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Değer SU, Can H. A predictive study on HCV using automated machine learning models. Comput Biol Med 2025; 188:109897. [PMID: 39983359 DOI: 10.1016/j.compbiomed.2025.109897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 02/04/2025] [Accepted: 02/18/2025] [Indexed: 02/23/2025]
Abstract
Hepatitis C virus (HCV) infection represents a significant contributor to chronic liver disease on a global scale. The prompt identification and management of HCV are imperative in order to avert complications and to maintain control over the disease. Nowadays, medical decision support systems that incorporate advanced diagnostic methods and effective treatment strategies are of great importance in order to make significant progress in the fight against HCV. Medical decision support systems have undergone a major evolution with the development of computer technologies. In the 2010s, the integration of big data and artificial intelligence technologies into medical decision support systems enabled rapid analysis of patient data. This has created significant synergies in the diagnostic and therapeutic approaches to various diseases. The ever-increasing volume of data on HCV infection offers opportunities to use machine learning techniques to diagnose and predict liver disorders. Although the implementation of machine learning necessitates a degree of proficiency in computer science, which frequently poses a challenge for healthcare practitioners, automated machine learning (AutoML) tools markedly mitigate this obstacle. Such tools empower users to construct highly effective machine learning models without requiring extensive technical expertise. In our investigation concerning HCV prediction, additional features were incorporated into the dataset sourced from the UCI Machine Learning Repository, and class imbalances were rectified. In our study on HCV prediction, which was conducted to address this deficiency, new features were added to the dataset obtained from the UCI Machine Learning Repository to address the deficiencies and inter-class imbalances were corrected. After this process, modeling was performed using 7 AutoML tools and high accuracy rates ranging from 99.29 % to 100 % were obtained. As an important result of this paper, these models may be regarded as a supplementary method for doctors in predicting Hepatitis C and its associated diseases.
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Affiliation(s)
- Serbun Ufuk Değer
- Kastamonu Vocational School, Kastamonu University, 37150, Kastamonu, Turkey.
| | - Hakan Can
- Kastamonu Vocational School, Kastamonu University, 37150, Kastamonu, Turkey.
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2
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Mubaraki AA, Alabdalli MA, Shawush AK, Alhusayni MA, Hammadi AA, Edries AA, Alaboud D, Abdel-Moneim AS. An 11-year retrospective study on hepatitis C in Saudi Arabia: Seroconversion, recovery rates, and viral genotype distribution. Virology 2025; 607:110505. [PMID: 40174332 DOI: 10.1016/j.virol.2025.110505] [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: 12/18/2024] [Revised: 03/11/2025] [Accepted: 03/17/2025] [Indexed: 04/04/2025]
Abstract
Hepatitis C virus (HCV) infection remains a global health concern. This study analyzed 95,864 plasma samples from Saudi patients between 2011 and 2022 to examine HCV seroconversion, viral load, and genotype distribution. Serological screening was performed using the ARCHITECT anti-HCV assay, and HCV RNA levels were quantified with real-time RT-PCR. Of the 970 HCV-positive cases, 47.9 % experienced spontaneous recovery, while 52.1 % had persistent infection. The annual seropositivity rate declined significantly from 2.05 % in 2011 to 0.34 % in 2022. Genotyping of 107 persistently infected samples showed genotypes 4 (49.5 %) and 1a (17.8 %) as the most common, with other genotypes appearing less frequently. Additionally, 13 (12.1 %) samples had untypable genotypes. This study highlights the decrease in HCV infection rates, the high rate of spontaneous recovery, and the predominance of genotypes 4 and 1a. Ongoing surveillance and genotyping, including untypable cases, are essential for effective HCV management in Saudi Arabia.
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Affiliation(s)
- Adnan A Mubaraki
- Department of Medicine, College of Medicine, Taif University, Taif, 21944, Saudi Arabia
| | - Mohammed A Alabdalli
- Al-Hada Armed Forces Hospital, Department of Molecular Pathology, Al-Taif, Saudi Arabia
| | - Ahmed K Shawush
- Al-Hada Armed Forces Hospital, Department of Molecular Pathology, Al-Taif, Saudi Arabia
| | | | | | - Awatief A Edries
- Department of Medicine, College of Medicine, Taif University, Taif, 21944, Saudi Arabia; Department of Tropical Medicine, College of Medicine Tanta University, Tanta, Egypt
| | - Daifallah Alaboud
- Department of Medicine, College of Medicine, Taif University, Taif, 21944, Saudi Arabia
| | - Ahmed S Abdel-Moneim
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, 123, Muscat, Oman.
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3
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Sarwar S, Randall G. HCV NS3/4A protease relocalizes CCTα to viral replication sites, enhancing phosphatidylcholine synthesis and viral replication. Proc Natl Acad Sci U S A 2025; 122:e2419632122. [PMID: 40042907 PMCID: PMC11912369 DOI: 10.1073/pnas.2419632122] [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: 09/25/2024] [Accepted: 01/28/2025] [Indexed: 03/19/2025] Open
Abstract
Positive-sense single-stranded RNA [(+)RNA] viruses constitute more than one-third of all virus genera, including numerous pathogens of clinical significance. All (+)RNA viruses reorganize cellular membranes from organelles to establish replication compartments (RCs). These RCs are thought to form a platform for membrane-associated replicases, in addition to protecting the viral RNAs from cytosolic innate immune signaling and RNA-degradation machinery. Previous work demonstrated that three families of (+)RNA viruses, namely Bromoviridae, Picornaviridae, and Flaviviridae, commonly induce the accumulation of phosphatidylcholine (PC) at their RCs. This phenomenon suggests a potential avenue for a broad-spectrum antiviral strategy targeting PC metabolism. Our study elucidates three key observations: i) hepatitis C virus (HCV) infection prompts the relocalization of CCTα, the rate-limiting enzyme in PC synthesis, to the RCs; ii) the enhancement of PC synthesis is contingent upon the protease activity of the NS3/4A protein; and iii) utilizing click chemistry, we demonstrate that HCV infection stimulates de novo PC synthesis at the viral replication site through the Kennedy pathway. These findings provide significant insights into the manipulation of lipid metabolism by HCV during RC formation, a mechanism likely conserved across various (+)RNA virus families.
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Affiliation(s)
- Shamila Sarwar
- Department of Microbiology, The University of Chicago, Chicago, IL 60637
| | - Glenn Randall
- Department of Microbiology, The University of Chicago, Chicago, IL 60637
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Basson AA, Weil C, Marx SE, Dylla DE, Collins M, Hadadi S, Chodick G, Rahamim-Cohen D, Lavi IK, Shibolet O. Road to Hepatitis C Elimination in Israel: Improvements in Linkage to Care (2009-2020). Adv Ther 2025; 42:1522-1536. [PMID: 39912989 PMCID: PMC11868148 DOI: 10.1007/s12325-024-03102-6] [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: 07/03/2024] [Accepted: 12/20/2024] [Indexed: 02/07/2025]
Abstract
INTRODUCTION Disrupted linkage to care is a major barrier to hepatitis C virus (HCV) elimination leading to high attrition rates. This study aimed to describe (1) flow through the HCV care-cascade (2009-2020), and (2) monthly patterns in HCV care during the coronavirus disease 2019 (COVID-19) pandemic (2020) in Israel. METHODS Data were obtained from Maccabi Healthcare Services, a 2.6-million-member healthcare provider in Israel. Flow through the HCV care-cascade in 2009-2020 was described from individuals' first positive HCV antibody (Ab+) test to sustained virological response (SVR), and monthly data were obtained on individuals newly attaining a given stage in the HCV care-cascade in 2020. RESULTS Among 2809 new patients who were Ab+, 2651 (94.4%) had an HCV polymerase chain reaction (PCR) test, and 1417 (50.4%) were PCR+ during the study. Median time from Ab+ to PCR+ was 3.9 years, with 39.7% PCR+ within 12 months. Median time from PCR+ to HCV treatment was 3.3 years, with 639 (55.5%) of patients who were PCR+ purchasing direct-acting anti-viral agents (DAAs), and 413/416 patients attained SVR. A significant reduction was observed in the time from first HCV detection (Ab+) to HCV confirmation (PCR+) and from PCR+ test to HCV treatment purchase in the pre-DAA era compared to the post-DAA. Monthly data during 2020 (Part B) indicates a decline in the numbers of patients receiving HCV care during the first pandemic-related closure. CONCLUSION Real-world data from a nationally representative healthcare provider database suggest that HCV linkage to care improved over time alongside increased access to DAAs, despite observed declines in access to care in 2020.
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Affiliation(s)
| | - Clara Weil
- Maccabi Healthcare Services, Tel Aviv, Israel
| | - Steven E Marx
- AbbVie Inc, North Chicago, IL, USA.
- , 26525 Riverwoods Blvd, Mettawa, IL, 60048, USA.
| | | | | | | | - Gabriel Chodick
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Maccabi Healthcare Services, Tel Aviv, Israel
| | | | | | - Oren Shibolet
- Liver Unit, Department of Gastroenterology, Tel Aviv Medical Center, Tel-Aviv, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Ran X, Xu Y, Wang Y, Zeng C, Gong C, Wang N, Cai D. Genotype 3 is linked to worse liver disease progression in hepatitis C patients even after SVR following DAA therapy. Front Cell Infect Microbiol 2025; 15:1510939. [PMID: 39963406 PMCID: PMC11830654 DOI: 10.3389/fcimb.2025.1510939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 01/13/2025] [Indexed: 02/20/2025] Open
Abstract
Background and aims HCV genotype (GT) 3 is associated with rapid liver disease progression. However, the liver disease progression and its risk factors in patients with HCV GT 3 infection after sustained virological response (SVR) following direct-acting antivirals (DAAs) remain unclear. Therefore, we aimed to investigate the liver disease progression of patients with GT 3 after SVR. Methods This was a retrospective cohort study of patients with HCV infection who achieved SVR by DAAs. The clinical outcome was overall liver disease progression (OLDP), defined as newly diagnosed compensated liver cirrhosis, decompensated liver cirrhosis, or hepatocellular carcinoma. The incidence of OLDP was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the risk factors for OLDP. Results A total of 409 patients (46.9% GT3) were followed for 43.7 (32.9, 58.7) months. The incidence of OLDP was higher in patients with GT 3 (4.63/100PY) than non-GT 3 (0.60/100PY; P < 0.001). According to Cox multivariate analysis, GT 3 was significantly associated with OLDP (HR 6.41, 95% CI 1.82 - 22.56; P=0.004). The predictors of OLDP in patients with GT 3 were HCV recurrence (HR 12.15, 95% CI 3.18 - 46.46; P < 0.001) and FIB-4 > 3.25 (HR 16.40, 95% CI 1.03 - 39.81; P = 0.046) at baseline. Conclusion HCV GT 3-infected patients remain at a higher risk of OLDP even after achieving SVR by DAAs, especially patients with advanced liver fibrosis and at high risk for reinfection or virological late relapse.
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Affiliation(s)
- Xiping Ran
- Department of Gastroenterology, Chonggang General Hospital, Chongqing, China
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yang Xu
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Ying Wang
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Cheng Zeng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Chen Gong
- Department of Neurology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Ni Wang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Dachuan Cai
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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Karin M, Kim JY. MASH as an emerging cause of hepatocellular carcinoma: current knowledge and future perspectives. Mol Oncol 2025; 19:275-294. [PMID: 38874196 PMCID: PMC11793012 DOI: 10.1002/1878-0261.13685] [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: 04/15/2024] [Accepted: 06/04/2024] [Indexed: 06/15/2024] Open
Abstract
Hepatocellular carcinoma is one of the deadliest and fastest-growing cancers. Among HCC etiologies, metabolic dysfunction-associated fatty liver disease (MAFLD) has served as a major HCC driver due to its great potential for increasing cirrhosis. The obesogenic environment fosters a positive energy balance and results in a continuous rise of obesity and metabolic syndrome. However, it is difficult to understand how metabolic complications lead to the poor prognosis of liver diseases and which molecular mechanisms are underpinning MAFLD-driven HCC development. Thus, suitable preclinical models that recapitulate human etiologies are essentially required. Numerous preclinical models have been created but not many mimicked anthropometric measures and the course of disease progression shown in the patients. Here we review the literature on adipose tissues, liver-related HCC etiologies and recently discovered genetic mutation signatures found in MAFLD-driven HCC patients. We also critically review current rodent models suggested for MAFLD-driven HCC study.
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Affiliation(s)
- Michael Karin
- Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of MedicineUniversity of California San DiegoLa JollaCAUSA
| | - Ju Youn Kim
- Department of Molecular and Life ScienceHanyang University ERICAAnsanKorea
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Kerkar N, Hartjes K. Hepatitis C Virus-Pediatric and Adult Perspectives in the Current Decade. Pathogens 2024; 14:11. [PMID: 39860972 PMCID: PMC11769290 DOI: 10.3390/pathogens14010011] [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: 11/02/2024] [Revised: 12/06/2024] [Accepted: 12/25/2024] [Indexed: 01/27/2025] Open
Abstract
Hepatitis C virus (HCV) infects both pediatric and adult populations and is an important cause of chronic liver disease worldwide. There are differences in the screening and management of HCV between pediatric and adult patients, which have been highlighted in this review. Direct-acting antiviral agents (DAA) have made the cure of HCV possible, and fortunately, these medications are approved down to three years of age. However, treatment in the pediatric population has its own set of challenges. The World Health Organization (WHO) has made a pledge to eliminate HCV as a public health threat by 2030. Despite this, HCV continues to remain a global health burden, leading to cirrhosis as well as hepatocellular carcinoma, and is a reason for liver transplantation in the adult population. Although rare, these complications can also affect the pediatric population. A variety of new technologies t have become available in the current era and can advance our understanding of HCV are discussed. Artificial intelligence, machine learning, liver organoids, and liver-on-chip are some examples of techniques that have the potential to contribute to our understanding of the disease and treatment process in HCV. Despite efforts over several decades, a successful vaccine against HCV has yet to be developed. This would be an important tool to help in worldwide efforts to eliminate the virus.
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Affiliation(s)
- Nanda Kerkar
- Massachusetts General Brigham for Children, 175 Cambridge Street, Boston, MA 02114, USA;
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Kassa GM, Walker JG, Alamneh TS, Tamiru MT, Bivegete S, Adane A, Amogne W, Dillon JF, Vickerman P, Dagne E, Yesuf EA, Hickman M, French CE, Lim AG. Prevalence, trends, and distribution of hepatitis C virus among the general population in sub-Saharan Africa: A systematic review and meta-analysis. Liver Int 2024; 44:3238-3249. [PMID: 39268900 PMCID: PMC11586889 DOI: 10.1111/liv.16102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 08/03/2024] [Accepted: 09/02/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND AND AIMS Although the evidence is uncertain, existing estimates for hepatitis C virus (HCV) in sub-Saharan Africa (SSA) indicate a high burden. We estimated HCV seroprevalence and viraemic prevalence among the general population in SSA. METHODS We searched Medline, Embase, Web of Science, APA PsycINFO, and World Health Organization Africa Index Medicus for community-based studies. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool, and heterogeneity using the index of heterogeneity (I2). Two approaches were deployed. First, we used random-effects meta-analysis to pool prevalence. Second, to derive representative estimates, we weighted each country's HCV seroprevalence using 2021 United Nations country population sizes. RESULTS We synthesized 130 studies. Overall, SSA HCV seroprevalence from the random-effects model was 4.17% (95% confidence interval [CI]: 3.71-4.66, I2 = 99.30%). There were no differences between males (4.31%) and females (4.03%). Seroprevalence was 2.25%, 3.31%, and 16.23% for ages ≤20, 21-64, and ≥65 years, respectively, and was higher in rural (6.63%) versus urban (2.93%). There was indication of decrement overtime from 5.74% to 4.35% to 3.03% in the years 1984-2000, 2001-2014, and 2015-2023, respectively. The weighted overall SSA HCV seroprevalence was estimated to be 2.30% (95% CI: 1.59-3.00) with regional variation: Africa-Southern (.79%), Africa-Central (1.47%), Africa-Eastern (2.71%), and Africa-Western (2.88%). HCV viremia among HCV seropositives was 54.77% (95% CI: 47.80-61.66). CONCLUSIONS HCV seroprevalence in SSA remains high. Populations aged ≥65 years, rural communities, Africa-Western, and some countries in Africa-Central and Africa-Eastern appear disproportionately affected. These results underline the need for governmental commitment to achieve the 2030 global HCV elimination targets.
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Affiliation(s)
- Getahun Molla Kassa
- Population Health Sciences, Bristol Medical SchoolUniversity of BristolBristolUK
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health SciencesUniversity of GondarGondarEthiopia
| | - Josephine G. Walker
- Population Health Sciences, Bristol Medical SchoolUniversity of BristolBristolUK
| | - Tesfa Sewunet Alamneh
- Population Health Sciences, Bristol Medical SchoolUniversity of BristolBristolUK
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health SciencesUniversity of GondarGondarEthiopia
| | - Melaku Tileku Tamiru
- Division of Molecular and Clinical Medicine, School of MedicineUniversity of DundeeDundeeUK
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health SciencesAddis Ababa UniversityAddis AbabaEthiopia
| | - Sandra Bivegete
- Population Health Sciences, Bristol Medical SchoolUniversity of BristolBristolUK
| | - Aynishet Adane
- Department of Internal Medicine, School of Medicine, College of Medicine and Health SciencesUniversity of GondarGondarEthiopia
| | - Wondwossen Amogne
- Department of Internal Medicine, School of Medicine, College of Health SciencesAddis Ababa UniversityAddis AbabaEthiopia
| | - John F. Dillon
- Division of Molecular and Clinical Medicine, School of MedicineUniversity of DundeeDundeeUK
| | - Peter Vickerman
- Population Health Sciences, Bristol Medical SchoolUniversity of BristolBristolUK
| | - Emebet Dagne
- Department of Internal Medicine, Institute of HealthJimma UniversityJimmaEthiopia
| | - Elias Ali Yesuf
- Department of Health Policy and Management, Institute of HealthJimma UniversityJimmaEthiopia
| | - Matthew Hickman
- Population Health Sciences, Bristol Medical SchoolUniversity of BristolBristolUK
| | - Clare E. French
- Population Health Sciences, Bristol Medical SchoolUniversity of BristolBristolUK
- NIHR Health Protection Research Unit in Behavioural Science and EvaluationUniversity of BristolBristolUK
| | - Aaron G. Lim
- Population Health Sciences, Bristol Medical SchoolUniversity of BristolBristolUK
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Ying JQ, Zhang YJ, Xia YQ, Ma HD, Zhang T, Tu L, Zheng AH, Gao P, Wang WH. The effectiveness of intervention in hepatitis C patients and improvement in their referral rate. Ann Med 2024; 56:2346537. [PMID: 38696817 PMCID: PMC11067552 DOI: 10.1080/07853890.2024.2346537] [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: 09/08/2023] [Accepted: 04/01/2024] [Indexed: 05/04/2024] Open
Abstract
BACKGROUND To investigate the effectiveness of the intervention with critical value management and push short messaging service (SMS), and to determine improvement in the referral rate of patients with positive hepatitis C antibody (anti-HCV). METHODS No intervention was done for patients with positive anti-HCV screening results from 1 January 2015 to 31 October 2021. Patients with positive anti-HCV results at our hospital from 1 November 2021 to 31 July 2022 were informed vide critical value management and push SMS. For inpatients, a competent physician was requested to liaise with the infectious disease physician for consultation, and patients seen in the OPD (outpatient department) were asked to visit the liver disease clinic. The Chi-square correlation test, one-sided two-ratio test and linear regression were used to test the relationship between intervention and referral rate. RESULTS A total of 638,308 cases were tested for anti-hepatitis C virus (HCV) in our hospital and 5983 of them were positive. 51.8% of the referred patients were aged 18-59 years and 10.8% were aged ≥75 years. The result of Chi-square correlation test between intervention and referral was p = .0000, p < .05. One-sided two-ratio test was performed for statistics of pre-intervention referral rate (p1) and post-intervention referral rate (p2). Normal approximation and Fisher's exact test for the results obtained were 0.000, p < .05, and the alternative hypothesis p1 - p2 < 0 was accepted. The linear regression equation was referral = 0.1396 × intervention + 0.3743, and the result model p = 8.79e - 09, p < .05. The model was significant, and the coefficient of intervention was 0.1396. CONCLUSIONS The interventions of critical value management and push SMS were correlated with the referral rate of patients with positive anti-HCV.
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Affiliation(s)
- Jiao-Qian Ying
- Department of Medical Affairs, China-Japan Friendship Hospital, Beijing, China
| | - Yu-jiao Zhang
- Department of Infectious Disease, China-Japan Friendship Hospital, Beijing, China
| | - Yun-qing Xia
- School of Mathematics and Statistics, Beijing Institute of Technology, Beijing, China
| | - Hao-di Ma
- Department of Computer & Information Science & Engineering, University of Florida, Gainesville, FL, USA
| | - Tie Zhang
- Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China
| | - Ling Tu
- Department of IT, China-Japan Friendship Hospital, Beijing, China
| | - Ai-hui Zheng
- Department of Nosocomial Infection Control and the Center for Disease Control and Prevention, China-Japan Friendship Hospital, Beijing, China
| | - Peng Gao
- Department of Medical Affairs, China-Japan Friendship Hospital, Beijing, China
| | - Wei-hua Wang
- Department of Medical Affairs, China-Japan Friendship Hospital, Beijing, China
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Kanokudom S, Poovorawan K, Nilyanimit P, Suntronwong N, Aeemjinda R, Honsawek S, Poovorawan Y. Comparison of anti-HCV combined with HCVcAg (Elecsys HCV Duo immunoassay) and anti-HCV rapid test followed by HCV RNA analysis using qRT-PCR to identify active infection for treatment. PLoS One 2024; 19:e0313771. [PMID: 39556526 PMCID: PMC11573151 DOI: 10.1371/journal.pone.0313771] [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: 08/17/2024] [Accepted: 10/31/2024] [Indexed: 11/20/2024] Open
Abstract
Hepatitis C virus (HCV) infection can cause acute and chronic hepatitis, leading to liver cirrhosis and hepatocellular carcinoma. The World Health Organization aims to eliminate viral hepatitis by 2030 through extensive screening and treatment. To achieve this goal, comprehensive and widespread screening is essential for diagnosis and treatment. This study aims to evaluate the diagnostic sensitivity and specificity of the Elecsys® HCV Duo immunoassay (Duo-assay), which simultaneously detects anti-HCV antibodies (Duo/anti-HCV) and HCV core antigen (Duo/HCVcAg) in a single sample, compared with initially antibody testing followed by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, this study aimed to evaluate a relationship between Duo/HCVcAg and qRT-PCR assay in different genotypes. A total of 769 plasma samples were tested using the Duo-assay to further evaluate the test's performance and conduct Duo/HCVcAg correlation analysis using qRT-PCR for each genotype. Among the active infection group (anti-HCV+/RNA+; n = 473), the Duo-assay showed 100% sensitivity for detecting Duo/anti-HCV and 70.6% for Duo/HCVcAg. In the resolved infection group (anti-HCV+/RNA-; n = 176), the assay showed 100% sensitivity for Duo/anti-HCV and 100% specificity for Duo/HCVcAg. In the non-infected group (anti-HCV-/RNA-; n = 120), the assay showed 100% specificity for both Duo/anti-HCV and Duo/HCVcAg. Moreover, no correlation was observed between the Duo/HCVcAg and HCV RNA tests, irrespective of genotype. These findings indicate that the Duo-assay is highly sensitive for detecting anti-HCV and specifically identifies patients with active infection. Nevertheless, cases with anti-HCV+/HCVcAg-results should undergo additional confirmation with western blot/immunoblot and qRT-PCR to ensure diagnostic accuracy, especially in Blood donation facilities.
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Affiliation(s)
- Sitthichai Kanokudom
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence in Osteoarthritis and Musculoskeleton, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok, Thailand
| | - Kittiyod Poovorawan
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Pornjarim Nilyanimit
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Nungruthai Suntronwong
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Ratchadawan Aeemjinda
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sittisak Honsawek
- Center of Excellence in Osteoarthritis and Musculoskeleton, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Fellow of the Royal Society of Thailand (FRS [T]), The Royal Society of Thailand, Sanam Sueapa, Dusit, Bangkok, Thailand
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Imsirovic H, Macphail G, Conway B, Fraser C, Borgia S, Smyth D, Wong A, Vachon ML, Webster D, Liu H, Feld J, Lee S, Cooper C. Mixed-Genotype HCV Direct Acting Antiviral Outcomes: A CANUHC Analysis. J Viral Hepat 2024; 31:775-779. [PMID: 39135466 DOI: 10.1111/jvh.13995] [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: 05/23/2024] [Revised: 07/11/2024] [Accepted: 07/24/2024] [Indexed: 10/23/2024]
Abstract
The prevalence of mixed hepatitis C virus (HCV) genotype infection in a representative Canadian HCV cohort is reported and virological response with direct acting antiviral (DAA) treatment was evaluated. 3272 HCV-positive participants were enrolled, of which 2945 (90.0%) initiated DAA therapy. 0.8% were identified with mixed genotype infection. Overall sustained virological response (SVR) was 99.1% and did not differ based on mixed genotype status. Any historical disadvantage to achieving cure with HCV treatment in mixed genotype infection has been overcome by current DAA regimens.
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Affiliation(s)
| | | | - Brian Conway
- Vancouver Infectious Diseases Centre, Vancouver, British Columbia, Canada
| | | | - Sergio Borgia
- William Osler Health System, Division of Infectious Diseases, Brampton, Canada
- McMaster University, Division of Infectious Diseases, Hamilton, Canada
| | | | | | | | | | | | | | - Sam Lee
- University of Calgary, Calgary, Canada
| | - Curtis Cooper
- Ottawa Hospital Research Institute, Ottawa, Canada
- University of Ottawa, Ottawa, Canada
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12
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Astley J, Saralamba S, Poovorawan K, White LJ, Aguas R, Pan-ngum W. Population and transmission dynamics model to determine WHO targets for eliminating Hepatitis C virus in Thailand. PLoS One 2024; 19:e0309313. [PMID: 39413060 PMCID: PMC11482681 DOI: 10.1371/journal.pone.0309313] [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: 05/07/2024] [Accepted: 08/08/2024] [Indexed: 10/18/2024] Open
Abstract
BACKGROUND Hepatitis C Virus is endemic to many areas of Thailand, whose population structure is tending towards older age groups as birth rate and mortality decrease. With around 790,000 cases in 2019, prevalence is still relatively high, but the World Health Organisation has called for elimination of HCV by 2030. METHODS An age structured compartmental transmission model was used to explore the effectiveness of screening strategies with respect to WHO elimination goals, as well as the effect of changing population structure on the success or failure of such strategies. RESULTS Population structure did not appear to affect the timeline of elimination targets and screening individuals over the age of 30 at a high (50% per year) coverage could bring forward achievement of the incidence elimination target by four years compared to baseline (approximately 6% per year). Achievement of mortality elimination targets was not reached until after the end of the simulation (2040), and intensive screening strategies did not appear to lead to incidence elimination by 2030. CONCLUSION The model suggested that with age-targeted screening programmes incidence elimination could be brought forward by several years. However, WHO elimination goals may not be met by 2030.
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Affiliation(s)
- Jennifer Astley
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
| | - Sompob Saralamba
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Kittiyod Poovorawan
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Lisa Jane White
- Department of Biology, University of Oxford, Oxford, United Kingdom
- Model Health Ltd, Oxford, United Kingdom
| | - Ricardo Aguas
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Wirichada Pan-ngum
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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13
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Amjad F, Javed MN, Tahir S, Batool Z, Usman M, Qammar B, Javed H, Butt A, Islam M. Assessing the Efficacy of Novel Antiviral Therapies in Treating Hepatitis C. Cureus 2024; 16:e72301. [PMID: 39583485 PMCID: PMC11585319 DOI: 10.7759/cureus.72301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/24/2024] [Indexed: 11/26/2024] Open
Abstract
Hepatitis C virus (HCV) infection is a major global health burden, with an estimated 58 million people chronically infected worldwide, according to the World Health Organization (WHO). While many people remain asymptomatic during the early stages of infection, chronic hepatitis C can cause long-term liver damage, significantly increasing the morbidity and mortality associated with the disease. The primary objective of this technical report is to find the efficacy of novel antiviral therapies in treating hepatitis C in a tertiary care hospital in Lahore. This technical report was done in Shalamar Hospital, Lahore, from June 2023 to June 2024. Data for the report were collected retrospectively from 500 patients through a review of patient medical records from the hospital. Medical and electronic health records provided the patient demographics (age, gender, ethnicity), hepatitis C genotype, liver disease stage (fibrosis or cirrhosis staging), previous treatment history, and type of antiviral therapy administered (direct-acting antivirals (DAA)). Out of 500, there were 280 (56%) male and 220 (44%) female patients. The mean age of the patients was 41.23±5.67 years. Patients were divided among mild, advanced, and post-liver transplant as 320 (64%), 150 (30%), and 30 (6%), respectively. Among the DAA regimens, sofosbuvir-based therapies had the highest sustained virologic response (SVR) rate of 95%, followed by glecaprevir/pibrentasvir at 93%. Ledipasvir/sofosbuvir and other DAAs showed slightly lower SVR rates, at 89% and 87%, respectively, indicating high overall efficacy across different therapies. This report concluded that DAAs are highly effective in treating hepatitis C, with an overall SVR rate of 92% and good tolerability across most patient groups. However, patients with genotype III, advanced liver disease, or post-liver transplant status may require personalized treatment approaches due to slightly lower efficacy.
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Affiliation(s)
- Fatima Amjad
- Internal Medicine Department, Shalamar Hospital, Lahore, PAK
| | | | - Sulaiman Tahir
- Surgery Department, Punjab Rangers Teaching Hospital, Lahore, PAK
| | - Zahra Batool
- Internal Medicine Department, Bahawal Victoria Hospital, Bahawalpur, PAK
| | - Muhammad Usman
- Internal Medicine Department, Jinnah Hospital, Lahore, PAK
| | - Bilal Qammar
- Department of Surgery, Shalamar Hospital, Lahore, PAK
| | - Hamna Javed
- Forensic Medicine Department, University Medical and Dental College, Faisalabad, PAK
| | - Aisha Butt
- Emergency Department, Services Hospital, Lahore, PAK
| | - Maryyam Islam
- Research and Innovation Department, Shalamar Medical and Dental College, Lahore, PAK
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14
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Morovati S, Baghkheirati AA, Sekhavati MH, Razmyar J. A Review on cLF36, a Novel Recombinant Antimicrobial Peptide-Derived Camel Lactoferrin. Probiotics Antimicrob Proteins 2024; 16:1886-1905. [PMID: 38722550 DOI: 10.1007/s12602-024-10285-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/01/2024] [Indexed: 10/02/2024]
Abstract
Lactoferrin is an antimicrobial peptide (AMP) playing a pivotal role in numerous biological processes. The primary antimicrobial efficacy of lactoferrin is associated with its N-terminal end, which contains various peptides, such as lactoferricin and lactoferrampin. In this context, our research team has developed a refined chimeric 42-mer peptide known as cLF36 over the past few years. This peptide encompasses the complete amino acid sequence of camel lactoferrampin and partial amino acid sequence of lactoferricin. The peptide's activity against human, avian, and plant bacterial pathogens has been assessed using different biological platforms, including prokaryotic (P170 and pET) and eukaryotic (HEK293) expression systems. The peptide positively influenced the growth performance and intestinal morphology of chickens challenged with pathogen bacteria. Computational methods and in vitro studies showed the peptide's antiviral effects against hepatitis C virus, influenza virus, and rotavirus. The chimeric peptide exhibited higher activity against certain tumor cell lines compared to normal cells, which may be attributed to the peptide's interaction with negatively charged glycosaminoglycans on the surface of tumor cells. Importantly, this peptide exhibited no toxicity against host cells and demonstrated remarkable thermal and protease stability in serum. In conclusion, while our investigations suggest that the chimeric peptide, cLF36, may offer potential as a candidate or complementary option to some available antibiotics, antiviral agents, and chemical pesticides, significant uncertainties remain regarding its cost-effectiveness, as well as its pharmacodynamic and pharmacokinetic characteristics, which require further elucidation.
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Affiliation(s)
- Solmaz Morovati
- Department of Pathobiology, Division of Biotechnology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | | | - Mohammad Hadi Sekhavati
- Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran.
| | - Jamshid Razmyar
- Department of Avian Diseases, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
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15
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Ryan P, Valencia J, Sepúlveda-Crespo D, Amigot-Sánchez R, Cuevas G, Lazarus JV, Pérez-García F, Martínez I, Resino S. Prevalence of HCV Infection Among People Experiencing Homelessness in Madrid, Spain. JAMA Netw Open 2024; 7:e2438657. [PMID: 39453657 PMCID: PMC11581514 DOI: 10.1001/jamanetworkopen.2024.38657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 08/19/2024] [Indexed: 10/26/2024] Open
Abstract
Importance Hepatitis C virus (HCV) microelimination aims to detect and treat hidden infections, especially in at-risk groups, like people experiencing homelessness (PEH) with alcohol or drug use disorders. Point-of-care HCV RNA testing and peer support workers are crucial for identifying and preventing HCV infection among marginalized populations, contributing to overall elimination goals. Objective To assess risk factors, prevalence, and trends of active HCV infection among PEH in Madrid, Spain (2019-2023). Design, Setting, and Participants This cross-sectional study was conducted between 2019 and 2023 in PEH, defined as people who lacked a fixed, regular, and adequate night residence, screened on the street or in homeless shelters via mobile unit using rapid HCV antibody testing, followed by HCV-RNA testing in Madrid, Spain. Data were analyzed from January to June 2024. Main Outcomes and Measures Active HCV infection among PEH was the main outcome. Risk factors analyzed included being born outside of Spain, alcohol misuse, lacking financial income, benzodiazepine use, injection drug use (IDU; including nonactive IDU and active IDU within the last year), opioid substitution therapy participation, and sexual behavior patterns. Data were analyzed using logistic regression. P values were adjusted for multiple testing using the false discovery rate (q-values). Results A total of 4741 individuals were screened for HCV infection, of whom 2709 (mean [SD] age, 42.2 [12.7]; 1953 [72.2%] men) were PEH and included in analysis. A total of 363 PEH (13.4%) had test results positive for HCV antibodies, of whom 172 (47.4%) had test results positive for HCV-RNA, and 148 of these (91.9%) started HCV treatment. Overall, active HCV infection prevalence was 6.3%, and the main risk factors associated with active HCV infection included IDU, encompassing both nonactive IDU (adjusted odds ratio [aOR], 10.9; 95% CI, 6.1-19.4; q < .001) and active IDU in the last year (aOR, 27.0; 95% CI, 15.2-48.0; q < .001); a lack of financial income (aOR, 1.8; 95% CI, 1.1-2.9; q = .03); and alcohol misuse (aOR, 1.8; 95% CI, 1.3-2.6; q = .008). There was a significant decrease between 2019 and 2023 in active HCV infection prevalence across the entire population, from 7.2% to 3.4% (P = .04). Conclusions and Relevance In this cross-sectional study of PEH in Madrid, IDU, lack of income, and alcohol misuse were primary risk factors associated with HCV infection. The significant decline in HCV rates observed across all risk groups during the study period suggests preventive policies were effective in reducing HCV prevalence among the homeless population.
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Affiliation(s)
- Pablo Ryan
- Hospital Universitario Infanta Leonor, Madrid, Spain
- Universidad Complutense de Madrid, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
| | - Jorge Valencia
- Hospital Universitario Infanta Leonor, Madrid, Spain
- Unidad de Reducción de Daños Servicio Móvil de Atención Sociosanitaria y Derivación a tratamiento, Madrid, Spain
| | - Daniel Sepúlveda-Crespo
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Unidad de Infección e Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Rafael Amigot-Sánchez
- Unidad de Infección e Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | | | - Jeffrey V. Lazarus
- Barcelona Institute for Global Health, Hospital Clínic, University of Barcelona, Barcelona, Spain
- Graduate School of Public Health and Health Policy, City University of New York, New York, New York
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Felipe Pérez-García
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Servicio de Microbiología Clínica, Hospital Universitario Príncipe de Asturias, Madrid, Spain
- Departamento de Biomedicina y Biotecnología, Facultad de Medicina, Universidad de Alcalá, Madrid, Spain
| | - Isidoro Martínez
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Unidad de Infección e Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Salvador Resino
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Unidad de Infección e Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
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Noskov S, Arefeva A, Radaeva K, Makarenko I, Gefen M, Drai R. Bioequivalence Study of Velpatasvir/Sofosbuvir Oral Coated Tablets in Healthy Volunteers Under Fasting Conditions. Clin Pharmacol Drug Dev 2024; 13:1123-1129. [PMID: 38881205 DOI: 10.1002/cpdd.1435] [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: 03/19/2024] [Accepted: 05/14/2024] [Indexed: 06/18/2024]
Abstract
This study was conducted as a single-site, open-label, randomized, replicated crossover trial with 4 treatment periods. The aim was to evaluate the bioequivalence of a generic test drug containing velpatasvir and sofosbuvir compared to an established brand-name medication in healthy White subjects under fasting conditions. Blood samples were collected at specified intervals up to 72 hours after dosing to measure the concentrations of velpatasvir and sofosbuvir using a certified high-performance liquid chromatography with tandem mass spectrometry method. The bioequivalence of the 2 formulations was confirmed when statistical analysis showed that confidence intervals for the log-transformed peak concentration and area under the concentration-time curve from time 0 to the last quantifiable sample were within an acceptable range from 80% to 125%. Criteria for bioequivalence were met for both area under the concentration-time curve from time 0 until the last quantifiable sample and peak concentration parameters. No adverse effects were reported during this trial in both groups.
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Affiliation(s)
| | | | | | | | - Maria Gefen
- R&D Center, GEROPHARM, Saint-Petersburg, Russia
| | - Roman Drai
- R&D Center, GEROPHARM, Saint-Petersburg, Russia
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17
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Simão M, Gonçalves C. Hepatitis C Virus Infection in Europe. Pathogens 2024; 13:841. [PMID: 39452713 PMCID: PMC11510056 DOI: 10.3390/pathogens13100841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 09/24/2024] [Accepted: 09/27/2024] [Indexed: 10/26/2024] Open
Abstract
The Hepatitis C Virus (HCV) is a significant public health challenge in European countries. Historically, healthcare-related procedures were the primary source of HCV infection in Europe. However, with the implementation of blood safety programs, injection drug use has become the main transmission route. The infection's distribution and genotype prevalence vary widely across the continent. Even with the availability of highly effective direct-acting antiviral (DAA) therapies, HCV infection is far from being controlled. A significant proportion of patients remain undiagnosed, contributing to the ongoing transmission of the virus. Additionally, several barriers hinder the widespread use of DAAs, including high treatment costs, stigma, poor linkage to care, and considerable geographical variations in prevalence and transmission routes. The World Health Organization has set ambitious targets to reduce liver-related deaths, decrease new viral hepatitis infections, and ensure that 90% of infected individuals are diagnosed by 2030. However, most European countries face challenges, highlighting the need for screening programs, funding mechanisms, and public health strategies to effectively control HCV infection in Europe.
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Affiliation(s)
| | - Cristina Gonçalves
- Pediatric Gastrenterology and Hepatology Unit, Pediatric Hospital Dona Estefânia, ULS S. José, 1169-045 Lisbon, Portugal
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18
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Sinclair S, Shearen S, Ghobrial Y, Trad G, Abdul Basit S, Shih D, Ryan JK. Review of the Effects of Antiviral Therapy on Hepatitis B/C-Related Mortality and the Regression of Fibrosis. Viruses 2024; 16:1531. [PMID: 39459866 PMCID: PMC11512229 DOI: 10.3390/v16101531] [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: 08/16/2024] [Revised: 09/19/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatitis B and Hepatitis C are viral causes of Hepatitis that lead to significant worldwide mortality and morbidity through the sequelae of fibrosis and hepatocellular carcinoma. In this review, we have summarized recent studies that have examined the effects of antiviral therapy on the regression of fibrosis and the reduction in mortalities associated with the viruses. Antiviral therapy significantly decreases mortality and induces the regression of fibrosis.
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Affiliation(s)
| | | | | | | | | | | | - John K. Ryan
- Comprehensive Digestive Institute of Nevada, Las Vegas, NV 89148, USA (S.A.B.); (D.S.)
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19
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Wasitthankasem R, Aiewsakun P, Lapchai S, Raksayot M, Keeratipusana C, Jarupund P, Nakhonsri V, Pimsing N, Tongsima S, Poovorawan Y. Historical drivers of HCV Subtypes 1b and 3a in Thailand and 6f in Phetchabun, an HCV endemic area of the country. Virus Evol 2024; 10:veae079. [PMID: 39386077 PMCID: PMC11463029 DOI: 10.1093/ve/veae079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 07/18/2024] [Accepted: 09/10/2024] [Indexed: 10/12/2024] Open
Abstract
The World Health Organization has set a target to eliminate viral hepatitis as a public threat by 2030. In pursuit of this goal, Thailand initiated a hepatitis C virus (HCV) microelimination project targeting Phetchabun province, a well-recognized high-burden HCV endemic area. However, the historical transmission dynamics of HCV in Phetchabun, and in Thailand in general, remain unclear. This study investigates the epidemic histories of HCV in Phetchabun, focusing on Subtypes 1b, 3a, and 6f, and their relationship with HCV in other regions of Thailand, using molecular phylogenetic analyses. Our results reveal nationwide the presence of Subtypes 1b and 3a, while Subtype 6f is mainly confined to Phetchabun. The initial spread of Subtype 1b was inferred to coincide with World War II and the period of suboptimal medical and hygienic standards in Thai blood transfusion services, suggesting a correlation between the two. The early expansion of Subtype 3a was, on the other hand, found to correlate with the epidemic of intravenous drug use in Thailand during the time of Vietnam War. The early expansion of Subtype 6f, in contrast, appears to coincide with the period of severe regional political conflict and social and economic instability. All these findings suggest the complex interplay between social determinants of health and HCV transmission. Post the mid-1990s/early 2000s, all subtypes showed significantly reduced population growth rates, aligning with improvements in blood transfusion safety standards, the nationwide "War on Drugs" policy, and enhanced accessibility to public healthcare and HCV treatments. These combined efforts likely have contributed to curbing the spread of HCV in Thailand. Nevertheless, our analyses reveal that the prevalence of HCV in Thailand remains high overall, emphasizing the need for further research and a nationwide approach to more effectively reduce the HCV burden in Thailand.
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Affiliation(s)
- Rujipat Wasitthankasem
- National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 144 Thailand Science Park (TSP), Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand
| | - Pakorn Aiewsakun
- Department of Microbiology, Faculty of Science, Mahidol University, 272 Rama VI Road, Thung Phaya Thai, Ratchathewi, Bangkok 10400, Thailand
- Pornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, 272 Rama VI Road, Thung Phaya Thai, Ratchathewi, Bangkok 10400, Thailand
| | - Sutthinee Lapchai
- National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 144 Thailand Science Park (TSP), Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand
| | - Maneerat Raksayot
- National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 144 Thailand Science Park (TSP), Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand
| | - Chantisa Keeratipusana
- National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 144 Thailand Science Park (TSP), Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand
| | - Pakawat Jarupund
- National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 144 Thailand Science Park (TSP), Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand
| | - Vorthunju Nakhonsri
- National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 144 Thailand Science Park (TSP), Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand
| | - Napaporn Pimsing
- Phetchabun Provincial Public Health Office, 72 Nikorn Bamrung Road, Nai Mueang, Mueang Phetchabun, Phetchabun 67000, Thailand
| | - Sissades Tongsima
- National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 144 Thailand Science Park (TSP), Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, 1873, Rama IV Road, Pathumwan, Bangkok 10330, Thailand
- Fellow of Royal Society of Thailand (FRS(T)), the Royal Society of Thailand, Sanam Sueapa, Sri Ayudhya Road, Dusit, Bangkok 10300, Thailand
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Njifon AM, Modiyinji AF, Monamele CG, Mbouyap PR, Ngono L, Tagnouokam-Ngoupo PA, Lissock SF, Zekeng MR, Assam JPA, Njouom R. A decade-long retrospective study of hepatitis C virus genetic diversity in Cameroon, 2013-2023: presence of a high proportion of unsubtypable and putative recombinant HCV strains. Arch Virol 2024; 169:197. [PMID: 39256207 DOI: 10.1007/s00705-024-06124-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 07/22/2024] [Indexed: 09/12/2024]
Abstract
While treatment options for hepatitis C virus (HCV) infection have expanded considerably over the past decade thanks to the development of pan-genotypic therapies, genotype testing remains a prerequisite for treatment in sub-Saharan African countries, including Cameroon, where multiple HCV genotypes and subtypes exist. The main objective of this study was to describe the trend in the distribution of HCV genotypes and subtypes from 2013 to 2023 in the Cameroonian population. Viral loads were determined using the Abbott real-time assay, and genotyping/subtyping was based on nested and semi-nested reverse transcription polymerase chain reaction (RT-PCR) amplification of the regions encoding the core and non-structural protein 5B (NS5B) regions, respectively, followed by sequencing and phylogenetic analysis. A total of 512 patients with NS5B and core sequencing results were included in our study. Genotyping revealed a predominance of both genotype 4 (38.48%) and genotype 1 (37.11%), followed by genotype 2, detected in 22.46% of patients. Interestingly, 10 samples (1.95%) had discordant genotypes in both regions, suggesting the presence of putative recombinant forms of HCV. Twelve different subtypes were detected during the study period, with a predominance of subtypes 4f (18.95%) and 1e (16.02%). Furthermore, phylogenetic analysis failed to assign a subtype to a relatively high proportion of sequences (38.67%) for the two genomic regions, and their classification was limited to genotype assignment. The frequency distribution of HCV genotypes did not show any statistical difference according to year or sex. These results confirm the genetic diversity of HCV in Cameroon and the potential for the generation of recombinant strains.
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Affiliation(s)
- Aristide Mounchili Njifon
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
- Department of Microbiology, Faculty of Sciences, University of Yaounde I, P.O. Box 337, Yaoundé, Cameroon
| | - Abdou Fatawou Modiyinji
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | - Chavely Gwladys Monamele
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | - Pretty Rose Mbouyap
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | - Laure Ngono
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | | | - Simon Frederic Lissock
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | - Martin Ridole Zekeng
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | - Jean Paul Assam Assam
- Department of Microbiology, Faculty of Sciences, University of Yaounde I, P.O. Box 337, Yaoundé, Cameroon
| | - Richard Njouom
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon.
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21
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Sarıkaya B, Yatar İD, Yılmaz S, Tiryaki Y, Sarıkaya VA, Çetinkaya RA, Kırkık D. The usefulness of anti-HCV signal to cut-off ratio in predicting hepatitis C viremia and the effect of genotype differences on signal to cut-off ratio. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2024; 70:e20240370. [PMID: 39230144 PMCID: PMC11370746 DOI: 10.1590/1806-9282.20240370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 05/27/2024] [Indexed: 09/05/2024]
Abstract
OBJECTIVE In the hepatitis C virus (HCV) diagnostic algorithm, an anti-HCV screening test is recommended first. In countries with low HCV prevalence, anti-HCV testing can often give false-positive results. This may lead to unnecessary retesting, increased costs, and psychological stress for patients. METHODS In this study, the most appropriate S/Co (signal-cutoff) value to predict HCV viremia in anti-HCV test(+) individuals was determined, and the effect of genotype differences was evaluated. Of the 96,515 anti-HCV tests performed between 2020 and 2023, 934 were reactive. A total of 332 retests and 65 patients without HCV-ribonucleic acid (RNA) analysis were excluded. Demographic data were calculated for 537 patients, and 130 patients were included in the study. RESULTS The average age of 537 patients was 55±18 years, and 57.1% were women. The anti-HCV positivity rate was 0.62% (602/96,515), and the actual anti-HCV positivity rate was 0.13% (130/96,515). Anti-HCV levels were higher in HCV-RNA(+) patients than in HCV-RNA-negative individuals (p<0.0001) (Table 1). Receiver operating characteristic curve analysis identified the optimal S/Co value to be 10.86 to identify true positive cases. Sensitivity was 96.1%, specificity was 61.2%, positive predictive value (PPV) was 44.2%, and negative predictive value (NPV) was 98% (Figure 2). A total of 107 (82.3%) of the patients were identified as GT1, and the most common subtype was GT1b (n=100). CONCLUSION If anti-HCV S/Co is ≥10.86, direct HCV RNA testing may be recommended; However, the possibility of false positivity should be considered in patients with a S/Co value below 10.86.
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Affiliation(s)
- Burak Sarıkaya
- University of Health Sciences, Sultan 2. Abdulhamid Han Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology – İstanbul, Turkey
| | - İrem Demiralp Yatar
- University of Health Sciences, Sultan 2. Abdulhamid Han Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology – İstanbul, Turkey
| | - Soner Yılmaz
- Gülhane Training and Research Hospital, Regional Blood Center – Ankara, Turkey
| | - Yasin Tiryaki
- University of Health Sciences, Sultan 2. Abdulhamid Han Training and Research Hospital, Department of Medical Microbiology – İstanbul, Turkey
| | - Vahibe Aydın Sarıkaya
- Haydarpaşa Numune Training and Research Hospital, Department of Infectious Diseases and Clinical Microbiology – İstanbul, Turkey
| | - Rıza Aytaç Çetinkaya
- Reyap Health Group, Department of Infectious Diseases and Clinical Microbiology – İstanbul, Turkey
| | - Duygu Kırkık
- University of Health Sciences, Hamidiye Medicine Faculty, Department of Medical Biology – İstanbul, Turkey
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22
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Nakano S, Suzuki M, Hatori R, Mizuochi T, Etani Y, Tajiri H. Natural history and clinical features of hepatitis C virus infection during childhood: A nationwide, observational survey in Japan. Hepatol Res 2024; 54:795-806. [PMID: 38459826 DOI: 10.1111/hepr.14032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 01/26/2024] [Accepted: 02/12/2024] [Indexed: 03/10/2024]
Abstract
AIM Few data on spontaneous clearance rates of cases of mother-to-child transmission of hepatitis C viral (HCV) infection are available in Japan. Furthermore, the treatment courses of interferon-based and direct-acting antiviral agent (DAA) therapies for children are also unclear. Our aim was thus to clarify the long-term natural progression of HCV infection and the treatment outcomes of children in Japan. METHODS We conducted a combined multicenter, observational survey involving 65 pediatric institutions in Japan. Pediatric HCV infection cases with patients born between 1973 and 2021 were collected over the 11-year period from 2012 to 2022. A total of 563 patients were enrolled, with 190 excluded for having insufficient laboratory data or treatment information, resulting in 373 eligible cases. RESULTS Of 328 cases of mother-to-child infection, 34 (10.4%) had spontaneous clearance, with a median time to spontaneous clearance of 3.1 years (range 0.9-7.2 years). Of the total 373 eligible cases, 190 received antiviral therapy (interferon-based therapy, 158; DAA therapy, 32). Sustained virologic response rates after first-line treatment were 75.3% (119/158) and 100% (32/32) for interferon-based therapy and DAA therapy, respectively, with the DAA group showing a shorter time from therapy initiation to viral negativity (2.7 vs. 1.0 months; p = 0.0031). CONCLUSIONS Approximately 10% of Japanese children infected by mother-to-child transmission achieve spontaneous resolution of HCV infection. Our findings indicate that DAA therapy is safe and highly effective in Japanese children, achieving higher sustained virologic response rates and shorter time to clearance of the virus compared with interferon-based therapy.
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Affiliation(s)
- Satoshi Nakano
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Reiko Hatori
- Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Tatsuki Mizuochi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Yuri Etani
- Department of Gastroenterology, Nutrition and Endocrinology, Research Institute Osaka Women's and Children's Hospital, Osaka, Japan
| | - Hitoshi Tajiri
- Department of Pediatrics, Wakayama Medical University, Wakayama, Japan
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Zhang J, Qian J. Advances in Computational Intelligence-Based Methods of Structure and Function Prediction of Proteins. Biomolecules 2024; 14:1083. [PMID: 39334850 PMCID: PMC11430421 DOI: 10.3390/biom14091083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 08/26/2024] [Indexed: 09/30/2024] Open
Abstract
Proteins serve as the building blocks of life and play essential roles in almost every cellular process [...].
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Affiliation(s)
- Jian Zhang
- School of Computer and Information Technology, Xinyang Normal University, Xinyang 464000, China;
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24
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Cao X, Chen Y, Chen Y, Jiang M. The Role of Tripartite Motif Family Proteins in Chronic Liver Diseases: Molecular Mechanisms and Therapeutic Potential. Biomolecules 2024; 14:1038. [PMID: 39199424 PMCID: PMC11352684 DOI: 10.3390/biom14081038] [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: 07/11/2024] [Revised: 08/20/2024] [Accepted: 08/20/2024] [Indexed: 09/01/2024] Open
Abstract
The worldwide impact of liver diseases is increasing steadily, with a consistent upswing evidenced in incidence and mortality rates. Chronic liver diseases (CLDs) refer to the liver function's progressive deterioration exceeding six months, which includes abnormal clotting factors, detoxification failure, and hepatic cholestasis. The most common etiologies of CLDs are mainly composed of chronic viral hepatitis, MAFLD/MASH, alcoholic liver disease, and genetic factors, which induce inflammation and harm to the liver, ultimately resulting in cirrhosis, the irreversible final stage of CLDs. The latest research has shown that tripartite motif family proteins (TRIMs) function as E3 ligases, which participate in the progression of CLDs by regulating gene and protein expression levels through post-translational modification. In this review, our objective is to clarify the molecular mechanisms and potential therapeutic targets of TRIMs in CLDs and provide insights for therapy guidelines and future research.
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Affiliation(s)
- Xiwen Cao
- The Queen Mary School, Jiangxi Medical College, Nanchang University, 999 Xuefu Road, Nanchang 330031, China;
| | - Yinni Chen
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, 999 Xuefu Road, Nanchang 330031, China;
| | - Yuanli Chen
- Key Laboratory of Major Metabolic Diseases, Nutritional Regulation of Anhui Department of Education, College of Food and Biological Engineering, Hefei University of Technology, Hefei 230002, China;
| | - Meixiu Jiang
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, 999 Xuefu Road, Nanchang 330031, China;
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25
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Qureshi H, Mahmood H, Nasir Z, Siddique S, Averhoff F, Cloherty G. A novel test and treat program for hepatitis C virus infection utilizing HCV core antigen testing, among police and general population, Islamabad, Pakistan, 2022. J Viral Hepat 2024; 31:500-503. [PMID: 38771312 DOI: 10.1111/jvh.13953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 04/18/2024] [Accepted: 05/05/2024] [Indexed: 05/22/2024]
Abstract
Hepatitis C virus core antigen (HCVcAg) testing can simplify and decrease costs of HCV infection confirmation compared to molecular testing (nucleic acid testing). We piloted HCVcAg testing for the confirmation of active infection. The study was conducted during June through December 2022 among the police and the general population of Islamabad, Pakistan age 18 years and older. Initial screening for HCV antibody was conducted using a rapid diagnostic test (RDT) for all consenting participants. Those who tested positive had venous blood samples tested for HCVcAg, platelets and aspartate aminotransferase (AST). Persons with HCVcAg values ≥3 fmol/L were defined as viremic, and they were offered treatment with direct acting antiviral (DAA) medications, sofosbuvir and daclatasvir. Aspartate aminotransferase to platelet ratio index (APRI) was calculated for each HCV infected person, and those with an APRI score <1.5 received treatment for 12 weeks, while those with APRI ≥ to 1.5 received 24 weeks of treatment. A total of 15,628 persons were screened for anti-HCV using RDT and 643 (4.1%) tested positive. HCVcAg values of ≥3 fmol/L was found in 399/643 (62.1%), and all were offered and accepted treatment. Of those treated, 273/399 (68.4%) returned for a follow-up SVR and HCVcAg was not detected in 261/273, a 95.6% cure rate. The pilot study demonstrated the effectiveness of reaching and treating an urban population using RDT for screening and HCVcAg for confirmation of infection and test of cure.
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Affiliation(s)
- Huma Qureshi
- National Focal Point Hepatitis for Pakistan, Islamabad, Pakistan
| | - Hassan Mahmood
- Hepatitis Planning, Development and Monitoring Unit (PDMU), Islamabad, Pakistan
| | | | - Saad Siddique
- Core Diagnostics, Abbott Pakistan, Karachi, Pakistan
| | - Francisco Averhoff
- Infectious Disease Research Abbott and the Abbott Pandemic Defense Coalition (APDC), Abbott Park, IL, USA
| | - Gavin Cloherty
- Infectious Disease Research Abbott and the Abbott Pandemic Defense Coalition (APDC), Abbott Park, IL, USA
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Fajar S, Dwi SP, Nur IS, Wahyu AP, Sukamto S M, Winda AR, Nastiti W, Andri F, Firzan N. Zebrafish as a model organism for virus disease research: Current status and future directions. Heliyon 2024; 10:e33865. [PMID: 39071624 PMCID: PMC11282986 DOI: 10.1016/j.heliyon.2024.e33865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 06/22/2024] [Accepted: 06/28/2024] [Indexed: 07/30/2024] Open
Abstract
Zebrafish (Danio rerio) have emerged as valuable models for investigating viral infections, providing insights into viral pathogenesis, host responses, and potential therapeutic interventions. This review offers a comprehensive synthesis of research on viral infections using zebrafish models, focusing on the molecular mechanisms of viral action and host-virus interactions. Zebrafish models have been instrumental in elucidating the replication dynamics, tissue tropism, and immune evasion strategies of various viruses, including Chikungunya virus, Dengue virus, Herpes Simplex Virus type 1, and Influenza A virus. Additionally, studies utilizing zebrafish have evaluated the efficacy of antiviral compounds and natural agents against emerging viruses such as SARS-CoV-2, Zika virus, and Dengue virus. The optical transparency and genetic tractability of zebrafish embryos enable real-time visualization of viral infections, facilitating the study of viral spread and immune responses. Despite challenges such as temperature compatibility and differences in host receptors, zebrafish models offer unique advantages, including cost-effectiveness, high-throughput screening capabilities, and conservation of key immune pathways. Importantly, zebrafish models complement existing animal models, providing a platform for rapid evaluation of potential therapeutics and a deeper understanding of viral pathogenesis. This review underscores the significance of zebrafish research in advancing our understanding of viral diseases and highlights future research directions to combat infectious diseases effectively.
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Affiliation(s)
- Sofyantoro Fajar
- Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
| | - Sendi Priyono Dwi
- Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
| | | | | | - Mamada Sukamto S
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, 90245, Indonesia
| | | | - Wijayanti Nastiti
- Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
| | - Frediansyah Andri
- Research Center for Food Technology and Processing (PRTPP), National Research and Innovation Agency (BRIN), Yogyakarta 55861, Indonesia
| | - Nainu Firzan
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, 90245, Indonesia
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27
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Rautela A, Raj N, Verma A, Agarwal J, Verma P, Garg J. Clinicoepidemiology and Diagnosis of Hepatitis C: Evaluating HCV Core Antigen Assay as a Diagnostic Tool in a Tertiary Care Teaching Hospital of North India. Euroasian J Hepatogastroenterol 2024; 14:176-181. [PMID: 39802859 PMCID: PMC11714113 DOI: 10.5005/jp-journals-10018-1446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 08/21/2024] [Indexed: 01/16/2025] Open
Abstract
Introduction One of the main causes of primary hepatocellular carcinoma and chronic hepatitis is the hepatitis C virus (HCV), with significant variability in its genotypes affecting pathogenicity and treatment outcomes. In India, prevalence ranges from 0.5 to 1.5%, with certain regions showing higher rates. Diagnostic methods include serological and molecular assays, with the HCV core antigen (HCV cAg) assay emerging as a cost-effective substitute for HCV RT-PCR testing. Materials and methods This study enrolled 292 suspected hepatitis cases from May 2019 to May 2020 in a North Indian tertiary care institute. Demographic, biochemical, and clinical data were collected. Seroprevalence was determined using QualisaTM HCV ELISA. Sixty seronegative and 30 seropositive samples underwent HCVc-Ag testing and HCV RT-PCR. Genotyping was carried out using AmpliSens® HCV-genotype PCR kit. The HCV core antigen assay was evaluated by taking HCV RT-PCR as the gold standard test. Results Of the 292 patients, 98 (30%) were seropositive for HCV, predominantly in the 40-59 age-group. Surgery and blood transfusion were significant risk factors. Co-infections included human immunodeficiency virus (HIV) (3.06%) and hepatitis B virus (HBV) (6.12%). Genotype 3a was the most prevalent. HCV core antigen assay showed 93.75% sensitivity, 93.10% specificity, 88.24% positive predictive value, 96.43% negative predictive value, and 93.33% accuracy. Conclusion Hepatitis C virus core antigen is a dependable and economical substitute to HCV RT-PCR for diagnosing HCV infection. Regular screening in high-risk groups is essential for early detection and prevention. How to cite this article Rautela A, Raj N, Verma A, et al. Clinicoepidemiology and Diagnosis of Hepatitis C: Evaluating HCV Core Antigen Assay as a Diagnostic Tool in a Tertiary Care Teaching Hospital of North India. Euroasian J Hepato-Gastroenterol 2024;14(2):176-181.
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Affiliation(s)
- Apurva Rautela
- Department of Microbiology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Nikhil Raj
- Department of Microbiology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Ashish Verma
- Department of Microbiology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Jyotsna Agarwal
- Department of Microbiology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Prashant Verma
- Department of Gastromedicine, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Jaya Garg
- Department of Microbiology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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28
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Siaw ADJ, Amugsi J, Owusu-Konadu MAA, Drah ST, Imbeah EG, Oduro-Donkor D, Duah A, Nartey YA. Prevalence and risk factors of Hepatitis C virus infection in the Upper East Region of Ghana; a community-based cross-sectional study. PLoS One 2024; 19:e0306292. [PMID: 38941280 PMCID: PMC11213332 DOI: 10.1371/journal.pone.0306292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 06/14/2024] [Indexed: 06/30/2024] Open
Abstract
Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and risk factors remain limited in sub-Saharan Africa. In Ghana, HCV-related deaths are estimated to have increased since 2015. Risk factors associated with HCV infection in Ghana are not well described. The aim of this study was to determine the prevalence of, and risk factors associated with hepatitis C virus infection in the Upper East Region located in the northern part of Ghana. A community-based cross-sectional study was conducted in 9 communities in the Upper East region of Ghana. A total of 1,769 participants aged ≥12 years were screened for HCV antibody (anti-HCV) using rapid diagnostic testing (RDT). Seventy-four participants undertook HCV RNA testing after a positive anti-HCV result. Multivariate logistic regression was used to determine risk factors associated with HCV seropositivity. The anti-HCV prevalence was 8.4%, with 149 out of 1,769 testing anti-HCV positive. Mean age (±SD) of seropositive persons was 45.4 (±16.3) years. The highest anti-HCV seroprevalence was amongst persons aged 60 years and above. Forty-four out of 74 (59.5%) seropositive cases had viremic infection and the estimated viremic prevalence in the screened population was 5.0%. Predictors of HCV seropositivity were age (OR 1.03 95% CI 1.01-1.04), history of female genital mutilation or circumcision (OR 1.63 95% CI 1.04-2.55), sexual activity (OR 2.57 95% CI 1.38-4.79), positive maternal HCV status (OR 10.38 95% CI 4.13-26.05) and positive HIV status (OR 4.03 95% CI 1.35-12.05). In conclusion, the Upper East Region demonstrates a high Hepatitis C antibody prevalence. Almost 60% of individuals have viremic infection, however the cost of RNA testing is a barrier to virological diagnosis. There is a need to educate the population about HCV-associated risk factors to reduce HCV transmission and burden of disease.
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Affiliation(s)
- Ampem Darko Jnr Siaw
- Department of Internal Medicine, Cape Coast Teaching Hospital, Cape Coast, Ghana
| | - James Amugsi
- Out-patient Department, Sandema Hospital, Sandema, Ghana
| | | | - Samuel Teye Drah
- Department of Internal Medicine, Ledzokuku-Krowor Municipal Assembly Hospital, Accra, Ghana
| | | | - Dominic Oduro-Donkor
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Coventry, United Kingdom
| | - Amoako Duah
- Department of Medicine, University of Ghana Medical Centre, Accra, Ghana
| | - Yvonne Ayerki Nartey
- Department of Internal Medicine, Cape Coast Teaching Hospital, Cape Coast, Ghana
- Department of Internal Medicine and Therapeutics, University of Cape Coast, School of Medical Sciences, Cape Coast, Ghana
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29
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Coppola N, Alessio L, De Pascalis S, Macera M, Di Caprio G, Messina V, Onorato L, Minichini C, Stanzione M, Stornaiuolo G, Starace M, Monari C, Calò F, Sagnelli C, Pisaturo M. Effectiveness of test-and-treat model with direct-acting antiviral for hepatitis C virus infection in migrants: a prospective interventional study in Italy. Infect Dis Poverty 2024; 13:39. [PMID: 38802954 PMCID: PMC11131219 DOI: 10.1186/s40249-024-01200-9] [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: 11/13/2023] [Accepted: 04/23/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND Migrants, mainly undocumented and low-income refugees, are at high risk of hepatitis C virus (HCV) infection, but are a difficult-to-reach and to-treat population. The aim of the study was to evaluate the effectiveness of a test and treat model with direct-acting antiviral for HCV infection in these migrants coming from low-income and living in southern Italy. METHODS A prospective, multicenter, collaborative study based on a four-phase-program (educational counseling, screening, linkage-to-care and treatment) was designed in southern Italy; the study started in June 2018, was stopped in February 2020 because of the outbreak of SARS-CoV2 infection in Italy and was resumed in February 2021 until November 2021. After educational counseling on infectious diseases that are transmitted through blood or sexually pseudonymized HCV screening was offered to all undocumented migrants and low-income refugees observed at one of the 1st level clinical centers. The HCV-RNA-positive subjects were referred to one of the 3rd level units of Infectious Diseases (ID) and treated with a 12-week course of sofosbuvir-velpatasvir and observed for 12 weeks after the end of direct antiviral agents (DAA) treatment. STATISTICAL ANALYSIS For the descriptive analysis, the categorical variables were reported as absolute numbers and relative frequencies. Continuous variables were summarized as mean and standard deviation (SD) if normally distributed, or as a median and interquartile range (IQR) if not normally distributed. We used Pearson chi-square or Fisher's exact test for categorical variables and Student's t test or Mann-Whitney test for continuous variables. A P value < 0.05 was considered to be statistically significant. Analyses were performed with SPSS 21.0. RESULTS Of the 3501migrants observed in the study period, 3417 (97.6%) agreed to be screened; 185 (4.7%) were anti-HCV-positive and, of these, 53 (28.6%) were HCV-RNA-positive. Of these 53 subjects, 48 (90.5%) were referred to an ID unit and started DAA treatment. The HCV-RNA-positive-subjects were older [median 36 years (IQR: 32-21) vs 27.19 (IQR: 30.5-19.25); P = 0.001], and less frequently males [35 (66.03 %) vs 119 (90.1%), P < 0 .0001] than seronegative participants. They more frequently came from Eastern Europe (70.8%) stayed longer in Italy [months of stay in Italy, mean ± SD: 51.02 ± 52.84 vs 25.7 ± 42.65, P = 0.001], and had more years of schooling [years of schooling, mean ± SD: 9.61±2.81 vs 7.10 ± 4, P = 0.0001]. HCV-RNA-positive-subjects less frequently reported piercing, tattoos and tribal scars as risk factors (23.6%). Of these 48 HCV RNA positive subjects who started DAA, 47 (97.9%) showed a sustained virological response and one dropped-out in follow-up after DAA treatment. No subject had any adverse event. CONCLUSIONS This model of HCV screening and linkage to care seems effective to eliminate HCV infectionin a difficult-to-reach and to-treat population, such as undocumented migrants and low-income refugees. The participation of cultural mediators in the study made possible a better interaction between migrants and physicians, as is evident from the large number of subjects enrolled. Eliminating HCV among migrants will have a long-term positive impact from a public health and healthcare perspective by reducing the number of individuals who potentially develop HCV-related complications such as liver cirrhosis and hepatocellular carcinoma and reducing the circulation of HCV in the regions that host them which often, as in the case of Italy, are low endemic for HCV infection.
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Affiliation(s)
- Nicola Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, " Former Canapificio Social Centre ", Caserta, Italy
| | - Loredana Alessio
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, " Former Canapificio Social Centre ", Caserta, Italy
- Medical Center, "Abraham's Tent" Reception Center, Caserta, Italy
| | - Stefania De Pascalis
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Margherita Macera
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, " Former Canapificio Social Centre ", Caserta, Italy
| | - Giovanni Di Caprio
- Medical Center, " Former Canapificio Social Centre ", Caserta, Italy
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Vincenzo Messina
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Lorenzo Onorato
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, " Former Canapificio Social Centre ", Caserta, Italy
| | - Carmine Minichini
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Maria Stanzione
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Gianfranca Stornaiuolo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Mario Starace
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Caterina Monari
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Federica Calò
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical Center, Center for the Protection of the Health of Immigrants, Naples, Italy
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
- Medical center, Center for the Missionary Sisters of Charity, Naples, Italy
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy.
- Medical Center, " Former Canapificio Social Centre ", Caserta, Italy.
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30
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Sallam M, Khalil R. Contemporary Insights into Hepatitis C Virus: A Comprehensive Review. Microorganisms 2024; 12:1035. [PMID: 38930417 PMCID: PMC11205832 DOI: 10.3390/microorganisms12061035] [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: 04/30/2024] [Revised: 05/15/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024] Open
Abstract
Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030.
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Affiliation(s)
- Malik Sallam
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
- Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman 11942, Jordan
| | - Roaa Khalil
- Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan
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Li H, Huang H, Huang W, Du M, Long D, Xu G, Mei W, Huang K. Hepatitis C virus subtype diversity and transmission clusters characteristics among drug users in Zhuhai, South China. BMC Infect Dis 2024; 24:451. [PMID: 38685009 PMCID: PMC11057121 DOI: 10.1186/s12879-024-09323-y] [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: 10/25/2023] [Accepted: 04/15/2024] [Indexed: 05/02/2024] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection poses a major public health challenge globally, especially among injecting drug users. China has the world's largest burden of HCV infections. However, little is known about the characteristics of transmission networks among drug user populations. This study aims to investigate the molecular epidemiology and transmission characteristics of HCV infections among drug users in Zhuhai, a bustling port city connecting Mainland China and its Special Administrative Regions. METHODS Participants enrolled in this study were drug users incarcerated at Zhuhai's drug rehabilitation center in 2015. Their sociodemographic and behavioral information, including gender, promiscuity, drug use method, and so forth, was collected using a standardized questionnaire. Plasmas separated from venous blood were analyzed for HCV infection through ELISA and RT-PCR methods to detect anti-HCV antibodies and HCV RNA. The 5'UTR fragment of the HCV genome was amplified and further sequenced for subtype identifications and phylogenetic analysis. The phylogenetic tree was inferred using the Maximum Likelihood method based on the Tamura-Nei model, and the transmission cluster network was constructed using Cytoscape3.8.0 software with a threshold of 0.015. Binary logistic regression models were employed to assess the factors associated with HCV infection. RESULTS The overall prevalence of HCV infection among drug users was 44.37%, with approximately 19.69% appearing to clear the HCV virus successfully. Binary logistic regression analysis revealed that those aged over 40, engaging in injecting drug use, and being native residents were at heightened risk for HCV infection among drug user cohorts. The predominant HCV subtypes circulating among those drug users were 6a (60.26%), followed by 3b (16.7%), 3a (12.8%), 1b (6.41%) and 1a (3.85%), respectively. Molecular transmission network analysis unveiled the presence of six transmission clusters, with the largest propagation cluster consisting of 41 individuals infected with HCV subtype 6a. Furthermore, distinct transmission clusters involved eight individuals infected with subtype 3b and seven with subtype 3a were also observed. CONCLUSION The genetic transmission networks revealed a complex transmission pattern among drug users in Zhuhai, emphasizing the imperative for a targeted and effective intervention strategy to mitigate HCV dissemination. These insights are pivotal for shaping future national policies on HCV screening, treatment, and prevention in port cities.
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Affiliation(s)
- Hongxia Li
- Zhuhai Center for Disease Control and Prevention, Zhuhai, Guangdong, China
- School of Public Health, Jinan University, Guangzhou, Guangdong, China
| | - Huitao Huang
- Zhuhai Center for Disease Control and Prevention, Zhuhai, Guangdong, China
| | - Wenyan Huang
- Zhuhai Center for Disease Control and Prevention, Zhuhai, Guangdong, China
| | - Man Du
- Zhuhai Center for Disease Control and Prevention, Zhuhai, Guangdong, China
| | - Dongling Long
- Zhuhai Center for Disease Control and Prevention, Zhuhai, Guangdong, China
| | - Guangxian Xu
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, China.
| | - Wenhua Mei
- Zhuhai Center for Disease Control and Prevention, Zhuhai, Guangdong, China.
- School of Public Health, Jinan University, Guangzhou, Guangdong, China.
| | - Kaisong Huang
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, China.
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Sistayanarain A, Kunthalert D. Molecular characterization of the nonstructural 5A (NS5A) region of hepatitis C virus in Thai blood donors. Arch Microbiol 2024; 206:215. [PMID: 38619622 DOI: 10.1007/s00203-024-03950-4] [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: 02/16/2024] [Revised: 03/27/2024] [Accepted: 04/01/2024] [Indexed: 04/16/2024]
Abstract
Direct acting antivirals (DAAs) have been developed for hepatitis C virus (HCV) therapy, and they are usually effective, however resistance to DAA regimens has also been reported to have a significant impact. Resistance associated substitutions (RASs) in the NS5A region are known to be correlated with failure of DAA therapy. HCV genotypes 3a and 1 are the most prevalent genotypes in Thailand. This study analyzed the type and frequency of RASs associated with DAA failure, focusing on the NS5A region. Serum samples of HCV genotype 3a, 1a, and 1b infection from Thai blood donors were selected. The NS5A region was amplified using reverse transcription-polymerase chain reaction (RT-PCR). A phylogenetic tree was constructed to identify the genotypes of HCV. Nucleotide sequencing and amino acid sequencing were conducted to determine the prevalence of RASs. Construction of the phylogenetic tree indicated that 29 samples were genotype 3a, 11 samples were genotype 1a, and 9 were genotype 1b. Both HCV genotypes 1a and 3a can be categorized into two subclades. Results showed that the NS5A substitutions A30V/K, A62T/V/I/M/P/S/L, and S98G were present in HCV genotype 3a. In HCV genotype 1a, only NS5A RASs H54Y was detected. NS5A amino acid substitutions Q54H and P58L were found in HCV genotype 1b. In conclusion, NS5A RASs at amino acid positions 30, 62, 54, 58, and 98 are present within HCV genotypes 3a and 1. While keeping in mind that additional information was not available on the anonymous blood donors tested in this study, these findings can contribute to understand the NS5A mutation. Further study with known patients under drug treatment is recommended.
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Affiliation(s)
- Anchalee Sistayanarain
- Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
| | - Duangkamol Kunthalert
- Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand
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Farooq HZ, James M, Abbott J, Oyibo P, Divall P, Choudhry N, Foster GR. Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection: A systematic review. World J Gastrointest Oncol 2024; 16:1596-1612. [PMID: 38660636 PMCID: PMC11037048 DOI: 10.4251/wjgo.v16.i4.1596] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/21/2023] [Accepted: 01/23/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis. AIM To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023. METHODS This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023. RESULTS Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC. CONCLUSION Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.
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Affiliation(s)
- Hamzah Z Farooq
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Michael James
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Jane Abbott
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Patrick Oyibo
- School of Health and Psychological Sciences, University of London, London EC1V 0HB, United Kingdom
| | - Pip Divall
- University Hospitals of Leicester Library, University Hospitals of Leicester NHS Trust, Leicester LE3 9QP, United Kingdom
| | - Naheed Choudhry
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
| | - Graham R Foster
- Blizard Institute, Queen Mary University of London, London E1 2AT, United Kingdom
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Sano T, Amano K, Ide T, Isoda H, Honma Y, Morita Y, Yano Y, Nakamura H, Itano S, Miyajima I, Shirachi M, Kuwahara R, Ohno M, Kawaguchi T, Tsutsumi T, Nakano D, Arinaga-Hino T, Kawaguchi M, Eguchi Y, Torimura T, Takahashi H, Harada M, Kawaguchi T. Metabolic management after sustained virologic response in elderly patients with hepatitis C virus: A multicenter study. Hepatol Res 2024; 54:326-335. [PMID: 37975277 DOI: 10.1111/hepr.13993] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 10/14/2023] [Accepted: 11/06/2023] [Indexed: 11/19/2023]
Abstract
AIMS Hepatocellular carcinoma (HCC) develops even in patients with hepatitis C virus (HCV) eradication by direct-acting antiviral agents. Fatty liver and metabolic dysfunction are becoming major etiologies of HCC. We aimed to evaluate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), a new definition of steatotic liver disease, on the development of HCC after HCV eradication. METHODS We enrolled 1280 elderly patients with HCV eradication and no history of HCC. We evaluated α-fetoprotein (AFP), Fibrosis-4 index and MASLD after 24 weeks of sustained virological response. Decision tree analysis was used to investigate factors associated with HCC development after HCV eradication. RESULTS A total of 86 patients (6.7%) developed HCC during the follow-up period (35.8 ± 23.7 months). On multivariate analysis, serum AFP level (HR 1.08, CI 1.04-1.11, P = 0.0008), Fibrosis-4 index (HR 1.17, CI 1.08-1.26, P = 0.0007), and MASLD (HR 3.04, CI 1.40-6.58, P = 0.0125) at 24 weeks of sustained virological response were independent factors associated with HCC development. In decision tree analysis, the initial classifier for HCC development was AFP ≥7 ng/mL. However, in patients with AFP <7 ng/mL, MASLD, rather than Fibrosis-4 index, was the classifier for HCC development. No significant difference was observed in the cumulative incidence of HCC between patients with AFP ≥7 ng/mL and patients with AFP <7 ng/mL and MASLD. CONCLUSION MASLD at 24 weeks of sustained virological response is a risk factor for HCC development in elderly patients with HCV eradication. Additionally, decision tree analysis revealed that MASLD was associated with HCC development, even in patients with serum AFP levels <7 ng/mL.
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Affiliation(s)
- Tomoya Sano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
- Fukuoka Consulting and Support Center for Liver Diseases, Kurume, Japan
| | - Keisuke Amano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
- Fukuoka Consulting and Support Center for Liver Diseases, Kurume, Japan
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
- Fukuoka Consulting and Support Center for Liver Diseases, Kurume, Japan
- Department of Gastroenterology, Kurume University Medical Center, Kurume, Japan
| | - Hiroshi Isoda
- Liver Center, Saga University Hospital, Faculty of Medicine, Saga University, Saga, Japan
| | - Yuichi Honma
- Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Yasuyo Morita
- Department of Gastroenterology, Nagata Hospital, Yanagawa, Japan
| | - Yoichi Yano
- Division of Gastroenterology, Department of Medicine, Saga Central Hospital, Saga, Japan
| | - Hiroki Nakamura
- Department of Gastroenterology, Shin Koga Hospital, Kurume, Japan
| | - Satoshi Itano
- Department of Gastroenterology, Kurume Chuo Hospital, Kurume, Japan
| | - Ichiro Miyajima
- Department of Gastroenterology, Kumamoto Central Hospital, Kikuchi, Japan
| | - Miki Shirachi
- Department of Gastroenterology, Chikugo City Hospital, Chikugo, Japan
| | - Reiichiro Kuwahara
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
- Department of Gastroenterology, Oita Saiseikai Hita Hospital, Hita, Japan
| | - Miki Ohno
- Department of Gastroenterology and Hepatology, Yanagawa Hospital, Yanagawa, Japan
| | - Toshihiro Kawaguchi
- Division of Gastroenterology, Department of Medicine, Social Insurance Tagawa Hospital, Tagawa, Japan
| | - Tsubasa Tsutsumi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Dan Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Teruko Arinaga-Hino
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Machiko Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Yuichiro Eguchi
- Liver Center, Saga University Hospital, Faculty of Medicine, Saga University, Saga, Japan
- Loco Medical General Institute, Ogi, Japan
| | - Takuji Torimura
- Department of Gastroenterology, Omuta City Hospital, Omuta, Japan
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, Faculty of Medicine, Saga University, Saga, Japan
| | - Masaru Harada
- Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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Pisa P, Kinge CW, Chasela C, Mothibi E, Thaung YM, Thwin HT, Aung NM, Chew KW, Gandhi MM, Clint C, Minior T, Lwin AA, Freiman MJ, Kyi KP, Sein YY, Marange F, van der Horst C, Mohamed S, Barralon M, Sanne I. Evaluation of GeneXpert and advanced biological laboratories UltraGene HCV diagnostic detection and performance against Roche real time PCR in Myanmar. J Clin Virol 2024; 171:105653. [PMID: 38408420 PMCID: PMC11178258 DOI: 10.1016/j.jcv.2024.105653] [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: 07/18/2023] [Revised: 02/06/2024] [Accepted: 02/10/2024] [Indexed: 02/28/2024]
Abstract
BACKGROUND Developing countries experience limited access to HCV laboratory tests for different reasons. Providing near to real-time HCV testing and results especially to at-risk populations including those in rural settings for timely initiation to treatment is key. Within a rural Myanmar setting, we compared HCV diagnostic detection and quantification of the GeneXpert, and Advanced Biological Laboratories UltraGene-HCV assays against the gold standard and reference method Roche real-time HCV in Myanmar. METHODS Blood samples from 158 high-risk individuals were assessed using three different methods at baseline. Results were checked for normality and log transformed. Log differences and bias between methods were calculated and correlated. Pearson's correlation coefficient was used to determine the association of HCV viral loads across all methods. The level of agreement with the standard method (Roche real time HCV) was assessed using Bland-Altman analyses. RESULTS There was a strong positive correlation coefficient between all three methods with GeneXpert and Roche having the strongest, r = 0.96, (p<0.001). Compared to Roche, ABL (mean difference, 95 % limits of agreement; -0.063 and -1.4 to 1.3 Log10IU/mL) and GeneXpert (mean difference, 95 % limits of agreement; -0.28 and -0.7 to 1.8 Log10IU/mL) showed a good level of agreement with the GeneXpert being slightly superior. CONCLUSION We demonstrate the excellent performance and no-inferiority, in terms of levels of agreements of both GeneXpert and ABL compared to the Roche platform and supporting the use of the POC assays as alternative a cost-effective methods in HCV detection and diagnosis in developing and low resource settings countries.
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Affiliation(s)
- Pedro Pisa
- Department of Strategic Information, Right to Care, Centurion, South Africa; Department of Human Nutrition, University of Pretoria, Faculty of Health Sciences, Pretoria, South Africa
| | - Constance Wose Kinge
- Department of Implementation Science, Right to Care, Centurion, South Africa; Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Charles Chasela
- Department of Implementation Science, Right to Care, Centurion, South Africa; Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
| | - Eula Mothibi
- Department of Implementation Science, Right to Care, Centurion, South Africa
| | | | - Hnin T Thwin
- Community Partners International, Yangon, Myanmar
| | - Nay M Aung
- Community Partners International, Yangon, Myanmar
| | - Kara W Chew
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Malini M Gandhi
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | | | | | - Aye A Lwin
- U.S. Agency for International Development, USA
| | - Morgan J Freiman
- Department of Medical Research, Ministry of Health and Sports, Yangon, Myanmar
| | - Khin P Kyi
- Myanmar Liver Foundation, Yangon, Myanmar
| | - Yi Y Sein
- Department of Medical Research, Ministry of Health and Sports, Yangon, Myanmar
| | | | | | - Sofiane Mohamed
- Advanced Biological Laboratories (ABL) SA.17, rue des Jardiniers, Luxembourg 1835
| | - Matthieu Barralon
- Advanced Biological Laboratories (ABL) SA.17, rue des Jardiniers, Luxembourg 1835
| | - Ian Sanne
- Clinical HIV Research Unit, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Khairat J, Hatta M, Abdullah N, Azman A, Calvin S, Syed Hassan S. Unearthing the role of septins in viral infections. Biosci Rep 2024; 44:BSR20231827. [PMID: 38372298 PMCID: PMC10920062 DOI: 10.1042/bsr20231827] [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: 10/23/2023] [Revised: 01/15/2024] [Accepted: 01/18/2024] [Indexed: 02/20/2024] Open
Abstract
Septin proteins are a subfamily of closely related GTP-binding proteins conserved in all species except for higher plants and perform essential biological processes. Septins self-assemble into heptameric or octameric complexes and form higher-order structures such as filaments, rings, or gauzes by end-to-end binding. Their close association with cell membrane components makes them central in regulating critical cellular processes. Due to their organisation and properties, septins function as diffusion barriers and are integral in providing scaffolding to support the membrane's curvature and stability of its components. Septins are also involved in vesicle transport and exocytosis through the plasma membrane by co-localising with exocyst protein complexes. Recently, there have been emerging reports of several human and animal diseases linked to septins and abnormalities in their functions. Most of our understanding of the significance of septins during microbial diseases mainly pertains to their roles in bacterial infections but not viruses. This present review focuses on the known roles of septins in host-viral interactions as detailed by various studies.
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Affiliation(s)
- Jasmine Elanie Khairat
- Institute of Biological Sciences (ISB), Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Muhammad Nur Adam Hatta
- Institute of Biological Sciences (ISB), Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Nurshariza Abdullah
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia
- School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
| | - Adzzie Shazleen Azman
- School of Science, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia
| | - Shee Yin Ming Calvin
- Institute of Biological Sciences (ISB), Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Sharifah Syed Hassan
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia
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Shin HD, Song IH, Lee SH, Kim HS, Lee TH, Eun HS, Kim SH, Lee BS, Chae HB, Kim SH, Song MJ, Ko SY, Kim SB. Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 83:111-118. [PMID: 38522854 DOI: 10.4166/kjg.2023.141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 01/15/2024] [Accepted: 02/04/2024] [Indexed: 03/26/2024]
Abstract
Background/Aims This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.
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Affiliation(s)
- Hyun Deok Shin
- Department of Gastroenterology, Dankook University College of Medicine, Cheonan, Korea
| | - Il Han Song
- Department of Gastroenterology, Dankook University College of Medicine, Cheonan, Korea
| | - Sae Hwan Lee
- Department of Gastroenterology, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Hong Soo Kim
- Department of Gastroenterology, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Tae Hee Lee
- Department of Gastroenterology, Konyang University College of Medicine, Daejeon, Korea
| | - Hyuk Soo Eun
- Department of Gastroenterology, Chungnam University College of Medicine, Daejeon, Korea
| | - Seok Hyun Kim
- Department of Gastroenterology, Chungnam University College of Medicine, Daejeon, Korea
| | - Byung Seok Lee
- Department of Gastroenterology, Chungnam University College of Medicine, Daejeon, Korea
| | - Hee Bok Chae
- Department of Gastroenterology, Chungbuk University College of Medicine, Cheongju, Korea
| | - Seok Hwan Kim
- Department of Gastroenterology, College of Medicine, The Catholic University of Korea, Daejeon, Korea
| | - Myung Joon Song
- Department of Gastroenterology, College of Medicine, The Catholic University of Korea, Daejeon, Korea
| | - Soon Yeong Ko
- Department of Gastroenterology, Konkuk University College of Medicine, Chungju, Korea
| | - Suk Bae Kim
- Department of Gastroenterology, Dankook University College of Medicine, Cheonan, Korea
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Chatterjee K, Kalita D, Deka S, Jha MK, Gupta R, Omar BJ, Gupta P. Influence of Hepatitis C virus genotype and other factors on the viral load. Indian J Med Microbiol 2024; 48:100560. [PMID: 38492927 DOI: 10.1016/j.ijmmb.2024.100560] [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: 11/21/2023] [Revised: 02/28/2024] [Accepted: 03/05/2024] [Indexed: 03/18/2024]
Abstract
Anti-HCV reactive subjects were selected and relevant data was collected. Viral load and genotype were determined for all patients and were divided into low (<800,000 IU/mL) and high viral load (>800,000 IU/mL). Correlation of viral load with parameters like age, gender, risk factors and genotype etc. was determined by binomial regression. Higher viral load was noted with genotype 4, males and high risk groups like People Who Inject Drugs (PWIDs), blood transfusion before routine testing or frequent transfusion, Intravenous drug therapy and MTP by unregistered medical practitioners (P ≤ 0.5). Prevention and treatment strategies for HCV should be tailored around these areas.
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Affiliation(s)
- Kuhu Chatterjee
- Dept. of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.
| | - Deepjyoti Kalita
- Dept. of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Sangeeta Deka
- Dept. of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Mithilesh Kumar Jha
- Dept. of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Rohit Gupta
- Dept. of Gastroenterology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Balram Ji Omar
- Dept. of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
| | - Pratima Gupta
- Dept. of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
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Paknia F, Roostaee M, Isaei E, Mashhoori MS, Sargazi G, Barani M, Amirbeigi A. Role of Metal-Organic Frameworks (MOFs) in treating and diagnosing microbial infections. Int J Biol Macromol 2024; 262:130021. [PMID: 38331063 DOI: 10.1016/j.ijbiomac.2024.130021] [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: 07/31/2023] [Revised: 01/22/2024] [Accepted: 02/05/2024] [Indexed: 02/10/2024]
Abstract
This review article highlights the innovative role of metal-organic frameworks (MOFs) in addressing global healthcare challenges related to microbial infections. MOFs, comprised of metal nodes and organic ligands, offer unique properties that can be applied in the treatment and diagnosis of these infections. Traditional methods, such as antibiotics and conventional diagnostics, face issues such as antibiotic resistance and diagnostic limitations. MOFs, with their highly porous and customizable structure, can encapsulate and deliver therapeutic or diagnostic molecules precisely. Their large surface area and customizable pore structures allow for sensitive detection and selective recognition of microbial pathogens. They also show potential in delivering therapeutic agents to infection sites, enabling controlled release and possible synergistic effects. However, challenges like optimizing synthesis techniques, enhancing stability, and developing targeted delivery systems remain. Regulatory and safety considerations for clinical translation also need to be addressed. This review not only explores the potential of MOFs in treating and diagnosing microbial infections but also emphasizes their unique approach and discusses existing challenges and future directions.
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Affiliation(s)
- Fatemeh Paknia
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14115-154, Iran
| | - Maryam Roostaee
- Department of Chemistry, Faculty of Sciences, Vali-e-Asr University of Rafsanjan, Rafsanjan, Iran
| | - Elham Isaei
- Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran.
| | - Mahboobeh-Sadat Mashhoori
- Department of Chemistry, Faculty of Science, University of Birjand, P.O.Box 97175-615, Birjand, Iran
| | - Ghasem Sargazi
- Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran
| | - Mahmood Barani
- Student Research Committee, Kerman University of Medical Sciences, Kerman 7616913555, Iran; Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences, Kerman 7616913555, Iran.
| | - Alireza Amirbeigi
- Department of General Surgery, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
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Jarasvaraparn C, Hartley C, Karnsakul W. Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children. Pathogens 2024; 13:180. [PMID: 38392918 PMCID: PMC10891648 DOI: 10.3390/pathogens13020180] [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: 12/15/2023] [Revised: 01/30/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Children represent only a small proportion of those infected with the hepatitis C virus (HCV) compared to adults. Nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications including cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma in adulthood. The overall prevalence of the HCV in children was estimated to be 0.87% worldwide. The HCV spreads through the blood. Children born to women with chronic hepatitis C should be evaluated and tested for HCV due to the known risk of infection. The course of treatment for hepatitis C depends on the type of HCV. Currently, there are two pan-genotype HCV treatments (Glecaprevir/pibrentasvir and Sofosbuvir/velpatasvir) for children. We aim to review the updated clinical guidelines on the management of HCV infection in children, including screening, diagnosis, and long-term monitoring, as well as currently published clinical trials and ongoing research on direct acting antiviral hepatitis C treatment in children.
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Affiliation(s)
- Chaowapong Jarasvaraparn
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, IN 46201, USA
| | - Christopher Hartley
- Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, MD 21287, USA;
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
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Tai CM, Yu ML. Hepatitis C virus micro-elimination in people who inject drugs: Challenges and chance in Taiwan and worldwide. Kaohsiung J Med Sci 2024; 40:112-118. [PMID: 38010851 DOI: 10.1002/kjm2.12788] [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: 10/30/2023] [Revised: 11/05/2023] [Accepted: 11/07/2023] [Indexed: 11/29/2023] Open
Abstract
With the introduction of direct-acting antivirals, elimination of hepatitis C virus (HCV) infection is becoming possible. People who inject drugs (PWID) represent a population with a high risk for HCV infection, which has been reported as high as 90% in Taiwanese PWID. To reach the goal of HCV elimination, PWID is a key population deserving special attention. Barriers in HCV care cascade still exist in PWID, and interventions to promote access to HCV diagnosis, link-to-care, treatment, and prevention for PWID are warranted. Although HCV micro-elimination can be achieved in some prisons and opioid substitution therapy (OST) centers by a multidisciplinary team and integrated care in Taiwan, there are still several unmet needs for HCV elimination in PWID. Continuous efforts, such as the participation of OST specialists and the continuum of care for HCV among PWID, are needed to achieve HCV elimination in Taiwan. In addition, the combination of harm reduction services, treatment as prevention and regular posttreatment HCV surveillance is critical to substantially reduce HCV transmission and prevalence in PWID.
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Affiliation(s)
- Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
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Ullah S, Naveed M, Ali A, Bibi S, Idrees W, Rafique S, Idrees M, Waqas M, Uddin J, Jan A, Khan A, Al-Harrasi A. Assessment of ubiquitin specific Peptidase-18 gene in peripheral blood of chronic hepatitis C patients treated with direct-acting antiviral drugs. Heliyon 2024; 10:e24581. [PMID: 38298711 PMCID: PMC10828700 DOI: 10.1016/j.heliyon.2024.e24581] [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: 10/23/2023] [Revised: 12/30/2023] [Accepted: 01/10/2024] [Indexed: 02/02/2024] Open
Abstract
Hepatitis C virus (HCV) infection remains one of the leading causes of liver complications globally. Ubiquitin Specific Peptidase-18 (USP18) is a ubiquitin-specific protease that cleaves interferon-stimulated gene 15 (ISG15) from ISGylated protein complexes and is involved in regulating interferon responsiveness. To study the effect of direct-acting antivirals (DAAs) on the USP18 gene using qPCR, 132 participants were recruited and classified into different groups based on treatment duration. USP18 expression was raised compared to rapid virologic response (RVR) and early virologic response (EVR) groups with P = 0.0026 and P = 0.0016, respectively. USP18 was found to be 7.36 folds higher in naïve patients than those with RVR and sustained viral response (SVR). In RVR and SVR groups where patients had cleared HCV RNA after treatment with direct-acting antiviral agents (DAA) therapy, the expression of USP18 was found to be low, with a fold change of 1.3 and 1.4 folds, respectively. Expression of USP18 was significantly higher in the non-RVR group than in the RVR group. In the No EVR group, gene expression was significantly higher than in the EVR group. It is concluded that targeting HCV proteins using DAAs can cause USP18 expression to be normalized more effectively. Moreover, USP18 is a vital marker indicating treatment resistance and distinguishing responders from non-responders during DAA therapy.
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Affiliation(s)
- Sami Ullah
- Molecular Virology laboratory Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Mariam Naveed
- Molecular Virology laboratory Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Amjad Ali
- Molecular Virology laboratory Centre for Applied Molecular Biology (CAMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
- Department of Biotechnology and Genetic Engineering, Hazara University Mansehra, Khyber Pakhtunkhwa, Pakistan
| | - Sadia Bibi
- Department of Botany, University of Malakand Chakdara, Dir lower, Khyber Pakhtunkhwa, Pakistan
| | - Wafa Idrees
- Khyber Medical College, Peshawar, Khyber Pakhtunkhwa, Pakistan
| | - Shazia Rafique
- Division of Molecular Virology, Centre of Excellence in Molecular Biology (CEMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
| | - Muhammad Idrees
- Division of Molecular Virology, Centre of Excellence in Molecular Biology (CEMB), 87-West Canal Bank Road Thokar Niaz Baig, University of the Punjab, Lahore, Pakistan
- Vice Chancellor, University of Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan
| | - Muhammad Waqas
- Department of Biotechnology and Genetic Engineering, Hazara University Mansehra, Khyber Pakhtunkhwa, Pakistan
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa, Sultanate of Oman
| | - Jalal Uddin
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, 62529, Kingdom of Saudi Arabia
| | - Afnan Jan
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Ajmal Khan
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa, Sultanate of Oman
| | - Ahmed Al-Harrasi
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa, Sultanate of Oman
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Tao XM, Zeng MH, Zhao YF, Han JX, Mi YQ, Xu L. Direct-acting antivirals failed to reduce the incidence of hepatocellular carcinoma occurrence in hepatitis C virus associated cirrhosis: A real-world study. World J Hepatol 2024; 16:41-53. [PMID: 38313240 PMCID: PMC10835484 DOI: 10.4254/wjh.v16.i1.41] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/18/2023] [Accepted: 01/09/2024] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND Direct-acting antivirals (DAAs) revolutionized the treatment of chronic hepatitis C virus (HCV)-associated disease achieving high rates of sustained virological response (SVR). However, whether DAAs can reduce the occurrence of hepatocellular carcinoma (HCC) in patients with HCV-associated cirrhosis who are at high risk have not been concluded. AIM To investigate the effect of DAAs on the occurrence of HCC in patients with HCV-associated cirrhosis after achieving SVR. METHODS Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020. 118 patients weren't received antiviral treatment with any reasons named non-antiviral treatment group, and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group. Demographic information and laboratory data were collected from baseline and the following up. Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups. Cox proportional risk regression was used to re-evaluate the risk factors for HCC. RESULTS HCC incidence was 4.68/100PY (95%CI, 3.09-6.81) in the DAAs treatment group, while it was 3.00/100PY (95%CI, 1.50-5.37) in the non-antiviral treatment group, and the relative risk was 1.82 (95%CI, 0.93-3.53, P > 0.05). The incidence of HCC at 12, 24, 36 and 48 months was 3.39%, 6.36%, 8.47% and 10.17% in the DAAs treatment group, and it was 0%, 0%, 3.39% and 9.32% in the non-antiviral treatment group, respectively. Age > 58 [hazard ratio (HR) = 1.089; 95%CI, 1.033-1.147; P = 0.002] and liver stiffness measurement > 27.85 kPa (HR = 1.043; 95%CI, 1.022-1.065; P = 0.000) were risk factors for HCC in all patients (n = 427), and DAAs treatment didn't show protective efficacy. CONCLUSION DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months, and even increased the incidence of HCC in 36 months.
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Affiliation(s)
- Xue-Mei Tao
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - Ming-Hui Zeng
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - You-Fei Zhao
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - Jia-Xin Han
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - Yu-Qiang Mi
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - Liang Xu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
- Department of Hepatology, Tianjin Research Institute of Liver Diseases, Tianjin 300192, China.
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Fernandez CJ, Alkhalifah M, Afsar H, Pappachan JM. Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Viral Hepatitis: The Interlink. Pathogens 2024; 13:68. [PMID: 38251375 PMCID: PMC10821334 DOI: 10.3390/pathogens13010068] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/05/2024] [Accepted: 01/07/2024] [Indexed: 01/23/2024] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one-third of the global population and has become the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) remain significant challenges to liver health even in the 21st century. The co-existence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. A thorough understanding of the pathobiological interactions between MAFLD and these two chronic viral infections is crucial for appropriately managing these patients. In this comprehensive clinical review, we discuss the various mechanisms of chronic viral hepatitis-mediated metabolic dysfunction and the impact of MAFLD on the progression of liver disease.
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Affiliation(s)
- Cornelius J. Fernandez
- Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, UK;
| | - Mohammed Alkhalifah
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
- Department of Family Medicine and Polyclinics, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh 11411, Saudi Arabia
| | - Hafsa Afsar
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
| | - Joseph M. Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, UK
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PL, UK
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Shahanas SM, Verma R, Kumar K, Verma M, Srivastavsa DC, Budhwani P. A Study on the Prevalence of HCV Genotypes and the Effect of Direct-Acting Antiviral Therapy on Clinical and Laboratory Parameters in HCV-Infected Patients at a Tertiary Care Center in North India. Indian J Community Med 2024; 49:203-208. [PMID: 38425980 PMCID: PMC10900459 DOI: 10.4103/ijcm.ijcm_865_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 11/06/2023] [Indexed: 03/02/2024] Open
Abstract
Background The purpose of this study was to investigate the prevalence and distribution of different HCV genotypes, as well as to evaluate clinical and laboratory parameters in HCV-infected patients before and after DAA treatment. Material and Methods An open-label prospective study was conducted on 50 HCV-infected individuals. The HCV-infected patients underwent a baseline evaluation with complete history, examination, and other clinical investigations. These patients received the appropriate DAA according to the genotype for 3 months. At the end of 3 months, these patients were again evaluated clinically. Results The majority of instances were among younger age groups. Genotype 3 (66%) was the most common. There was a statistically significant difference found in clinical parameters regarding total bilirubin (p=0.008), SGOT (p=0.001), SGPT (p=0.035), ALP (p=<0.001) and Blood Urea Nitrogen (p = 0.004). When 1a vs 1b intragroup comparison was drawn, there was a significant mean difference found in SGOT (p value= 0.053) and Creatinine (p=0.050) parameters while rest shows no significant difference when associated. In the comparison of 1a vs 3 or 4, none of the parameters shows significant difference while; when 1b vs 3 or 4 comparison was laid out, SGOT and Creatinine was found near to significant. Conclusion This study concludes that with the availability of DAAs, highly effective, short-duration, and safe regimens have created better outcomes for patients with HCV infection, especially in those groups where SVR was low with prior therapies or in those where IFN-based treatment strategies were contraindicated.
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Affiliation(s)
| | - Rajeev Verma
- Department of Medicine, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India
| | - Kanishka Kumar
- Department of Medicine, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India
| | - Manisha Verma
- Department of Pediatrics, King George’s Medical University, Lucknow, Uttar Pradesh, India
| | | | - Priyanka Budhwani
- Department of Medicine, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh, India
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Cooke GS. Viral Hepatitis. MANSON'S TROPICAL DISEASES 2024:152-166. [DOI: 10.1016/b978-0-7020-7959-7.00018-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Luo S, Zhang P, Wang Y, Huang Y, Ma X, Deng Q, Zou P, Wang C, Zhang L, Li Y, Fu Y, Li T, Li C. Adenoviruses vectored hepatitis C virus vaccine cocktails induce broadly specific immune responses against multi-genotypic HCV in mice. Biomed Pharmacother 2024; 170:115901. [PMID: 38056238 DOI: 10.1016/j.biopha.2023.115901] [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: 08/17/2023] [Revised: 11/06/2023] [Accepted: 11/14/2023] [Indexed: 12/08/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) vaccines are an urgent need to prevent hepatitis C and its further progression of hepatocellular carcinoma. Since the promising T cell based chimpanzee adenovirus and modified vaccinia virus Ankara vectorial HCV vaccines were failed in clinical phase II trial, the vaccine designs to improve protection efficacy in combination of cellular and humoral immunity have been hypothesized against multi-genotypic HCV. METHODS Eight HCV vaccine strains were constructed with two novel adenovirus vectors (Sad23L and Ad49L) encoding E1E2 or NS3-5B proteins of HCV genotype (Gt) 1b and 6a isolates, covering 80 % HCV strains prevalent in south China and south-east Asia. Eight HCV vaccine strains were grouped into Sad23L-based vaccine cocktail-1 and Ad49L-based vaccine cocktail-2 for vaccinating mice, respectively. RESULTS The immunogenicity of a single dose of 107-1010 PFU HCV individual vaccines was evaluated in mice, showing weak specific antibody to E1 and E2 protein but a dose-dependent T cell response to E1E2/NS3-5B peptides, which could be significantly enhanced by boosting with an alternative vector vaccine carrying homologous antigen. Prime-boost vaccinations with vaccine cocktail-1 and cocktail-2 induced significantly higher cross-reactive antibody and stronger T cell responses to HCV Gt-1b/6a. The high frequency of intrasplenic and intrahepatic NS31629-1637 CD8+ T cell responses were identified, in which the high proportion of TRM and TEM cells might play an important role against HCV infection in liver. CONCLUSIONS Prime-boost regimens with HCV vaccine cocktails elicited the broad cross-reactive antibody and robust T cell responses against multi-genotypic HCV in mice.
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Affiliation(s)
- Shengxue Luo
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China; Guangzhou Blood Center, Guangzhou, China
| | - Panli Zhang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Yilin Wang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China; Department of Pathology, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi'an, China
| | - Yunzhu Huang
- Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou 501180, China
| | - Xiaorui Ma
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Qitao Deng
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Peng Zou
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Cong Wang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China; Guangzhou Bai Rui Kang (BRK) Biological Science and Technology Limited Company, China
| | - Ling Zhang
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Yiping Li
- Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou 501180, China
| | | | - Tingting Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
| | - Chengyao Li
- Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
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Farghaly TA, Masaret GS, Riyadh SM, Harras MF. A Literature Review Focusing on the Antiviral Activity of [1,2,4] and [1,2,3]-triazoles. Mini Rev Med Chem 2024; 24:1602-1629. [PMID: 38008942 DOI: 10.2174/0113895575277122231108095511] [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: 08/12/2023] [Revised: 09/07/2023] [Accepted: 09/09/2023] [Indexed: 11/28/2023]
Abstract
Out of a variety of heterocycles, triazole scaffolds have been shown to play a significant part in a wide array of biological functions. Many drug compounds containing a triazole moiety with important antimicrobial, anticancer and antidepressant properties have been commercialized. In addition, the triazole scaffold exhibits remarkable antiviral activity either incorporated into nucleoside analogs or non-nucleosides. Many synthetic techniques have been produced by scientists around the world as a result of their wide-ranging biological function. In this review, we have tried to summarize new synthetic methods produced by diverse research groups as well as provide a comprehensive description of the function of [1,2,4] and [1,2,3]-triazole derivatives as antiviral agents. Antiviral triazole compounds have been shown to target a wide variety of molecular proteins. In addition, several strains of viruses, including the human immunodeficiency virus, SARS virus, hepatitis B and C viruses, influenza virus, Hantavirus, and herpes virus, were discovered to be susceptible to triazole derivatives. This review article covered the reports for antiviral activity of both 1,2,3- and 1,2,4-triazole moieties up to 2022.
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Affiliation(s)
- Thoraya A Farghaly
- Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukaramah, 21514, Saudi Arabia
| | - Ghada S Masaret
- Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukaramah, 21514, Saudi Arabia
| | - Sayed M Riyadh
- Chemistry Department, Faculty of Science, University of Cairo, Giza 12613, Egypt
| | - Marwa F Harras
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
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Choi K. The Structure-property Relationships of Clinically Approved Protease Inhibitors. Curr Med Chem 2024; 31:1441-1463. [PMID: 37031455 DOI: 10.2174/0929867330666230409232655] [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: 11/05/2022] [Revised: 01/17/2023] [Accepted: 02/24/2023] [Indexed: 04/11/2023]
Abstract
BACKGROUND Proteases play important roles in the regulation of many physiological processes, and protease inhibitors have become one of the important drug classes. Especially because the development of protease inhibitors often starts from a substrate- based peptidomimetic strategy, many of the initial lead compounds suffer from pharmacokinetic liabilities. OBJECTIVE To reduce drug attrition rates, drug metabolism and pharmacokinetics studies are fully integrated into modern drug discovery research, and the structure-property relationship illustrates how the modification of the chemical structure influences the pharmacokinetic and toxicological properties of drug compounds. Understanding the structure- property relationships of clinically approved protease inhibitor drugs and their analogues could provide useful information on the lead-to-candidate optimization strategies. METHODS About 70 inhibitors against human or pathogenic viral proteases have been approved until the end of 2021. In this review, 17 inhibitors are chosen for the structure- property relationship analysis because detailed pharmacological and/or physicochemical data have been disclosed in the medicinal chemistry literature for these inhibitors and their close analogues. RESULTS The compiled data are analyzed primarily focusing on the pharmacokinetic or toxicological deficiencies found in lead compounds and the structural modification strategies used to generate candidate compounds. CONCLUSION The structure-property relationships hereby summarized how the overall druglike properties could be successfully improved by modifying the structure of protease inhibitors. These specific examples are expected to serve as useful references and guidance for developing new protease inhibitor drugs in the future.
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Affiliation(s)
- Kihang Choi
- Department of Chemistry, Korea University, Seoul, 02841, Korea (ROK)
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Akkaya M, Akcaalan S, Perrone FL, Sandiford N, Gehrke T, Citak M. Organism profile and C-reactive protein (CRP) response are different in periprosthetic joint infection in patients with hepatitis. Arch Orthop Trauma Surg 2024; 144:341-346. [PMID: 37742285 DOI: 10.1007/s00402-023-05059-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 09/01/2023] [Indexed: 09/26/2023]
Abstract
PURPOSE Hepatitis B and C are important and relatively common health issues. It is known that many patients who underwent total knee and hip arthroplasty were also diagnosed with hepatitis. These patients are at higher risk of periprosthetic joint infection (PJI). This study aimed to investigate the differences in PJI cases in hepatitis B and C patients. METHODS This is a retrospective case-controlled single-center study. A total of 270 patients with hepatitis and non-hepatitis (control group) who underwent one-stage septic exchange to the hip and knee joints were included in the study. All patients' previous surgical histories, infective organisms, C-reactive protein (CRP) values before septic exchange, and demographic data were evaluated. All microbiological and laboratory evaluations were performed separately for knee and hip arthroplasty. RESULTS The mean CRP levels of Hep B- and C-positive patients, who underwent one-stage septic exchange in the knee joint, were 23.6 mg/L. In the control group, this value was 43.1 mg/L and a statistically significant difference was found between the groups (p = 0.004). Gram-negative organisms were identified in a larger proportion of patients with hepatitis who developed PJI in both hip and knee joints and underwent one-stage septic exchange (p = 0.041/p = 0.044). CONCLUSION PJIs caused by Gram-negative bacteria are encountered more frequently in patients with hepatitis than in the control group. In addition, the CRP rise is less in patients with hepatitis compared to PJI cases in the control group. Patient-specific evaluation is required in cases of PJI in patient groups with co-existing hepatitis.
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Affiliation(s)
- Mustafa Akkaya
- Department of Orthopaedic Surgery, Helios ENDO-Klinik, Holstenstr. 2, 22767, Hamburg, Germany
| | - Serhat Akcaalan
- Department of Orthopaedic Surgery, Helios ENDO-Klinik, Holstenstr. 2, 22767, Hamburg, Germany
| | - Fabio Luigi Perrone
- Department of Orthopaedic Surgery, Helios ENDO-Klinik, Holstenstr. 2, 22767, Hamburg, Germany
| | - Nemandra Sandiford
- Joint Reconstruction Unit, Southland Hospital, Invercargill, New Zealand
| | - Thorsten Gehrke
- Department of Orthopaedic Surgery, Helios ENDO-Klinik, Holstenstr. 2, 22767, Hamburg, Germany
| | - Mustafa Citak
- Department of Orthopaedic Surgery, Helios ENDO-Klinik, Holstenstr. 2, 22767, Hamburg, Germany.
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