi ; 29(1): 83-86, 2021 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-33548971

RESUMO

Sofosbuvir has ushered in a new era of hepatitis C treatment with its strong inhibition on the replication of hepatitis C virus, favorable safety profile and less interactions with other drugs. Sofosbuvir-based regimens have been included as the first-line therapies for the treatment of adults with chronic hepatitis C (CHC) in international guidelines. Available clinical trial data show that sofosbuvir with ribavirin and ledipasvir/sofosbuvir are highly efficacious and safe in CHC patients aged 3-17 years old; therefore, they can meet the unmet medical needs of adolescents and children with CHC in China. Furthermore, the pan-genotypic sofosbuvir/velpatasvir is being investigated in adolescents and children with CHC, which is expected to make the treatment in such patients more convenient upon approval.


Assuntos
Antivirais , Hepatite C Crônica , Adolescente , Adulto , Antivirais/uso terapêutico , Criança , Pré-Escolar , China , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do Tratamento
9.
Artigo em Inglês | MEDLINE | ID: mdl-33533809

RESUMO

The efficacy of direct-acting antivirals (DAAs) in the treatment of chronic hepatitis C (CHC) in liver transplant recipients is poorly understood, and several factors, including immunosuppression, drug interactions, elevated viraemia, and intolerance to ribavirin (RBV), can reduce cure rates. We conducted a real-life study on liver transplant recipients with CHC treated with a combination of sofosbuvir (SOF) and daclatasvir (DCV) or simeprevir (SIM), with or without RBV, followed-up for 12 to 24 weeks. The treatment effectiveness was assessed by determining the sustained virological response (SVR) rates at 12 or 24 weeks after the treatment cessation. Eighty-four patients were evaluated, with a mean age of 63.4 ± 7.4 years, HCV genotype 1 being the most prevalent (63.1%). Nineteen patients (22.7%) had mild fibrosis (METAVIR < F2) and 41 (48.8%) significant fibrosis (METAVIR ≥ F2). The average time between liver transplantation and the start of treatment was 4 years (2.1-6.6 years). The SOF + DCV regimen was used in 58 patients (69%). RBV in combination with DAAs was used in seven patients (8.3%). SVR was achieved in 82 patients (97.6%), and few relevant adverse events could be attributed to DAA therapy, including a patient who stopped treatment due to a headache. There was a significant reduction in ALT, AST, GGT and FA levels, or the APRI index after 4 weeks of treatment, which remained until 12/24 weeks post-treatment. DAA treatment of CHC in liver-transplanted patients achieved a high SVR rate and resulted in the normalization of serum levels of liver enzymes.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Ribavirina/uso terapêutico , Idoso , Antivirais/efeitos adversos , Brasil , DNA Viral/genética , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Humanos , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Ribavirina/efeitos adversos , Transplantados , Resultado do Tratamento
10.
Rev Soc Bras Med Trop ; 54: e02532020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33605377

RESUMO

INTRODUCTION: We compared the hepatitis C virus (HCV) core antigen test with the HCV RNA assay to confirm anti-HCV results to determine whether the HCV core antigen test could be used as an alternative confirmatory test to the HCV RNA test. METHODS: Sera from 156 patients were analyzed for anti-HCV and HCV core antigen using a chemiluminescent microparticle immunoassay (Architect i2000SR) and for HCV RNA using the artus HCV RG RT-PCR Kit (QIAGEN) in a Rotor-Gene Q instrument. RESULTS: The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 77.35%, 100%, 100%, and 89.38%, respectively. HCV core antigen levels showed a good correlation with those from HCV RNA quantification (r =0.872). However, 13 samples with a viral load of less than 4000 IU/mL were negative in the HCV core antigen assay. All gray-zone reactive samples were also RNA positive and were positive on repeat testing. CONCLUSIONS: The Architect HCV core antigen assay is highly specific and has an excellent positive predictive value. At the present level of sensitivity (77%), the study is still relevant in a low-income setting in which most of the HCV-positive patients would go undiagnosed, since HCV RNA testing is not available and/or not affordable. HCV core antigen testing can also help determine the true burden of infection in a population, considering the fact that almost 50% of the anti-HCV positive cases are negative for HCV RNA.


Assuntos
Hepacivirus , Hepatite C , Hepacivirus/genética , Hepatite C/diagnóstico , Anticorpos Anti-Hepatite C , Antígenos da Hepatite C , Humanos , RNA Viral , Sensibilidade e Especificidade
11.
Mikrobiyol Bul ; 55(1): 30-40, 2021 Jan.
Artigo em Turco | MEDLINE | ID: mdl-33590979

RESUMO

Genotype distribution of hepatitis C virus (HCV) can vary over the years between different patient groups and regions. The prevalence of intravenous drug users (IVDU) is known to increase in our country, yet there are a limited number of studies investigating the distribution of HCV genotypes in this group. These data are essential for monitorization of the changes in HCV epidemiology. The present study aimed to evaluate the five-year results of HCV genotyping among patients infected with HCV related to IVDU and unrelated to drug use. Plasma samples of 720 patients (HCV antibody, HCV RNA positive), which were sent to our laboratory for HCV genotyping between January 2014-March 2019 were analyzed. HCV RNA extraction from plasma samples was performed in the automated-extraction system of EZ1 advanced (Qiagen, Germany) using the EZ1 virus mini kit v2.0 (Qiagen, Germany). Amplicons were obtained by amplifying the 5'NCR and core gene region in the Rotorgene 6000 real-time PCR (Qiagen, Germany) device with the HCV RNA real-time quantitative 2.0 (NLM, Italy) kit. For the genotyping, a commercial line probe assay (LIPA) based on in vitro reverse hybridization GEN-C2.0 kit (NLM, Italy) which can distinguish 1, 2, 3, 4, 6 genotypes and 1a, 1b, 2a/c, 2b, 3a, 3b, 3c, 3k, 4a, 4b, 4c/d, 4e, 4f, 4h, 5a, 6a/b, 6g, 6f/q, 6m, 7a subtypes of HCV, based on variations in the 5'-NCR and core regions was used. HCV genotype distribution of 266 IVDU (93.2%: male; median age: 25 ± 6.82) and 454 non-drug users (51.3%: male; median age: 56.5 ± 16.06) were examined. In order of frequency in the group with IVDU; genotype 1a, 3a, 1b, 4c/d, 2b, 4, 3 were observed and genotype 1, 2a/c and mixed genotype (1+3a) were detected in one patient. In the group without IVDU, in order of frequency; genotype 1b, 1a, 3a, 1, 2a/c, 4 were observed and genotype 2b, 4c/d, 5a, 6a/b, 6 and mixed genotype (3+4) were detected in one patient. Genotypes 1a and 3a were significantly higher in the IVDU group (p< 0.00001, p< 0.00001), while 1b was significantly higher in patients without IVDU (p< 0.00001). Genotypes 1a and 3a were more common in young men (p< 0.00001, p= 0.000163), while 1b was higher in middleaged women (p< 0.00001). The incidence of genotypes 1b (p= 0.021) and 3a (p= 0.012) was higher in foreign nationals than the Turkish patients. When the HCV genotype distribution was examined by years, it was observed that the percentages of genotype 1b and 1a were decreasing, while the percentage of genotype 3a was increasing. As a result, in this study, HCV genotype distribution among IVDU was observed to be different from the general population without IVDU. It was found that genotypes 1a and 3a were more common in the IVDU group. As in the other regions of our country, genotype 1b was found most frequently in the general population. Genotype 3a increases significantly compared to years. In our study, the determination of genotypes existing in different parts of the world may be due to the foreign nationals living in our city and our region is a tourism center. It is also necessary to investigate whether there is an increase in IVDU over the years.


Assuntos
Hepacivirus , Hepatite C , Adolescente , Adulto , Idoso , Usuários de Drogas/estatística & dados numéricos , Feminino , Genótipo , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Abuso de Substâncias por Via Intravenosa , Turquia/epidemiologia , Adulto Jovem
12.
Arch Virol ; 166(4): 1047-1056, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33528661

RESUMO

Risk and progression of liver fibrosis and cirrhosis in chronic hepatitis C (CHC) patients is significantly influenced by host genetic factors in a polygenic manner. The rs12979860 genetic polymorphism in the interferon-λ3-interferon-λ4 (IFNL3-IFNL4) region has been found to be a major determinant of hepatic inflammatory and fibrotic progression in CHC patients of mainly Caucasian origin; however, it is not known if this association applies to other ethnicities, including Pakistani CHC patients. Here, we genotyped IFNL3-IFNL4 rs12979860 genetic variants in a sample set of 502 Pakistani patients with CHC and used logistic regression analysis to determine its association with the risk and progression of HCV-related fibrosis and cirrhosis. We demonstrate that the rs12979860 major (CC) genotype, despite not determining the risk of stage-specific hepatic fibrosis independently, is associated with a marginally significant risk of liver cirrhosis (OR: 1.64, p = 0.049) after an adjustment for age, gender, body mass index, HCV viral load, and liver enzymes. In a subgroup of CHC patients with sustained ALT levels of <60 IU/L, a more pronounced impact of the IFNL3-IFNL4 rs12979860 major (CC) genotype on advanced liver fibrosis (OR: 4.99, p = 0.017) and cirrhosis (OR: 3.34, p = 0.005) was seen. The present study suggests that IFNL3-IFNL4 rs12979860 polymorphism may also be a significant predictor of hepatic fibrosis and cirrhosis in Pakistani CHC patients, especially in those with normal or near-normal liver enzyme levels.


Assuntos
Predisposição Genética para Doença/genética , Hepatite C Crônica/genética , Interferons/genética , Interleucinas/genética , Cirrose Hepática/genética , Adulto , Feminino , Estudos de Associação Genética , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/patologia , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Polimorfismo de Nucleotídeo Único
13.
Arch Virol ; 166(4): 1071-1081, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33533976

RESUMO

Elimination of hepatitis C virus (HCV) may fail, leading to a non-response outcome because of inappropriate testing for viral RNA in peripheral blood mononuclear cells (PBMCs). Sequelae of HCV genotype 4 therapy with sofosbuvir and daclatasvir ± ribavirin were assessed in our study at the 12th week after end of treatment (EOT) by screening for viral genomic RNA in serum and PBMCs with correlation to hepatic parenchymal changes. We recruited 102 out of 2165 patients who had received sofosbuvir/daclatasvir, either alone (n = 1573) or together with ribavirin (n = 592). Subjects were classified into three groups based on testing by single-step reverse transcription PCR: group I, HCV negative in both serum and PBMCs (n = 25); group II, HCV positive in PBMCs only (n = 52); and group III, HCV positive in both serum and PBMCs (n = 25). Groups I and II (n = 77) were selected out of 2102 (every 27th subject), while group III (n = 25) were selected from every second or third serologic relapse (n = 63). The pre-sampling population (n = 2165) showed sustained virologic response (SVR) in 33.21%; serologic relapse in 2.91%; HCV RNA only in PBMCs (66.79%) compared to serologic relapses and potential cure (P < 0.0001); higher serologic (38 out of 63, P = 0.03210) and cellular (36 out of 52, P = 0.0002) relapses in dual therapy than in triple therapy. The post-sampling population (n = 102) showed more HCV relapses in dual (50 out of 60) than in triple (27 out of 42) therapy (P = 0.0351); increased HCV antisense RNA strand in relapses compared to positive-sense strands alone (P < 0.001); and significant SVR events in undetectable (15 out of 31) compared to early (10 out of 55, P = 0.0058) and cirrhotic liver tissue changes (0 out of 16, P = 0.0006). In summary, HCV treatment with sofosbuvir/daclatasvir is followed by higher rates of serologic and intracellular viral RNA relapse than treatment with sofosbuvir/daclatasvir plus ribavirin. Cellular and serum viral RNA relapses are accompanied by HCV-induced hepatic pathology. An increased SVR with no detectable liver tissue changes was observed after triple therapy due to elimination of HCV RNA from PBMCs.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , RNA Viral/efeitos dos fármacos , Ribavirina/uso terapêutico , Adulto , Carbamatos/uso terapêutico , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Imidazóis/uso terapêutico , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/virologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Tecido Parenquimatoso/efeitos dos fármacos , Tecido Parenquimatoso/patologia , Pirrolidinas/uso terapêutico , RNA Viral/análise , Prevenção Secundária , Sofosbuvir/uso terapêutico , Resultado do Tratamento , Valina/análogos & derivados , Valina/uso terapêutico
14.
Viruses ; 13(2)2021 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573191

RESUMO

Hepatocytes, the major target of hepatitis C virus (HCV), are highly polarized. HCV infection requires extensive trafficking to distinct subcellular domains in the polarized hepatocyte. Polarized cells and three-dimensional organoids are commonly used to study liver functions and differentiation. Researchers have begun adapting these cell culture models that morphologically and physiologically resemble hepatocytes in vivo to study HCV infection. This review summarizes the use of three-dimensional cell culture systems in studies of HCV infection.


Assuntos
Técnicas de Cultura de Células/métodos , Hepacivirus/fisiologia , Hepatite C/virologia , Animais , Técnicas de Cultura de Células/instrumentação , Hepacivirus/genética , Hepacivirus/crescimento & desenvolvimento , Hepatócitos/virologia , Humanos , Organoides/virologia
15.
New Microbiol ; 44(1): 12-18, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33453702

RESUMO

Currently, treatment of chronic hepatitis C is based on a combination of direct-acting antiviral agents (DAAs) which achieve HCV clearance in more than 95% of patients. Despite this high rate of cure, treatment failures can occur in about 3-5% of treated patients. Resistance associated substitutions (RAS) are commonly detected after virological failure, although their role in real-life DAA failures is still debated. This study aimed to evaluate in real-life DAA-failing patients the prevalence of clinically relevant RASs for the different DAA classes and to identify possible predictors. Fifty consecutive HCV-infected patients who experienced a virological failure to a DAA-containing regimen were included in the study. Direct sequencing of HCV regions involved in DAA resistance (NS3, NS5A and NS5B) was performed with Sanger-based homemade protocols. The presence of mutations in the NS3 and NS5A regions was statistically associated with regimens containing protease inhibitors (p<0.0032) and NS5A inhibitors (p<0.0006), respectively. On the contrary, for the NS5B region, the known mutations associated with the NS5B RNA polymerase inhibitors were detected in treated HCV patients, although there was no statistical significance (p>0.5). A significant correlation was found between the presence of RASs and advanced fibrosis/cirrhosis, but not with age, sex and viral load. Our study demonstrates a high frequency of RASs in patients with DAA failure, thus highlighting the usefulness of genotypic tests in this setting. The identification of RASs may guide the choice of the most appropriate drugs for HCV re-treatment.


Assuntos
Antivirais , Hepatite C Crônica , Antivirais/farmacologia , Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Mutação , Falha de Tratamento , Proteínas não Estruturais Virais/genética
16.
Arch Virol ; 166(2): 501-510, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33394169

RESUMO

With the introduction of direct-acting antiviral treatment (DAA), Tunisia has committed to achieving the international goal of eliminating viral hepatitis. Because the specific DAA prescribed depends on viral genotype, viral genotyping remains of great importance. The aim of the present study was to outline the trends in the distribution of HCV genotypes from 2002 to 2017 in the Tunisian general population in order to guide authorities towards the most appropriate therapeutic strategies for preventing HCV infection. A total of 2532 blood samples were collected over a 16-year period and from all regions of Tunisia. Genotyping showed that genotype 1 (subtype 1b) was the most prevalent genotype in the country (n = 2012; 79.5%), followed by genotype 2 (n = 339; 13.3%). Genotypes 3, 4 and 5 were detected in 4.8%, 2.2% and 0.1% of the country's population, respectively. Mixed infections with different HCV genotypes were detected in 0.1% of the population (one case each of genotypes 1b + 4, 1b + 2 and 2 + 4). Interestingly, a significant increase in genotypes 2, 3 and 4 was observed over time (p = 0.03). Sixteen different subtypes were detected over the study period, most of which were subtypes of genotype 2, and some of these subtypes appeared to be new. Patients infected with genotypes 1a, 3 and 4 were significantly younger than those infected with genotypes 1b and 2 (p < 0.01). Furthermore, genotypes 1b and 2 were detected more often in women than men, while genotypes 1a and 3 were detected mostly in men (P < 0.01). Our study confirms a large predominance of genotype1/subtype1b in Tunisia and shows a significant increase in the prevalence of other genotypes over time. These findings reinforce the need for an additional HCV genotype survey to improve the design of treatment strategies in Tunisia.


Assuntos
Hepacivirus/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Coinfecção/virologia , Feminino , Genótipo , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Tunísia , Adulto Jovem
17.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(1): 153-159, 2021 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-33503713

RESUMO

HCV infection is of global concern with the characteristic of insidious onset. Laboratory testing stands indispensably for clinical diagnosis with antibody assay and nucleic acid testing the main methods being adopted. For early detection and diagnosis of HCV infection, it is important to choose the best detection method and diagnostic strategy. This paper reviews the HCV nucleic acid testing methods, as well as performance evaluation of reagents and current strategies.


Assuntos
Hepatite C , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/diagnóstico , Anticorpos Anti-Hepatite C , Humanos , Técnicas de Amplificação de Ácido Nucleico , Ácidos Nucleicos , RNA Viral/genética
18.
Medicine (Baltimore) ; 100(2): e24137, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466187

RESUMO

ABSTRACT: To provide information and a basis for improved hepatitis C prevention and treatment, we aimed to determine the distribution of hepatitis C virus (HCV) genotypes among patients with hepatitis C from 4 ethnic minorities in Liaoning Province of China over the past 8 years and analyze and explore the virus' genotype evolution and possible clinical significance.For gene-sequencing, we collected peripheral blood samples of HCV-infected patients belonging to the Korean, Hui, Mongol, and Manchu ethnic minorities in Liaoning Province who were diagnosed at the Second Hospital of Dalian Medical University, Anshan Central Hospital, and the Second People's Hospital of Fuxin City between November 2011 and November 2019. To analyze genotype evolution and possible influencing factors, we determined the ratio of various genotypes. Among the 102 HCV-infected patients from 4 ethnic minorities in Liaoning Province, 46 had gene typing (GT)1b (45.10%), 15 had GT2a (14.71%), 14 had GT3a (13.73%), 13 had GT6a (12.75%), 3 had GT1a (2.94%), and 11 had an unclassified genotype (10.78%). The distribution of various genotypes in the Korean, Mongol, and Manchu ethnic minorities was significantly different (χ2 = 10.788, P = .029; χ2 = 7.846, P = .049; and χ2 = 22.400, P = .000, respectively). All ethnic minorities exhibited >40% of GT1b. In the Korean (14/33) and Manchu (14/30) ethnic minorities, the proportion of GT1b was significantly higher than those of other genotypes (P < .05). The ethnic Koreans had a high proportion of GT3a (18.18%, 6/33), whereas the ethnic Mongolians had a high proportion of GT6a (23.08%, 6/26). GT1a was only found in the Korean (6.06%, 2/33) and Manchu (3.33%, 1/30) ethnic minorities; in the Hui ethnic minority, only 3 genotypes were prevalent: GT1b, GT2, and GT3a. The ethnic minorities in Liaoning Province currently have diverse HCV genotypes; the most prevalent genotype is GT1b, followed by GT2a and GT3a, and the prevalence of GT3 and GT6 has increased. The distribution of HCV genotypes varies across different ethnic minorities. The Korean and Manchu ethnic minorities have the most prevalent genotypes, whereas the Hui ethnic minority has a relatively single distribution of the HCV genotype.


Assuntos
Grupos Étnicos/genética , Genótipo , Hepacivirus/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/etnologia , Grupos Étnicos/estatística & dados numéricos , Feminino , Hepatite C/etnologia , Hepatite C/genética , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade
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