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Wang YP, Yang SW, Jia F, Wang W, Xu X, Wang YX, Bi JF, Li BA. Effect of concentration, temperature, and time on the stability of hepatitis C virus nucleic acid in serum. Microbiol Spectr 2024; 12:e0076924. [PMID: 39269208 PMCID: PMC11448131 DOI: 10.1128/spectrum.00769-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Accepted: 07/11/2024] [Indexed: 09/15/2024] Open
Abstract
To explore the influence of storage temperature and time on the stability of different concentrations of hepatitis C virus nucleic acid (HCV RNA) samples and to provide data reference for laboratory quality control. Serum samples of 10 patients with HCV RNA detection quantitation of 106-108 IU/mL were collected. The samples of each patient were diluted into three concentrations: high, medium, and low. Then the samples of each concentration were divided into 21, which were divided into three groups according to the storage conditions of -20°C, 4°C, and 25°C, with seven samples in each group. The samples were selected from each group for quantitative detection of HCV RNA on day 0, day 1, day 3, day 5, day 7, day 14, and day 30. The results of each concentration and storage temperature sample remained stable within 5 days. Based on the mixed-effect linear model, the main effects of temperature, time, and concentration were statistically significant (P < 0.01). There was an interaction effect between concentration and time (P = 0.0448), and there was also an interaction effect between temperature and time (P < 0.01). There was no interaction effect between concentration and temperature (P = 0.11) or between concentration, temperature, and time (P = 0.90). The results of serum samples with different concentrations of the HCV RNA remained stable within 5 days. The lower the initial concentration of HCV RNA serum sample, the worse the stability; the higher the storage temperature, the worse the stability. If conditions permit, the laboratory should store such samples at -20°C. IMPORTANCE Previously, there were few reports about the influence of different concentrations of sample nucleic acid on the stability of samples at various temperatures and times in various literatures. Therefore, it is necessary to analyze the influence of concentration factors on the stability of samples and test results at different storage times and temperatures. This study took the concentration of hepatitis C virus nucleic acid as the research object to further understand the stability of hepatitis C virus nucleic acid test samples under various storage conditions, to provide data reference for the treatment of hepatitis C virus nucleic acid and RNA test samples before clinical laboratory test, and provide guidance and help for the improvement of laboratory quality control.
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Affiliation(s)
- Ya-Pei Wang
- Laboratory Department, Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Shu-Wen Yang
- Grade 2022 Postgraduate Class, School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China
- Phase I Clinical Trial Ward, Senior Department of Infectious Diseases Medicine, Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Fan Jia
- Laboratory Department, Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Wei Wang
- Laboratory Department, Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xue Xu
- Phase I Clinical Trial Ward, Senior Department of Infectious Diseases Medicine, Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
- Grade 2021 Postgraduate Class, School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yi-Xuan Wang
- Grade 2022 Postgraduate Class, School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China
- Phase I Clinical Trial Ward, Senior Department of Infectious Diseases Medicine, Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Jing-Feng Bi
- Phase I Clinical Trial Ward, Senior Department of Infectious Diseases Medicine, Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China
| | - Bo-An Li
- Laboratory Department, Fifth Medical Center of PLA General Hospital, Beijing, China
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Begum TF, Patil VS, Zhu L, Yeh MC, González E, Fraser MA, Lu W, Zhu S, Rubio-Torio N, Ma GX, Tan Y. Assessing Physicians' Recommendations for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Testing Among Minority Populations in Greater Philadelphia and New York City. J Community Health 2024; 49:588-597. [PMID: 38286964 DOI: 10.1007/s10900-023-01316-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/26/2023] [Indexed: 01/31/2024]
Abstract
Deaths from liver cancer are on the rise and disproportionately affect minority racial/ethnic groups. In this study, we examined associations between physicians' recommendations for hepatitis B virus (HBV) and hepatitis C virus (HCV) screening and sociodemographic and lifestyle factors among minority populations in the areas of Greater Philadelphia and New York City. Using Poisson regression with robust variance estimation, we evaluated potential associations for 576 Hispanic American (HA), African American (AA), and Asian Pacific American (APA) adults, using blood tests as an outcome measure, with adjustment for sociodemographic factors We found that APAs (34.2%) were most likely to have a physician recommend HBV and HCV screening tests (34.2% and 27.1%, respectively), while HAs were least likely to receive an HBV recommendation (15.0%) and AAs were least likely to receive an HCV recommendation (15.3%). HAs were significantly likely to have never received a blood test for either HBV or HCV (RR = 1.25, 95% CI: 1.05, 1.49). APAs were significantly more likely to receive a screening recommendation for HBV (RR = 1.10, 95%CI: 1.01, 1.20) and to have a blood test (RR = 1.57, 95% CI: 1.06, 2.33). Our findings show that, among HAs, AAs, and APAs, physician recommendations are strongly associated with patients undergoing blood tests for HBV and HCV and that minority populations should increasingly be recommended to screen for HBV and HCV, especially given their elevated risk.
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Affiliation(s)
- Thoin F Begum
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
| | - Vidya S Patil
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
| | - Lin Zhu
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
- Department of Urban Health and Population Science, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
| | - Ming-Chin Yeh
- Nutrition Program, Hunter College, City University of New York, New York, NY, USA
| | - Evelyn González
- Office of Community Outreach, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA
| | | | - Wenyue Lu
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
| | - Steven Zhu
- Pennsylvania United Chinese Coalition, Philadelphia, PA, USA
| | | | - Grace X Ma
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
- Department of Urban Health and Population Science, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
| | - Yin Tan
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
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Lam L, Carrieri P, Hejblum G, Bellet J, Bourlière M, Carrat F. Real-world economic burden of hepatitis C and impact of direct-acting antivirals in France: A nationwide claims data analysis. Liver Int 2024; 44:1233-1242. [PMID: 38375961 DOI: 10.1111/liv.15872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 01/04/2024] [Accepted: 02/08/2024] [Indexed: 02/21/2024]
Abstract
BACKGROUND AND AIMS The economic impact of managing patients with hepatitis C virus (HCV) infection remains unknown. This study aimed to assess the economic burden of chronic HCV infection from a national health insurance perspective and the impact of direct-acting antivirals (DAAs) using nationwide real-world data. METHODS Patients with chronic HCV infection were identified from the French Health Insurance Claims Databases (SNDS) and matched for age and sex to the general population. Health resource utilization and reimbursements were summarized according to healthcare expenditure items from 2012 to 2021. The economic burden attributable to chronic HCV infection was evaluated over a 10-year period. Finally, the impact of DAAs was estimated using economic data derived from the SNDS. RESULTS A total of 145 187 patients with chronic HCV infection were identified. Among the patients eligible for DAA therapy, 81.5% had received DAA by the end of 2021. Over a 10-year period, managing patients with chronic HCV infection resulted in an additional cost of €9.71 billion (95% confidence interval [CI]: €9.66-€9.78 billion) or €9191 (95% CI: €9134-€9252) per patient per year compared to the general population. After DAA therapy, patients with chronic HCV infection had a higher economic burden than the general population, with an additional cost of €5781 (95% CI: €5540-€6028) per patient at the fifth-year post-DAA therapy. CONCLUSIONS A significant economic burden persists among patients with HCV infection after DAA treatment. The high proportion of patients not treated with DAA therapy supports reinforcing policies for universal access.
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Affiliation(s)
- Laurent Lam
- INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Sorbonne Université, Paris, France
| | - Patrizia Carrieri
- INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Aix Marseille Univ, Marseille, France
| | - Gilles Hejblum
- INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Sorbonne Université, Paris, France
| | - Jonathan Bellet
- INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Sorbonne Université, Paris, France
| | - Marc Bourlière
- Department of Hepatology and Gastroenterology, Hôpital Saint Joseph, Marseille, France
- INSERM, UMR 1252 IRD SESSTIM, Aix Marseille Université, Marseille, France
| | - Fabrice Carrat
- INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Sorbonne Université, Paris, France
- Department of Public Health, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Sorbonne Université, Paris, France
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4
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Cusato J, Mulasso A, Ferrara M, Manca A, Antonucci M, Accardo G, Palermiti A, Bianco G, Chiara F, Mula J, Maddalone MG, Tettoni MC, Cuomo S, Trevisan G, Bonora S, Di Perri G, Lupo C, Rainoldi A, D’Avolio A. Studying the Changes in Physical Functioning and Oxidative Stress-Related Molecules in People Living with HIV after Switching from Triple to Dual Therapy. Antioxidants (Basel) 2024; 13:518. [PMID: 38790623 PMCID: PMC11117521 DOI: 10.3390/antiox13050518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 04/19/2024] [Accepted: 04/24/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND Physical activity could increase the production of oxidative stress biomarkers, affecting the metabolism and excretion of antiretroviral drugs and, consequently, the clinical outcome. Nowadays, people living with HIV (PLWH) are mostly switching from triple to dual therapy, but no data are available in terms of physical functioning and oxidative stress. The aim of this study was to evaluate if some antioxidant biomarkers and physical functioning tests could be different according to triple or dual antiretroviral therapy. METHODS PLWH were evaluated at baseline (BL), while treated with three drugs, and six months after the switch to dual therapy. Physical functioning was quantified using validated tools. Mitochondrial and cytosol antioxidant molecules were evaluated through liquid chromatography. RESULTS Twenty-five patients were analyzed. A statistically significant difference between triple and dual therapy was found for mitochondrial glutathione, but not for physical tests. Evaluating differences between physically active and inactive individuals, the following statistically significant differences were suggested, considering triple therapy (mitochondrial n-formyl-methionine p = 0.022, triglycerides p = 0.023) and double therapy (mitochondrial glycine p = 0.035, cytosol glutamic acid p = 0.007, cytosol s-adenosylmethionine p = 0.021). CONCLUSIONS For the first time, this study suggests possible differences in terms of antioxidant molecules and physical functioning in PLWH switching from triple to dual therapy.
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Affiliation(s)
- Jessica Cusato
- Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (J.C.); (A.P.); (G.B.); (J.M.); (M.G.M.)
| | - Anna Mulasso
- NeuroMuscolarFunction|Research Group, Department of Medical Sciences, University of Turin, 10128 Turin, Italy; (A.M.); (S.C.); (C.L.); (A.R.)
| | - Micol Ferrara
- ASL Città di Torino, Amedeo di Savoia Hospital, 10149 Turin, Italy; (M.F.); (M.A.); (M.C.T.)
| | - Alessandra Manca
- Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (J.C.); (A.P.); (G.B.); (J.M.); (M.G.M.)
| | - Miriam Antonucci
- ASL Città di Torino, Amedeo di Savoia Hospital, 10149 Turin, Italy; (M.F.); (M.A.); (M.C.T.)
| | - Guido Accardo
- Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (G.A.); (G.T.); (S.B.); (G.D.P.)
| | - Alice Palermiti
- Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (J.C.); (A.P.); (G.B.); (J.M.); (M.G.M.)
| | - Gianluca Bianco
- Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (J.C.); (A.P.); (G.B.); (J.M.); (M.G.M.)
| | - Francesco Chiara
- Laboratory of Clinical Pharmacology S. Luigi A.O.U., Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole, Orbassano, 10043 Turin, Italy;
| | - Jacopo Mula
- Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (J.C.); (A.P.); (G.B.); (J.M.); (M.G.M.)
| | - Maria Grazia Maddalone
- Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (J.C.); (A.P.); (G.B.); (J.M.); (M.G.M.)
| | - Maria Cristina Tettoni
- ASL Città di Torino, Amedeo di Savoia Hospital, 10149 Turin, Italy; (M.F.); (M.A.); (M.C.T.)
| | - Simone Cuomo
- NeuroMuscolarFunction|Research Group, Department of Medical Sciences, University of Turin, 10128 Turin, Italy; (A.M.); (S.C.); (C.L.); (A.R.)
| | - Giulia Trevisan
- Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (G.A.); (G.T.); (S.B.); (G.D.P.)
| | - Stefano Bonora
- Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (G.A.); (G.T.); (S.B.); (G.D.P.)
| | - Giovanni Di Perri
- Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (G.A.); (G.T.); (S.B.); (G.D.P.)
| | - Corrado Lupo
- NeuroMuscolarFunction|Research Group, Department of Medical Sciences, University of Turin, 10128 Turin, Italy; (A.M.); (S.C.); (C.L.); (A.R.)
| | - Alberto Rainoldi
- NeuroMuscolarFunction|Research Group, Department of Medical Sciences, University of Turin, 10128 Turin, Italy; (A.M.); (S.C.); (C.L.); (A.R.)
| | - Antonio D’Avolio
- Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy; (J.C.); (A.P.); (G.B.); (J.M.); (M.G.M.)
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Lin J, Yang LY, Pan ZD. Identification of Potential Bioactive Compounds from Aspergillus terreus against HCV NS3 Serine Protease. Chem Biodivers 2023; 20:e202300532. [PMID: 37369824 DOI: 10.1002/cbdv.202300532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 06/24/2023] [Accepted: 06/27/2023] [Indexed: 06/29/2023]
Abstract
This study was aimed to isolate bioactive compounds from the fermentation products of Aspergillus terreus, which could inhibit NS3 protease of hepatitis C virus (HCV). The bioactive compounds were isolated by reverse-phase silica-gel column chromatography, semi-preparative reversed-phase, and Sephadex LH-20, and then their structures were elucidated through spectroscopic analysis. As a result, two small molecule compounds were isolated. Compound 1 was identified as a new benzaldehyde, (E)-2,4-dihydroxy-6-propenylbenzaldehyde. Compound 2 was identified as pleurone, which was obtained from microorganisms for the first time. Their inhibitory activities against HCV NS3 protease (IC50 ) were 32.6 μM and 78.9 μM, respectively. This study provided a new option for the development of anti-HCV drugs.
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Affiliation(s)
- Jun Lin
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, China
| | - Li-Yuan Yang
- State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, China
| | - Zhi-Di Pan
- State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, China
- Jecho Institute, Co., Ltd., Shanghai, 200240, China
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Luo ML, Zhao Q, He XH, Xie X, Zhu HP, You FM, Peng C, Zhan G, Huang W. Research progress of indole-fused derivatives as allosteric modulators: Opportunities for drug development. Biomed Pharmacother 2023; 162:114574. [PMID: 36996677 DOI: 10.1016/j.biopha.2023.114574] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 03/12/2023] [Accepted: 03/21/2023] [Indexed: 03/30/2023] Open
Abstract
Allosteric modulation is a direct and effective method for regulating the function of biological macromolecules, which play vital roles in various cellular activities. Unlike orthosteric modulators, allosteric modulators bind to sites distant from the protein's orthosteric/active site and can have specific effects on the protein's function or activity without competing with endogenous ligands. Compared to traditional orthosteric modulators, allosteric modulators offer several advantages, including reduced side effects, greater specificity, and lower toxicity, making them a promising strategy for developing novel drugs. Indole-fused architectures are widely distributed in natural products and bioactive drug leads, displaying diverse biological activities that attract the interest of both chemists and biologists in drug discovery. Currently, an increasing number of indole-fused compounds have exhibited potent activities in allosteric modulation. In this review, we provide a brief summary of examples of allosteric modulators based on the indole-fused complex architecture, highlighting the strategies for drug design/discovery and the structure-activity relationships of allosteric modulators from the perspective of medicinal chemistry.
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7
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Salama II, Sami SM, Salama SI, Abdel-Latif GA, Shaaban FA, Fouad WA, Abdelmohsen AM, Raslan HM. Current and novel modalities for management of chronic hepatitis B infection. World J Hepatol 2023; 15:585-608. [PMID: 37305370 PMCID: PMC10251278 DOI: 10.4254/wjh.v15.i5.585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 03/13/2023] [Accepted: 04/12/2023] [Indexed: 05/24/2023] Open
Abstract
Over 296 million people are estimated to have chronic hepatitis B viral infection (CHB), and it poses unique challenges for elimination. CHB is the result of hepatitis B virus (HBV)-specific immune tolerance and the presence of covalently closed circular DNA as mini chromosome inside the nucleus and the integrated HBV. Serum hepatitis B core-related antigen is the best surrogate marker for intrahepatic covalently closed circular DNA. Functional HBV “cure” is the durable loss of hepatitis B surface antigen (HBsAg), with or without HBsAg seroconversion and undetectable serum HBV DNA after completing a course of treatment. The currently approved therapies are nucleos(t)ide analogues, interferon-alpha, and pegylated-interferon. With these therapies, functional cure can be achieved in < 10% of CHB patients. Any variation to HBV or the host immune system that disrupts the interaction between them can lead to reactivation of HBV. Novel therapies may allow efficient control of CHB. They include direct acting antivirals and immunomodulators. Reduction of the viral antigen load is a crucial factor for success of immune-based therapies. Immunomodulatory therapy may lead to modulation of the host immune system. It may enhance/restore innate immunity against HBV (as toll-like-receptors and cytosolic retinoic acid inducible gene I agonist). Others may induce adaptive immunity as checkpoint inhibitors, therapeutic HBV vaccines including protein (HBsAg/preS and hepatitis B core antigen), monoclonal or bispecific antibodies and genetically engineered T cells to generate chimeric antigen receptor-T or T-cell receptor-T cells and HBV-specific T cells to restore T cell function to efficiently clear HBV. Combined therapy may successfully overcome immune tolerance and lead to HBV control and cure. Immunotherapeutic approaches carry the risk of overshooting immune responses causing uncontrolled liver damage. The safety of any new curative therapies should be measured in relation to the excellent safety of currently approved nucleos(t)ide analogues. Development of novel antiviral and immune modulatory therapies should be associated with new diagnostic assays used to evaluate the effectiveness or to predict response.
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Affiliation(s)
- Iman Ibrahim Salama
- Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
| | - Samia M Sami
- Department of Child Health, National Research Centre, Giza 12411, Dokki, Egypt
| | - Somaia I Salama
- Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
| | - Ghada A Abdel-Latif
- Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
| | - Fatma A Shaaban
- Department of Child Health, National Research Centre, Giza 12411, Dokki, Egypt
| | - Walaa A Fouad
- Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
| | - Aida M Abdelmohsen
- Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt
| | - Hala M Raslan
- Department of Internal Medicine, National Research Centre, Giza 12411, Dokki, Egypt
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Carvalho TL, Mertens Brainer de Queiroz Lima AC, de Araújo NS, de Sousa Fernandes MS, Lira GB, de Melo MMM, Vasconcelos LRS, de Moura PMMF, da Cunha Correia C. Aspects of cognitive assessments and spectroscopic magnetic resonance imaging in people with chronic hepatitis C: a systematic review. PSYCHOL HEALTH MED 2023; 28:1013-1029. [PMID: 35075963 DOI: 10.1080/13548506.2022.2029915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Extrahepatic manifestations are common in people with hepatitis C virus (HCV). Cognitive changes are pointed out, but the mechanisms are still uncertain. The aim of this systematic review was to analyze studies involving spectroscopic magnetic resonance in people infected with HCV, which also included cognitive tests. The research occurred in six databases (Directory of Open Access Journals, Lilacs, Medcaribe, Medline, Scielo and ScienceDirect) and the selection of studies was carried out in two stages: search for titles and abstracts, then reading of the full articles, excluding those that did not meet the eligibility criteria. 12,888 titles and abstracts were selected, but only 6 articles were included in the review. Impairments in attention, concentration, speed of information processing, memory, verbal fluency and executive functions were identified as well as an increase in the Cho/Cr and mI/Cr ratios and a reduction in the NAA/Cr ratio in some included studies. Longitudinal studies, with more homogeneous samples and methods, as well as with better controlled confounding factors, are necessary to adequately identify the effect of HCV on the brain.
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Affiliation(s)
- Tatiana Lins Carvalho
- Hospital Universitário Oswaldo Cruz, Pós-Graduação em Ciências da Saúde, Universidade de Pernambuco (UPE), Recife, Brazil
| | | | | | - Matheus Santos de Sousa Fernandes
- Departamento de Fisiologia e Farmacologia, Pós-graduação Em Neuropsiquiatria e Ciências do Comportamento, Universidade Federal de Pernambuco (UFPE), Recife, Brazil
| | - Gabriela Barza Lira
- Programa de Pós-graduação de Saúde da Criança e do Adolescente, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil
| | | | | | | | - Carolina da Cunha Correia
- Professor of Neurology and Post Graduate Course in Health Sciences, Universidade de Pernambuco (UPE), Recife, PE, Brazil
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Pandey B, Baral R, Kaundinnyayana A, Panta S. Promising hepatoprotective agents from the natural sources: a study of scientific evidence. EGYPTIAN LIVER JOURNAL 2023. [DOI: 10.1186/s43066-023-00248-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/31/2023] Open
Abstract
Abstract
Background
Natural bioactive components derived from plant secondary metabolites have been pronounced as valuable alternatives for anticipating and subsiding hepatotoxic effects and its chronic complications based on experimental verification. The focus of this review is to elucidate the commonly used modern medicine for the treatment of liver disease and how major phytoconstituents have been tested for hepatoprotective activity, mechanism of action of some promising agents from natural sources, and clinical trial data for treating in patients with different liver diseases by the aid of natural phytoconstituents.
Main text
The review shows fifteen major isolated phytoconstituents, their biological sources, chemical structures, utilized plant parts, type of extracts used, hepatoprotective assay method, and their possible mechanism of action on the hepatoprotection. Nine promising hepatoprotective leads from natural sources with their chemistry and hepatoprotective mechanism are mentioned briefly. The review further includes the recent clinical trial studies of some hepatoprotective leads and their clinical outcome with different liver disease patients. Scientific studies revealed that antioxidant properties are the central mechanism for the phytoconstituents to subside different disease pathways by upsurging antioxidant defense system of cells, scavenging free radicals, down surging lipid peroxidation, improving anti-inflammatory potential, and further protecting the hepatic cell injury. In this review, we summarize recent development of natural product-based hepatoprotective leads and their curative potential for various sort of liver diseases. Furthermore, the usefulness of hit and lead molecules from natural sources for significant clinical benefit to discover new drug molecule and downsizing the problems of medication and chemical-induced hepatotoxic effects is extrapolated.
Conclusion
Further research are encouraged to elucidate the pharmacological principle of these natural-based chemical agents which will stimulate future pharmaceutical development of therapeutically beneficial hepatoprotective regimens.
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Kovács ZM, Óvári J, Dienes C, Magyar J, Bányász T, Nánási PP, Horváth B, Feher A, Varga Z, Szentandrássy N. ABT-333 (Dasabuvir) Increases Action Potential Duration and Provokes Early Afterdepolarizations in Canine Left Ventricular Cells via Inhibition of I Kr. Pharmaceuticals (Basel) 2023; 16:488. [PMID: 37111245 PMCID: PMC10143825 DOI: 10.3390/ph16040488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 03/17/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
ABT-333 (dasabuvir) is an antiviral agent used in hepatitis C treatment. The molecule, similarly to some inhibitors of hERG channels, responsible for the delayed rectifier potassium current (IKr), contains the methanesulfonamide group. Reduced IKr current leads to long QT syndrome and early afterdepolarizations (EADs), therefore potentially causing life-threatening arrhythmias and sudden cardiac death. Our goal was to investigate the acute effects of ABT-333 in enzymatically isolated canine left ventricular myocardial cells. Action potentials (APs) and ion currents were recorded with a sharp microelectrode technique and whole-cell patch clamp, respectively. Application of 1 μM ABT-333 prolonged the AP in a reversible manner. The maximal rates of phases 0 and 1 were irreversibly decreased. Higher ABT-333 concentrations caused larger AP prolongation, elevation of the early plateau potential, and reduction of maximal rates of phases 0, 1, and 3. EADs occurred in some cells in 3-30 μM ABT-333 concentrations. The 10 μM ABT-333-sensitive current, recorded with AP voltage clamp, contained a late outward component corresponding to IKr and an early outward one corresponding to transient outward potassium current (Ito). ABT-333 reduced hERG-channel-mediated ion current in a concentration-dependent, partially reversible manner with a half-inhibitory concentration of 3.2 μM. As the therapeutic plasma concentration of ABT-333 can reach the low μM range, ABT-333 application carries a risk of cardiac side effects especially in case of coadministration with strong inhibitors of CYP2C8.
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Affiliation(s)
- Zsigmond Máté Kovács
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Doctoral School of Molecular Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - József Óvári
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Doctoral School of Dental Sciences, University of Debrecen, H-4032 Debrecen, Hungary
| | - Csaba Dienes
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Doctoral School of Molecular Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - János Magyar
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Tamás Bányász
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Péter P. Nánási
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, H-4032 Debrecen, Hungary
| | - Balázs Horváth
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Adam Feher
- Doctoral School of Molecular Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Zoltan Varga
- Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
| | - Norbert Szentandrássy
- Department of Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
- Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, H-4032 Debrecen, Hungary
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11
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ZABARA M, TROFIN AM, CADAR R, NASTASE A, BLAJ M, CIUNTU BM, GARLEANU I, LUPASCU-URSULESCU C, LUPASCU C. Prognostic factors for outcome of liver transplantion hepatitis C cirrhosis. Chirurgia (Bucur) 2023. [DOI: 10.23736/s0394-9508.22.05393-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
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12
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Lam L, Fontaine H, Lapidus N, Bellet J, Lusivika-Nzinga C, Nicol J, Dorival C, Cagnot C, Hejblum G, Pol S, Bourlière M, Carrat F. Performance of algorithms for identifying patients with chronic hepatitis B or C infection in the french health insurance claims databases using the ANRS CO22 HEPATHER cohort. J Viral Hepat 2023; 30:232-241. [PMID: 36529681 DOI: 10.1111/jvh.13788] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 02/16/2023]
Abstract
The validity of algorithms for identifying patients with chronic hepatitis B or C virus (HBV or HCV) infection in claims databases has been little explored. The performance of 15 algorithms was evaluated. Data from HBV- or HCV-infected patients enrolled between August 2012 and December 2015 in French hepatology centres (ANRS CO22 HEPATHER cohort) were individually linked to the French national health insurance system (SNDS). The SNDS covers 99% of the French population and contains healthcare reimbursement data. Performance metrics were calculated by comparing the viral status established by clinicians with those obtained with the algorithms identifying chronic HBV- and HCV-infected patients. A total of 14 751 patients (29% with chronic HBV and 63% with chronic HCV infection) followed-up until December 2018 were selected. Despite good specificity, the algorithms relying on ICD-10 codes performed poorly. By contrast, the multi-criteria algorithms combining ICD-10 codes, antiviral dispensing, laboratory diagnostic tests (HBV DNA or HCV RNA detection and quantification, HCV genotyping), examinations for the assessment of liver fibrosis and long-term disease registrations were the most effective (sensitivity 0.92, 95% CI, 0.91-0.93 and specificity 0.96, 95% CI, 0.95-0.96 for identifying chronic HBV-infected patients; sensitivity 0.94, 95% CI, 0.94-0.94 and specificity 0.85, 95% CI, 0.84-0.86 for identifying chronic HCV-infected patients). In conclusion, the multi-criteria algorithms perform well in identifying patients with chronic hepatitis B or C infection and can be used to estimate the magnitude of the public health burden associated with hepatitis B and C in France.
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Affiliation(s)
- Laurent Lam
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Hélène Fontaine
- Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France
| | - Nathanael Lapidus
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France.,Department of Public Health, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Sorbonne Université, Paris, France
| | - Jonathan Bellet
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Clovis Lusivika-Nzinga
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Jérôme Nicol
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Céline Dorival
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France
| | | | - Gilles Hejblum
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Stanislas Pol
- Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France.,Université de Paris Cité, Paris, France
| | - Marc Bourlière
- Department of Hepatology and Gastroenterology, Hôpital Saint Joseph, Marseille, France.,INSERM, UMR 1252 IRD SESSTIM, Aix Marseille Université, Marseille, France
| | - Fabrice Carrat
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France.,Department of Public Health, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Sorbonne Université, Paris, France
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13
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Behmard E, Abdulabbas HT, Abdalkareem Jasim S, Najafipour S, Ghasemian A, Farjadfar A, Barzegari E, Kouhpayeh A, Abdolmaleki P. Design of a novel multi-epitope vaccine candidate against hepatitis C virus using structural and nonstructural proteins: An immunoinformatics approach. PLoS One 2022; 17:e0272582. [PMID: 36040967 PMCID: PMC9426923 DOI: 10.1371/journal.pone.0272582] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 07/21/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatitis C virus (HCV) infects the liver and causes chronic infection. Several mutations in the viral genome have been associated with drug resistance development. Currently, there is no approved vaccine against the HCV. The employment of computational biology is the primary and crucial step for vaccine design or antiviral therapy which can substantially reduce the duration and cost of studies. Therefore, in this study, we designed a multi-epitope vaccine using various immunoinformatics tools to elicit the efficient human immune responses against the HCV. Initially, various potential (antigenic, immunogenic, non-toxic and non-allergenic) epitope segments were extracted from viral structural and non-structural protein sequences using multiple screening methods. The selected epitopes were linked to each other properly. Then, toll-like receptors (TLRs) 3 and 4 agonists (50S ribosomal protein L7/L12 and human β-defensin 2, respectively) were added to the N-terminus of the final vaccine sequence to increase its immunogenicity. The 3D structure of the vaccine was modeled. Molecular dynamics simulations studies verified the high stability of final free vaccines and in complex with TLR3 and TLR4. These constructs were also antigenic, non-allergenic, nontoxic and immunogenic. Although the designed vaccine traits were promising as a potential candidate against the HCV infection, experimental studies and clinical trials are required to verify the protective traits and safety of the designed vaccine.
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Affiliation(s)
- Esmaeil Behmard
- School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Hussein T. Abdulabbas
- Department of Medical Laboratory Techniques, Faculty of Health and Medical Techniques, Imam Ja’afar Al-Sadiq University, Al Muthanna, Iraq
| | | | - Sohrab Najafipour
- School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Abdolmajid Ghasemian
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
- * E-mail: (PA); (AK); (AG)
| | - Akbar Farjadfar
- Department of Medical Biotechnology, Fasa University of Medical Sciences, Fasa, Iran
| | - Ebrahim Barzegari
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amin Kouhpayeh
- Department of Pharmacology, Fasa University of Medical Sciences, Fasa, Iran
- * E-mail: (PA); (AK); (AG)
| | - Parviz Abdolmaleki
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
- * E-mail: (PA); (AK); (AG)
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14
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Global dynamics of an age-dependent multiscale hepatitis C virus model. J Math Biol 2022; 85:21. [PMID: 35972543 DOI: 10.1007/s00285-022-01773-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 12/09/2020] [Accepted: 11/17/2021] [Indexed: 10/15/2022]
Abstract
In this paper, we focus on the global dynamics of a multiscale hepatitis C virus model. The model takes into account the evolution of the virus in cells and RNA. For the model, we establish the globally asymptotical stability of both infection-free and infected equilibria. We first give the basic reproduction number [Formula: see text] of the model, and then find that the system holds infected equilibrium when [Formula: see text]. Using eigenvalue analysis, Lyapunov functional, persistence theory and so on, it is proved that infection-free and infected equilibria are globally asymptotically stable when [Formula: see text] and [Formula: see text], respectively. Thus, extinction and persistence of viruses in cells are theoretically judged. Finally, we show our theoretical results by means of numerical simulation.
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15
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Russo FP, Viganò M, Stock P, Ferrarese A, Pugliese N, Burra P, Aghemo A. HBV-positive and HIV-positive organs in transplantation: A clinical guide for the hepatologist. J Hepatol 2022; 77:503-515. [PMID: 35398460 DOI: 10.1016/j.jhep.2022.03.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 02/08/2022] [Accepted: 03/02/2022] [Indexed: 12/04/2022]
Abstract
Organ transplantation is a life-saving treatment for patients with end-stage organ disease, a severe condition associated with a high risk of waitlist mortality. It is primarily limited by a shortage of available organs. Maximising available donors can increase access to transplantation. Transplantation from donors positive for HBV and HIV has increased in many countries. However, antiviral therapies need to be readily available for recipients after transplantation to prevent possible reactivation of the virus following the administration of immunosuppressive therapies. Furthermore, the intentional transmission of a virus has practical, ethical, and clinical implications. In this review, we summarise the current research, focusing on grafts from donors positive for the HBV surface antigen, antibodies against the HBV core antigen, and HIV, to help hepatologists and physicians interested in transplantation to select the best antiviral and/or prophylactic regimens for after transplantation.
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Affiliation(s)
- Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale Università-Padova, Italy
| | - Mauro Viganò
- Division of Hepatology, San Giuseppe Hospital, MultiMedica IRCCS, Milan, Italy
| | - Peter Stock
- Department of Surgery, University of California at San Francisco, San Francisco, California, USA
| | - Alberto Ferrarese
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, Verona, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale Università-Padova, Italy.
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
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16
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Patauner F, Stanzione M, Stornaiuolo G, Martone V, Palladino R, Coppola N, Durante-Mangoni E, Zampino R. Safety and Efficacy of Direct Antiviral Agents for Hepatitis C in Patients with Malignancies Other Than Liver Cancer: A Case Series. Pathogens 2022; 11:860. [PMID: 36014981 PMCID: PMC9414735 DOI: 10.3390/pathogens11080860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 07/25/2022] [Accepted: 07/28/2022] [Indexed: 01/27/2023] Open
Abstract
(1) Background: direct-acting antivirals (DAA) are the current standard of care for chronic hepatitis C. Oncologic patients remain among the most difficult-to-treat subgroups of hepatitis C virus (HCV)-infected patients due to their clinical frailty and complex therapeutic protocols received. (2) Methods: we retrospectively collected and analysed clinical data of 30 consecutive patients treated with DAA, between 2015 and 2022, for chronic HCV infection in the context of oncologic disease. (3) Results: most patients were females (63.3%), median age was 67 years, HCV genotype 1 was prevalent (60%), and median HCV RNA levels were 2.2 × 106 IU/mL. The most common malignancy was breast cancer (37%), and the chief oncologic drugs co-administered with DAAs were tamoxifen, platinum derivatives, cyclophosphamide, paclitaxel, rituximab and doxorubicin. Overall, 50% of patients had chronic hepatitis. A total of 76.7% underwent a sofosbuvir-based treatment. Sustained virological response 12 weeks after the end of therapy (SVR12) was reached in all patients. After SVR12, two patients died. DAA treatment was well tolerated; no patients had to stop DAA treatment or showed any adverse event or drug-drug interaction specifically attributable to DAAs. (4) Conclusions: DAA treatment should be promptly offered to oncologic patients with chronic hepatitis C in order to achieve aminotransferase normalization and viremia control, making antineoplastic therapy feasible and safe.
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Affiliation(s)
- Fabian Patauner
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (F.P.); (V.M.); (R.Z.)
| | - Maria Stanzione
- Department of Mental Health and Public Medicine, Infectious Diseases Unit, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (M.S.); (G.S.); (R.P.); (N.C.)
| | - Gianfranca Stornaiuolo
- Department of Mental Health and Public Medicine, Infectious Diseases Unit, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (M.S.); (G.S.); (R.P.); (N.C.)
| | - Veronica Martone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (F.P.); (V.M.); (R.Z.)
| | - Roberta Palladino
- Department of Mental Health and Public Medicine, Infectious Diseases Unit, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (M.S.); (G.S.); (R.P.); (N.C.)
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Infectious Diseases Unit, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (M.S.); (G.S.); (R.P.); (N.C.)
| | - Emanuele Durante-Mangoni
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy
- Unit of Infectious and Transplant Medicine, AORN Ospedali Dei Colli-Monaldi Hospital, 80131 Naples, Italy
| | - Rosa Zampino
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Napoli, Italy; (F.P.); (V.M.); (R.Z.)
- Unit of Infectious and Transplant Medicine, AORN Ospedali Dei Colli-Monaldi Hospital, 80131 Naples, Italy
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Venkatesan A, Dhanabalan AK, Rajendran S, Shanmugasundharam SG, Gunasekaran K, Febin Prabhu Dass J. Structure-based pharmacophore modeling, virtual screening approaches to identifying the potent hepatitis C viral protease and polymerase novel inhibitors. J Cell Biochem 2022; 123:1366-1380. [PMID: 35726444 DOI: 10.1002/jcb.30298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 05/25/2022] [Accepted: 05/30/2022] [Indexed: 11/07/2022]
Abstract
Hepatitis C is an infectious disease that leads to acute and chronic liver illnesses. Currently, there are no effective vaccines against this deadly virus. Direct acting antiviral (DAA) drugs are given in the combination with ribavirin and pegylated interferon which lead to adverse effects. Through in silico analysis, the structure-based docking study was performed against NS3/4A protease and NS5B polymerase proteins of HCV. In the current study, multiple e-pharmacophore-based virtual screening methods such as HTVS, SP, and XP were carried out to screen natural compounds and enamine databases. Our result outcomes revealed that CID AE-848/13196185 and CID AE-848/36959205 compounds show good binding interactions with protease protein. In addition, CID 15081408 and CID 173568 show better binding interactions with the polymerase protein. Further to validate the docking results, we performed molecular dynamics simulation for the top hit compounds bound with protease and polymerase proteins to illustrate conformational differences in the stability compared with the active site of the cocrystal inhibitor. Thus, the current study emphasizes these compounds could be an effective drug to treat HCV.
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Affiliation(s)
- Arthi Venkatesan
- Department of Integrative Biology, School of Bio Sciences and Technology (SBST), VIT, Vellore, India
| | - Anantha Krishnan Dhanabalan
- Centre of Advance study in Crystallography and Biophysics & Bioinformatics Infrastructure Facility, University of Madras, Chennai, India
| | - Selvakumar Rajendran
- Centre of Advance study in Crystallography and Biophysics & Bioinformatics Infrastructure Facility, University of Madras, Chennai, India
| | | | - Krishnasamy Gunasekaran
- Centre of Advance study in Crystallography and Biophysics & Bioinformatics Infrastructure Facility, University of Madras, Chennai, India
| | - J Febin Prabhu Dass
- Department of Integrative Biology, School of Bio Sciences and Technology (SBST), VIT, Vellore, India
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18
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El-Kassas M, Awad A. Metabolic aspects of hepatitis C virus. World J Gastroenterol 2022; 28:2429-2436. [PMID: 35979265 PMCID: PMC9258278 DOI: 10.3748/wjg.v28.i22.2429] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/18/2022] [Accepted: 04/25/2022] [Indexed: 02/06/2023] Open
Abstract
Many metabolic factors are associated with chronic hepatitis C virus (HCV) infection and can influence the course of the illness and impact the progression of liver and non-liver-related diseases through complex interactions. Several of these factors impact the course of chronic HCV (CHC) and result in the conceptual translation of CHC from a localized to systemic disease. Besides the traditional liver manifestations associated with CHC infection, such as cirrhosis and hepatocellular carcinoma, various extrahepatic disorders are associated with HCV infection, including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases. The coexistence of metabolic disorders and CHC is known to influence the chronicity and virulence of HCV and accelerates the progression to liver fibrosis and hepatocellular carcinoma. Insulin resistance is one of the key factors that have a tremendous metabolic impact on CHC. Therefore, there is a great need to properly evaluate patients with CHC infection and correct the modifiable metabolic risk factors. Furthermore, patients with HCV who achieved a sustained virological response showed an overall improvement in glucose metabolism, but the exact evidence still requires further studies with long-term follow-up. This review delineates the most recent evidence on the main metabolic factors associated with CHC and the possible influence of chronic HCV infection on metabolic features.
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Affiliation(s)
- Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
| | - Abeer Awad
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
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Shakeel S, Nawaz H, Majeed MI, Rashid N, Javed MR, Tariq A, Majeed B, Sehar A, Murtaza S, Sadaf N, Rimsha G, Amin I. Surface-enhanced Raman spectroscopic analysis of the centrifugally filtered blood serum samples of the hepatitis C patients. Photodiagnosis Photodyn Ther 2022; 39:102949. [PMID: 35661826 DOI: 10.1016/j.pdpdt.2022.102949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/12/2022] [Accepted: 06/01/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Previously Raman spectroscopy technique is a use to analyze non-invasive disease related to body fluids. OBJECTIVES For the qualitative and quantitative analysis of HCV serum samples surface-enhanced Raman spectroscopy (SERS) based method is developed. METHOD Surface-enhanced Raman spectroscopy (SERS) technique is employed for analysis of filtrate portions of blood serum samples of hepatitis C virus (HCV) infected patients and healthy ones by using 50 kDa centrifugal filter device. The filtrate portions of the serum obtained in this way contain proteins smaller than 50 kDa and removal of bigger size protein which allows to acquire SERS spectral features of smaller proteins more effectively which are probably associated with Hepatitis C infection. Moreover, SERS spectral features of the filtrates of different level of viral load including low, medium and high viral loads are compared with SERS spectral features of the filtrate portions of healthy/control serum samples. SERS spectral data sets of different samples are further analyzed by using multivariate data analysis techniques such as principal component analysis (PCA) and partial least square regression (PLSR). Some SERS spectral features are solely observed in the filtrate portions of the serum samples of hepatitis C and their intensities are increased as the level of viral load increases and might be used for HCV diagnosis. RESULTS PCA was found helpful for differentiation of SERS spectral data sets of filtrate portions of the serum samples of hepatitis C and healthy persons. The PLSR model helped for the quantification of viral loads in the unknown serum samples with 99 % accuracy.
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Affiliation(s)
- Samra Shakeel
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Haq Nawaz
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan.
| | - Muhammad Irfan Majeed
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan.
| | - Nosheen Rashid
- Department of Chemistry, University of Education, Faisalabad Campus, Faisalabad 38000, Pakistan.
| | - Muhammad Rizwan Javed
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad (GCUF), Faisalabad 38000, Pakistan
| | - Ayesha Tariq
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Beenish Majeed
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Aafia Sehar
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Sania Murtaza
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Nimra Sadaf
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Gull Rimsha
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Imran Amin
- PCR Laboratory, PINUM Hospital, Faisalabad 38000, Pakistan
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Toll-like Receptor Response to Hepatitis C Virus Infection: A Recent Overview. Int J Mol Sci 2022; 23:ijms23105475. [PMID: 35628287 PMCID: PMC9141274 DOI: 10.3390/ijms23105475] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/11/2022] [Accepted: 05/13/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatitis C virus (HCV) infection remains a major global health burden, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors that detect pathogen-associated molecular patterns and activate downstream signaling to induce proinflammatory cytokine and chemokine production. An increasing number of studies have suggested the importance of TLR responses in the outcome of HCV infection. However, the exact role of innate immune responses, including TLR response, in controlling chronic HCV infection remains to be established. A proper understanding of the TLR response in HCV infection is essential for devising new therapeutic approaches against HCV infection. In this review, we discuss the progress made in our understanding of the host innate immune response to HCV infection, with a particular focus on the TLR response. In addition, we discuss the mechanisms adopted by HCV to avoid immune surveillance mediated by TLRs.
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Determination of Risk Factors Associated with the Failure of 12 Weeks of Direct-Acting Antiviral Therapy in Patients with Hepatitis C: A Prospective Study. BIOMED RESEARCH INTERNATIONAL 2022; 2022:6054677. [PMID: 35572735 PMCID: PMC9106452 DOI: 10.1155/2022/6054677] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 04/04/2022] [Accepted: 04/07/2022] [Indexed: 11/21/2022]
Abstract
Introduction Direct-acting antivirals (DAAs) have significantly improved the efficacy and tolerability of the treatment of hepatitis C virus (HCV). However, studies conducted on actual patients with the aim of predicting the risk associated with treatment failure are lacking. Methods Our study enrolled 334 new HCV patients and assessed the effectiveness of treatment and predicted the risk of failure to achieve sustained virological response (SVR) by developing a multiple logistic model. Our study compared the variables between the two groups, those who did (group 0, n = 239) and did not achieve SVR (group 1, n = 95). Results The cure rate of HCV at 12th week in our study was 71.56%. We found that advanced cirrhosis, HCV genotype, HBV coinfection, rapid virological response (RVR), fibrosis index (FIB-4) score, serum levels of AST, ALP, hemoglobin, and viral load before treatment were prognostic factors associated with rate of failure to achieve SVR at week 12 of DAA therapy. In the multiple logistic model, eight significant predictors including advanced cirrhosis status, HCV genotype, RVR, AST/ALP levels, FIB-4 score, and viral load before treatment predicted the risk of failure with excellent model performance (area under the receiver operating characteristic curve (AUCROC) [95% CI] =0.986 (0.971-0.999)). RVR and advanced cirrhosis were the two strongest predictors with odd ratios (95% CI) =9.72 (2.8, 39.28) and 51.54 (6.39, 139.82), respectively. Conclusion The multiple logistic regression model included significant factors to estimate the probability of failure to achieve SVR, which could improve HCV treatment strategy.
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22
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Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study. Lancet Gastroenterol Hepatol 2022; 7:396-415. [PMID: 35180382 DOI: 10.1016/s2468-1253(21)00472-6] [Citation(s) in RCA: 296] [Impact Index Per Article: 98.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 12/08/2021] [Accepted: 12/09/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. METHODS This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age ≥0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. FINDINGS Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0·7% (95% UI 0·7-0·9), corresponding to 56·8 million (95% UI 55·2-67·8) infections, on Jan 1, 2020. This number represents a decrease of 6·8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63·6 million (61·8-75·8) infections (0·9% [0·8-1·0] prevalence). By the end of 2020, an estimated 12·9 million (12·5-15·4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. INTERPRETATION At the beginning of 2020, there were an estimated 56·8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. FUNDING John C Martin Foundation, Gilead Sciences, AbbVie, ZeShan Foundation, and The Hepatitis Fund.
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23
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Toygar Deniz M, Akhan S, Sayan M, Sönmez Tamer G, Azak E. Evaluation of HCV-Core Antigen in Diagnosis of Chronic Hepatitis C Patients under Direct-Acting Antiviral Treatment. Egypt J Immunol 2022. [DOI: 10.4274/vhd.galenos.2022.2021-3-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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24
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Durand CM, Florman S, Motter JD, Brown D, Ostrander D, Yu S, Liang T, Werbel WA, Cameron A, Ottmann S, Hamilton JP, Redd AD, Bowring MG, Eby Y, Fernandez RE, Doby B, Labo N, Whitby D, Miley W, Friedman-Moraco R, Turgeon N, Price JC, Chin-Hong P, Stock P, Stosor V, Kirchner V, Pruett T, Wojciechowski D, Elias N, Wolfe C, Quinn TC, Odim J, Morsheimer M, Mehta SA, Rana MM, Huprikar S, Massie A, Tobian AA, Segev DL. HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV. Am J Transplant 2022; 22:853-864. [PMID: 34741800 PMCID: PMC9997133 DOI: 10.1111/ajt.16886] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 10/26/2021] [Accepted: 10/29/2021] [Indexed: 01/25/2023]
Abstract
Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.
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Affiliation(s)
- Christine M. Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Sander Florman
- Recanati-Miller Transplantation Institute, The Mount Sinai Hospital, New York, NY
| | - Jennifer D. Motter
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Diane Brown
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Darin Ostrander
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Sile Yu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Tao Liang
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - William A. Werbel
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Andrew Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Shane Ottmann
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - James P. Hamilton
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Andrew D. Redd
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Mary G. Bowring
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Yolanda Eby
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
| | | | | | - Nazzarena Labo
- Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
| | - Denise Whitby
- Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
| | - Wendell Miley
- Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
| | | | | | - Jennifer C. Price
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Peter Chin-Hong
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Peter Stock
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Valentina Stosor
- Divisions of Infectious Diseases and Organ Transplantation Feinberg School of Medicine, Northwestern University, Chicago, IL
| | | | | | | | | | - Cameron Wolfe
- Division of Infectious Diseases, Duke University Medical Center, Durham, NC
| | - Thomas C. Quinn
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Jonah Odim
- Division of Allergy, Immunology and Transplantation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Megan Morsheimer
- Division of Allergy, Immunology and Transplantation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Sapna A. Mehta
- New York University Langone Transplant Institute, New York, NY
| | - Meenakshi M. Rana
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York NY
| | - Shirish Huprikar
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York NY
| | - Allan Massie
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Aaron A.R. Tobian
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Dorry L. Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
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25
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Valencia A, Vergara C, Thio CL, Vince N, Douillard V, Grifoni A, Cox AL, Johnson EO, Kral AH, Goedert JJ, Mangia A, Piazzolla V, Mehta SH, Kirk GD, Kim AY, Lauer GM, Chung RT, Price JC, Khakoo SI, Alric L, Cramp ME, Donfield SM, Edlin BR, Busch MP, Alexander G, Rosen HR, Murphy EL, Wojcik GL, Carrington M, Gourraud PA, Sette A, Thomas DL, Duggal P. Trans-ancestral fine-mapping of MHC reveals key amino acids associated with spontaneous clearance of hepatitis C in HLA-DQβ1. Am J Hum Genet 2022; 109:299-310. [PMID: 35090584 PMCID: PMC8874224 DOI: 10.1016/j.ajhg.2022.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 12/14/2021] [Indexed: 12/27/2022] Open
Abstract
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.
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Affiliation(s)
- Ana Valencia
- Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; Universidad Pontificia Bolivariana, Medellín, Antioquia 050031, Colombia
| | - Candelaria Vergara
- Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - Chloe L Thio
- Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA
| | - Nicolas Vince
- Université de Nantes, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes 44000, France
| | - Venceslas Douillard
- Université de Nantes, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes 44000, France
| | - Alba Grifoni
- Center for infectious Diseases and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
| | - Andrea L Cox
- Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA
| | - Eric O Johnson
- GenOmics, Bioinformatics, and Translational Research Center, RTI International, Research Triangle Park, NC 27709, USA
| | - Alex H Kral
- GenOmics, Bioinformatics, and Translational Research Center, RTI International, Research Triangle Park, NC 27709, USA
| | - James J Goedert
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
| | - Alessandra Mangia
- Liver Unit, Medical Sciences Department, Fondazione "Casa Sollievo della Sofferenza" IRCCS, 71013 San Giovanni Rotondo, Italy
| | - Valeria Piazzolla
- Liver Unit, Medical Sciences Department, Fondazione "Casa Sollievo della Sofferenza" IRCCS, 71013 San Giovanni Rotondo, Italy
| | - Shruti H Mehta
- Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - Gregory D Kirk
- Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - Arthur Y Kim
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Georg M Lauer
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Raymond T Chung
- Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Jennifer C Price
- Division of Gastroenterology, Department of Medicine, School of Medicine, University of California, San Francisco, CA 94143, USA
| | - Salim I Khakoo
- University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
| | - Laurent Alric
- Internal Medicine-Department of Digestive Diseases, Rangueil Hospital, Toulouse University, 1, 31400 Toulouse, France
| | | | | | - Brian R Edlin
- SUNY Downstate College of Medicine, Brooklyn, NY 11203, USA
| | - Michael P Busch
- University of California San Francisco and Vitalant Research Institute, San Francisco, CA 94118, USA
| | - Graeme Alexander
- UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond St, Hampstead, London NW3 2QG, UK
| | | | - Edward L Murphy
- University of California San Francisco and Vitalant Research Institute, San Francisco, CA 94118, USA
| | - Genevieve L Wojcik
- Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - Mary Carrington
- Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
| | - Pierre-Antoine Gourraud
- Université de Nantes, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes 44000, France
| | - Alessandro Sette
- Center for infectious Diseases and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92093, USA
| | - David L Thomas
- Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA
| | - Priya Duggal
- Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA.
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26
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Adedotun IO, Abdul-Hammed M, Hamzat BA, Adepoju AJ, Akinboade MW, Afolabi TI, Ismail UT. Molecular docking, ADMET analysis, and bioactivity studies of phytochemicals from Phyllanthus niruri as potential inhibitors of hepatitis C virus NSB5 polymerase. J INDIAN CHEM SOC 2022. [DOI: 10.1016/j.jics.2021.100321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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27
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Zamzami MA. Inosine Triphosphate Pyrophosphatase (ITPase): Functions, Mutations, Polymorphisms and Its Impact on Cancer Therapies. Cells 2022; 11:384. [PMID: 35159194 PMCID: PMC8833965 DOI: 10.3390/cells11030384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/18/2022] [Accepted: 01/19/2022] [Indexed: 11/16/2022] Open
Abstract
Inosine triphosphate pyrophosphatase (ITPase) is an enzyme encoded by the ITPA gene and functions to prevent the incorporation of noncanonical purine nucleotides into DNA and RNA. Specifically, the ITPase catalyzed the hydrolysis of (deoxy) nucleoside triphosphates ((d) NTPs) into the corresponding nucleoside monophosphate with the concomitant release of pyrophosphate. Recently, thiopurine drug metabolites such as azathioprine have been included in the lists of ITPase substrates. Interestingly, inosine or xanthosine triphosphate (ITP/XTP) and their deoxy analogs, deoxy inosine or xanthosine triphosphate (dITP/dXTP), are products of important biological reactions such as deamination that take place within the cellular compartments. However, the incorporation of ITP/XTP, dITP/dXTP, or the genetic deficiency or polymorphism of the ITPA gene have been implicated in many human diseases, including infantile epileptic encephalopathy, early onset of tuberculosis, and the responsiveness of patients to cancer therapy. This review provides an up-to-date report on the ITPase enzyme, including information regarding its discovery, analysis, and cellular localization, its implication in human diseases including cancer, and its therapeutic potential, amongst others.
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Affiliation(s)
- Mazin A. Zamzami
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
- Centre of Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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28
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Adeboyejo K, Grosche VR, José DP, Ferreira GM, Shimizu JF, King BJ, Tarr AW, Soares MMCN, Ball JK, McClure CP, Jardim ACG. Simultaneous determination of HCV genotype and NS5B resistance associated substitutions using dried serum spots from São Paulo state, Brazil. Access Microbiol 2022; 4:000326. [PMID: 35693474 PMCID: PMC9175972 DOI: 10.1099/acmi.0.000326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 12/30/2021] [Indexed: 11/26/2022] Open
Abstract
Hepatitis C virus (HCV) is responsible for more than 180 million infections worldwide, and about 80 % of infections are reported in Low and Middle-income countries (LMICs). Therapy is based on the administration of interferon (INF), ribavirin (RBV) or more recently Direct-Acting Antivirals (DAAs). However, amino acid substitutions associated with resistance (RAS) have been extensively described and can contribute to treatment failure, and diagnosis of RAS requires considerable infrastructure, not always locally available. Dried serum spots (DSS) sampling is an alternative specimen collection method, which embeds drops of serum onto filter paper to be transported by posting to a centralized laboratory. Here, we assessed feasibility of genotypic analysis of HCV from DSS in a cohort of 80 patients from São Paulo state Brazil. HCV RNA was detected on DSS specimens in 83 % of samples of HCV infected patients. HCV genotypes 1a, 1b, 2a, 2c and 3a were determined using the sequence of the palm domain of NS5B region, and RAS C316N/Y, Q309R and V321I were identified in HCV 1b samples. Concerning therapy outcome, 75 % of the patients who used INF +RBV as a previous protocol of treatment did not respond to DAAs, and 25 % were end-of-treatment responders. It suggests that therapy with INF plus RBV may contribute for non-response to a second therapeutic protocol with DAAs. One patient that presented RAS (V321I) was classified as non-responder, and combination of RAS C316N and Q309R does not necessarily imply in resistance to treatment in this cohort of patients. Data presented herein highlights the relevance of studying circulating variants for a better understanding of HCV variability and resistance to the therapy. Furthermore, the feasibility of carrying out genotyping and RAS phenotyping analysis by using DSS card for the potential of informing future treatment interventions could be relevant to overcome the limitations of processing samples in several location worldwide, especially in LMICs.
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Affiliation(s)
- Kazeem Adeboyejo
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.,School of Life Sciences, University of Nottingham, Nottingham, UK
| | - Victória Riquena Grosche
- Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.,Institute of Bioscience, Language and Exact Sciences, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
| | | | - Giulia Magalhães Ferreira
- Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
| | - Jacqueline Farinha Shimizu
- Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.,Institute of Bioscience, Language and Exact Sciences, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
| | - Barnabas J King
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.,School of Life Sciences, University of Nottingham, Nottingham, UK.,MRC/EPSRC Nottingham Molecular Pathology Node, University of Nottingham, Nottingham, UK
| | - Alexander W Tarr
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.,School of Life Sciences, University of Nottingham, Nottingham, UK.,MRC/EPSRC Nottingham Molecular Pathology Node, University of Nottingham, Nottingham, UK
| | | | - Jonathan K Ball
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.,School of Life Sciences, University of Nottingham, Nottingham, UK.,MRC/EPSRC Nottingham Molecular Pathology Node, University of Nottingham, Nottingham, UK
| | - C Patrick McClure
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.,School of Life Sciences, University of Nottingham, Nottingham, UK.,MRC/EPSRC Nottingham Molecular Pathology Node, University of Nottingham, Nottingham, UK
| | - Ana Carolina Gomes Jardim
- Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.,Institute of Bioscience, Language and Exact Sciences, São Paulo State University, São José do Rio Preto, São Paulo, Brazil
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29
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Yilmaz B, Kayadibi H, Yeniova AO, Koseoglu H, Simsek Z. The age, bilirubin and albumin (ABA) index: a novel noninvasive index for predicting liver fibrosis in patients with chronic hepatitis C infection. Eur J Gastroenterol Hepatol 2021; 33:e290-e296. [PMID: 33405426 DOI: 10.1097/meg.0000000000002038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AIM It was to assess the diagnostic performance characteristics of a novel index, (ABA), which utilizes age, bilirubin and albumin to predict significant and severe fibrosis, and cirrhosis in patients with chronic hepatitis C infection. METHODS A total of 114 patients were included in this study. The liver biopsies were graded using the Ishak scoring system. Diagnostic performance of the ABA index was compared to aspartate aminotransferase (AST) to alanine aminotransferase ratio, age platelet index, AST to platelet ratio index, γ-glutamyl transpeptidase (GGT) to platelet ratio index, FIB-4, FibroQ, Goteborg University Cirrhosis Index, King's score, GGT/international normalization ratio, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, white blood cell to platelet distribution width ratio and mean platelet volume to platelet distribution width ratio (MPV/PDW) by receiver operating characteristics (ROC) curve analysis. RESULTS The ABA index was formulated as 1.5 + (0.065 × age) + (1.85 × bilirubin) - (1.65 × albumin) according to the multivariate logistic regression analysis. According to the ROC curve analyses, the ABA index had the area under these ROC curves (AUROCs) of 0.805 [95% confidence interval (CI), 0.727-0.883] for significant fibrosis, 0.874 (95% CI, 0.804-0.943) for severe fibrosis and 0.895 (95% CI, 0.828-0.961) for cirrhosis. CONCLUSION The ABA index was found to be superior to other evaluated noninvasive indexes of liver fibrosis by use of the cutoff point of 0 and 1. These findings should be confirmed by prospective and multicenter studies in patients with chronic hepatitis C infection.
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Affiliation(s)
- Baris Yilmaz
- Department of Gastroenterology, Biruni University School of Medicine, İstanbul
- Department of Gastroenterology, Hitit University School of Medicine, Corum
| | - Huseyin Kayadibi
- Department of Medical Biochemistry, Eskisehir Osmangazi University School of Medicine, Eskisehir
- Department of Medical Biochemistry, Hitit University School of Medicine, Corum
| | - Abdullah O Yeniova
- Department of Gastroenterology, Tokat Gaziosmanpasa University School of Medicine, Tokat
| | - Huseyin Koseoglu
- Department of Gastroenterology, Hitit University School of Medicine, Corum
| | - Zahide Simsek
- Clinic of Gastroenterology, Diskapi Yildirim Beyazit Education and Research Hospital, Ankara, Turkey
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30
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Baeka GB, Oloke JK, Opaleye OO. Detection of hepatitis C virus among HIV patients in Port Harcourt, Rivers State. Afr Health Sci 2021; 21:1010-1015. [PMID: 35222562 PMCID: PMC8843266 DOI: 10.4314/ahs.v21i3.8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background Hepatitis C virus (HCV) a major human pathogen infecting millions of individuals worldwide, thereby increasing the risks for chronic liver diseases and has been discovered that HIV/HCV co-infected patients have a greater risk. Objective To determine the prevalence of HCV infection among HIV infected people in Port Harcourt, Rivers State. Methodology The patients were from the ages of 18 and above attending the antiretroviral clinic for over 6 months. The mean age of the participants was 36.91±8.38. Data were gotten from the 550 patients using a modified questionnaire and 5mls of blood samples were collected through venepuncture into EDTA bottles and spun at 3000rpm for 10 minutes separating the plasma from the whole blood. The CD4+ count was gotten from the patients' file and the samples kept at -700C till analized. HCV antibody was detected using a commercially available third generation kit manufactured by Melsin Medical Co and statistical analysis was done using a Stata version 16. P value was determined using ANOVA Result Total number positive to the HCV antibody was 24(4.4%) of which 8(33.3%) were males, while 16(66.7%) were females. Prevalence (29.2%) was among patients in the 31–35 age range. The CD4+ count ranged from 22–864 cells/µl with a mean value of 303.08±194. Conclusion From this study HIV/HCV co-infection occurs among HIV infected people in Port Harcourt. The CD4+ count was discovered to be low and was not age, nor gender dependent. HIV infected people should therefore be routinely screened for HCV.
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Affiliation(s)
- Glory Barinuaka Baeka
- Department of Pure and Applied Biology (Microbiology/Virology Unit), Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.,Department of Microbiology, Rivers State University, Port Harcourt, Rivers State
| | - Julius Kola Oloke
- Department of Pure and Applied Biology (Microbiology/Virology Unit), Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - Oluyinka Oladele Opaleye
- Department of Pure and Applied Biology (Microbiology/Virology Unit), Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.,Department of Medical Microbiology and Parasitology, College of Health Sciences, Ladoke Akintola University of Technology, Nigeria
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Kayesh MEH, Sanada T, Kohara M, Tsukiyama-Kohara K. Tree Shrew as an Emerging Small Animal Model for Human Viral Infection: A Recent Overview. Viruses 2021; 13:v13081641. [PMID: 34452505 PMCID: PMC8402676 DOI: 10.3390/v13081641] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/04/2021] [Accepted: 08/16/2021] [Indexed: 02/08/2023] Open
Abstract
Viral infection is a global public health threat causing millions of deaths. A suitable small animal model is essential for viral pathogenesis and host response studies that could be used in antiviral and vaccine development. The tree shrew (Tupaia belangeri or Tupaia belangeri chinenesis), a squirrel-like non-primate small mammal in the Tupaiidae family, has been reported to be susceptible to important human viral pathogens, including hepatitis viruses (e.g., HBV, HCV), respiratory viruses (influenza viruses, SARS-CoV-2, human adenovirus B), arboviruses (Zika virus and dengue virus), and other viruses (e.g., herpes simplex virus, etc.). The pathogenesis of these viruses is not fully understood due to the lack of an economically feasible suitable small animal model mimicking natural infection of human diseases. The tree shrew model significantly contributes towards a better understanding of the infection and pathogenesis of these important human pathogens, highlighting its potential to be used as a viable viral infection model of human viruses. Therefore, in this review, we summarize updates regarding human viral infection in the tree shrew model, which highlights the potential of the tree shrew to be utilized for human viral infection and pathogenesis studies.
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Affiliation(s)
- Mohammad Enamul Hoque Kayesh
- Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan;
- Department of Microbiology and Public Health, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Barishal 8210, Bangladesh
| | - Takahiro Sanada
- Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan; (T.S.); (M.K.)
| | - Michinori Kohara
- Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan; (T.S.); (M.K.)
| | - Kyoko Tsukiyama-Kohara
- Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan;
- Correspondence: ; Tel.: +81-99-285-3589
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Pagani I, Poli G, Vicenzi E. TRIM22. A Multitasking Antiviral Factor. Cells 2021; 10:cells10081864. [PMID: 34440633 PMCID: PMC8391480 DOI: 10.3390/cells10081864] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/03/2021] [Accepted: 07/16/2021] [Indexed: 02/06/2023] Open
Abstract
Viral invasion of target cells triggers an immediate intracellular host defense system aimed at preventing further propagation of the virus. Viral genomes or early products of viral replication are sensed by a number of pattern recognition receptors, leading to the synthesis and production of type I interferons (IFNs) that, in turn, activate a cascade of IFN-stimulated genes (ISGs) with antiviral functions. Among these, several members of the tripartite motif (TRIM) family are antiviral executors. This article will focus, in particular, on TRIM22 as an example of a multitarget antiviral member of the TRIM family. The antiviral activities of TRIM22 against different DNA and RNA viruses, particularly human immunodeficiency virus type 1 (HIV-1) and influenza A virus (IAV), will be discussed. TRIM22 restriction of virus replication can involve either direct interaction of TRIM22 E3 ubiquitin ligase activity with viral proteins, or indirect protein–protein interactions resulting in control of viral gene transcription, but also epigenetic effects exerted at the chromatin level.
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Affiliation(s)
- Isabel Pagani
- Viral Pathogenesis and Biosafety Unit, IRCCS-Ospedale San Raffaele, 20132 Milan, Italy;
| | - Guido Poli
- Human Immuno-Virology Unit, IRCCS-Ospedale San Raffaele, 20132 Milan, Italy;
- School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Elisa Vicenzi
- Viral Pathogenesis and Biosafety Unit, IRCCS-Ospedale San Raffaele, 20132 Milan, Italy;
- Correspondence:
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Ryu HC, Windisch M, Lim JW, Choi I, Lee EK, Yoo HH, Kim TK. Thiophen urea derivatives as a new class of hepatitis C virus entry inhibitors. J Enzyme Inhib Med Chem 2021; 36:462-468. [PMID: 33455472 PMCID: PMC7822064 DOI: 10.1080/14756366.2020.1870456] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
To develop unique small-molecule inhibitors of hepatitis C virus (HCV), thiophen urea (TU) derivatives were synthesised and screened for HCV entry inhibitory activities. Among them, seven TU compounds exhibited portent anti-viral activities against genotypes 1/2 (EC50 < 30 nM) and subsequently, they were further investigated; based on the pharmacological, metabolic, pharmacokinetic, and safety profiles, J2H-1701 was selected as the optimised lead compound as an HCV entry inhibitor. J2H-1701 possesses effective multi-genotypic antiviral activity. The docking results suggested the potential interaction of J2H-1701 with the HCV E2 glycoprotein. These results suggest that J2H-1701 can be a potential candidate drug for the development of HCV entry inhibitors.
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Affiliation(s)
- Hyung Chul Ryu
- R&D Center, J2H Biotech, Suwon, Gyeonggi-do, Republic of Korea
| | - Marc Windisch
- Medicinal Chemistry, Institut Pasteur Korea, Seongnam, Gyeonggi-do, Republic of Korea
| | - Jee Woong Lim
- R&D Center, J2H Biotech, Suwon, Gyeonggi-do, Republic of Korea
| | - Inhee Choi
- Medicinal Chemistry, Institut Pasteur Korea, Seongnam, Gyeonggi-do, Republic of Korea
| | - Eun Kyu Lee
- Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea
| | - Hye Hyun Yoo
- Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, Republic of Korea
| | - Tae Kon Kim
- College of Science and Engineering, Jungwon University, Geosan-gun, Chungbuk, Republic of Korea
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Ullah S, Ali M, Shaheen A, Zia F, Rahman L, Rahman S, Ali H, Din M, Waris A, Shinwari ZK. Sofosbuvir Resistance-associated Substitutions in the Palm Domain of HCV-NS5B RNA Dependent RNA Polymerase; Study of two Sofosbuvir non-responders. Int J Infect Dis 2021:S1201-9712(21)00426-4. [PMID: 34000421 DOI: 10.1016/j.ijid.2021.05.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 05/08/2021] [Accepted: 05/11/2021] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE In current study we performed sequencing of palm domain of HCV-NS5B gene, its ancestral analysis along with amino acids substitution analysis. These analysis were done to find the molecular basis of the viral resistance against Sofosbuvir drug. METHODS Blood samples from individuals with chronic Hepatitis C infection that were resistant to Sofosbuvir were collected. The samples were processed for their molecular characterization that included RNA extraction, Complementary DNA (cDNA) synthesize, nested PCR, gel elution, Sequencing, ancestral and 3D structure analysis. RESULTS Evolutionary analysis revealed that current study sequences (QAU-01, QAU-02) clustered with a previously studied sequence, KY971494.1. Moreover, we reports multiple novel amino acid substitutions in the palm domain of NS5B gene such as Ile116Val, Asn117Gly, Glu246Ala, Val252Ala, Glu258Gln, Cys262Leu, Ser269Arg, Ala272Thr, Ile293Leu, Lys304Arg, Asn307Gly, Ala338Val and Arg345Gly in our query sequence (QAU-01). At 246 and 269 position in (QAU-02), no substitution was observed. CONCLUSIONS We have noticed that the current sequences are relatively emerging and could have been originated from aforementioned sequence recently. Based on the current results, we suggests that these substitutions could be associated with structural or functional impairment of protein and could also be may be considered as resistance associated substitutions (RAS) to Sofosbuvir drug.
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Affiliation(s)
- Sana Ullah
- Department of Biotechnology, Quaid-i-Azam University Islamabad, 45320, Pakistan.
| | - Muhammad Ali
- Department of Biotechnology, Quaid-i-Azam University Islamabad, 45320, Pakistan.
| | - Asmat Shaheen
- Department of Biochemistry, Khyber Medical University-Institute of Medical Sciences, Kohat, Pakistan.
| | - Fatima Zia
- Department of Biotechnology, Quaid-i-Azam University Islamabad, 45320, Pakistan.
| | - Lubna Rahman
- Department of Biotechnology, Quaid-i-Azam University Islamabad, 45320, Pakistan.
| | - Sidra Rahman
- Department of Biotechnology, Quaid-i-Azam University Islamabad, 45320, Pakistan.
| | - Hammad Ali
- Department of Biotechnology, Quaid-i-Azam University Islamabad, 45320, Pakistan.
| | - Misbahud Din
- Department of Biotechnology, Quaid-i-Azam University Islamabad, 45320, Pakistan.
| | - Abdul Waris
- Department of Biotechnology, Quaid-i-Azam University Islamabad, 45320, Pakistan.
| | - Zabta Khan Shinwari
- Department of Plant Sciences, Quaid-i-Azam University Islamabad, 45320, Pakistan.
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Chaudhari R, Fouda S, Sainu A, Pappachan JM. Metabolic complications of hepatitis C virus infection. World J Gastroenterol 2021; 27:1267-1282. [PMID: 33833481 PMCID: PMC8015302 DOI: 10.3748/wjg.v27.i13.1267] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/10/2021] [Accepted: 03/12/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.
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Affiliation(s)
- Rahul Chaudhari
- Department of Medicine, Pennsylvania Hospital of the University of Pennsylvania, Pennsylvania, PA 19104, United States
| | - Sherouk Fouda
- School of Health and Biomedical Sciences, RMIT University, Melbourne VIC 3000, Australia
| | - Ashik Sainu
- Department of Gastroenterology and Hepatology, Aster Oman Hospital, Al Ghubra, Muscat OM 133, Oman
| | - Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
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Akimov IA, Timofeev DI, Mavzyutov AR, Ivanov MK. Detection of circulating HCV recombinant form RF1_2k/1b in blood serum of patients by real-time RT-PCR. Klin Lab Diagn 2021; 66:122-128. [PMID: 33734647 DOI: 10.51620/0869-2084-2021-66-2-122-128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
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.
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Affiliation(s)
| | | | - A R Mavzyutov
- Research Center «Laboratory».,Bashkir State Medical University
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DeepLiverNet: a deep transfer learning model for classifying liver stiffness using clinical and T2-weighted magnetic resonance imaging data in children and young adults. Pediatr Radiol 2021; 51:392-402. [PMID: 33048183 PMCID: PMC8675279 DOI: 10.1007/s00247-020-04854-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/24/2020] [Accepted: 09/13/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Although MR elastography allows for quantitative evaluation of liver stiffness to assess chronic liver diseases, it has associated drawbacks related to additional scanning time, patient discomfort, and added costs. OBJECTIVE To develop a machine learning model that can categorically classify the severity of liver stiffness using both anatomical T2-weighted MRI and clinical data for children and young adults with known or suspected pediatric chronic liver diseases. MATERIALS AND METHODS We included 273 subjects with known or suspected chronic liver disease. We extracted data including axial T2-weighted fast spin-echo fat-suppressed images, clinical data (e.g., demographic/anthropomorphic data, particular medical diagnoses, laboratory values) and MR elastography liver stiffness measurements. We propose DeepLiverNet (a deep transfer learning model) to classify patients into one of two groups: no/mild liver stiffening (<3 kPa) or moderate/severe liver stiffening (≥3 kPa). We conducted internal cross-validation using 178 subjects, and external validation using an independent cohort of 95 subjects. We assessed diagnostic performance using accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AuROC). RESULTS In the internal cross-validation experiment, the combination of clinical and imaging data produced the best performance (AuROC=0.86) compared to clinical (AuROC=0.83) or imaging (AuROC=0.80) data alone. Using both clinical and imaging data, the DeepLiverNet correctly classified patients with accuracy of 88.0%, sensitivity of 74.3% and specificity of 94.6%. In our external validation experiment, this same deep learning model achieved an accuracy of 80.0%, sensitivity of 61.1%, specificity of 91.5% and AuROC of 0.79. CONCLUSION A deep learning model that incorporates clinical data and anatomical T2-weighted MR images might provide a means of risk-stratifying liver stiffness and directing the use of MR elastography.
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Kim TK. Validated High-performance Liquid Chromatography Method for the Determination of JW5624, A New Class Of Hepatitis C Virus Inhibitor, in Rat Plasma and its Application in the Pharmacokinetic Study of JW5624. Drug Res (Stuttg) 2021; 71:312-316. [PMID: 33535254 DOI: 10.1055/a-1369-8867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
We developed unique small-molecule inhibitors of hepatitis C virus (HCV), which had potent activity for HCV entry inhibition and multi-genotypic antiviral activity. In this study, a sensitive and reliable method for the quantitation of JW5624 in rat plasma was developed and validated using high performance liquid chromatography. Chromatographic separation was achieved using a reversed-phase (C18) column. The mobile phase, 0.02 M ammonium acetate buffer:acetonitrile (30:70, v/v), was run at a flow rate of 1.0 mL/min, and the column eluent was monitored using an ultraviolet detector at 254 nm at room temperature. The retention times of sildenafil (an internal standard), and JW5624 were approximately 5.9 and 7.3 min, respectively. The detection limit of JW5624 in rat plasma was 0.03 μg/mL. Pharmacokinetic parameters of JW5624 was evaluated after intravenous (i. v.; at doses of 5 mg/kg) and oral (p.o.; at doses of 10 mg/kg) administration of JW5624 in rats. After p.o. administration (10 mg/kg) of JW5624, F value was approximately 71.0%. These results suggest that JW5624 can be a potential candidate drug for the development of HCV entry inhibitors.
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The Significance of HCV Viral Load in the Incidence of HCC: a Correlation Between Mir-122 and CCL2. J Gastrointest Cancer 2021; 51:412-417. [PMID: 31385234 DOI: 10.1007/s12029-019-00281-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common cancer, the third leading cause of cancer deaths worldwide with over 500,000 people affected. It is a major cause of death in patients with chronic hepatitis C virus (HCV) infection. Overwhelming lines of epidemiological evidence have indicated that persistent infection with HCV is a major risk for the development of HCC. Although a proportion of patients with a chronic hepatitis C virus infection progress to HCC, the peak incidence of HCC associated with HCV infection has not yet occurred. AIM This review aimed to assess the impact of hepatitis C viral load on the development of HCC as a correlation between mir-122 and, the key factor in fibrogenesis, CCL2. CONCLUSION According to the detailed explanation of the role of mir-122 and CCL2 in HCV and HCC and the evidence of the inverse correlation between them, it may be concluded that HCV may affect mir-122 expression level of the hepatocytes with different patterns depending on the viral genotype. Collectively, HCV viral load alone is not sufficient to predict the HCC development and progression. Besides the quantitative evaluation of the HCV, mir-122 and CCL2 determinations should also be taken into consideration.
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Study of membrane deformations induced by Hepatitis C protein NS4B and its terminal amphipathic peptides. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2020; 1863:183537. [PMID: 33383025 DOI: 10.1016/j.bbamem.2020.183537] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 11/27/2020] [Accepted: 12/13/2020] [Indexed: 11/21/2022]
Abstract
Many viruses destabilize cellular membranous compartments to form their replication complexes, but the mechanism(s) underlying membrane perturbation remains unknown. Expression in eukaryotic cells of NS4B, a protein of the hepatitis C virus (HCV), alters membranous complexes and induces structures similar to the so-called membranous web that appears crucial to the formation of the HCV replication complex. As over-expression of the protein is lethal to both prokaryotic and eukaryotic cells, NS4B was produced in large quantities in a "cell-free" system in the presence of detergent, after which it was inserted into lipid membranes. X-ray diffraction revealed that NS4B modifies the phase diagram of synthetic lipid aqueous phases considerably, perturbing the transition temperature and cooperativity. Cryo-electron microscopy demonstrated that NS4B introduces significant disorder in the synthetic membrane as well as discontinuities that could be interpreted as due to the formation of pores and membrane merging events. C- and N-terminal fragments of NS4B are both able to destabilize liposomes. While most NS4B amphipathic peptides perforate membranes, one NS4B peptide induces membrane fusion. Cryo-electron microscopy reveals a particular structure that can be interpreted as arising from hemi-fusion-like events. Amphipathic domains are present in many proteins, and if exposed to the aqueous cytoplasmic medium are sufficient to destabilize membranes in order to form viral replication complexes. These domains have important functions in the viral replication cycle, and thus represent potential targets for the development of anti-viral molecules.
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Kashif M, Majeed MI, Hanif MA, Rehman AU. Surface Enhanced Raman Spectroscopy of the serum samples for the diagnosis of Hepatitis C and prediction of the viral loads. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2020; 242:118729. [PMID: 32712574 DOI: 10.1016/j.saa.2020.118729] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 07/10/2020] [Accepted: 07/13/2020] [Indexed: 06/11/2023]
Abstract
In this study, Surface Enhanced Raman Spectroscopy (SERS) was used for the characterization of Hepatitis C virus (HCV) in blood serum samples. For this purpose silver nanoparticles (Ag NPs) were used as substrates and SERS spectra were acquired from different clinically diagnosed HCV positive serum samples as well as from healthy individuals. Notably, same set of samples were also evaluated with Raman spectroscopy and SERS was found to be more helpful for the identification of the spectral features associated with the development of HCV infection. Different SERS features associated with the RNA bases were observed solely in the HCV positive serum as compared to the healthy samples which can be considered as SERS spectral markers of the HCV infection. Furthermore, principal component analysis (PCA) of the SERS spectral data was found to be very helpful in differentiation of spectral data of serum samples with different viral loads PLSR model was constructed to compare the capability of SERS and Raman analysis in the prediction of viral loads. It is found that SERS shows lower root mean square error of cross validation (RMSECV) and higher goodness of the model (R2) values than Raman data.
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Affiliation(s)
- Muhammad Kashif
- Department of Chemistry, University of Agriculture, Faisalabad, Pakistan
| | | | | | - Ateeq Ur Rehman
- Department of Physics, University of Agriculture, Faisalabad, Pakistan
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Mazzaro C, Mauro E, Ermacora A, Doretto P, Fumagalli S, Tonizzo M, Toffolutti F, Gattei V. Hepatitis C virus-related cryoglobulinemic vasculitis. Minerva Med 2020; 112:175-187. [PMID: 33198444 DOI: 10.23736/s0026-4806.20.07120-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection affects about 170 million people worldwide. HCV is responsible for both hepatitis and extra-hepatic manifestations. Chronic infection has been shown to develop in about 70% of cases, and it can progress to cirrhosis or hepatocellular carcinoma. Ten percent of HCV patients may develop extra-hepatic manifestations, including mixed cryoglobulinemia (MC) and non-Hodgkin lymphomas (NHL). Cryoglobulinemic vasculitis (CV) varies, ranging from mild-moderate clinical symptoms (purpura on the legs, asthenia and arthralgias) and chronic hepatitis to severe symptoms (ulcers on the legs, peripheral neuropathy, glomerulonephritis, low-grade NHL to life threatening complications (rapid progressive glomerulonephritis, gastrointestinal vasculitis, acute hyper-viscosity). EVIDENCE ACQUISITION CV is associated with significant morbidity and mortality. Some studies have shown kidney involvement, cirrhosis, central nervous system involvement, and heart involvement as unfavorable prognostic factors. Many studies have demonstrated that, after antiviral therapy, CV can disappear along with HCV. After the introduction of the new direct antiviral agents (DAAs), the combination of pegylated interferon and ribavirin has been abandoned. EVIDENCE SYNTHESIS Several studies on new DAAs have reported remarkable 90% to 100% HCV eradication rates, regardless of genotype. Treatment with DAAs has comparable efficacy on viral eradication in CV patients but definite clinical improvements of vasculitis can be observed only in half the patients. CONCLUSIONS In patients with mild to moderate CV disease, DAAs therapy should be used as first line approach. In patients with severe vasculitis, DAAs therapy and a second-line treatment with RTX with or without aphaeresis are a required.
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Affiliation(s)
- Cesare Mazzaro
- Unit of Clinical of Experimental Onco-Hematology, IRCCS Centro di Riferimento Oncologico (CRO), Aviano, Pordenone, Italy -
| | - Endri Mauro
- Unit of Hematology, Department of Internal Medicine, Cà Foncello Hospital, Treviso, Italy
| | - Anna Ermacora
- Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
| | - Paolo Doretto
- Unit of Laboratory, Pordenone General Hospital, Pordenone, Italy
| | - Silvia Fumagalli
- Unit of Hematology, Department of Internal Medicine, Cà Foncello Hospital, Treviso, Italy
| | - Maurizio Tonizzo
- Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
| | - Federica Toffolutti
- Unit of Cancer Epidemiology, IRCCS Centro di Riferimento Oncologico (CRO), Aviano, Pordenone, Italy
| | - Valter Gattei
- Unit of Clinical of Experimental Onco-Hematology, IRCCS Centro di Riferimento Oncologico (CRO), Aviano, Pordenone, Italy
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Asiri YI, Alsayari A, Muhsinah AB, Mabkhot YN, Hassan MZ. Benzothiazoles as potential antiviral agents. J Pharm Pharmacol 2020; 72:1459-1480. [PMID: 32705690 PMCID: PMC7405065 DOI: 10.1111/jphp.13331] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 06/03/2020] [Accepted: 06/13/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The recent viral pandemic poses a unique challenge for healthcare providers. Despite the remarkable progress, the number of novel antiviral agents in the pipeline is woefully inadequate against the evolving virulence and drug resistance of current viruses. This highlights the urgent need for new and improved vaccines, diagnostics and therapeutic agents to obviate the viral pandemic. KEY FINDINGS Benzothiazole plays a pivotal role in the design and development of antiviral drugs. This is evident from the fact that it comprises many clinically useful agents. The current review is aimed to provide an insight into the recent development of benzothiazole-based antiviral agents, with a special focus on their structure-activity relationships and lead optimisation. One hundred and five articles were initially identified, and from these studies, 64 potential novel lead molecules and main findings were highlighted in this review. SUMMARY We hope this review will provide a logical perspective on the importance of improving the future designs of novel broad-spectrum benzothiazole-based antiviral agents to be used against emerging viral diseases.
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Affiliation(s)
- Yahya I Asiri
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Abdulrhman Alsayari
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Abdullatif B Muhsinah
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Yahia N Mabkhot
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Mohd Z Hassan
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
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Fathi HM, Abdel Wahed WY, Gomaa AA, Hassan EA, Eid HM, Reheem FA, Senara SH. A prospective study in hepatitis C virus treatment-naïve patients showing rheumatologic extra-hepatic manifestations of hepatitis C with associated risk factors: efficacy and safety using sofosbuvir-based direct antiviral therapy. EGYPTIAN RHEUMATOLOGY AND REHABILITATION 2020. [DOI: 10.1186/s43166-020-00023-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
To study the most common rheumatologic manifestations of hepatitis C viral (HCV) infection in Egyptian patients and associated risk factors with assessment the effect of current therapies on these manifestations. A prospective study was carried out to HCV patients attending the tropical medicine department referred to rheumatology department, over a year. A total of 204 hepatitis C virus treatment-naïve patients aged 21–71 years old suffering from rheumatologic manifestations were recruited, and history taking, general and musculoskeletal examination, laboratory and serological investigations, imaging, and liver fibrosis findings were assessed: baseline, end of treatment, and 12 weeks later, either sofosbuvir/ribavirin or sofosbuvir/simeprevir regimens and through three consecutive visits: joint activity and functional scores were taken.
Results
Common observed rheumatologic manifestations were fibromyalgia (74.5%), arthralgia (73.5%), Raynaud’s phenomenon (54.9%), peripheral neuropathy (29.4%),chronic fatigue syndrome and purpura (24.5%), arthritis (16.7%), Sicca symptoms and skin ulcers (9.8%), and vasculitic CNS involvement (5.9%), mostly seen in females. VAS and FAS scales have improved across visits (p value < 0.001) with lowered number and percentage of arthralgia (tender joint counts), arthritis (swollen joint counts), improvement of fibromyalgia, purpura, peripheral neuropathy, anemia, and thrombocytopenia (p < 0.001). Common reported risk factors were barber shaving (52 %), dental procedures (44.1%), and surgical interventions (36.3%). Non-reactive cases shown by HCV-PCR response increased at the end of study reaching 62%. The percent of improvement was significantly higher in patients receiving sofosbuvir/simeprevir regimen (100%) versus sofosbuvir/ribavirin (58.2%).
Conclusion
Direct antiviral drugs seem to improve the rheumatic extra-hepatic manifestations of HCV patients and lowering viremia level especially sofosbuvir/simeprevir regimen in hepatitis C treatment-naïve patients.
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Oluremi AS, Ajadi TA, Opaleye OO, Alli OAT, Ogbolu DO, Enitan SS, Alaka OO, Adelakun AA, Adediji IO, Ogunleke AO, Suleiman IE, Olowoyeye EA, Adewumi OO, Ojo AT, Adeyeye-Adetunji OO, Hammed SS. High seroprevalence of viral hepatitis among animal handlers in Abeokuta, Ogun State, Nigeria. J Immunoassay Immunochem 2020; 42:34-47. [PMID: 33044898 DOI: 10.1080/15321819.2020.1814810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Viral hepatitis is a deadly disease which can manifest as acute, chronic, hepatocellular carcinoma, and liver failure. Information about hepatitis is scarce among animal handlers. Due to Federal Government of Nigeria diversification programmes, many people are now involved in animal farming which can make them susceptible to viral hepatitis. This study aimed at determining the prevalence of Hepatitis B, C, and E viruses among animal handlers in Abeokuta, southwestern Nigerian. A total of 156 subjects were recruited for the study. Sociodemographic and risks factors data were fetched from subjects using interviewer-administered questionnaire. Blood samples were collected via venepuncture and tested for HCV, HBV, and HEV using ELISA technique. Results were analyzed using SPSS software version 21.0 and P value ≤ 0.05 was considered significant. The prevalence of HCV, HBV, and HEV were 46 (29.5%), 20 (12.8%), and 4 (2.6%) respectively while 6 (3.8%), 1 (0.6%), and 1 (0.6%) had co-infection of HBV-HCV, HBV-HEV, and HCV- HEV respectively. This study concludes that there is high prevalence of hepatitis C and B viruses among animal handlers in Abeokuta, Ogun state which is of significant public health problem, warranting further attention and research.
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Affiliation(s)
- A S Oluremi
- Department of Medical Laboratory Science, Babcock University, Ilishan Remo, Nigeria.,Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.,Department of Medical Laboratory Science, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - T A Ajadi
- Department of Medical Laboratory Science, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - O O Opaleye
- Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - O A T Alli
- Department of Medical Laboratory Science, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - D O Ogbolu
- Department of Medical Laboratory Science, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - S S Enitan
- Department of Medical Laboratory Science, Babcock University, Ilishan Remo, Nigeria
| | - O O Alaka
- Department of Medical Microbiology and Parasitology, Obafemi Awolowo University Teaching Hospital Complex, Ile Ife, Nigeria
| | - A A Adelakun
- Department of Medical Laboratory Science, Babcock University, Ilishan Remo, Nigeria
| | - I O Adediji
- Department of Medical Laboratory Science, Babcock University, Ilishan Remo, Nigeria
| | - A O Ogunleke
- LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria
| | - I E Suleiman
- Department of Chemical Pathology & Immunology, University of Ilorin Teaching Hospital, Ilorin, Kwara, Nigeria
| | - E A Olowoyeye
- College of Health Sciences & Technology, Ijero Ekiti, Nigeria
| | | | - A T Ojo
- LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria
| | | | - S S Hammed
- Federal Medical Centre, Abeokuta, Ogun State, Nigeria
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Papaluca T, Roberts SK, Strasser SI, Stuart KA, Farrell G, MacQuillan G, Dore GJ, Wade AJ, George J, Hazeldine S, O'Beirne J, Wigg A, Fisher L, McGarity B, Sawhney R, Sinclair M, Thomas J, Valiozis I, Weltman M, Wilson M, Woodward A, Ahlenstiel G, Haque M, Levy M, Prewett E, Sievert W, Sood S, Tse E, Valaydon Z, Bowden S, Douglas M, New K, O'Keefe J, Hellard M, Doyle J, Stoove M, Thompson AJ. Efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir for HCV NS5A-inhibitor experienced patients with difficult to cure characteristics. Clin Infect Dis 2020; 73:e3288-e3295. [PMID: 32887983 DOI: 10.1093/cid/ciaa1318] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND In clinical trials, HCV salvage treatment with Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. METHODS We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). FINDINGS Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n=46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n=82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n=18/18, GT1b n=2/4), 89% in GT3 (n=59/66) and 100% in GT6 (n=3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were four serious AEs including one death and three hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. CONCLUSION This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most however serious AEs can occur in those with advanced liver disease.
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Affiliation(s)
- Timothy Papaluca
- St Vincent's Hospital Melbourne, Victoria, Australia.,The University of Melbourne, Victoria, Australia
| | - Stuart K Roberts
- The Alfred Hospital Melbourne, Victoria, Australia.,Monash University, Victoria, Australia
| | - Simone I Strasser
- Royal Prince Alfred Hospital, New South Wales, Australia.,The University of Sydney, New South Wales, Australia
| | | | | | - Gerry MacQuillan
- Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.,Medical School, University of Western Australia, Nedlands, Western Australia, Australia
| | - Gregory J Dore
- Kirby Institute, UNSW Sydney, New South Wales, Australia.,St Vincent's Hospital Sydney, New South Wales, Australia
| | - Amanda J Wade
- University Hospital Geelong, Victoria, Australia.,Burnet Institute, Victoria, Australia
| | - Jacob George
- Westmead Hospital, New South Wales, Australia.,Westmead Institute for Medical Research, The University of Sydney, New South Wales, Australia
| | | | - James O'Beirne
- Sunshine Coast University Hospital, Queensland, Australia.,University of Sunshine Coast, Queensland, Australia
| | - Alan Wigg
- Flinders Medical Centre, South Australia, Australia
| | - Leslie Fisher
- The University of Melbourne, Victoria, Australia.,Bendigo Health, Victoria, Australia
| | | | - Rohit Sawhney
- Monash University, Victoria, Australia.,Eastern Health, Victoria, Australia
| | - Marie Sinclair
- The University of Melbourne, Victoria, Australia.,Austin Health, Victoria, Australia
| | - James Thomas
- Princess Alexandra Hospital, Queensland, Australia.,Sunshine Coast University Hospital, Queensland, Australia.,The Prince Charles Hospital, Queensland, Australia.,University of Queensland, St Lucia, Queensland, Australia
| | | | | | | | - Aidan Woodward
- University of Queensland, St Lucia, Queensland, Australia.,Mater Hospital Brisbane, Queensland Australia
| | | | - Mazhar Haque
- University of Queensland, St Lucia, Queensland, Australia.,Mater Hospital Brisbane, Queensland Australia
| | - Miriam Levy
- Liverpool Hospital, New South Wales, Australia
| | - Emily Prewett
- University Hospital Geelong, Victoria, Australia.,Deakin University, Victoria, Australia
| | - William Sievert
- Monash University, Victoria, Australia.,Monash Health, Victoria, Australia
| | - Siddharth Sood
- The University of Melbourne, Victoria, Australia.,Royal Melbourne Hospital, Victoria, Australia
| | - Edmund Tse
- Royal Adelaide Hospital, South Australia, Australia
| | - Zina Valaydon
- The University of Melbourne, Victoria, Australia.,Western Health, Victoria, Australia
| | - Scott Bowden
- Victorian Infectious Diseases Reference Laboratory, Victoria, Australia
| | - Mark Douglas
- Westmead Hospital, New South Wales, Australia.,Westmead Institute for Medical Research, The University of Sydney, New South Wales, Australia
| | - Kate New
- St Vincent's Hospital Melbourne, Victoria, Australia
| | - Jacinta O'Keefe
- Victorian Infectious Diseases Reference Laboratory, Victoria, Australia
| | - Margaret Hellard
- The Alfred Hospital Melbourne, Victoria, Australia.,Monash University, Victoria, Australia.,Burnet Institute, Victoria, Australia
| | - Joseph Doyle
- The Alfred Hospital Melbourne, Victoria, Australia.,Monash University, Victoria, Australia.,Burnet Institute, Victoria, Australia
| | - Mark Stoove
- Monash University, Victoria, Australia.,Burnet Institute, Victoria, Australia
| | - Alexander J Thompson
- St Vincent's Hospital Melbourne, Victoria, Australia.,The University of Melbourne, Victoria, Australia
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Cooper CL, Read D, Vachon ML, Conway B, Wong A, Ramji A, Borgia S, Tam E, Barrett L, Smyth D, Feld JJ, Lee S. Hepatitis C virus infection characteristics and treatment outcomes in Canadian immigrants. BMC Public Health 2020; 20:1345. [PMID: 32883249 PMCID: PMC7469277 DOI: 10.1186/s12889-020-09464-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 08/27/2020] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND There are multiple obstacles encountered by immigrants attempting to engage hepatitis C virus (HCV) care and treatment. We evaluated the diversity and treatment outcomes of HCV-infected immigrants evaluated for Direct Acting Antiviral (DAA) therapy in Canada. METHODS The Canadian Network Undertaking against Hepatitis C (CANUHC) Cohort contains demographic information and DAA treatment information prospectively collected at 10 Canadian sites. Information on country of origin and race are collected. Characteristics and outcomes (sustained virological response; SVR) were compared by immigration status and race. RESULTS Between January 2016 and May 2018, 725 HCV-infected patients assessed for DAA therapy were enrolled in CANUHC (mean age: 52.66 ± 12.68 years); 65.66% male; 82.08% White, 5.28% Indigenous, 4.64% South East Asian, 4.64% East Indian, 3.36% Black). 18.48% were born outside of Canada. Mean age was similar [immigrants: 54.36 ± 13.95 years), Canadian-born: 52.27 ± 12.35 years); (p = 0.085)]. The overall baseline fibrosis score (in kPa measured by transient elastography) was similar among Canadian and foreign-born patients. Fibrosis score was not predicted by race or genotype. The proportion initiating DAA therapy was similar by immigrant status (56.72% vs 49.92%). SVR rates by intent-to-treat analysis were similar (immigrants-89.47%, Canadian-born-92.52%; p = 0.575). CONCLUSION A diverse immigrant population is engaging care in Canada, initiating HCV antiviral therapy in an equitable fashion and achieving SVR proportions similar to Canada-born patients. Our Canadian experience may be of value in informing HCV elimination efforts in economically developed regions.
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Affiliation(s)
- Curtis L Cooper
- University of Ottawa, Roger Guindon Hall, 451 Smyth Rd #2044, Ottawa, ON, K1H 8M5, Canada.
- University of Ottawa, The Ottawa Hospital-General Campus, G12-501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada.
| | - Daniel Read
- University of Ottawa, Roger Guindon Hall, 451 Smyth Rd #2044, Ottawa, ON, K1H 8M5, Canada
| | - Marie-Louise Vachon
- Laval University, Ferdinand Vandry Pavillon, 1050 Avenue de la Médecine, Quebec City, Quebec, G1V 0A6, Canada
| | - Brian Conway
- Vancouver Infectious Diseases Centre, 1200 Burrard St, Vancouver, BC, V6Z 2C7, Canada
| | - Alexander Wong
- University of Saskatchewan, 107 Wiggins Rd, Saskatoon, SK, S7N 5E5, Canada
| | - Alnoor Ramji
- University of British Columbia, 317 - 2194 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada
| | - Sergio Borgia
- McMaster University, Michael DeGroote Centre for Learning and Discovery (MDCL) - 3104, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada
| | - Ed Tam
- Liver Health Centre, 750 W Broadway, Vancouver, BC, V5Z 1H2, Canada
| | - Lisa Barrett
- Dalhousie University, 5849 University Ave, Halifax, NS, B3H 4R2, Canada
| | - Dan Smyth
- Dalhousie University, 5849 University Ave, Halifax, NS, B3H 4R2, Canada
| | - Jordan J Feld
- Toronto General Hospital Research Institute, 200 Elizabeth St, Toronto, ON, M5G 2C4, Canada
| | - Sam Lee
- Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada
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Prevalence and high risk behaviours associated with HCV testing among people who inject drugs: a systematic review and Meta-analysis. SUBSTANCE ABUSE TREATMENT PREVENTION AND POLICY 2020; 15:64. [PMID: 32831107 PMCID: PMC7445934 DOI: 10.1186/s13011-020-00306-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 08/19/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hepatitis C diagnosis could be a gateway to behavioral change and subsequent decline in transmission among people who inject drugs (PWIDs). We assessed the association between the social determinants of PWID, their risk behaviors and hepatitis C testing. METHODS We searched for studies in English published before May 1, 2020, on PubMed, Scopus, Cochrane, and Web of Science to identify primary studies on the factors associated with hepatitis C virus (HCV) testing among PWID. After reviewing for study duplicates, the full-text of selected articles were assessed for eligibility using Population, Intervention, Comparator, Outcomes (PICO) criteria. i) population: individuals who report injecting drugs; ii) intervention: HCV testing in the past year; iii) comparator: PWIDs who did not have an HCV test; iv) outcome: HCV testing among PWIDs and v) study type: cross-sectional, cohort, and case-control studies. Two independent reviewers (author BA and AB) chose the references in a two-phased monitoring process. The authors gathered data from selected papers, including the surname of the first author, publication date, participant demographic data (age, sex, and level of education) and other characteristics like previous HCV testing, past treatment attempts, duration of injecting drug use and condomless sex. We used fixed and random-effects meta-analysis models to estimate the pooled prevalence, pooled odds ratio (OR), and 95% confidence intervals. The data were analyzed using Stata 12.0 software. RESULTS After a detailed assessment of over 12,000 articles, a total of 16 studies containing 38,952 participants met the eligibility criteria. Our findings showed a pooled prevalence rate of 61.01% (95% CI, 34.65-84.32%) for recent HCV testing among PWIDs. Being female (OR = 1.69, 95%CI = 1.13, 2.26), aged > 30 years, (OR = 2.61, 95%CI = 1.66-3.56) having past treatment attempt (OR = 2.24, 95%CI = 1.80-2.68), and reporting a previous test (OR = 2.03, 95%CI = 1.23-2.82). were significantly associated with having a recent HCV test.,,. Finding of present study was that unprotected sex had a negative association with HCV testing. Those PWIDs who had unprotected sex were 0.56 times less likely to have completed HCV testing during last year (OR = 0.56, 95%CI = 0.33-0.78). CONCLUSION Prevention programs that address age > 30 years, being female, past treatment attempt, previous testing of safe sexual practices, are strongly recommended to prioritize HCV risk reduction strategies.
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Turken M, Kose S, Colak Ergun N, Tatar B. Rapid virologic response in chronic hepatitis C genotype 1: Evaluation of pretreatment factors in patients. Arab J Gastroenterol 2020; 21:278-281. [PMID: 32830089 DOI: 10.1016/j.ajg.2020.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/29/2020] [Accepted: 08/11/2020] [Indexed: 11/25/2022]
Abstract
BACKGROUND AND STUDY AIMS Rapid virologic response (RVR) is defined as undetectable hepatitis C virus (HCV) RNA in serum after 4 weeks of treatment for chronic hepatitis C (CHC). Paritaprevir/ritonavir/ombitasvir (PRO) and/or dasabuvir (D), with or without ribavirin [PRO (D) ± ribavirin], which are direct-acting antivirals (DAAs), is the currently approved treatment regimen for CHC genotype 1; this regimen can also be used in patients with end-stage renal failure (ESRF). In this study, we aimed to evaluate the effect of pretreatment factors on RVR in patients treated with PRO (D) ± ribavirin. PATIENTS AND METHODS This study included 60 patients with CHC genotype 1 who were treated with PRO (D) ± ribavirin and achieved RVR. Patients' demographic data; baseline HCV RNA levels; HCV genotype information; biochemical, histologic, and radiologic results; and previous treatment history were recorded. Patients were categorized into two groups: virologic responses achieved in the first week (group 1) and in the first to the fourth week (group 2). Pretreatment factors were compared between the groups. RESULTS Patients in group 1 who achieved ultraRVR (undetectable HCV RNA after 1 week of treatment) had significantly lower mean pretreatment HCV RNA levels and lower prevalence of ESRF than patients in group 2. CONCLUSIONS RVR has been indicated to be a robust positive predictor of sustained virologic response. We concluded that some pretreatment factors such as low HCV RNA level and absence of ESRF might lead to faster RVR and shorter treatment duration with DAAs for CHC.
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Affiliation(s)
- Melda Turken
- University of Health Sciences, Izmir Tepecik Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, 35120 Yenisehir-Izmir, Turkey.
| | - Sukran Kose
- University of Health Sciences, Izmir Tepecik Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, 35120 Yenisehir-Izmir, Turkey
| | - Nadide Colak Ergun
- University of Health Sciences, Izmir Tepecik Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, 35120 Yenisehir-Izmir, Turkey
| | - Bengu Tatar
- University of Health Sciences, Izmir Tepecik Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, 35120 Yenisehir-Izmir, Turkey
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50
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Elsadek HM, Abdelbaser ES, Emara MH, Soliman HH, Farag AA. Morbidity and mortality during hepatitis C treatment using sofosbuvir and daclatasvir with or without ribavirin, in a cohort of Egyptian patients. Eur J Gastroenterol Hepatol 2020; 32:1046-1053. [PMID: 33216478 DOI: 10.1097/meg.0000000000001695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Though direct-acting antiviral agents (DAAs) therapy is associated with a high cure rate of hepatitis C virus infection, a potential risk of serious adverse events (SAEs) exists. The aim of this study was to determine the incidence and predictors of morbidity and mortality related to DAAs therapy. METHODS This prospective study was conducted on a real word cohort of 1562 treatment naïve chronic hepatitis C (CHC) Egyptian patients, who received 12-weeks therapy with sofosbuvir (SOF) plus daclatasvir (DCV) ± ribavirin (RBV). The incidence and predictors of SAEs and mortality during treatment course and over the following 12 weeks were recorded. RESULTS The mean age of study participants was 51.38 ± 9.70 years (55.22%, males). Liver cirrhosis was defined in 72.4% of participants. SAEs were recorded in 120 participants (7.68%), including hepatic decompensation, gastrointestinal bleeding, anemia and hepatocellular carcinoma. Nine patients (0.58%) died and 69 patients (4.42%) discontinued therapy due to SAEs. Severity of cirrhosis was the significant predictor of morbidities and mortality. Hepatic decompensation was predicted by baseline serum albumin [cutoff value: 3.00 g/dL, area under the receiver operating characteristic curve (AUROC): 0.953] and serum bilirubin (cutoff value: 1.75 mg/dL, AUROC: 0.940). CONCLUSION The risk of morbidity and mortality related to SOF/DCV ± RBV therapy in CHC patients is small and is significantly linked to advanced cirrhosis.
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Affiliation(s)
- Hany M Elsadek
- Gastroenterology and Hepatology Unit, Internal Medicine Department
| | | | - Mohamed H Emara
- Hepatology, Gastroenterology and Infectious Diseases Department, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh
| | - Hanan H Soliman
- Community Medicine Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Alaa A Farag
- Gastroenterology and Hepatology Unit, Internal Medicine Department
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