المؤلفون: Morgan, Jake R, Marsh, Elizabeth, Savinkina, Alexandra, Shilton, Sonjelle, Shadaker, Shaun, Tsertsvadze, Tengiz, Kamkamidze, George, Alkhazashvili, Maia, Morgan, Timothy, Belperio, Pam, Backus, Lisa, Doss, Waheed, Esmat, Gamal, Hassany, Mohamed, Elsharkawy, Aisha, Elakel, Wafaa, Mehrez, Mai, Foster, Graham R, Kinge, Constance Wose, Chew, Kara W, Chasela, Charles S, Sanne, Ian M, Thanung, Yin M, Loarec, Anne, Aslam, Khawar, Balkan, Suna, Easterbrook, Philippa J, Linas, Benjamin P

المصدر: Journal of Viral Hepatitis. 29(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis - C, Liver Disease, Emerging Infectious Diseases, Digestive Diseases, Infectious Diseases, Hepatitis, Chronic Liver Disease and Cirrhosis, Clinical Research, Infection, Good Health and Well Being, Antiviral Agents, Female, Genotype, Hepacivirus, Hepatitis C, Hepatitis C, Chronic, Humans, Limit of Detection, Male, RNA, Viral, Sustained Virologic Response, Treatment Outcome, Viral Load, Viremia, diagnostics, HCV, limit of detection, point-of-care testing, Microbiology, Medical Microbiology, Gastroenterology & Hepatology, Clinical sciences, Medical microbiology

الوصف: Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9sr287vtTest

المؤلفون: Malik Sallam, Roaa Khalil

المصدر: Microorganisms, Vol 12, Iss 6, p 1035 (2024)

مصطلحات موضوعية: HCV, viral hepatitis, virology, hepatology, genotype, drug resistance, Biology (General), QH301-705.5

الوصف: Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2076-2607/12/6/1035Test; https://doaj.org/toc/2076-2607Test

الوصول الحر: https://doaj.org/article/4cc02d0a55874339bb2b111bb32b01cfTest

المؤلفون: Valencia, Ana, Vergara, Candelaria, Thio, Chloe L, Vince, Nicolas, Douillard, Venceslas, Grifoni, Alba, Cox, Andrea L, Johnson, Eric O, Kral, Alex H, Goedert, James J, Mangia, Alessandra, Piazzolla, Valeria, Mehta, Shruti H, Kirk, Gregory D, Kim, Arthur Y, Lauer, Georg M, Chung, Raymond T, Price, Jennifer C, Khakoo, Salim I, Alric, Laurent, Cramp, Matthew E, Donfield, Sharyne M, Edlin, Brian R, Busch, Michael P, Alexander, Graeme, Rosen, Hugo R, Murphy, Edward L, Wojcik, Genevieve L, Carrington, Mary, Gourraud, Pierre-Antoine, Sette, Alessandro, Thomas, David L, Duggal, Priya

المصدر: American Journal of Human Genetics. 109(2)

مصطلحات موضوعية: Biological Sciences, Biomedical and Clinical Sciences, Immunology, Genetics, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Infectious Diseases, Hepatitis, Hepatitis - C, Liver Disease, Emerging Infectious Diseases, Prevention, Good Health and Well Being, Acute Disease, Alleles, Amino Acid Substitution, Black People, Female, Gene Expression, Genome-Wide Association Study, Genotype, HLA-DQ beta-Chains, Hepacivirus, Hepatitis C, Host-Pathogen Interactions, Humans, Leucine, Male, Polymorphism, Single Nucleotide, Proline, Protein Isoforms, Remission, Spontaneous, White People, GWAS, HCV clearance, HLA imputation, HLA-DQβ1, MHC, fine-mapping, hepatitis C virus, host genetics, infection, trans-ancestral, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences

الوصف: Spontaneous clearance of acute hepatitis C virus (HCV) infection is associated with single nucleotide polymorphisms (SNPs) on the MHC class II. We fine-mapped the MHC region in European (n = 1,600; 594 HCV clearance/1,006 HCV persistence) and African (n = 1,869; 340 HCV clearance/1,529 HCV persistence) ancestry individuals and evaluated HCV peptide binding affinity of classical alleles. In both populations, HLA-DQβ1Leu26 (p valueMeta = 1.24 × 10-14) located in pocket 4 was negatively associated with HCV spontaneous clearance and HLA-DQβ1Pro55 (p valueMeta = 8.23 × 10-11) located in the peptide binding region was positively associated, independently of HLA-DQβ1Leu26. These two amino acids are not in linkage disequilibrium (r2 < 0.1) and explain the SNPs and classical allele associations represented by rs2647011, rs9274711, HLA-DQB1∗03:01, and HLA-DRB1∗01:01. Additionally, HCV persistence classical alleles tagged by HLA-DQβ1Leu26 had fewer HCV binding epitopes and lower predicted binding affinities compared to clearance alleles (geometric mean of combined IC50 nM of persistence versus clearance; 2,321 nM versus 761.7 nM, p value = 1.35 × 10-38). In summary, MHC class II fine-mapping revealed key amino acids in HLA-DQβ1 explaining allelic and SNP associations with HCV outcomes. This mechanistic advance in understanding of natural recovery and immunogenetics of HCV might set the stage for much needed enhancement and design of vaccine to promote spontaneous clearance of HCV infection.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8xj3s0tjTest

المؤلفون: Lim, Joseph K, Liapakis, Ann Marie, Shiffman, Mitchell L, Lok, Anna S, Zeuzem, Stefan, Terrault, Norah A, Park, James S, Landis, Charles S, Hassan, Mohamed, Gallant, Joel, Kuo, Alexander, Pockros, Paul J, Vainorius, Monika, Akushevich, Lucy, Michael, Larry, Fried, Michael W, Nelson, David R, Ben-Ari, Ziv, Group, HCV-TARGET Study

المصدر: Clinical Gastroenterology and Hepatology. 16(11)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Chronic Liver Disease and Cirrhosis, Hepatitis, Emerging Infectious Diseases, Hepatitis - C, Digestive Diseases, Clinical Research, Infectious Diseases, Liver Disease, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Antiviral Agents, Benzimidazoles, Drug Therapy, Combination, Drug-Related Side Effects and Adverse Reactions, Europe, Female, Fluorenes, Genotype, Hepacivirus, Hepatitis C, Chronic, Humans, Liver Cirrhosis, Longitudinal Studies, Male, Middle Aged, North America, Prospective Studies, Ribavirin, Sofosbuvir, Sustained Virologic Response, Treatment Outcome, Young Adult, Real World, Viral Hepatitis, Therapy, HCV-TARGET, HCV-TARGET Study Group, Gastroenterology & Hepatology, Clinical sciences

الوصف: BACKGROUND & AIMS:We aimed to evaluate the safety and effectiveness of 12 or 24 weeks treatment with ledipasvir and sofosbuvir, with or without ribavirin, in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis in routine clinical practice. Patients were followed in a multi-center, prospective, observational cohort study (HCV-TARGET). METHODS:We collected data from 667 treatment-experienced adults with chronic genotype 1 HCV infection who began treatment with ledipasvir and sofosbuvir, with or without ribavirin, from 2011 through September 15, 2016, according to the regional standards of care, at academic (n = 39) and community (n = 18) centers in the United States, Canada, Germany, and Israel. Information was collected from medical records and abstracted into a unique centralized data core. Independent monitors systematically reviewed data entries for completeness and accuracy. Demographic, clinical, adverse event, and virologic data were collected every 12 weeks during treatment and during the follow-up period. The primary efficacy endpoint was sustained virologic response, defined as a level of HCV RNA below the lower limit of quantification or undetectable at a minimum 64 days after the end of treatment (SVR12). The per-protocol population (n = 610) was restricted to patients who completed 12 or 24 weeks of treatment (±2 weeks) and had final virologic outcomes available. RESULTS:The per-protocol analysis revealed that 579 patients (93.8%) achieved an SVR12, including 50/51 patients who received ledipasvir and sofosbuvir for 12 weeks (98%), 384/408 patients who received ledipasvir and sofosbuvir for 24 weeks (94.1%), 68/70 patients who received ledipasvir and sofosbuvir with ribavirin for 12 weeks (97.1%), and 57/60 patients who received ledipasvir and sofosbuvir with ribavirin for 24 weeks (95%). On multivariate analysis, neither treatment duration nor the addition of ribavirin was associated with SVR12. Compensated cirrhosis (odds ratio [OR] compared to decompensated cirrhosis, 2.41; 95% CI, 1.16-5.02), albumin ≥ 3.5 g/dL (OR, 3.15; 95% CI 1.46-6.80), or total bilirubin ≤ 1.2 mg/dL (OR 3.34; 95% CI, 1.59-7.00) were associated with SVR12. CONCLUSIONS:In an analysis of safety and effectiveness data from the HCV-TARGET study, we found treatment with ledipasvir and sofosbuvir, with or without ribavirin, to be effective and well tolerated by treatment-experienced patients with genotype 1 HCV infection and compensated cirrhosis. There were no significant differences in rate of SVR12 among patients treated with ledipasvir and sofosbuvir for 12 or 24 weeks, with or without ribavirin. Patients with decompensated cirrhosis appear to benefit from the addition of ribavirin or extension of ledipasvir and sofosbuvir treatment to 24 weeks. ClinicalTrials.gov no: NCT10474811.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0sg8z5mvTest

المؤلفون: Mohammad Asrar Izhari

المصدر: Diagnostics, Vol 13, Iss 19, p 3102 (2023)

مصطلحات موضوعية: HCV, DAA, RAAS, HCC, genotype, multidrug-resistant, Medicine (General), R5-920

الوصف: Hepatitis C virus (HCV) is a hepatotropic virus that affects millions of human lives worldwide. Direct-acting antiviral (DAA) regimens are the most effective HCV treatment option. However, amino acid substitution-dependent resistance to DAAs has been a major challenge. This study aimed to determine the increasing risk of DAA resistance due to substitutions in DAA target non-structural proteins (NS3/4A, NS5A, and NS5B). Using a Sequence Retrieval System (SRS) at the virus pathogen resource (ViPR/BV-BRC), n = 32763 target protein sequences were retrieved and analyzed for resistance-associated amino acid substitutions (RAASs) by the Sequence Feature Variant Type (SFVT) antiviral-resistance assessment modeling tool. Reference target protein sequences with 100% identity were retried from UniProt following NCBI BLAST. The types and locations of RAASs were identified and visualized by AlphaFold and PyMol. Linux-r-base/R-studio was used for the data presentation. Multi-drug-resistant variants of NS3/4A in genotype 1 (n = 9) and genotype 5 (n = 5) along with DAA-specific NS3/4A, NS5A, and NS5B variants were identified pan-genotypically. A total of 27 variants (RAASs) of all the targets were identified. Fourteen genotype 1-specific substitutions: V1196A, V1158I, D1194A/T/G, R1181K, T1080S, Q1106R, V1062A, S1148G, A1182V, Y2065N, M2000T, and L2003V were identified. The most frequent substitutions were V1062L and L2003M, followed by Q2002H. L2003V, Q2002H, M2000T, Y2065N, and NL2003M of NS5A and L2003M of NS5B conferred resistance to daclatasvir. S2702T NS5B was the sofosbuvir-resistant variant. D1194A NS3/4A was triple DAA (simeprevir, faldaprevir, and asunaprevir) resistant. The double-drug resistant variants R1181K (faldaprevir and asunaprevir), A1182V and Q1106K/R (faldaprevir and simeprevir), T1080S (faldaprevir and telaprevir), and single drug-resistant variants V1062L (telaprevir), D1194E/T (simeprevir), D1194G (asunaprevir), S1148A/G (simeprevir), and Q1106L (Boceprevir) of NS3/4A were determined. The molecular phenomenon of DAA resistance is paramount in the development of HCV drug candidates. RAASs in NS3, NS5A, and NS5B reduce the susceptibility to DAAs; therefore, continuous RAAS-dependent resistance profiling in HCV is recommended to minimize the probability of DAA therapeutic failure.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2075-4418/13/19/3102Test; https://doaj.org/toc/2075-4418Test

الوصول الحر: https://doaj.org/article/6311819cd5d5483aa85018e45d3d68d1Test

المؤلفون: Mehdi Samadi, Vahid Salimi, Mohammad Reza Haghshenas, Seyed Mohammad Miri, Seyed Reza Mohebbi, Amir Ghaemi

المصدر: Virology Journal, Vol 19, Iss 1, Pp 1-14 (2022)

مصطلحات موضوعية: HPgV-1, GBV-C, HIV, HCV, Co-infection, Genotype, Infectious and parasitic diseases, RC109-216

الوصف: Abstract Background Human pegivirus 1 (HPgV-1) is a Positive-sense single-stranded RNA (+ ssRNA) virus, discovered in 1995 as a Flaviviridae member, and the closest human virus linked to HCV. In comparison to HCV, HPgV-1 seems to be lymphotropic and connected to the viral group that infects T and B lymphocytes. HPgV-1 infection is not persuasively correlated to any known human disease; nevertheless, multiple studies have reported a connection between chronic HPgV-1 infection and improved survival in HPgV-1/HIV co-infected patients with a delayed and favorable impact on HIV infection development. While the process has not been thoroughly clarified, different mechanisms for these observations have been proposed. HPgV-1 is categorized into seven genotypes and various subtypes. Infection with HPgV-1 is relatively common globally. It can be transferred parenterally, sexually, and through vertical ways, and thereby its co-infection with HIV and HCV is common. In most cases, the clearance of HPgV-1 from the body can be achieved by developing E2 antibodies after infection. Main body In this review, we thoroughly discuss the current knowledge and recent advances in understanding distinct epidemiological, molecular, and clinical aspects of HPgV-1. Conclusion Due to the unique characteristics of the HPgV-1, so advanced research on HPgV-1, particularly in light of HIV co-infection and other diseases, should be conducted to explore the essential mechanisms of HIV clearance and other viruses and thereby suggest novel strategies for viral therapy in the future.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1743-422XTest

الوصول الحر: https://doaj.org/article/54cc8c69bb08412b9a3ea8fe7a9b32cfTest

المؤلفون: Moreno-Torres, Víctor, de Mendoza, Carmen, Martínez-Urbistondo, María, Mills, Patricia, Treviño, Ana, de la Fuente, Sara, Diaz de Santiago, Alberto, Calderon-Parra, Jorge, Pintos, Ilduara, Corpas, Manuel, Soriano, Vicente

مصطلحات موضوعية: Coronavirus Disease 2019, HCV, genotype, JCR, Scopus

الوصف: Background Underlying immunodeficiency is associated with severe COVID-19, but the prognosis of persons with human immunodeficiency virus (HIV) (PWH) with COVID-19 is under debate. Aim: assessment of the mortality rate and major determinants of death in HIV-infected patients hospitalized with COVID-19 in Spain before vaccine availability. Design: Retrospective nationwide public database analysis. Methods Nationwide, retrospective, observational analysis of all hospitalizations with COVID-19 during year 2020 in Spain. Stratification was made according to HIV status. The National Registry of Hospital Discharges was used with the ICD-10 coding list. Results A total of 117 694 adults were hospitalized with COVID-19 during 2020. Only 234 (0.2%) were HIV-positives. More than 95% were on antiretroviral therapy. Compared to HIV-negatives, PWH were younger (mean age 53.2 vs. 66.5 years old; P<0.001) and more frequently male (74.8% vs. 56.6%; P<0.001). Most co-morbidities predisposing to severe COVID-19 (diabetes, hypertension, dementia and cardiovascular disease) were more frequent in HIV-negatives. In contrast, the rate of baseline liver disease was over 6-fold higher in PWH (27.4% vs. 4.4%; P<0.001). In-hospital mortality was lower in PWH (9.4% vs. 16%; P=0.004). In multivariate analysis, older age, dementia and especially advanced liver disease (relative risk (RR): 7.6) were the major determinants of death in PWH hospitalized with COVID-19. Conclusion HIV-infected patients hospitalized in Spain with COVID-19 during 2020 had better survival than HIV-negatives, most likely explained by younger age and lower rate of co-morbidities. However, advanced liver disease was a major predictor of death in PWH hospitalized with COVID-19.

العلاقة: vol. 116, nº 1; https://academic.oup.com/qjmed/article/116/1/57/6680200Test; V Moreno-Torres, C de Mendoza, M Martínez-Urbistondo, P Mills, A Treviño, S de la Fuente, A Díaz de Santiago, J Calderón-Parra, I Pintos-Pascual, M Corpas, V Soriano, Predictors of in-hospital mortality in HIV-infected patients with COVID-19, QJM: An International Journal of Medicine, Volume 116, Issue 1, January 2023, Pages 57–62, https://doi.org/10.1093/qjmed/hcac215Test; https://reunir.unir.net/handle/123456789/14539Test; https://doi.org/10.1093/qjmed/hcac215Test

الإتاحة: https://doi.org/10.1093/qjmed/hcac215Test
https://reunir.unir.net/handle/123456789/14539Test

المؤلفون: Pegoraro, Karem Aline, Folador, Edson Luiz, Bertolini, Dennis Armando, Campanha, Angela Maria

المصدر: Acta Scientiarum. Health Sciences; Vol 45 (2023): Publicação contínua; e62343 ; Acta Scientiarum. Health Sciences; v. 45 (2023): Publicação contínua; e62343 ; 1807-8648 ; 1679-9291

مصطلحات موضوعية: HCV, antivirals agents, direct-acting antivirals, pharmaceutical services, genotype

الوصف: To report the sociodemographic and clinical profile of patients treated with direct-action antivirals (DAAs). Patients infected with hepatitis C virus in current treatment were followed up in a pharmaceutical office. Sociodemographic, clinical and medicines uses characteristics were obtained. A total of 62 patients were enrolled, with a higher proportion of men, aged between 40 and 69 years, low schooling, and workers. Were predominant the HCV virus genotype 1 (45.2%) and 3 (48.4%), and 19.4% were cirrhotic. Of the referred comorbidities, stood out those diseases related to the cardiovascular system (19.8%), psychiatric disorders (17.6%), endocrine and metabolic disorders (14.5%). Co-infections represented 5.2%, and were distributed between acute hepatitis A (1.0%), chronic viral hepatitis B (2.1%), and HIV (2.1%). Previous or current use of licit / illicit substances was reported by 33.9% of patients. A significant difference was identified in the youngest age group (25 to 39 years, p = 0.02), with a lower average viral load compared to the other age groups. The pharmacotherapeutic follow-up carried out in the period resulted in 157 pharmaceutical consultations. Patients with hepatitis C using DDAs were mostly men, aged between 40 and 69 years. Type 3 HCV genotype was most frequently identified. The presence of cirrhosis and other comorbidities serves as an alert for health professionals in the implementation of public health policies. ; To report the sociodemographic and clinical profile of patients treated with direct-action antivirals (DAAs). Patients infected with hepatitis C virus in current treatment were followed up in a pharmaceutical office. Sociodemographic, clinical and medicines uses characteristics were obtained. A total of 62 patients were enrolled, with a higher proportion of men, aged between 40 and 69 years, low schooling, and workers. Were predominant the HCV virus genotype 1 (45.2%) and 3 (48.4%), and 19.4% were cirrhotic. Of the referred comorbidities, stood out those diseases related to the ...

وصف الملف: application/pdf

العلاقة: http://eduemojs.uem.br/ojs/index.php/ActaSciHealthSci/article/view/62343/751375156655Test; http://eduemojs.uem.br/ojs/index.php/ActaSciHealthSci/article/view/62343Test

الإتاحة: https://doi.org/10.4025/actascihealthsci.v45i1.62343Test
http://eduemojs.uem.br/ojs/index.php/ActaSciHealthSci/article/view/62343Test

المؤلفون: Bajpai, Priyanka Shukla, Collignon, Laura, Sølund, Christina, Madsen, Lone Wulff, Christensen, Peer Brehm, Øvrehus, Anne Lindebo Holm, Weis, Nina, Holmbeck, Kenn, Fahnøe, Ulrik, Bukh, Jens

المصدر: Bajpai , P S , Collignon , L , Sølund , C , Madsen , L W , Christensen , P B , Øvrehus , A L H , Weis , N , Holmbeck , K , Fahnøe , U & Bukh , J 2023 , ' Full-length sequence analysis of hepatitis C virus genotype 3b strains and development of an in vivo infectious 3b cDNA clone ' , Journal of Virology , vol. 97 , no. 12 , e0092523 . https://doi.org/10.1128/jvi.00925-23Test

مصطلحات موضوعية: HCV, RAS, genotype 3b, hepatitis C virus, human-liver chimeric mice, in vivo infectious cDNA clone, resistance-associated substitutions, Genome, Viral, Hepacivirus/genetics, Humans, Hepatitis C/virology, Genotype, DNA, Complementary/genetics, Animals, Antiviral Agents/therapeutic use, Mice, Sequence Analysis

الوصف: Worldwide, genotype 3 is the second most prevalent major variant among patients with chronic hepatitis C virus (HCV) infection and the most difficult to treat with direct-acting antivirals (DAAs). Further, subtype 3b, which is highly prevalent in Southeast Asia with increasing transmission in high-risk populations, carries paired NS5A resistance-associated substitutions (RAS), NS5A-A30K+L31M, conferring resistance to DAA therapy and lowering cure rates with pan-genotypic regimens. However, no complete genomic sequence or infectious clone exists for HCV genotype 3b. We determined the entire genome sequences, including 5′ and 3′ termini, of HCV genotype 3b isolates from three treatment naïve chronic hepatitis C patients, and by clonal analysis of the entire coding sequence demonstrated heterogeneous genome population compositions all carrying RAS A30K+L31M in NS5A. We generated a full-length HCV genotype 3b cDNA clone (pODN) and transfected Huh7.5 and Huh-Lunet/SEC14L2 cells with derived RNA transcripts without detecting HCV antigens by immunofluorescence staining. In contrast, intrahepatic transfection with RNA transcripts from pODN, and subsequent virus passages, in human-liver chimeric mice resulted in robust infection with serum HCV RNA titers of up to 7.9 log 10 genome equivalents/mL. Consensus HCV sequences of virus recovered from the transfected mouse contained no coding mutations exceeding 5% frequency, and sequences from the passage-infected mice likewise had no consensus changes. Thus, we developed the first HCV genotype 3b full-length cDNA clone which by its infectivity and genetic stability in human-liver chimeric mice proved functionality, and potential utility in future development of infectious cell culture systems needed for this DAA treatment-resistant subtype. IMPORTANCE HCV genotype 3b is a difficult-to-treat subtype, associated with accelerated progression of liver disease and resistance to antivirals. Moreover, its prevalence has significantly increased among persons who inject drugs posing a ...

العلاقة: https://portal.findresearcher.sdu.dk/da/publications/2259b410-a96b-42b4-b402-1d0078bb63afTest

الإتاحة: https://doi.org/10.1128/jvi.00925-23Test
https://portal.findresearcher.sdu.dk/da/publications/2259b410-a96b-42b4-b402-1d0078bb63afTest
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10734419/pdf/jvi.00925-23.pdfTest

المؤلفون: Karem Aline Pegoraro, Edson Luiz Folador, Dennis Armando Bertolini, Angela Maria Campagna

المصدر: Acta Scientiarum. Health Sciences, Vol 45, Iss 1 (2023)

مصطلحات موضوعية: HCV, antivirals agents, direct-acting antivirals, pharmaceutical services, genotype, Medicine (General), R5-920, Pharmacy and materia medica, RS1-441

الوصف: To report the sociodemographic and clinical profile of patients treated with direct-action antivirals (DAAs). Patients infected with hepatitis C virus in current treatment were followed up in a pharmaceutical office. Sociodemographic, clinical and medicines uses characteristics were obtained. A total of 62 patients were enrolled, with a higher proportion of men, aged between 40 and 69 years, low schooling, and workers. Were predominant the HCV virus genotype 1 (45.2%) and 3 (48.4%), and 19.4% were cirrhotic. Of the referred comorbidities, stood out those diseases related to the cardiovascular system (19.8%), psychiatric disorders (17.6%), endocrine and metabolic disorders (14.5%). Co-infections represented 5.2%, and were distributed between acute hepatitis A (1.0%), chronic viral hepatitis B (2.1%), and HIV (2.1%). Previous or current use of licit / illicit substances was reported by 33.9% of patients. A significant difference was identified in the youngest age group (25 to 39 years, p = 0.02), with a lower average viral load compared to the other age groups. The pharmacotherapeutic follow-up carried out in the period resulted in 157 pharmaceutical consultations. Patients with hepatitis C using DDAs were mostly men, aged between 40 and 69 years. Type 3 HCV genotype was most frequently identified. The presence of cirrhosis and other comorbidities serves as an alert for health professionals in the implementation of public health policies.

العلاقة: https://periodicos.uem.br/ojs/index.php/ActaSciHealthSci/article/view/62343Test; https://doaj.org/toc/1679-9291Test; https://doaj.org/toc/1807-8648Test; https://doaj.org/article/b3e49827c3fb4e459b577dceebfc8cffTest

الإتاحة: https://doi.org/10.4025/actascihealthsci.v45i1.62343Test
https://doaj.org/article/b3e49827c3fb4e459b577dceebfc8cffTest