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Pereira CM, Shimizu JF, Cassani NM, Santos IA, Bittar C, Oliveira Cintra AC, Sampaio SV, Harris M, Rahal P, Gomes Jardim AC. Bothropstoxins I and II as potent phospholipase A2 molecules from Bothrops jararacussu to impair Hepatitis C virus infection. Biochimie 2025:S0300-9084(25)00081-1. [PMID: 40288437 DOI: 10.1016/j.biochi.2025.04.006] [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: 06/25/2024] [Revised: 03/26/2025] [Accepted: 04/18/2025] [Indexed: 04/29/2025]
Abstract
Hepatitis C is a hepatological disorder induced by the Hepacivirus hominis (Hepatitis C virus, HCV), with approximately 170 million individuals estimated to be presently affected globally. The current treatment for infected patients primarily relies on direct-acting antivirals (DAAs). However, this treatment is marked by its high cost, numerous side effects, and documented instances of antiviral resistance. These challenges underscore the imperative for developing novel therapeutic strategies. In this framework, naturally occurring compounds have exhibited considerable medical significance attributable to their biological functionalities. Compounds extracted from snake venoms have evidenced antiviral efficacy against a variety of viral pathogens including Orthoflavivirus denguei (DENV), Orthoflavivirus flavi (YFV), Orthoflavivirus zikaense (ZIKV), and HCV. Here, the activity of 10 proteins isolated from snakes' venom of Bothrops genus were evaluated against HCV replicative cycle. The full-length JFH-1 HCV system was used to infect the Huh-7.5 cell. Cell viability was measured simultaneously through MTT assay. Eight compounds inhibited up to 99% of HCV infection, being the most potent inhibitory rates observed in BthTX-I and BthTX-II, with an SI of 13.5 and 1736, respectively, being able to block 84.7% and 96% of HCV infectivity, in the same order. BthTX-II also demonstrated a protective effect in cells treated prior to HCV infection of approximately 86.7%. Molecular docking calculations suggest interactions between the two proteins with HCV E1-E2 glycoprotein complex. BthTX-II exhibited stronger interactions, indicated by 22 hydrophobic interactions. In conclusion, these compounds were shown to inhibit HCV infectivity by either acting on the virus particles or protecting the cells against infection.
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Affiliation(s)
- Carina Machado Pereira
- Genomics Study Laboratory, São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil
| | - Jacqueline Farinha Shimizu
- Genomics Study Laboratory, São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil; Laboratory of Antiviral Research, Institute of Biomedical Science, ICBIM, Federal University of Uberlândia, Uberlândia, MG, Brazil
| | - Natasha Marques Cassani
- Laboratory of Antiviral Research, Institute of Biomedical Science, ICBIM, Federal University of Uberlândia, Uberlândia, MG, Brazil
| | - Igor Andrade Santos
- Laboratory of Antiviral Research, Institute of Biomedical Science, ICBIM, Federal University of Uberlândia, Uberlândia, MG, Brazil
| | - Cintia Bittar
- Genomics Study Laboratory, São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil
| | | | - Suely Vilela Sampaio
- Laboratory of Toxinology, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, SP, Brazil
| | - Mark Harris
- School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
| | - Paula Rahal
- Genomics Study Laboratory, São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil
| | - Ana Carolina Gomes Jardim
- Genomics Study Laboratory, São Paulo State University, IBILCE, S. José do Rio Preto, SP, Brazil; Laboratory of Antiviral Research, Institute of Biomedical Science, ICBIM, Federal University of Uberlândia, Uberlândia, MG, Brazil.
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Zhao L, Hall M, Giridhar P, Ghafari M, Kemp S, Chai H, Klenerman P, Barnes E, Ansari MA, Lythgoe K. Genetically distinct within-host subpopulations of hepatitis C virus persist after Direct-Acting Antiviral treatment failure. PLoS Pathog 2025; 21:e1012959. [PMID: 40168433 PMCID: PMC11981120 DOI: 10.1371/journal.ppat.1012959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 04/09/2025] [Accepted: 02/05/2025] [Indexed: 04/03/2025] Open
Abstract
Analysis of viral genetic data has previously revealed distinct within-host population structures in both untreated and interferon-treated chronic hepatitis C virus (HCV) infections. While multiple subpopulations persisted during the infection, each subpopulation was observed only intermittently. However, it was unknown whether similar patterns were also present after Direct-Acting Antiviral (DAA) treatment, where viral populations were often assumed to go through narrow bottlenecks. Here we tested for the maintenance of population structure after DAA treatment failure, and whether there were different evolutionary rates along distinct lineages where they were observed. We analysed whole-genome next-generation sequencing data generated from a randomised study using DAAs (the BOSON study). We focused on samples collected from patients (N=84) who did not achieve sustained virological response (i.e., treatment failure) and had sequenced virus from multiple timepoints. Given the short-read nature of the data, we used a number of methods to identify distinct within-host lineages including tracking concordance in intra-host nucleotide variant (iSNV) frequencies, applying sequenced-based and tree-based clustering algorithms to sliding windows along the genome, and haplotype reconstruction. Distinct viral subpopulations were maintained among a high proportion of individuals post DAA treatment failure. Using maximum likelihood modelling and model comparison, we found an overdispersion of viral evolutionary rates among individuals, and significant differences in evolutionary rates between lineages within individuals. These results suggest the virus is compartmentalised within individuals, with the varying evolutionary rates due to different viral replication rates and/or different selection pressures. We endorse lineage awareness in future analyses of HCV evolution and infections to avoid conflating patterns from distinct lineages, and to recognise the likely existence of unsampled subpopulations.
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Affiliation(s)
- Lele Zhao
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
| | - Matthew Hall
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
| | | | - Mahan Ghafari
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom
| | - Steven Kemp
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom
| | - Haiting Chai
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
| | - Paul Klenerman
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
| | - Eleanor Barnes
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
| | - M. Azim Ansari
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom
| | - Katrina Lythgoe
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom
- Department of Biology, University of Oxford, Oxford, United Kingdom
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Dashjamts G, Ganzorig AE, Tsedendorj Y, Daramjav D, Khayankhyarvaa E, Ulziitsogt B, Nergui O, Dondov G, Badamjav T, Lonjid T, Huang CF, Liang PC, Batsaikhan B, Dai CY. Change in Estimated Glomerular Filtration Rate After Direct-Acting Antiviral Treatment in Chronic Hepatitis C Patients. Diseases 2025; 13:26. [PMID: 39997033 PMCID: PMC11854603 DOI: 10.3390/diseases13020026] [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: 11/19/2024] [Revised: 01/17/2025] [Accepted: 01/17/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection accelerates the progression of chronic kidney disease (CKD), increasing the risk of kidney failure and end-stage renal disease. Direct-acting antiviral (DAA) therapies for HCV infection inhibit viral replication by 95-97%, leading to a sustained virologic response. Our objective was to assess renal function in patients with chronic HCV infection in Taiwan after receiving DAA therapy. GOAL Our study included 4823 patients with HCV infection who were undergoing DAA therapy. Renal function was evaluated by calculating the glomerular filtration rate (eGFR). eGFR assessed at the initiation of the treatment, during treatment, and at 3 months, 6 months, 1 year, and 3 years after completion of treatment. The baseline demographic and laboratory parameters of the study participants were evaluated, and the results were analyzed using statistical methods. RESULTS The average age of the study participants was 61.35 ± 12.50 years, and 54.5% of were male. The mean of eGFR in baseline and after treatment showed a decrease. Liver fibrosis scores (FIB4, APRI, Fibroscan) and liver function tests were significantly improved after DAA treatment (p = 0.001). However, white blood count (5.41 ± 1.7 vs. 5.73 ± 1.9), platelet count (168.04 ± 74.0 vs. 182.11 ± 69.4), and creatinine levels (1.05 ± 1.3 vs. 1.12 ± 1.3) increased after treatment (p = 0.001). The number of patients with an eGFR of 60 mL/min/1.73 m2 decreased both during and after treatment (p < 0.001). Among patients with CKD, eGFR improved after DAA treatment (n = 690, 35.93 ± 19.7 vs. 38.71 ± 23.8; 95% CI -3.56-1.98; p = 0.001). Logistic regression analysis revealed that renal function improved in patients with CKD who had an eGFR of less than 60 mL/min/1.73 m2 before DAA treatment (OR 1.62, 95% CI 1.37-1.91, p = 0.001). CONCLUSIONS In individuals with CKD and a baseline eGFR < 60 mL/min per 1.73 m2, eGFR level was increased during DAA treatment. This suggests that initiating DAA therapy in HCV-infected patients, even those without clinical manifestations, could be a crucial strategy to prevent further decline in renal function.
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Affiliation(s)
- Gantogtokh Dashjamts
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Amin-Erdene Ganzorig
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Yumchinsuren Tsedendorj
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Dolgion Daramjav
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Enkhmend Khayankhyarvaa
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Bolor Ulziitsogt
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Otgongerel Nergui
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Ganchimeg Dondov
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Tegshjargal Badamjav
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
- Department of Biological Sciences, School of Life Sciences, Inner Mongolia University, Hohhot 010031, China
| | - Tulgaa Lonjid
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
| | - Chung-Feng Huang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (C.-F.H.); (P.-C.L.)
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Po-Cheng Liang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (C.-F.H.); (P.-C.L.)
- Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Batbold Batsaikhan
- Department of Internal Medicine, Institute of Medical Sciences, Ministry of Economy and Development, Ulaanbaatar 14210, Mongolia; (G.D.); (A.-E.G.); (Y.T.); (D.D.); (E.K.); (B.U.); (O.N.); (G.D.); (T.B.); (T.L.)
- Department of Health Research, Graduate School, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
| | - Chia-Yen Dai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan; (C.-F.H.); (P.-C.L.)
- Ph.D. Program in Environmental and Occupational Medicine, Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- College of Professional Studies, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan
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4
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Shafqat A, Li M, Zakirullah, Liu F, Tong Y, Fan J, Fan H. A comprehensive review of research advances in the study of lactoferrin to treat viral infections. Life Sci 2025; 361:123340. [PMID: 39730037 DOI: 10.1016/j.lfs.2024.123340] [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: 07/12/2024] [Revised: 12/17/2024] [Accepted: 12/23/2024] [Indexed: 12/29/2024]
Abstract
Lactoferrin (Lf) is a naturally occurring glycoprotein known for its antiviral and antibacterial properties and is present in various physiological fluids. Numerous studies have demonstrated its antiviral effectiveness against multiple viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus (IFV), herpes simplex virus (HSV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV). Lf, a vital component of the mucosal defense system, plays a crucial role in inhibiting viral infection by binding to both host cells and viral particles, such as the Hepatitis C virus (HCV). This interaction enables Lf to keep viral particles away from their target cells, emphasizing its significance as a fundamental element of mucosal defense against viral infections. Additionally, Lf has the ability to modulate cytokine expression and enhance cellular immune responses. In the innate immune system, Lf serves as a unique iron transporter and helps suppress various pathogens like bacteria, fungi, and viruses. This article summarises the potential antiviral properties of Lf against various viruses, along with its other mentioned functions. The advancement of Lf-based therapies supports the homology of food and medicine, providing a promising avenue to address viral infections and other public health challenges.
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Affiliation(s)
- Amna Shafqat
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Maochen Li
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Zakirullah
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Feitong Liu
- H&H Group, H&H Research, China Research and Innovation, Guangzhou, China.
| | - Yigang Tong
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
| | - Junfen Fan
- Institute of Cerebrovascular Diseases Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
| | - Huahao Fan
- School of Life Sciences, Tianjin University, Tianjin, China.
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5
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Smolobochkin A, Gazizov A, Appazov N, Sinyashin O, Burilov A. Progress in the Stereoselective Synthesis Methods of Pyrrolidine-Containing Drugs and Their Precursors. Int J Mol Sci 2024; 25:11158. [PMID: 39456938 PMCID: PMC11508981 DOI: 10.3390/ijms252011158] [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] [Received: 09/09/2024] [Revised: 10/11/2024] [Accepted: 10/12/2024] [Indexed: 10/28/2024] Open
Abstract
The presented review systematizes and summarizes the data on the synthesis of pyrrolidine derivatives, which are precursors for obtaining drugs. Based on the analysis of published data, the most promising directions in the synthesis of biologically active compounds containing a pyrrolidine ring are identified. Stereoselective synthesis methods are classified based on the source of the pyrrolidine ring. The first group includes methods that use a pyrrolidine ring as the starting compound. The second group combines stereoselective methods of cyclization of acyclic starting compounds, which lead to optically pure pyrrolidine derivatives.
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Affiliation(s)
- Andrey Smolobochkin
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str., 8, Kazan 420088, Russia; (A.G.); (O.S.); (A.B.)
| | - Almir Gazizov
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str., 8, Kazan 420088, Russia; (A.G.); (O.S.); (A.B.)
| | - Nurbol Appazov
- Laboratory of Engineering Profile, Department of Engineering Technology, Korkyt Ata Kyzylorda University, Aiteke bi Str., 29A, Kyzylorda 120014, Kazakhstan
| | - Oleg Sinyashin
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str., 8, Kazan 420088, Russia; (A.G.); (O.S.); (A.B.)
| | - Alexander Burilov
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str., 8, Kazan 420088, Russia; (A.G.); (O.S.); (A.B.)
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Abdelaziz AI, Abdelsameea E, Abdel-Samiee M, Ghanem SE, Wahdan SA, Elsherbiny DA, Zakaria Z, Azab SS. Effect of immunogenetics polymorphism and expression on direct-acting antiviral drug response in chronic hepatitis C. Clin Exp Med 2024; 24:184. [PMID: 39117877 PMCID: PMC11310263 DOI: 10.1007/s10238-024-01432-x] [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] [Received: 04/10/2024] [Accepted: 07/09/2024] [Indexed: 08/10/2024]
Abstract
The prevalence of HCV infection in Egypt has decreased following the introduction of direct-acting antiviral therapy. However, treatment response is influenced by various factors, particularly host immunogenetics such as IL-28B and FOXP3 polymorphisms. The current study examined the impact of SNPs in the FOXP3 gene promoter region on HCV-infected Egyptian patients, along with SNPs in the IL28B gene.This study involved 99 HCV patients who achieved SVR12 after a 12 week DAA treatment while 63 HCV patients experienced treatment failure. IL28B rs12979860 SNP was identified using real-time PCR, while IL28B rs8099917, FOXP3 rs3761548, and rs2232365 SNPs were analyzed using RFLP-PCR. Serum levels of IL28B and FOXP3 were quantified using ELISA technique in representative samples from both groups. The IL28B rs12979860 T > C (P = 0.013) and FOXP3 rs2232365 A > G polymorphisms (P = 0.008) were found to significantly increase the risk of non-response. Responders had higher IL28B serum levels (P = 0.046) and lower FOXP3 levels (P < 0.001) compared to non-responders. Regression analysis showed an association between IL28B rs12979860 and FOXP3 rs2232365 with treatment response, independent of age and gender. A predictive model was developed with 76.2% sensitivity and 91.9% specificity for estimating DAAs response in HCV patients.Our findings confirmed the IL28B rs12979860 T > C and FOXP3 rs2232365 A > G polymorphisms significantly affect DAA treatment response in HCV Egyptian patients. Lower levels of IL-28B along with higher levels of FOXP3 are linked to poor response. Our results may lead to new insights into DAA responsiveness contributing to personalized medicine and improving therapeutic decision-making for HCV patients.
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Affiliation(s)
- Aya Ismail Abdelaziz
- Department of Research and Development, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt
| | - Eman Abdelsameea
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Mohamed Abdel-Samiee
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Samar E Ghanem
- Department of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Sara A Wahdan
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt
| | - Doaa A Elsherbiny
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt
| | - Zeinab Zakaria
- Department of Research and Development, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt
| | - Samar S Azab
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.
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Vo-Quang E, Pawlotsky JM. 'Unusual' HCV genotype subtypes: origin, distribution, sensitivity to direct-acting antiviral drugs and behaviour on antiviral treatment and retreatment. Gut 2024; 73:1570-1582. [PMID: 38782565 PMCID: PMC11347264 DOI: 10.1136/gutjnl-2024-332177] [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: 02/14/2024] [Accepted: 04/30/2024] [Indexed: 05/25/2024]
Abstract
The high genetic diversity of hepatitis C virus (HCV) has led to the emergence of eight genotypes and a large number of subtypes in limited geographical areas. Currently approved pangenotypic DAA regimens have been designed and developed to be effective against the most common subtypes (1a, 1b, 2a, 2b, 2c, 3a, 4a, 5a and 6a). However, large populations living in Africa and Asia, or who have migrated from these regions to industrialised countries, are infected with 'unusual', non-epidemic HCV subtypes, including some that are inherently resistant to currently available direct-acting antiviral (DAA) drugs due to the presence of natural polymorphisms at resistance-associated substitution positions. In this review article, we describe the origin and subsequent global spread of HCV genotypes and subtypes, the current global distribution of common and unusual HCV subtypes, the polymorphisms naturally present in the genome sequences of unusual HCV subtypes that may confer inherently reduced susceptibility to DAA drugs and the available data on the response of unusual HCV subtypes to first-line HCV therapy and retreatment. We conclude that the problem of unusual HCV subtypes that are inherently resistant to DAAs and its threat to the global efforts to eliminate viral hepatitis are largely underestimated and warrant vigorous action.
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Affiliation(s)
- Erwan Vo-Quang
- National Reference Centre for Viral Hepatitis B, C and D, Department of Virology, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Institut Mondor de Recherche Biomédicale (INSERM U955), Créteil, France
- Department of Hepatology, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
| | - Jean-Michel Pawlotsky
- National Reference Centre for Viral Hepatitis B, C and D, Department of Virology, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Institut Mondor de Recherche Biomédicale (INSERM U955), Créteil, France
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8
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Hashem M, Medhat MA, Abdeltawab D, Makhlouf NA. Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time? World J Transplant 2024; 14:90382. [PMID: 38947961 PMCID: PMC11212581 DOI: 10.5500/wjt.v14.i2.90382] [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: 12/01/2023] [Revised: 02/29/2024] [Accepted: 04/12/2024] [Indexed: 06/13/2024] Open
Abstract
Liver transplantation (LT) provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma. Despite the increasing number of liver transplants performed each year, the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality. Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates. Nevertheless, further strategies can be implemented to increase the pool of potential donors in deceased donor LT, such as reducing the rate of organ discards. Utilizing hepatitis C virus (HCV) seropositive liver grafts is one of the expanded donor organ criteria. A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients. Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation. The American Society of Transplantation advises against performing transplants from HCV-infected liver donors (D+) into HCV-negative recipient (R-) unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants. Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is important. National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.
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Affiliation(s)
- Mai Hashem
- Fellow of Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut 71515, Egypt
| | - Mohammed A Medhat
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Doaa Abdeltawab
- Department of Tropical Medicine and Gastroenterology, Al-Rajhi Liver Hospital, Assiut University, Assiut 71515, Egypt
| | - Nahed A Makhlouf
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
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9
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Kothapalli Y, Jones RA, Chu CK, Singh US. Synthesis of Fluorinated Nucleosides/Nucleotides and Their Antiviral Properties. Molecules 2024; 29:2390. [PMID: 38792251 PMCID: PMC11124531 DOI: 10.3390/molecules29102390] [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: 04/02/2024] [Revised: 05/10/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous drugs are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral and anticancer activity. The insertion of a fluorine atom, either in the base or sugar of nucleos(t)ides, alters its electronic and steric parameters and transforms the lipophilicity, pharmacodynamic, and pharmacokinetic properties of these moieties. The fluorine atom restricts the oxidative metabolism of drugs and provides enzymatic metabolic stability towards the glycosidic bond of the nucleos(t)ide. The incorporation of fluorine also demonstrates additional hydrogen bonding interactions in receptors with enhanced biological profiles. The present article discusses the synthetic methodology and antiviral activities of FDA-approved drugs and ongoing fluoro-containing nucleos(t)ide drug candidates in clinical trials.
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Affiliation(s)
| | | | - Chung K. Chu
- Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA; (Y.K.); (R.A.J.)
| | - Uma S. Singh
- Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA; (Y.K.); (R.A.J.)
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10
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Dobrowolska K, Brzdęk M, Rzymski P, Flisiak R, Pawłowska M, Janczura J, Brzdęk K, Zarębska-Michaluk D. Revolutionizing hepatitis C treatment: next-gen direct-acting antivirals. Expert Opin Pharmacother 2024; 25:833-852. [PMID: 38768013 DOI: 10.1080/14656566.2024.2358139] [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: 04/11/2024] [Accepted: 05/17/2024] [Indexed: 05/22/2024]
Abstract
INTRODUCTION With the introduction of highly effective and safe therapies with next-generation direct-acting antivirals (DAAs), that act without interferon, hepatitis C virus (HCV) infection remains the only treatable chronic infectious disease. AREAS COVERED The review aims to provide an overview of the therapy revolution with a description of specific DAAs, their mechanisms of action, a summary of the safety and efficacy of specific regimens, and a discussion of populations requiring special therapeutic approaches. EXPERT OPINION DAAs are highly effective, safe, and easy to use. However, challenges such as access to health services and loss of patients from the cascade of care, especially in groups disproportionately affected by HCV infection, such as substance abusers, make it difficult to achieve the WHO's goal of HCV elimination. The proposed strategy to combat these difficulties involves a one-step approach to diagnosing and treating the infection, the availability of long-lasting forms of medication, and the development of an effective vaccine. The aforementioned opportunities are all the more important as the world is facing an opioid epidemic that is translating into an increase in HCV prevalence. This phenomenon is of greatest concern in women of childbearing age and in those already pregnant due to treatment limitations.
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Affiliation(s)
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | - Piotr Rzymski
- Department of Environmental Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
| | - Jakub Janczura
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
| | - Kinga Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
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11
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Petkevičienė J, Voeller A, Čiupkevičienė E, Razavi-Shearer D, Liakina V, Jančorienė L, Kazėnaitė E, Zaksas V, Urbonas G, Kupčinskas L. Hepatitis C screening in Lithuania: first-year results and scenarios for achieving WHO elimination targets. BMC Public Health 2024; 24:1055. [PMID: 38622549 PMCID: PMC11020450 DOI: 10.1186/s12889-024-18470-5] [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: 12/13/2023] [Accepted: 03/28/2024] [Indexed: 04/17/2024] Open
Abstract
BACKGROUND The World Health Organization (WHO) has outlined a set of targets to achieve eliminating hepatitis C by 2030. In May 2022, Lithuanian health authorities initiated a hepatitis C virus (HCV) screening program to start working towards elimination. In the program, bonus was given to general practitioners (GPs) to promote and conduct anti-HCV tests for two situations: (1) one time testing for individuals born in 1945-1994 and (2) annual HCV testing for persons who inject drugs or are living with human immunodeficiency virus (HIV) regardless of age. This study aimed to model the current viral hepatitis C epidemiological status in Lithuania and to outline the requirements for WHO elimination targets using the first-year HCV screening results. METHODS Individuals were invited to participate in the anti-HCV screening by GPs during routine visits. Patients who tested positive were then referred to a gastroenterologist or infectious disease doctor for further confirmatory testing. If a patient received a positive RNA test and a fibrosis staging result of ≥ F2, the doctor prescribed direct-acting antivirals. Information on the patients screened, diagnosed, and treated was obtained from the National Health Insurance Fund. The Markov disease progression model, developed by the CDA Foundation, was used to evaluate the screening program results and HCV elimination progress in Lithuania. RESULTS Between May 2022 and April 2023, 790,070 individuals underwent anti-HCV testing, with 11,943 individuals (1.5%) receiving positive results. Anti-HCV seroprevalence was found to be higher among males than females, 1.9% and 1.2%, respectively. Within the risk population tested, 2087 (31.1%) seropositive individuals were identified. When comparing the screening program results to WHO elimination targets through modelling, 2180 patients still need to be treated annually until 2030, along with expanding fibrosis restrictions. If an elimination approach was implemented, 1000 new infections would be prevented, while saving 150 lives and averting 90 decompensated cirrhosis cases and 110 hepatocellular carcinoma cases. CONCLUSIONS During the first year of the Lithuanian screening program, GPs were able to screen 44% of the target population. However, the country will not meet elimination targets as it currently stands without increasing treatment levels and lifting fibrosis restrictions.
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Affiliation(s)
- Janina Petkevičienė
- Health Research Institute, Faculty of Public Health, Lithuanian University of Health Sciences, Tilžės str. 18, LT47181, Kaunas, Lithuania.
- Department of Preventive Medicine, Faculty of Public Health, Lithuanian University of Health Sciences, Tilžės str. 18, LT47181, Kaunas, Lithuania.
| | - Alexis Voeller
- Center for Disease Analysis Foundation, 1120 W South Boulder Rd, Suite 102, Lafayette, CO, USA
| | - Eglė Čiupkevičienė
- Health Research Institute, Faculty of Public Health, Lithuanian University of Health Sciences, Tilžės str. 18, LT47181, Kaunas, Lithuania
| | - Devin Razavi-Shearer
- Center for Disease Analysis Foundation, 1120 W South Boulder Rd, Suite 102, Lafayette, CO, USA
| | - Valentina Liakina
- Faculty of Medicine, Vilnius University, Universiteto str. 3, LT01513, Vilnius, Lithuania
- Faculty of Fundamental Sciences, Vilnius Tech, Saulėtekio av. 11, LT10223, Vilnius, Lithuania
| | - Ligita Jančorienė
- Clinic of Infectious Diseases and Dermatovenerology, Institute of Clinical Medicine, Medical Faculty, Vilnius University, Santariškių str. 14, 08406, Vilnius, Lithuania
| | - Edita Kazėnaitė
- Faculty of Medicine, Vilnius University, Universiteto str. 3, LT01513, Vilnius, Lithuania
- Vilnius University Hospital Santaros Klinikos, Santariškių str. 2, LT08661, Vilnius, Lithuania
| | - Viačeslavas Zaksas
- National Health Insurance Fund under the Ministry of Health, Europos Sq. 1, LT03505, Vilnius, Lithuania
| | - Gediminas Urbonas
- Department of Family Medicine, Lithuanian University of Health Sciences, Eivenių str. 2, LT50161, Kaunas, Lithuania
| | - Limas Kupčinskas
- Department of Gastroenterology, Lithuanian University of Health Sciences, Eivenių str. 2, LT50161, Kaunas, Lithuania
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12
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Nasr MS, Talaat W, Morshedy S, Kaddah MMY, Omran G, Keshk RM. A new fluorescence probe for sofosbuvir analysis in dosage form and spiked human plasma. LUMINESCENCE 2024; 39:e4742. [PMID: 38637644 DOI: 10.1002/bio.4742] [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] [Received: 07/17/2023] [Revised: 03/09/2024] [Accepted: 03/15/2024] [Indexed: 04/20/2024]
Abstract
A simple, rapid, and low-cost technique was developed to allow reliable analysis of the anti-hepatitis C drug sofosbuvir in bulk, tablet form, and spiked human plasma. This method depends on the ability of sofosbuvir to quench the fluorescence of the newly synthesized 2-amino-3-cyano-4,6-dimethylpyridine (reagent 3). Elemental analysis and spectral data were used to validate the structure of the synthesized reagent. The newly synthesized reagent exhibited a satisfactory level of fluorescence emission at 365 nm after excitation at 247 nm. All experimental variables that might affect the quenching process were analyzed and optimized. Linearity, range, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ) were all validated in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. The concentration range was shown to be linear between 0.1 and 1.5 μg/mL. The technique was effectively utilized for sofosbuvir analysis in both its tablet dosage form and spiked human plasma, with mean percentage recoveries of 100.13 ± 0.35 and 94.26 ± 1.69, respectively.
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Affiliation(s)
- Mohamed S Nasr
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Wael Talaat
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Samir Morshedy
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Mohamed M Y Kaddah
- Pharmaceutical and Fermentation Industries Development Center, City of Scientific Research and Technological Applications, New Borg El-Arab, Alexandria, Egypt
| | - Gamal Omran
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Reda M Keshk
- Department of Chemistry, Faculty of Science, Damanhour University, Damanhour, Egypt
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13
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Alghamdi AS, Alghamdi H, Alserehi HA, Babatin MA, Alswat KA, Alghamdi M, AlQutub A, Abaalkhail F, Altraif I, Alfaleh FZ, Sanai FM. SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024. Saudi J Gastroenterol 2024; 30:S1-S42. [PMID: 38167232 PMCID: PMC10856511 DOI: 10.4103/sjg.sjg_333_23] [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: 09/20/2023] [Revised: 11/27/2023] [Accepted: 12/03/2023] [Indexed: 01/05/2024] Open
Abstract
ABSTRACT Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.
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Affiliation(s)
- Abdullah S. Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Hamdan Alghamdi
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Haleema A. Alserehi
- General Directorate of Communicable Diseases, Ministry of Health, Riyadh, Saudi Arabia
| | - Mohammed A. Babatin
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Khalid A. Alswat
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Medicine, Division of Gastroenterology, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Adel AlQutub
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
| | - Ibrahim Altraif
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | | | - Faisal M. Sanai
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- Gastroenterology Section, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
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14
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Almutawakel S, Halleck F, Dürr M, Grittner U, Schrezenmeier E, Budde K, Althoff CE, Hamm B, Sack I, Fischer T, Marticorena Garcia SR. Shear Wave Elastography for Assessing Liver Stiffness in HCV-Infected Kidney Transplant Recipients after Direct-Acting Antiviral Treatment: A Comparative Study with Magnetic Resonance Elastography. J Clin Med 2023; 12:7547. [PMID: 38137615 PMCID: PMC10743898 DOI: 10.3390/jcm12247547] [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: 10/19/2023] [Revised: 11/22/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatitis C virus (HCV) infection can lead to hepatic fibrosis. The advent of direct-acting antivirals (DAAs) has substantially improved sustained virological response (SVR) rates. In this context, kidney transplant recipients (KTRs) are of particular interest due to their higher HCV infection rates and uncertain renal excretion and bioavailability of DAAs. We investigated liver stiffness after DAA treatment in 15 HCV-infected KTRs using ultrasound shear wave elastography (SWE) in comparison with magnetic resonance elastography (MRE). KTRs were treated with DAAs (daclatasvir and sofosbuvir) for three months and underwent SWE at baseline, end of therapy (EOT), and 3 (EOT+3) and 12 months (EOT+12) after EOT. Fourteen patients achieved SVR12. Shear wave speed (SWS)-as a surrogate parameter for tissue stiffness-was substantially lower at all three post-therapeutic timepoints compared with baseline (EOT: -0.42 m/s, p < 0.01; CI = -0.75--0.09, EOT+3: -0.43 m/s, p < 0.01; CI = -0.75--0.11, and EOT+12: -0.52 m/s, p < 0.001; CI = -0.84--0.19), suggesting liver regeneration after viral eradication and end of inflammation. Baseline SWS correlated positively with histopathological fibrosis scores (r = 0.48; CI = -0.11-0.85). Longitudinal results correlated moderately with APRI (r = 0.41; CI = 0.12-0.64) but not with FIB-4 scores (r = 0.12; CI = -0.19-0.41). Although higher on average, SWE-derived measurements correlated strongly with MRE (r = 0.64). In conclusion, SWE is suitable for non-invasive therapy monitoring in KTRs with HCV infection.
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Affiliation(s)
- Salma Almutawakel
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
| | - Fabian Halleck
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Michael Dürr
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Ulrike Grittner
- Institute of Biometry and Clinical Epidemiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Eva Schrezenmeier
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Christian E. Althoff
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
| | - Bernd Hamm
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
| | - Ingolf Sack
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
| | - Thomas Fischer
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
| | - Stephan R. Marticorena Garcia
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
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15
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Georgieva M, Xenodochidis C, Krasteva N. Old age as a risk factor for liver diseases: Modern therapeutic approaches. Exp Gerontol 2023; 184:112334. [PMID: 37977514 DOI: 10.1016/j.exger.2023.112334] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 11/12/2023] [Accepted: 11/14/2023] [Indexed: 11/19/2023]
Abstract
Recent scientific interest has been directed towards age-related diseases, driven by the significant increase in global life expectancy and the growing population of individuals aged 65 and above. The ageing process encompasses various biological, physiological, environmental, psychological, behavioural, and social changes, leading to an augmented susceptibility to chronic illnesses. Cardiovascular, neurological, musculoskeletal, liver and oncological diseases are prevalent in the elderly. Moreover, ageing individuals demonstrate reduced regenerative capacity and decreased tolerance towards therapeutic interventions, including organ transplantation. Liver diseases, such as non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis, fibrosis, and cirrhosis, have emerged as significant public health concerns. Paradoxically, these conditions remain underestimated despite their substantial global impact. Age-related factors are closely associated with the severity and unfavorable prognosis of various liver diseases, warranting further investigation to enhance clinical management and develop novel therapeutic strategies. This comprehensive review focuses specifically on age-related liver diseases, their treatment strategies, and contemporary practices. It provides a detailed account of the global burden, types, molecular mechanisms, and epigenetic alterations underlying these liver pathologies.
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Affiliation(s)
- Milena Georgieva
- Institute of Molecular Biology "Acad. Roumen Tsanev", Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
| | - Charilaos Xenodochidis
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Natalia Krasteva
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
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16
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Odenwald MA, Roth HF, Reticker A, Segovia M, Pillai A. Evolving challenges with long-term care of liver transplant recipients. Clin Transplant 2023; 37:e15085. [PMID: 37545440 DOI: 10.1111/ctr.15085] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/17/2023] [Accepted: 07/23/2023] [Indexed: 08/08/2023]
Abstract
The number of liver transplants (LT) performed worldwide continues to rise, and LT recipients are living longer post-transplant. This has led to an increasing number of LT recipients requiring lifelong care. Optimal care post-LT requires careful attention to both the allograft and systemic issues that are more common after organ transplantation. Common causes of allograft dysfunction include rejection, biliary complications, and primary disease recurrence. While immunosuppression prevents rejection and reduces incidences of some primary disease recurrence, it has detrimental systemic effects. Most commonly, these include increased incidences of metabolic syndrome, various malignancies, and infections. Therefore, it is of utmost importance to optimize immunosuppression regimens to prevent allograft dysfunction while also decreasing the risk of systemic complications. Institutional protocols to screen for systemic disease and heightened clinical suspicion also play an important role in providing optimal long-term post-LT care. In this review, we discuss these common complications of LT as well as unique considerations when caring for LT recipients in the years after transplant.
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Affiliation(s)
- Matthew A Odenwald
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Hannah F Roth
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
| | - Anesia Reticker
- Department of Pharmacy, University of Chicago Medicine, Chicago, USA
| | - Maria Segovia
- Department of Medicine, Section of Gastroenterology, Duke University School of Medicine, Durham, USA
| | - Anjana Pillai
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, USA
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17
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Debzi N, Berkane S, Manouni C, Amani N, Hemmam S, Yousfi M, Taleb A, Guessab N, Moulay Brahim AS, Helal S, Benbitour I, Noual L, Kerbouche R, Cheikh IO, Drir O, Belimi HA, Gourari S, Frigga I, Kassah-laouar A, Khaberi M, Afredj N. Efficacy of Sofosbuvir/Daclatasvir in a Single Tablet for Treating Chronic Viral Hepatitis C. J Clin Pharm Ther 2023; 2023:1-9. [DOI: 10.1155/2023/8297332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Background. Published data regarding the real-life application of the combination sofosbuvir/daclatasvir in Algeria are lacking. Therefore, we conducted an observational study to assess the efficacy and safety of this regimen in Algerian patients with chronic hepatitis C. Methods. We carried out a multicentric, observational, open-label study to assess the efficacy and safety of the generic fixed-dose combination (FDC) sofosbuvir/daclatasvir in patients with chronic hepatitis C. We included 100 patients with all genotypes for 12 or 24 weeks of treatment without ribavirin. The primary outcome was the proportion of patients with a sustained virologic response (SVR) 12 weeks after treatment cessation. The secondary outcome assessed the safety and occurrence of adverse events. This study is registered with ClinicalTrials.gov identifier: NCT05138523. Results. The full analysis set included 99 patients with a mean age of 51.4 ± 14.4 years and a sex ratio of M/F = 0.86. Our patients were infected with HCV genotype 1b (n = 47), 2 (n = 17), 1a (n = 3), 2a/2c (n = 2), 3 (n = 2), and 4 (n = 1). A total of 27 patients had missing genotype data. Most patients were naive noncirrhotic (n = 70) and took 12 weeks of treatment, 19 patients had cirrhosis, of which 68.42% (n = 13) were classified as Child–Pugh A, and 5 patients were treatment-experienced. Both cirrhotic and treatment-experienced patients took 24 weeks of treatment. Efficacy analysis was conducted on 95 patients, and the results showed that 91 patients achieved SVR12 with a response rate of 95.8% (95% CI: 92–100%). Six adverse events occurred and were minor and manageable. Conclusion. Our results demonstrate the efficacy and safety of sofosbuvir/daclatasvir in single tablets in treating Algerian HCV patients without ribavirin for 12 or 24 weeks. The promising results of this study warrant further trials to assess the efficacy and safety of this combination in treating special populations.
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Affiliation(s)
- Nabil Debzi
- Hepatology Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
| | - Saadi Berkane
- Gastroenterology Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
| | - Chafika Manouni
- Gastroenterology Department, Etablissement Hospitalier Universitaire, Oran, Algeria
| | - Nassima Amani
- Gastroenterology Department, Centre Hospitalo-Universitaire Benaouda Benzerdjeb, Oran, Algeria
| | - Sonia Hemmam
- Internal Medicine Department, Etablissement Public Hospitalier Nouvel Hôpital, Khenchela, Algeria
| | - Mohamed Yousfi
- Infectious Diseases Department, Etablissement Public Hospitalier, Boufarik, Algeria
| | - Ayoub Taleb
- Gastroenterology Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
| | - Nawal Guessab
- Hepatology Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
| | | | | | | | | | - Rafik Kerbouche
- Hepatology Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
| | - Ibtissem Ouled Cheikh
- Hepatology Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
| | - Othmane Drir
- Hepatology Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
| | - Hibat Allah Belimi
- Hepatology Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
| | - Samir Gourari
- Microbiology Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
| | - Issam Frigga
- Blood Transfusion Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
| | | | | | - Nawal Afredj
- Hepatology Department, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria
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18
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Derayea SM, Abu-Hassan AA, Hamad AA, Eltoukhi WE, Hamad AE, Mohammed BS. Mathematical processing of absorption as green smart spectrophotometric methods for concurrent assay of hepatitis C antiviral drugs, Sofosbuvir and Simeprevir: application to combined pharmaceutical dosage forms and evaluation of the method greenness. BMC Chem 2023; 17:75. [PMID: 37452429 PMCID: PMC10347804 DOI: 10.1186/s13065-023-00984-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 06/30/2023] [Indexed: 07/18/2023] Open
Abstract
The present work was developed to create three rapid, simple, eco-friendly, cheap spectrophotometric methods for concurrent assay of Sofosbuvir (SOF) and Simeprevir (SMV) in their pure, laboratory prepared mixture and pharmaceutical dosage form with high degree of accuracy and precision. Three methods were developed including iso-absorptive point, ratio subtraction and dual wavelength. The linear range of the proposed methods was 3.0-50.0 and 2.0-50.0 µg mL-1 for SMV and SOF, respectively. The proposed methods were validated according to ICH guidelines in terms of linearity, accuracy, precision, limit of detection and limit of quantitation. The proposed approach is highly simple and the procedure is environmentally green making it suitable for the drug analysis in routine works.
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Affiliation(s)
- Sayed M Derayea
- Department of Analytical Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt
| | - Ahmed A Abu-Hassan
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt
| | - Ahmed A Hamad
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt
| | - Walid E Eltoukhi
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt
| | - Amal E Hamad
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Menoufia University, Shebin El-Kom, Menoufia, Egypt
| | - Bassam Shaaban Mohammed
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
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19
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Xie S, Zhu C, Yang L, Li H, Zhu H, Nie Z, Lei C. Programmable Proteolysis-Activated Transcription for Highly Sensitive Ratiometric Electrochemical Detection of Viral Protease. Anal Chem 2023. [PMID: 37410966 DOI: 10.1021/acs.analchem.3c01720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/08/2023]
Abstract
Viral proteases play a crucial role in viral infection and are regarded as promising targets for antiviral drug development. Consequently, biosensing methods that target viral proteases have contributed to the study of virus-related diseases. This work presents a ratiometric electrochemical sensor that enables highly sensitive detection of viral proteases through the integration of target proteolysis-activated in vitro transcription and the DNA-functionalized electrochemical interface. In particular, each viral protease-mediated proteolysis triggers the transcription of multiple RNA outputs, leading to amplified ratiometric signals on the electrochemical interface. Using the NS3/4A protease of the hepatitis C virus as a model, this method achieves robust and specific NS3/4A protease sensing with sub-femtomolar sensitivity. The feasibility of this sensor was demonstrated by monitoring NS3/4A protease activities in virus-infected cell samples with varying viral loads and post-infection times. This study provides a new approach to analyzing viral proteases and holds the potential for developing direct-acting antivirals and novel therapies for viral infections.
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Affiliation(s)
- Shiyi Xie
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha 410082, P. R. China
| | - Cong Zhu
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha 410082, P. R. China
| | - Lijuan Yang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha 410082, P. R. China
| | - Huiyi Li
- Institute of Pathogen Biology and Immunology of College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, P. R. China
| | - Haizhen Zhu
- Institute of Pathogen Biology and Immunology of College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, P. R. China
| | - Zhou Nie
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha 410082, P. R. China
| | - Chunyang Lei
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha 410082, P. R. China
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20
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Ivashkin VT, Chulanov VP, Mamonova NA, Maevskaya MV, Zharkova MS, Tikhonov IN, Bogomolov PO, Volchkova EV, Dmitriev AS, Znojko OO, Klimova EA, Kozlov KV, Kravchenko IE, Malinnikova EY, Maslennikov RV, Mikhailov MI, Novak KE, Nikitin IG, Syutkin VE, Esaulenko EV, Sheptulin AA, Shirokova EN, Yushchuk ND. Clinical Practice Guidelines of the Russian Society for the Study of the Liver, the Russian Gastroenterological Association, the National Scientific Society of Infectious Disease Specialists for the Diagnosis and Treatment of Chronic Hepatitis C. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2023; 33:84-124. [DOI: 10.22416/1382-4376-2023-33-1-84-124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
Аim:diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary.Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion.Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.
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Affiliation(s)
- V. T. Ivashkin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - V. P. Chulanov
- Center for Epidemiologically Significant Infectious Diseases, National Medical Research Center for Phthisiopulmonology and Infectious Diseases
| | - N. A. Mamonova
- Center for Epidemiologically Significant Infectious Diseases, National Medical Research Center for Phthisiopulmonology and Infectious Diseases
| | - M. V. Maevskaya
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M. S. Zharkova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - I. N. Tikhonov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - P. O. Bogomolov
- M.F. Vladimirsky Moscow Regional Research Clinical Institute
| | - E. V. Volchkova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - A. S. Dmitriev
- Sechenov First Moscow State Medical University (Sechenov University)
| | - O. O. Znojko
- Moscow State University of Medicine and Dentistry
| | | | | | | | - E. Yu. Malinnikova
- Department of Virology, Russian Medical Academy of Continuing Professional Education
| | - R. V. Maslennikov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - M. I. Mikhailov
- North-Western State Medical University named after I.I. Mechnikov
| | | | | | - V. E. Syutkin
- Sklifosovsky Clinical and Research Institute for Emergency Medicine; Russian State Research Center — Burnazyan Federal Medical Biophysical Center
| | | | - A. A. Sheptulin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - E. N. Shirokova
- Sechenov First Moscow State Medical University (Sechenov University)
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21
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Chudhary HF, Ali A, Bibi S, Waqas M, Rafique S, Idrees M, Halim SA, Abdellattif MH, Khan A, Al-Harrasi A. Transcriptional Analysis of TP53 Gene in Chronic Hepatitis C Patients Treated with Sofosbuvir, Daclatasvir, Pegylated Interferon, and Ribavirin. ACS OMEGA 2023; 8:14784-14791. [PMID: 37125127 PMCID: PMC10134244 DOI: 10.1021/acsomega.3c00903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 03/20/2023] [Indexed: 05/03/2023]
Abstract
Hepatitis C virus (HCV) is a major public health problem that affects more than 170 million people globally. HCV is a principal cause of hepatocellular carcinoma (HCC) around the globe due to the high frequency of hepatitis C infection, and the high rate of HCC is seen in patients with HCV cirrhosis. TP53 is considered as a frequently altered gene in all cancer types, and it carries an interferon response element in its promoter region. In addition to that, the TP53 gene also interacts with different HCV proteins. HCV proteins especially NS3 protein and core protein induce the mutations in the TP53 gene that lower the expression of this gene in HCV patients and leads to HCC development. In this study, we examined the transcriptional analysis of the TP53 gene in HCV-infected patients administered with different combinations of antiviral therapies including sofosbuvir + daclatasvir, sofosbuvir + ribavirin, and pegylated interferon + ribavirin. This study included 107 subjects; 15 treated with sofosbuvir + daclatasvir, 58 treated with sofosbuvir + ribavirin, 11 treated with interferon + ribavirin, 8 untreated, 10 HCC patients, and 5 were healthy controls. Total RNA was extracted from the PMBCs of HCV infected patients and reverse transcribed into cDNA using a gene specific reverse primer. The expression level of TP53 mRNA was analyzed using quantitative PCR. The expression of TP53 mRNA was notably upregulated in rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR) groups as compared to non-responders and naïve groups. The expression of TP53 mRNA was seen high in HCC as compared to control groups. Additionally, it has been demonstrated that sofosbuvir + daclatasvir treatment stimulates significant elevation in TP53 gene expression as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. This study indicates that the TP53 gene expression is highly upregulated in RVR, EVR, and SVR groups as compared to control groups. Moreover, sofosbuvir + daclatasvir therapy induces significant rise in TP53 mRNA expression levels as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. According to these results, it can be concluded that sofosbuvir + daclatasvir plays a significant role in preventing HCV patients from developing severe liver complications as compared to other administered therapies. This study is novel as no such type of study has been conducted previously on the expression of TP53 in local HCV-infected population treated with different combinations of therapies. This study is helpful for the development of new therapeutic strategies and for improving existing therapies.
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Affiliation(s)
- Hafiza
Rida Farooq Chudhary
- Division
of Molecular Virology, Center for Applied Molecular Biology (CAMB), University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig, Lahore 54590, Pakistan
| | - Amjad Ali
- Division
of Molecular Virology, Center for Applied Molecular Biology (CAMB), University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig, Lahore 54590, Pakistan
- Department
of Biotechnology and Genetic Engineering, Hazara University Mansehra, Mansehra 2100, Pakistan
| | - Sadia Bibi
- Department
of Botany, University of Malakand, Chakdara Dir Lower, Khyber
Pakhtunkhwa 18800, Pakistan
| | - Muhammad Waqas
- Department
of Biotechnology and Genetic Engineering, Hazara University Mansehra, Mansehra 2100, Pakistan
- Natural
and Medical Sciences Research Center, University
of Nizwa, Birkat-ul-Mouz, Nizwa 616, Sultanate of Oman
| | - Shazia Rafique
- Division
of Molecular Virology, Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig, Lahore 54590, Pakistan
| | - Muhammad Idrees
- Division
of Molecular Virology, Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, 87-West Canal Bank Road Thokar Niaz Baig, Lahore 54590, Pakistan
| | - Sobia Ahsan Halim
- Natural
and Medical Sciences Research Center, University
of Nizwa, Birkat-ul-Mouz, Nizwa 616, Sultanate of Oman
| | - Magda H. Abdellattif
- Department
of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Ajmal Khan
- Natural
and Medical Sciences Research Center, University
of Nizwa, Birkat-ul-Mouz, Nizwa 616, Sultanate of Oman
| | - Ahmed Al-Harrasi
- Natural
and Medical Sciences Research Center, University
of Nizwa, Birkat-ul-Mouz, Nizwa 616, Sultanate of Oman
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22
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Moustafa AH, Pasha HF, Abas MA, Aboregela AM. The ameliorating role of sofosbuvir and daclatasvir on thioacetamide-induced kidney injury in adult albino rats. Anat Cell Biol 2023; 56:109-121. [PMID: 36543744 PMCID: PMC9989782 DOI: 10.5115/acb.22.200] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/06/2022] [Accepted: 11/21/2022] [Indexed: 12/24/2022] Open
Abstract
Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson's trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis.
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Affiliation(s)
- Ahmed H Moustafa
- Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt
| | - Heba F Pasha
- Department of Medical Biochemistry and Genetics, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Manar A Abas
- Department of Biochemistry, Faculty of Science, Zagazig University, Zagazig, Egypt
| | - Adel M Aboregela
- Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.,Department of Basic Medical Sciences, College of Medicine, University of Bisha, Bisha, Saudi Arabia
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23
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Etiologic fractions in patients of hepatocellular carcinoma in India with and without a background of cirrhosis: a multi-centric study. Hepatol Int 2023; 17:745-752. [PMID: 36940070 DOI: 10.1007/s12072-023-10498-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/04/2023] [Indexed: 03/21/2023]
Abstract
BACKGROUND Hepatocellular cancer (HCC) typically arises in the background of cirrhosis. The epidemiology of HCC has changed in recent years due to availability of newer antivirals, changing life-styles and greater possibility for early detection. We undertook a multicentric national sentinel surveillance for liver cirrhosis and HCC to assess the attributable risk factors for the development of HCC, both with and without a background of cirrhosis. METHODS Data from January 2017 till August 2022 from hospital-based records of eleven participating centers were included. Diagnosed cases of cirrhosis [radiological (multiphase and/or histopathological] and HCC [as per AASLD 2018] were included. History of significant alcohol intake was elicited by AUDIT-C questionnaire. RESULTS Altogether 5798 enrolled patients were assessed, of which 2664 patients had HCC. The mean age was 58.2 ± 11.7 years and 84.3% (n = 2247) were males. Diabetes was found in over a third of those with HCC (n = 1032;39.5%). The most common etiology of HCC was NAFLD (n = 927;35.5%) followed by viral hepatitis B and C and harmful levels of alcohol. Among those with HCC, 27.9% (n = 744) had no cirrhosis. Higher proportion of cirrhotic HCC patients had alcohol as an etiological factor as compared to non-cirrhotic (17.5 vs. 4.7%, p ≤ 0.001). NAFLD was an etiological factor for a higher proportion of non-cirrhotic HCC patients as compared to cirrhotic HCC (48.2 vs. 30.6%, p ≤0.001). Diabetics more commonly had non-cirrhotic HCC (50.5 vs. 35.2%). The following factors were associated with an occurrence of cirrhotic HCC: male gender (OR 1.372 and 95% CI 1.070-1.759), age above 60 years (OR 1.409 and 95% CI 1.176-1.689), HBV (OR 1.164 and 95% CI 0.928-1.460), HCV (OR 1.228 and 95 CI 0.964-1.565) and harmful consumption of alcohol (OR 3.472 and 95% CI 2.388-5.047). The adjusted odds of non-cirrhotic patients having NAFLD was 1.553 (95% CI 1.290-1.869). CONCLUSION This large multi-centric study demonstrates that NAFLD is the most important risk factor for development of both cirrhotic and non-cirrhotic HCC in India and has overtaken viral hepatitis. Awareness campaigns and large-scale screening are required to reduce the high burden of NAFLD-related HCC in India.
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24
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McPhail JA, Burke JE. Molecular mechanisms of PI4K regulation and their involvement in viral replication. Traffic 2023; 24:131-145. [PMID: 35579216 DOI: 10.1111/tra.12841] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/07/2022] [Accepted: 03/30/2022] [Indexed: 11/28/2022]
Abstract
Lipid phosphoinositides are master signaling molecules in eukaryotic cells and key markers of organelle identity. Because of these important roles, the kinases and phosphatases that generate phosphoinositides must be tightly regulated. Viruses can manipulate this regulation, with the Type III phosphatidylinositol 4-kinases (PI4KA and PI4KB) being hijacked by many RNA viruses to mediate their intracellular replication through the formation of phosphatidylinositol 4-phosphate (PI4P)-enriched replication organelles (ROs). Different viruses have evolved unique approaches toward activating PI4K enzymes to form ROs, through both direct binding of PI4Ks and modulation of PI4K accessory proteins. This review will focus on PI4KA and PI4KB and discuss their roles in signaling, functions in membrane trafficking and manipulation by viruses. Our focus will be the molecular basis for how PI4KA and PI4KB are activated by both protein-binding partners and post-translational modifications, with an emphasis on understanding the different molecular mechanisms viruses have evolved to usurp PI4Ks. We will also discuss the chemical tools available to study the role of PI4Ks in viral infection.
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Affiliation(s)
- Jacob A McPhail
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
| | - John E Burke
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.,Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada
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25
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Nyein PP, Tillakeratne S, Phyu S, Yee MM, Lwin MM, Htike KL, Aung MT, Grebely J, Applegate T, Hanson J, Matthews G, Lin KS. Evaluation of Simplified HCV Diagnostics in HIV/HCV Co-Infected Patients in Myanmar. Viruses 2023; 15:v15020521. [PMID: 36851736 PMCID: PMC9967037 DOI: 10.3390/v15020521] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 02/06/2023] [Accepted: 02/08/2023] [Indexed: 02/16/2023] Open
Abstract
To evaluate a decentralised testing model and simplified treatment protocol of hepatitis C virus (HCV) infection to facilitate treatment scale-up in Myanmar, this prospective, observational study recruited HIV-HCV co-infected outpatients receiving sofosbuvir/daclatasvir in Yangon, Myanmar. The study examined the outcomes and factors associated with a sustained virological response (SVR). A decentralised "hub-and-spoke" testing model was evaluated where fingerstick capillary specimens were transported by taxi and processed centrally. The performance of the Xpert HCV VL Fingerstick Assay in detecting HCV RNA was compared to the local standard of care ( plasma HCV RNA collected by venepuncture). Between January 2019 and February 2020, 162 HCV RNA-positive individuals were identified; 154/162 (95%) initiated treatment, and 128/154 (84%) returned for their SVR12 visit. A SVR was achieved in 119/154 (77%) participants in the intent-to-treat population and 119/128 (93%) participants in the modified-intent-to-treat population. Individuals receiving an antiretroviral therapy were more likely to achieve a SVR (with an odds ratio (OR) of 7.16, 95% CI 1.03-49.50), while those with cirrhosis were less likely (OR: 0.26, 95% CI 0.07-0.88). The sensitivity of the Xpert HCV VL Fingerstick Assay was 99.4% (95% CI 96.7-100.0), and the specificity was 99.2% (95% CI 95.9-99.9). A simplified treatment protocol using a hub-and-spoke testing model of fingerstick capillary specimens can achieve an SVR rate in LMIC comparable to well-resourced high-income settings.
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Affiliation(s)
| | - Shane Tillakeratne
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
- Correspondence:
| | - Sabai Phyu
- Department of Tropical and Infectious Diseases, Specialist Hospital Waibargi, Yangon W5C4+6J7, Myanmar
| | | | - Mya Mya Lwin
- Department of Microbiology, University of Medicine 2, Yangon 644-704, Myanmar
| | - Kyaw Linn Htike
- Myanmar-Australia Research Collaboration for Health Laboratory, Yangon W5C4+6J7, Myanmar
| | - May Thu Aung
- Myanmar-Australia Research Collaboration for Health Laboratory, Yangon W5C4+6J7, Myanmar
| | - Jason Grebely
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
| | - Tanya Applegate
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
| | - Josh Hanson
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
- Cairns and Hinterland Hospital and Health Service, Cairns North, QLD 4870, Australia
| | - Gail Matthews
- The Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
| | - Kyaw Swar Lin
- Specialist Hospital Mingaladon, Yangon X42H+J4, Myanmar
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26
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Sabry N, Kamel AM, Cordie A, Esmat G. Daclatasvir as a hepatitis C infection treatment option: an up-to-date evaluation. Expert Opin Pharmacother 2023; 24:159-170. [PMID: 36369914 DOI: 10.1080/14656566.2022.2145883] [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: 11/15/2022]
Abstract
INTRODUCTION Globally, it is estimated that 290,000 patients infected with hepatitis C virus (HCV) died from hepatitis C consequences, including cirrhosis and hepatocellular carcinoma in 2019. Although daclatasvir (DCV), combined with sofosbuvir (SOF), is effective in HCV patients, the new pan-genotypic combinations are considered by many as more cost-effective and successful in eradicating HCV infection. AREAS COVERED This review discusses the safety, efficacy, and cost-effectiveness of DCV as an HCV treatment option based on real-world studies and pharmacoeconomic evaluations. EXPERT OPINION Real-life studies suggest that SOF/DCV has acceptable sustained virological response and can be used successfully to manage HCV. Nonetheless, the use of SOF/DCV is limited by the longer treatment duration in genotype (GT)-3 patients and the need for ribavirin (RBV) in treatment-experienced patients which increases the likelihood of adverse effects. DCV is likely to remain as a therapeutic option for the management of GT-1, GT-2, and GT-4 patients in resource limited settings, while GT-3 patients are more likely to benefit from RBV-free direct-acting antiviral combinations such as SOF/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks. The introduction of generics for these new pan-genotypic drugs would likely eliminate the need for SOF/DCV in the near future.
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Affiliation(s)
- Nirmeen Sabry
- Clinical Pharmacy Department, College of Pharmacy, Cairo University, Cairo, 11562, Egypt
| | - Ahmed M Kamel
- Clinical Pharmacy Department, College of Pharmacy, Cairo University, Cairo, 11562, Egypt
| | - Ahmed Cordie
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt.,Kasr Alaini HIV and Viral Hepatitis Fighting Group, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt
| | - Gamal Esmat
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, 11562, Egypt
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27
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Grebely J, Robaeys G, Bruggmann P, Aghemo A, Backmund M, Bruneau J, Byrne J, Dalgard O, Feld JJ, Hellard M, Hickman M, Kautz A, Litwin A, Lloyd AR, Mauss S, Prins M, Swan T, Schaefer M, Taylor LE, Dore GJ. Recommandations pour la prise en charge de l'infection par le virus de l'hépatite C chez les usagers de drogues par injection. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2023; 111:101669. [PMID: 26847504 DOI: 10.1016/j.drugpo.2015.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
| | - Geert Robaeys
- Department of Gastroenterology and Hepatology, Ziekenhuis Oost Limburg, Genk, Belgium; Department of Hepatology, UZ Leuven, Leuven, Belgium; Faculty of Medicine and Life Sciences, Limburg Clinical Research Program, Hasselt University, Hasselt, Belgium
| | | | - Alessio Aghemo
- A.M. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Markus Backmund
- Ludwig-Maximilians-University, Munich, Germany; Praxiszentrum im Tal Munich, Munich, Germany
| | | | - Jude Byrne
- International Network of People who Use Drugs, Canberra, Australia
| | - Olav Dalgard
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway
| | | | - Margaret Hellard
- Burnet Institute, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - Matthew Hickman
- School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom
| | - Achim Kautz
- European Liver Patients Association, Cologne, Germany
| | - Alain Litwin
- Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, United States
| | - Andrew R Lloyd
- Inflammation and Infection Research Centre, School of Medical Sciences, UNSW Australia, Sydney, Australia
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | - Maria Prins
- Department of Research, Cluster Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands; Department of Internal Medicine, CINIMA, Academic Medical Centre, Amsterdam, The Netherlands
| | - Tracy Swan
- Treatment Action Group, New York, United States
| | - Martin Schaefer
- Department of Psychiatry, Psychotherapy and Addiction Medicine, Kliniken Essen-Mitte, Essen, Germany; Department of Psychiatry and Psychotherapy-CCM, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Lynn E Taylor
- Department of Medicine, Brown University, Providence, RI, United States
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Grebely J, Robaeys G, Bruggmann P, Aghemo A, Backmund M, Bruneau J, Byrne J, Dalgard O, Feld JJ, Hellard M, Hickman M, Kautz A, Litwin A, Lloyd AR, Mauss S, Prins M, Swan T, Schaefer M, Taylor LE, Dore GJ. Empfehlungen zur Hepatitis Versorgung bei Drogenkonsumierenden. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2023; 111:101670. [PMID: 26749563 DOI: 10.1016/j.drugpo.2015.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
| | - Geert Robaeys
- Department of Gastroenterology and Hepatology, Ziekenhuis Oost Limburg, Genk, Belgium; Department of Hepatology, UZ Leuven, Leuven, Belgium; Faculty of Medicine and Life Sciences, Limburg Clinical Research Program, Hasselt University, Hasselt, Belgium
| | | | - Alessio Aghemo
- A.M. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Markus Backmund
- Ludwig-Maximilians-University, Munich, Germany; Praxiszentrum im Tal Munich, Munich, Germany
| | | | - Jude Byrne
- International Network of People who Use Drugs, Canberra, Australia
| | - Olav Dalgard
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway
| | | | - Margaret Hellard
- Burnet Institute, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - Matthew Hickman
- School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom
| | - Achim Kautz
- European Liver Patients Association, Cologne, Germany
| | - Alain Litwin
- Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, United States
| | - Andrew R Lloyd
- Inflammation and Infection Research Centre, School of Medical Sciences, UNSW Australia, Sydney, Australia
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | - Maria Prins
- Department of Research, Cluster Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands; Department of Internal Medicine, CINIMA, Academic Medical Centre, Amsterdam, The Netherlands
| | - Tracy Swan
- Treatment Action Group, New York, United States
| | - Martin Schaefer
- Department of Psychiatry, Psychotherapy and Addiction Medicine, Kliniken Essen-Mitte, Essen, Germany; Department of Psychiatry and Psychotherapy-CCM, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Lynn E Taylor
- Department of Medicine, Brown University, Providence, RI, United States
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Lei S, Chen X, Wu J, Duan X, Men K. Small molecules in the treatment of COVID-19. Signal Transduct Target Ther 2022; 7:387. [PMID: 36464706 PMCID: PMC9719906 DOI: 10.1038/s41392-022-01249-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/02/2022] [Accepted: 11/08/2022] [Indexed: 12/11/2022] Open
Abstract
The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and Mpro, interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.
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Affiliation(s)
- Sibei Lei
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Xiaohua Chen
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Jieping Wu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China
| | - Xingmei Duan
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
| | - Ke Men
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
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Burgui C, San Miguel R, Goñi-Esarte S, Juanbeltz R, Úriz-Otano JI, Reparaz J, Sarobe M, Zozaya JM, Castilla J. Effectiveness of hepatitis C antiviral treatment and feasibility of hepatitis C elimination goal. Postgrad Med 2022; 135:352-360. [PMID: 36305320 DOI: 10.1080/00325481.2022.2141499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVES Second-generation direct-acting antivirals (DAAs) have shown high efficacy in the treatment of chronic hepatitis C virus (HCV) infections in clinical trials. This study aimed to estimate the effectiveness in real-life conditions and their capacity to eliminate HCV infection in the general population. METHODS In this observational cohort study, patients with active HCV infection who commenced DAA treatment between 2015 and 2020 in Navarre, Spain, were studied. Sustained virological response (SVR), defined as an undetectable viral load 12 weeks after the end of treatment, was evaluated until the end of 2021. RESULTS Of a total 1366 HCV-infected patients that commenced treatment, 19.3% (n = 263) were HIV-coinfected. After the first DAA treatment, SVR was achieved in 96.6% (n = 1320/1366) of patients and in 97.7% (95% confidence interval [CI] 96.6%-98.3%) of those who completed treatment (per-protocol analysis; n = 1320/1351). SVR was achieved in 97.9% (n = 1066/1089) and 96.9% (n = 254/262) of mono-infected and HIV-coinfected patients, respectively. Thirty-one patients had virological failure due to non-response (n = 19), poor compliance (n = 9), and with adverse events (n = 3). Of 27 patients that received a second treatment, 24 attained SVR (one after a third treatment), two died, and one that did not achieve SVR declined a third treatment. Three patients were re-infected, re-treated, and achieved SVR. At the end of the study, 1344 patients (98.4%, 95% CI 97.6%-98.9%) had achieved SVR, and only 1.8% needed more than one course of treatment. All patients who completed the treatment and were followed-up achieved SVR. CONCLUSION With DAAs, SVR was achieved in all patients with active HCV infection who completed follow-up, and a second course of treatment was only necessary in a small proportion of patients. Adherence to treatment is essential for HCV infection elimination.
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Affiliation(s)
- Cristina Burgui
- Instituto de Salud Pública de Navarra, Pamplona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Ramón San Miguel
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Farmacia Hospitalaria, Hospital Universitario de Navarra, Pamplona, Spain
| | - Silvia Goñi-Esarte
- Servicio de Digestivo, Hospital Universitario de Navarra, Pamplona, Spain
| | - Regina Juanbeltz
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Farmacia Hospitalaria, Hospital Universitario de Navarra, Pamplona, Spain
| | - Juan Isidro Úriz-Otano
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Digestivo, Hospital Universitario de Navarra, Pamplona, Spain
| | - Jesús Reparaz
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Medicina Interna, Hospital Universitario de Navarra, Pamplona, Spain
| | - Maite Sarobe
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Farmacia Hospitalaria, Hospital Universitario de Navarra, Pamplona, Spain
| | - José Manuel Zozaya
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Digestivo, Hospital Universitario de Navarra, Pamplona, Spain
| | - Jesús Castilla
- Instituto de Salud Pública de Navarra, Pamplona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
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Long-Term Follow-Up of Thalassemia Major Patients with Hepatitis C Virus Treated with Sofosbuvir and Daclatasvir: A Cohort Study. Arch Med Res 2022; 53:666-672. [DOI: 10.1016/j.arcmed.2022.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 09/01/2022] [Accepted: 09/22/2022] [Indexed: 11/17/2022]
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Rendina M, Paoletti E, Labarile N, Marra A, Iannone A, Castellaneta A, Bussalino E, Ravera M, Schena A, Castellaneta NM, Barone M, Simone S, Gesualdo L, Di Leo A. HCV-positive kidney transplant patients treated with direct-acting antivirals maintain stable medium-term graft function despite persistent reduction in tacrolimus trough levels. Ther Adv Chronic Dis 2022; 13:20406223221117975. [PMID: 36147292 PMCID: PMC9486264 DOI: 10.1177/20406223221117975] [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: 02/27/2022] [Accepted: 07/19/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND/AIM Direct-acting antivirals (DAAs) have improved the treatment of HCV-positive kidney transplant recipients (KTRs). However, their medium-term follow-up effects on graft function are conflicting. This study aimed to analyze how the interplay between DAAs, calcineurin inhibitors (CNI), and HCV eradication impacts 12-month kidney graft function. METHODS This double-center retrospective study with a prospective follow-up enrolled 35 KTRs with HCV treated with DAAs for 12 weeks. We compared three parameters: estimated glomerular filtration rate (eGFR), 24-h proteinuria, and CNI trough levels at three time points: baseline, end of treatment (EOT), and 12 months later. RESULTS Kidney allograft function remained stable when comparing baseline and 12-month post-treatment values of eGFR (60.7 versus 57.8 ml/min; p = 0.28) and 24-h proteinuria (0.3 versus 0.2 g/24 h; p = 0.15), while tacrolimus (Tac) trough levels underwent a statistically significant decline (6.9 versus 5.4 ng/ml; p = 0.004). Using an ongoing triple Tac-based maintenance therapy as a conservative measure, a dose escalation of Tac was applied only in seven patients. No variation in CyA and mTOR levels was detected. CONCLUSION DAA therapy is safe and effective in HCV-positive KTRs. It also produces a persistent significant reduction in Tac trough levels that does not influence graft function at 12 months.
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Affiliation(s)
- Maria Rendina
- Gastroenterology and Digestive Endoscopy,
University Hospital, Bari, Italy
| | - Ernesto Paoletti
- Nephrology, Dialysis, and Transplantation,
University of Genova and Policlinico San Martino, Genova, Italy
| | - Nunzia Labarile
- Gastroenterology Unit, National Institute of
Gastroenterology IRCCS “Saverio de Bellis’, Research Hospital, Castellana
Grotte, 70013 Bari, Italy
| | - Antonella Marra
- Gastroenterology and Digestive Endoscopy,
University Hospital, Bari, Italy
| | - Andrea Iannone
- Gastroenterology and Digestive Endoscopy,
University Hospital, Bari, Italy
| | | | - Elisabetta Bussalino
- Nephrology, Dialysis, and Transplantation,
University of Genova and Policlinico San Martino, Genova, Italy
| | - Maura Ravera
- Nephrology, Dialysis, and Transplantation,
University of Genova and Policlinico San Martino, Genova, Italy
| | - Antonio Schena
- Nephrology, Dialysis and Transplantation,
University of Bari, Bari, Italy
| | | | - Michele Barone
- Gastroenterology and Digestive Endoscopy,
University Hospital, Bari, Italy
| | - Simona Simone
- Nephrology, Dialysis and Transplantation,
University of Bari, Bari, Italy
| | - Loreto Gesualdo
- Nephrology, Dialysis and Transplantation,
University of Bari, Bari, Italy
| | - Alfredo Di Leo
- Gastroenterology and Digestive Endoscopy,
University Hospital, Bari, Italy
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Bishai N, Nabawy WE, Fiki ME, Ibrahim M, Garem NE. Dual versus triple therapy in treatment of hepatitis C virus (HCV). Ir J Med Sci 2022:10.1007/s11845-022-03120-9. [PMID: 36040651 DOI: 10.1007/s11845-022-03120-9] [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: 03/25/2022] [Accepted: 08/01/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND The goal of HCV treatment is eradication of the virus to prevent complications associated with the disease and decrease all-cause mortality. This work compared sustained viral response (SVR) 12 weeks after end of treatment of chronic HCV patients with different treatment regimens, namely 4 regimens. Two hundred treatment naive chronic HCV patients were selected and divided into 4 equal groups as follows: group A received pegylated interferon (peg IFN) and ribavirin (RBV); group B received peg IFN, RBV, and sofosbuvir (SOF); group C received RBV and SOF; group D received SOF, daclatasvir (DCV), and RBV. RESULTS The sustained viral response after 12 months of treatment is 57.23%, 72.09%, 64.40%, and 96.42% of patients in groups A, B, C, and D, respectively. Hence, group D regimen showed the best results. CONCLUSION SOF and DCV and RBV have the highest SVR12 and least side effects compared to other treatment regimens. Although group D patients initially had poor pretreatment investigations relative to other groups, they proved to have the highest tolerability to this regimen. Such findings hold promising line of treatment and better prognosis even for chronic HCV patients with poor liver condition.
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Affiliation(s)
- Nevine Bishai
- Department of Internal Medicine, Faculty of Medicine, Cairo University Hospitals, Kasr El Aini, Cairo, Egypt.
| | - Walid El Nabawy
- Faculty of Medicine, Beni-Sueif University Hospitals, Beni Sueif, Egypt
| | - Mohamed El Fiki
- Faculty of Medicine, Beni-Sueif University Hospitals, Beni Sueif, Egypt
| | - Mohamed Ibrahim
- Faculty of Medicine, Beni-Sueif University Hospitals, Beni Sueif, Egypt
| | - Nouman El Garem
- Faculty of Medicine, Cairo University Hospitals, Kasr El Aini, Cairo, Egypt
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Elshafie S, Trivedi‐Kapoor R, Ebell M. Safety and efficacy of sofosbuvir-based medication regimens with and without ribavirin in hepatitis C patients: A systematic review and meta-analysis. J Clin Pharm Ther 2022; 47:1149-1158. [PMID: 35678040 PMCID: PMC9545628 DOI: 10.1111/jcpt.13698] [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: 03/24/2022] [Revised: 04/03/2022] [Accepted: 04/25/2022] [Indexed: 12/09/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Sofosbuvir (SOF) is a new and highly effective medication that dramatically improved hepatitis C virus (HCV) management. However, ribavirin (RBV) is still added to SOF-based medication regimens in several clinical scenarios, despite its well-known toxicities. The aim of our study is to systematically review and analyse the impact of adding RBV to SOF-based medication regimens on clinical outcomes among HCV patients. METHODS Included studies were randomized trials comparing the same SOF-based medication regimens with and without RBV in HCV patients and measuring serious adverse events (SAEs) and/or sustained virologic response at 12 weeks post-treatment (SVR-12). Two investigators independently searched PubMed and Cochrane Library through September 2021. The Cochrane Risk of Bias tool was used to assess trials quality. Clinical outcomes were analysed as risk ratios (RR) using a random effects model using R version 4.1.2. RESULTS AND DISCUSSION Our study included a total of 26 trials with 5058 HCV patients. Quality assessment showed moderate risk of bias for most trials. Upon adding RBV, there was no significant difference in SAEs (RR 1.07, 95% CI: 0.77-1.48, I2 = 10%), nor an impact on SVR-12 (RR 1.00, 95% CI: 0.98-1.01, I2 = 41%). There was no evidence of publication bias for either outcome. Subgroup analysis consistently showed lack of benefit among HCV subgroups. Additionally, NCT01826981 was identified as the main source of heterogeneity in the SVR-12 outcome. WHAT IS NEW AND CONCLUSION Our findings suggest nonsignificant differences in safety and efficacy between SOF-based medication regimens with and without RBV which should be considered in clinical practice.
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Affiliation(s)
- Shaimaa Elshafie
- Department of Clinical and Administrative Pharmacy, College of PharmacyUniversity of GeorgiaGeorgiaUSA
- Central Administration for Drug ControlEgyptian Drug AuthorityCairoEgypt
| | - Rupal Trivedi‐Kapoor
- Department of Clinical and Administrative Pharmacy, College of PharmacyUniversity of GeorgiaGeorgiaUSA
| | - Mark Ebell
- Department of Epidemiology, College of Public HealthUniversity of GeorgiaAthensGeorgiaUSA
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Neufeldt CJ, Cortese M. Membrane architects: how positive-strand RNA viruses restructure the cell. J Gen Virol 2022; 103. [PMID: 35976091 DOI: 10.1099/jgv.0.001773] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Virus infection is a process that requires combined contributions from both virus and host factors. For this process to be efficient within the crowded host environment, viruses have evolved ways to manipulate and reorganize host structures to produce cellular microenvironments. Positive-strand RNA virus replication and assembly occurs in association with cytoplasmic membranes, causing a reorganization of these membranes to create microenvironments that support viral processes. Similarities between virus-induced membrane domains and cellular organelles have led to the description of these structures as virus replication organelles (vRO). Electron microscopy analysis of vROs in positive-strand RNA virus infected cells has revealed surprising morphological similarities between genetically diverse virus species. For all positive-strand RNA viruses, vROs can be categorized into two groups: those that make invaginations into the cellular membranes (In-vRO), and those that cause the production of protrusions from cellular membranes (Pr-vRO), most often in the form of double membrane vesicles (DMVs). In this review, we will discuss the current knowledge on the structure and biogenesis of these two different vRO classes as well as comparing morphology and function of vROs between various positive-strand RNA viruses. Finally, we will discuss recent studies describing pharmaceutical intervention in vRO formation as an avenue to control virus infection.
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Affiliation(s)
- Christopher John Neufeldt
- Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Mirko Cortese
- Telethon Institute of Genetics and Medicine, Pozzuoli, Italy
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Ferraz MLG, Piccoli LDZ, Rezende R, Borba LA, Junior AP, Cheinquer H, Silva GF, Ferreira PRA, Villela-Nogueira CA, Mazo DF, Souza FF, Codes L, Ivantes CAP, Gomide GPM, Pereira GHS, Pessôa MG, França AVC, Pinto ADS, Teixeira R, Bittencourt PL. National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents. Braz J Infect Dis 2022; 26:102388. [PMID: 35905930 PMCID: PMC9459029 DOI: 10.1016/j.bjid.2022.102388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 10/27/2022] Open
Abstract
BACKGROUND AND AIMS Treatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs. PATIENTS AND METHODS Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included. RESULTS As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions. CONCLUSION The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.
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Affiliation(s)
| | | | - Rosamar Rezende
- Secretária Municipal de Saúde de Ribeirão Preto, Centro de Referência em Especialidades, Ribeirão Preto, SP, Brazil; Universidade São Paulo, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP, Brazil
| | - Luiz Augusto Borba
- Prefeitura Municipal de Criciúma, Ambulatório de Hepatites Virais, Criciúma, SC, Brazil
| | | | - Hugo Cheinquer
- Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Giovanni Faria Silva
- Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, Botucatu, SP, Brazil
| | | | | | - Daniel Ferraz Mazo
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Divisão de Gastroenterologia do Departamento de Clínica Médica, Campinas, SP, Brazil; Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Gastroenterologia e Hepatologia, São Paulo, SP, Brazil
| | - Fernanda Fernandes Souza
- Universidade São Paulo, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP, Brazil
| | - Liana Codes
- Hospital Português, Salvador, BA, Brazil; Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil
| | | | | | - Gustavo Henrique Santos Pereira
- Hospital Federal de Bonsucesso (Ministério da Saúde), Serviço de Gastroenterologia e Hepatologia, Rio de Janeiro, RJ, Brazil
| | | | | | - Arlene Dos Santos Pinto
- Fundação de Medicina Tropical do Amazonas, Programa de Pós-graduação em Medicina Tropical, Manaus, AM, Brazil
| | | | - Paulo Lisboa Bittencourt
- Hospital Português, Salvador, BA, Brazil; Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil
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Geographic Distribution of HCV Genotypes and Efficacy of Direct-Acting Antivirals in Chronic HCV-Infected Patients in North and Northeast China: A Real-World Multicenter Study. Can J Gastroenterol Hepatol 2022; 2022:7395506. [PMID: 35531123 PMCID: PMC9076341 DOI: 10.1155/2022/7395506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 03/22/2022] [Accepted: 03/24/2022] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE To assess the geographic distribution of HCV genotypes, effectiveness, and safety of DAA treatment for HCV-infected patients in North and Northeast China. METHODS The geographic distribution of HCV genotypes was analyzed in 2162 patients recruited from April 2018 to February 2021. Sustained virologic response rates at 12 (SVR12) or 24 (SVR24) weeks posttreatment and safety were analyzed in 405 patients who completed DAA treatment according to patient baseline characteristics and treatment. RESULTS Four genotypes and six subtypes were identified as follows: 1b (1187, 54.90%), 2a (790, 36.54%), 3a/b (134, 6.20%), 6a/n (44, 2.04%), mixed genotypes (2a-6a or 2a-3a) (7, 0.32%). Overall, 99.01% patients achieved SVR12, while 98.43% achieved SVR24. All patients treated with elbasvir/grazoprevir (EBR/GZR), sofosbuvir/velpatasvir ± ribavirin (SOF/VEL ± RBV), and SOF/ledipasvir (LDV) achieved SVR12 or SVR24; 92.86% SVR12 and 95.83% SVR24 were observed in patients using SOF + RBV. SVR12 was higher in noncirrhosis versus compensated cirrhosis patients (100% vs. 97.09%, p=0.022). No severe drug-related adverse event was observed. CONCLUSIONS Genotypes 1b and 2a were dominant subtypes in North and Northeast China. The approved drug regimens EBR/GZR and SOF/LDV for subtype 1b and SOF/VEL for nongenotype 1b are the optimal effective and safety profile.
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Mushtaq S, Hashmi AH, Khan A, Asad Raza Kazmi SM, Manzoor S. Emergence and Persistence of Resistance-Associated Substitutions in HCV GT3 Patients Failing Direct-Acting Antivirals. Front Pharmacol 2022; 13:894460. [PMID: 35571102 PMCID: PMC9091354 DOI: 10.3389/fphar.2022.894460] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 03/28/2022] [Indexed: 11/16/2022] Open
Abstract
Background: The hepatitis C virus has a high mutation rate, which results in the emergence of resistance-associated substitutions (RASs). Despite direct-acting antivirals (DAAs) efforts to treat chronically infected HCV genotype 3 (GT3) patients, there are concerns about the emergence and persistence of RASs in DAA failures. The objective of this study was to determine the prevalence of clinically relevant RASs in HCV NS5A and NS5B regions before and after treatment to better understand the role of RASs in treatment failures. Methods: Viral RNA was extracted before and after treatment from serum samples. NS5A and NS5B regions of HCV were amplified by nested PCR, followed by Sanger sequencing. The nucleotide sequences were aligned against HCV GT3 reference sequences, and amino acid substitutions were analyzed using the geno2pheno [hcv] webserver. Results: A total of 76 patients failing DAA therapy were stratified from the cohort of 1388. RASs were detected at the baseline in 15/76 patients and at relapse in 20/76 patients with cirrhosis and previously treated with interferons. The most prevalent NS5A RAS was Y93H found in all treatment-failing patients (14/54 in DCV vs. 6/22 in VEL), followed by A62S/T and A30K. No RASs were identified in NS5B. RASs that were present at the baseline persisted through the 24-week follow-up period and were enriched with emerging RASs during the treatment. The presence of RASs may be one of the causes of treatment failures in 26.3% of patients. Amino acid substitutions were present at the baseline in most of the patients with RASs against NS5A inhibitors. Patients with the baseline Y93H and/or A30K relapse more frequently than patients harboring A62S/T. Conclusion: Treatment-failing patients harbored NS5A RASs, and the most frequent were A30K (5/20), A62S/T (20/20), and Y93H (20/20). Direct resistance testing is recommended for optimizing re-treatment strategies in treatment-failing patients.
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Affiliation(s)
- Saima Mushtaq
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | | | - Amjad Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | | | - Sobia Manzoor
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
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Odenwald MA, Paul S. Viral hepatitis: Past, present, and future. World J Gastroenterol 2022; 28:1405-1429. [PMID: 35582678 PMCID: PMC9048475 DOI: 10.3748/wjg.v28.i14.1405] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 03/04/2022] [Accepted: 03/06/2022] [Indexed: 02/06/2023] Open
Abstract
Each hepatitis virus-Hepatitis A, B, C, D, E, and G-poses a distinct scenario to the patient and clinician alike. Since the discovery of each virus, extensive knowledge regarding epidemiology, virologic properties, and the natural clinical and immunologic history of acute and chronic infections has been generated. Basic discoveries about host immunologic responses to acute and chronic viral infections, combined with virologic data, has led to vaccines to prevent Hepatitis A, B, and E and highly efficacious antivirals for Hepatitis B and C. These therapeutic breakthroughs are transforming the fields of hepatology, transplant medicine in general, and public and global health. Most notably, there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade. While attainable, there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local, national, and international scales. Herein, we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.
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Affiliation(s)
- Matthew August Odenwald
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, University of Chicago, Chicago, IL 60637, United States
| | - Sonali Paul
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, University of Chicago, Chicago, IL 60637, United States
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Inukai Y, Imai N, Yamamoto K, Ito T, Ishizu Y, Honda T, Okamoto S, Kanematsu T, Suzuki N, Matsushita T, Ishigami M, Fujishiro M. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia. Ann Hepatol 2022; 27:100545. [PMID: 34571264 DOI: 10.1016/j.aohep.2021.100545] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Hepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia. PATIENTS AND METHODS The study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR. RESULTS Compared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years. Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups. CONCLUSION Hemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.
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Affiliation(s)
- Yosuke Inukai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Norihiro Imai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine.
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Shuichi Okamoto
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine
| | | | - Nobuaki Suzuki
- Department of Transfusion Medicine, Nagoya University Hospital
| | - Tadashi Matsushita
- Department of Clinical Laboratory, Nagoya University Hospital; Department of Transfusion Medicine, Nagoya University Hospital
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
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41
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Sobotka LA, Mumtaz K, Wellner MR, Kelly SG, Conteh LF, Hanje AJ, Schenk A, El-Hinnawi A, Black S, Washburn K, Pesavento T, Daloul R, Michaels AJ. Outcomes of hepatitis C virus seropositive donors to hepatitis C virus seronegative liver recipients: A large single center analysis. Ann Hepatol 2022; 24:100318. [PMID: 33515801 DOI: 10.1016/j.aohep.2021.100318] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 12/18/2020] [Accepted: 01/04/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES The success of direct-acting antivirals (DAA) has transformed the management of hepatitis C virus (HCV) infection and has led to the expansion of the deceased donor organ pool for liver transplantation. MATERIAL AND METHODS We present a single center retrospective review of liver transplantations performed on HCV-seronegative recipients from HCV-seropositive organs from 11/2017 to 05/2020. HCV nucleic acid testing (NAT) was performed on HCV-seropositive donors to assess active HCV infection. RESULTS 42 HCV-seronegative recipients underwent a liver transplant from a HCV-seropositive donor, including 21 NAT negative (20 liver, 1 simultaneous liver kidney transplant) and 21 NAT positive liver transplants. Two (9.5%) HCV antibody positive/NAT negative recipients developed HCV viremia and achieved sustained virologic response with DAA therapy. The remaining patients with available data (19 patients) remained polymerase chain reaction (PCR) negative at 6 months. 20 (95%) of HCV antibody positive/NAT positive recipients had a confirmed HCV viremia. 100% of patients with available data (15 patients) achieved SVR. Observed events include 1 mortality and graft loss and equivalent rates of post-transplant complications between NAT positive and NAT negative recipients. CONCLUSIONS HCV-seropositive organs can be safely transplanted into HCV-seronegative patients with minimal complications post-transplant.
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Affiliation(s)
- Lindsay A Sobotka
- Division of Internal Medicine, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus OH, USA
| | - Khalid Mumtaz
- Division of Internal Medicine, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus OH, USA
| | - Michael R Wellner
- Division of Internal Medicine, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus OH, USA
| | - Sean G Kelly
- Division of Internal Medicine, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus OH, USA
| | - Lanla F Conteh
- Division of Internal Medicine, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus OH, USA
| | - A James Hanje
- Division of Internal Medicine, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus OH, USA
| | - Austin Schenk
- Division of Surgery, Department of Transplantation, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Ashraf El-Hinnawi
- Division of Surgery, Department of Transplantation, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Sylvester Black
- Division of Surgery, Department of Transplantation, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Kenneth Washburn
- Division of Surgery, Department of Transplantation, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Todd Pesavento
- Division of Internal Medicine, Department of Nephrology, The Ohio State University Wexner Medical Center, Columbus OH, USA
| | - Reem Daloul
- Division of Internal Medicine, Department of Nephrology, The Ohio State University Wexner Medical Center, Columbus OH, USA
| | - Anthony J Michaels
- Division of Internal Medicine, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus OH, USA.
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Abstract
The development of direct-acting antivirals (DAA) has revolutionized the treatment of chronic hepatitis C, enabling cure of hepatitis C virus (HCV) infection in more than 95% of cases. There are essentially no contraindications, so almost any patient can now be successfully treated. The result is the prevention or amelioration of cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Consequently, the 2020 Nobel Prize in Medicine and Physiology was awarded for the discovery of HCV. Due to the high efficacy of therapy, even global HCV elimination is conceivable even without a vaccine. Here, we would like to venture a SWOT analysis of current HCV therapies aimed at HCV elimination.
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Affiliation(s)
- Markus Cornberg
- Department of Gastroenterology, Hepatology, and Endocrinology, 9177Hannover Medical School Hannover, Hannover, Germany.,Centre for Individualised Infection Medicine (CiiM), a joint venture of Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner-Site Hannover-Braunschweig, Hannover, Germany
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Sofia MJ. Curing Hepatitis C with Direct‐Acting Antiviral Therapy. METHODS AND PRINCIPLES IN MEDICINAL CHEMISTRY 2022:13-57. [DOI: 10.1002/9783527810697.ch2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Lourenço MS, Zitelli PMY, Cunha-Silva M, Oliveira AIN, Oliveira CP, Sevá-Pereira T, Carrilho FJ, Pessoa MG, Mazo DF. Direct-acting antivirals for chronic hepatitis C treatment: The experience of two tertiary university centers in Brazil. World J Hepatol 2022; 14:195-208. [PMID: 35126848 PMCID: PMC8790388 DOI: 10.4254/wjh.v14.i1.195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/22/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) treatment has undergone major changes in recent years. Previous interferon-based therapies have been replaced by oral direct-acting antivirals (DAA) regimens, with high sustained virologic response (SVR) rates, and a lower incidence of adverse events (AEs). AIM To evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil. METHODS This is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C (CHC), undergoing treatment with interferon-free regimens from November 2015 to November 2019. The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment. Demographic, anthropometric, clinical, and laboratory variables were evaluated. SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat (ITT), and modified ITT (m-ITT) analysis. AEs and serious adverse events (SAEs) were registered. In the statistical analysis, a P value of < 0.05 was considered significant. RESULTS The mean age was 56.88 years, with 415 (78.5%) being HCV genotype 1, followed by genotype 3 (20.1%). Moreover, 306 (57.5%) subjects had cirrhosis, and a third of them had decompensated cirrhosis. Sofosbuvir (SOF) plus daclatasvir ± ribavirin was the most frequently used treatment (66.9%), followed by SOF plus simeprevir (21.2%). The overall ITT SVR was 92.6% (493/532), while the m-ITT SVR was 96.8% (493/509). Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy (OR: 4.320; 95%CI: 1.920-9.721, P = 0.0004), presence of esophageal varices (OR: 2.381; 95%CI: 1.137-4.988, P = 0.0215), previous portal hypertensive bleeding (OR: 2.756; 95%CI: 1.173-6.471, P = 0.02), higher model for end-stage liver disease scores (OR: 1.143, 95%CI: 1.060-1.233, P = 0.0005), lower serum albumin levels (OR: 0.528, 95%CI: 0.322-0.867, P = 0.0115), higher serum creatinine (OR: 1.117, 95%CI: 1.056-1.312, P = 0.0033), and international normalized ratio (INR) levels (OR: 5.542, 95%CI: 2.023-15.182, P = 0.0009). AEs were reported in 41.1% (211/514) of patients, and SAEs in 3.7%. The female gender, higher body mass index, esophageal varices, higher INR values, and longer treatment duration were independently associated with AE occurrence. CONCLUSION Treatment with oral DAAs attains a high SVR rate, with fewer SAEs in a real-life cohort of subjects with CHC, from two tertiary university centers in Brazil.
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Affiliation(s)
- Mariana Sandoval Lourenço
- Division of Gastroenterology, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Sao Paulo 13083-878, Brazil
| | - Patricia Momoyo Y Zitelli
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Brazil
| | - Marlone Cunha-Silva
- Division of Gastroenterology, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Sao Paulo 13083-878, Brazil
| | - Arthur Ivan N Oliveira
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Brazil
| | - Cláudia P Oliveira
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Brazil
| | - Tiago Sevá-Pereira
- Division of Gastroenterology, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Sao Paulo 13083-878, Brazil
| | - Flair José Carrilho
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Brazil
| | - Mario G Pessoa
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Brazil
| | - Daniel F Mazo
- Division of Gastroenterology, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Sao Paulo 13083-878, Brazil
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, Sao Paulo 05403-900, Brazil.
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Kondili LA, Andreoni M, Alberti A, Lobello S, Babudieri S, De Michina A, Merolla R, Marrocco W, Craxì A. A mathematical model by route of transmission and fibrosis progression to estimate undiagnosed individuals with HCV in different Italian regions. BMC Infect Dis 2022; 22:58. [PMID: 35038987 PMCID: PMC8761836 DOI: 10.1186/s12879-022-07042-w] [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: 05/07/2021] [Accepted: 11/17/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Although an increase in hepatitis C virus (HCV) prevalence from Northern to Southern Italy has been reported, the burden of asymptomatic individuals in different Italian regions is currently unknown. METHODS A probabilistic approach, including a Markov chain for liver disease progression, was applied to estimate current HCV viraemic burden. The model defined prevalence by geographic area using an estimated annual historical HCV incidence by age, treatment rate, and migration rate from the Italian National database. Viraemic infection by age group was estimated for each region by main HCV transmission routes of individuals for stage F0-F3 (i.e. patients without liver cirrhosis and thus potentially asymptomatic) and F4 (patients with liver cirrhosis, thus potentially symptomatic). RESULTS By January 2020, it was estimated that there were 409,184 Italian individuals with HCV (prevalence of 0.68%; 95% CI: 0.54-0.82%), of which 300,171 (0.50%; 95% CI: 0.4-0.6%) were stage F0-F3. Considering all individuals with HCV in stage F0-F3, the geographical distributions (expressed as the proportion of HCV infected individuals by macroarea within the overall estimated number of F0-F3 individuals and prevalence values, expressed as the percentage of individuals with HCV versus the overall number of individuals for each macroarea) were as follows: North 42.1% (0.45%; 95% CI: 0.36-0.55%), Central 24.1% (0.61%; 95% CI: 0.48-0.74%), South 23.2% (0.50%; 95% CI: 0.4-0.61%), and the Isles 10.6% (0.49%; 95% CI: 0.39-0.59%). The population of people who inject drugs accounted for 50.4% of all individuals infected (F0-F3). Undiagnosed individuals (F0-F3) were ~ 15 years younger (⁓ 50 years) compared with patients with stage F4 (⁓ 65 years), with similar age distributions across macroareas. In contrast to what has been reported on HCV epidemiology in Italy, an increasing trend in the proportion of potentially undiagnosed individuals with HCV (absolute number within the F0-F3) from South (23.2%) to North (42.1%) emerged, independent of similar regional prevalence values. CONCLUSION This targeted approach, which addresses the specific profile of undiagnosed individuals, is helpful in planning effective elimination strategies by region in Italy and could be a useful methodology for other countries in implementing their elimination plans.
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Affiliation(s)
- Loreta A Kondili
- National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.
| | | | - Alfredo Alberti
- Department of Molecular Medicine DMM, University of Padova, Padua, Italy
| | | | | | | | | | | | - Antonio Craxì
- Gastroenterology and Liver Unit, DiBiMIS, University of Palermo, Palermo, Italy
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Tornesello AL, Reimer U, Holenya P, Knaute T, Pezzuto F, Izzo F, Buonaguro L, Megna AS, Buonaguro FM, Tornesello ML. Profiling the HCV Immune Response in Patients with Chronic Liver Diseases and Hepatocellular Carcinoma by Peptide Microarray Analysis. Curr Med Chem 2022; 29:2736-2747. [PMID: 34736375 DOI: 10.2174/0929867328666211104093718] [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] [Received: 04/20/2021] [Revised: 09/07/2021] [Accepted: 09/08/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Chronic infection with hepatitis C virus (HCV) is among the major causes of hepatic fibrosis, cirrhosis, as well as hepatocellular carcinoma (HCC), and it is associated with a significant risk of developing lymphoproliferative disorders. The rate of clinical disease progression is variable depending on multiple host and viral factors, including immune response. METHODS To perform a comprehensive epitope mapping of anti-HCV antibodies in patients suffering from HCV-related liver or lymphoproliferative diseases, we analyzed clinical samples on a peptide microarray platform made of 5952 overlapping 15-mer synthetic peptides derived from the whole HCV proteome. We evaluated the antibody profile of 71 HCV-positive patients diagnosed with HCC, mixed cryoglobulinemia (MC), and HCV chronic infection. Antibody reactivity against virus peptides was detected in all HCVpositive patients. Importantly, the signal amplitude varied significantly within and between diverse patient groups. RESULTS Antibody reactivity against C peptides were found generally low in HCV chronically infected asymptomatic subjects and increasingly high in HCC and MC patients. Moreover, we found a statistically significant higher IgG response in HCC and MC patients against specific domains of HCV C, E2, NS3, NS4A, NS4B, NS5A, and p7 compared to HCV-positive subjects. CONCLUSION In conclusion, our data suggest that immune response against specific HCV protein domains may represent useful biomarkers of disease progression among HCVpositive patients and suggest that peptide microarrays are good tools for the screening of immunotherapy targets in preclinical HCV research.
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Affiliation(s)
- Anna Lucia Tornesello
- Department of Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS \'Fondazione G. Pascale\', 80131 Napoli, Italy
| | - Ulf Reimer
- JPT Peptide Technologies GmbH, Berlin,Germany
| | | | | | - Francesca Pezzuto
- Department of Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS \'Fondazione G. Pascale\', 80131 Napoli, Italy
| | - Francesco Izzo
- Hepatobiliary Surgery Unit, Istituto Nazionale Tumori IRCCS \'Fondazione G. Pascale\', 80131 Napoli, Italy
| | - Luigi Buonaguro
- Innovative Immunological Models, Istituto Nazionale Tumori IRCCS \'Fondazione G. Pascale, 80131 Napoli, Italy
| | | | - Franco Maria Buonaguro
- Department of Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS \'Fondazione G. Pascale\', 80131 Napoli, Italy
| | - Maria Lina Tornesello
- Department of Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS \'Fondazione G. Pascale\', 80131 Napoli, Italy
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Atta NF, Galal A, El-Gohary AR. Electrochemical sensing of dobutamine, paracetamol, amlodipine, and daclatasvir in serum based on thiourea SAMs over nano-gold particles-CNTs composite. NEW J CHEM 2022. [DOI: 10.1039/d2nj01822e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
We report in this work a one-step approach for the formation of self-assembled monolayers (SAMs) from thiourea (TU) over gold nanoparticles dispersed in carbon nanotubes (CNTs-Aunano). The fabrication of the...
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Abstract
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
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Affiliation(s)
- Michael P. Manns
- grid.10423.340000 0000 9529 9877Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- grid.10423.340000 0000 9529 9877Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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Ibrahim MK, AbdElrahman M, Bader El Din NG, Tawfik S, Abd-Elsalam S, Omran D, Barakat AZ, Farouk S, Elbatae H, El Awady MK. The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients. Microb Pathog 2022; 162:105311. [PMID: 34843922 DOI: 10.1016/j.micpath.2021.105311] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 11/20/2021] [Accepted: 11/22/2021] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) is the leading cause of liver diseases worldwide. At present, combinations of different classes of direct-acting antiviral agents (DAAs) are used as treatment options for HCV, in which sofosbuvir (SOF) is the common DAA among different therapeutic regimes. In Egypt, SOF plus daclatasvir (DCV) is the widely used anti-HCV treatment protocol. Herein, we aimed to assess the association between 3 single-nucleotide polymorphisms (SNPs) at the genes coding for 2 SOF metabolizing enzymes: histidine triad nucleotide-binding protein 1 (HINT1) rs4696/rs7728773 and nucleoside diphosphate kinase 1 (NME1) rs3760468, together with the most potent anti-HCV innate molecule, i.e., interferon lambda 3 (IFNL3) rs12979860 and the response to SOF/DCV in Egyptian patients chronically infected with genotype 4 (GT4). SNPs were genotyped using real-time PCR in DNA from patients who achieved sustained virological response (SVR) at 12 weeks post-SOF/DCV treatment (i.e., responders; n = 188), patients who failed to achieve SVR12 (i.e., non-responders; n = 109), and healthy controls (n = 62). Our results demonstrated that patients bearing HINT1 rs7728773 CT/TT (odds ratio 2.119, 95% CI 1.263-3.559, p = 0.005) and IFNL3 rs12979860 CC (odds ratio 3.995, 95% CI 2.126-7.740, p = 0.0001) were more likely to achieve SVR12. However, neither HINT1 rs4696 nor NME1 rs3760468 seems to contribute to the responsiveness to SOF/DCV. Binary regression analysis defined 5 predictor factors independently associated with SVR12: age, bilirubin, hemoglobin, early stages of fibrosis, and combined HINT1 rs7728773 and IFNL3 rs12979860 favorable and mixed genotypes (odds ratio 3.134, 95% CI 1.518-6.47, p = 0.002), and that was confirmed by the combined ROC curve for the 5 predictor factors (AUC = 0.91, 95% CI 0.869-0.95, P = 0.0001). In conclusion, these data suggest that the two SNPs have the potential in predicting the response rate to SOF/DCV treatment in patients infected with HCV GT4. This study is the first to investigate the pharmacogenetics of SOF metabolizing enzyme and introduce HINT1 rs7728773 as a novel SNP that predicts the treatment efficacy.
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Affiliation(s)
- Marwa K Ibrahim
- Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, 33 EL Bohouth St. (formerly El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt.
| | - Mohamed AbdElrahman
- Department of Pharmacy, Al-Mustaqbal University College, Babylon, Iraq; Clinical Pharmacy Unit, Badr University Hospital, Faculty of Medicine, Helwan University, Egypt
| | - Noha G Bader El Din
- Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, 33 EL Bohouth St. (formerly El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt
| | - Salwa Tawfik
- Department of Internal Medicine, National Research Center, 33 EL Bohouth St. (formerly El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt
| | - Sherief Abd-Elsalam
- Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Dalia Omran
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Egypt
| | - Amal Z Barakat
- Department of Molecular Biology, Biotechnology Research Institute, National Research Center, 33 EL Bohouth St. (formerly El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt
| | - Sally Farouk
- Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, 33 EL Bohouth St. (formerly El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt
| | - Hassan Elbatae
- Department of Tropical Medicine, Faculty of Medicine, Kafer Elshiek University, Kafer Elshiek, Egypt
| | - Mostafa K El Awady
- Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, 33 EL Bohouth St. (formerly El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt
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Quaranta MG, Ferrigno L, Tata X, D'Angelo F, Massari M, Coppola C, Biliotti E, Giorgini A, Laccabue D, Ciancio A, Blanc PL, Margotti M, Ieluzzi D, Brunetto MR, Barbaro F, Russo FP, Beretta I, Morsica G, Verucchi G, Saracino A, Galli M, Kondili LA. Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort. Dig Liver Dis 2021; 53:1603-1609. [PMID: 33893040 DOI: 10.1016/j.dld.2021.03.020] [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: 12/04/2020] [Revised: 03/08/2021] [Accepted: 03/15/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. METHODS Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. RESULTS Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. CONCLUSION Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.
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Affiliation(s)
| | - Luigina Ferrigno
- Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Xhimi Tata
- University of Tor Vergata, Nostra Signora del Buon Consiglio di Tirana, Albania
| | - Franca D'Angelo
- Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
| | - Marco Massari
- Infectious Diseases, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Italy
| | | | - Elisa Biliotti
- Hepatology Unit, Department of Clinical Medicine, Sapienza University, Rome, Italy
| | - Alessia Giorgini
- Gastroenterology and Hepatology Unit, ASST Santi Paolo e Carlo, Milan, Italy
| | - Diletta Laccabue
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | | | - Pier Luigi Blanc
- Infectious Disease Unit, Santa Maria Annunziata Hospital, Florence, Italy
| | - Marzia Margotti
- Department of Internal Medicine, University Hospital of Modena, Italy
| | - Donatella Ieluzzi
- Clinical Unit of Gastroenterology, University Hospital of Verona, Verona, Italy
| | - Maurizia Rossana Brunetto
- Hepatology and Liver Physiopathology Laboratory and Internal Medicine, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
| | - Francesco Barbaro
- Infectious and Tropical Diseases Unit, Azienda Ospedaliera di Padova, Padua, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Ilaria Beretta
- Division of Infectious Diseases, San Gerardo Hospital, Monza, Italy
| | - Giulia Morsica
- Department of Infectious Diseases, San Raffaele Hospital, Milan, Italy
| | - Gabriella Verucchi
- Department of Medical and Surgical Sciences, Clinic of Infectious Diseases and Microbiology Unit, Alma Mater Studiorum Bologna University, Bologna, Italy
| | - Annalisa Saracino
- Division of Infectious Diseases, Bari University Hospital, University of Bari, Italy
| | - Massimo Galli
- Department of Biomedical and Clinical Sciences 'Luigi Sacco', University of Milan, Italy
| | - Loeta A Kondili
- Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.
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