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Bakshi S, Dutta S, Biswas A, Das R, Nath S, Ghosh A, Baskey U, Sadhukhan PC. Impact of hepatitis C virus genotype on the efficacy of the direct-acting antivirals in chronic kidney disease patients in West Bengal, India. BMC Infect Dis 2025; 25:706. [PMID: 40380327 PMCID: PMC12083046 DOI: 10.1186/s12879-025-10947-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 04/08/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection increases the risk of mortality and morbidity among chronic kidney disease (CKD) patients. However, the advancement of HCV treatment has made this viral infection curable. Thus, the main objective of this study was to comprehend the HCV genotype (GT) distribution and the efficacy of direct-acting antivirals (DAAs) among CKD patients in West Bengal. METHODS Over five years (January 2017 to December 2021), 310 HCV sero-reactive patients were enrolled in this observational prospective study. HCV RNA was quantified using qRT-PCR. The partial amplification of the core (405 bp) and NS5B (389 bp) region was performed by nested RT-PCR followed by Sanger sequencing for HCV genotype analysis using the NCBI genotyping tool. The phylogenetic tree was constructed using the MEGA-X tool. RESULTS The occurrence of HCV RNA positivity was 50.64% (n = 157), and of these 157 patients, 141 (89.81%) completed the DAAs treatment. The most important observation of the study was the prevalence of uncommon HCV genotype GT-1c (67.52%) followed by 1a, 4a, 3a, 1b, and 3b among CKD patients. The overall DAAs efficacy between January 2017 and December 2018 was ~ 97%, and in January 2019 and December 2021, ~ 95% among CKD patients. At the same time, in these two phases, DAAs efficacy among GT-1c-infected CKD patients was ˜ 96% and ˜ 93%, respectively. CONCLUSIONS The prevalence of GT-1c among CKD patients was unusual in this geographic region. The overall efficacy of DAAs among the CKD population was encouraging. However, the downtrend of the DAAs efficacy in GT-1c may increase concern among this high-risk group in the future. CLINICAL TRIAL Not applicable.
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Affiliation(s)
- Sagnik Bakshi
- Division of ICMR-NICED Virus Laboratory, Indian Council of Medical Research- National Institute for Research in Bacterial Infections (ICMR- NIRBI, formerly ICMR-NICED), P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, West Bengal, 700010, India
| | - Supradip Dutta
- Division of ICMR-NICED Virus Laboratory, Indian Council of Medical Research- National Institute for Research in Bacterial Infections (ICMR- NIRBI, formerly ICMR-NICED), P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, West Bengal, 700010, India
| | - Aritra Biswas
- Division of ICMR-NICED Virus Laboratory, Indian Council of Medical Research- National Institute for Research in Bacterial Infections (ICMR- NIRBI, formerly ICMR-NICED), P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, West Bengal, 700010, India
| | - Raina Das
- Division of ICMR-NICED Virus Laboratory, Indian Council of Medical Research- National Institute for Research in Bacterial Infections (ICMR- NIRBI, formerly ICMR-NICED), P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, West Bengal, 700010, India
| | - Shreyasi Nath
- Division of ICMR-NICED Virus Laboratory, Indian Council of Medical Research- National Institute for Research in Bacterial Infections (ICMR- NIRBI, formerly ICMR-NICED), P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, West Bengal, 700010, India
| | - Anwesha Ghosh
- Division of ICMR-NICED Virus Laboratory, Indian Council of Medical Research- National Institute for Research in Bacterial Infections (ICMR- NIRBI, formerly ICMR-NICED), P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, West Bengal, 700010, India
| | - Upasana Baskey
- Division of ICMR-NICED Virus Laboratory, Indian Council of Medical Research- National Institute for Research in Bacterial Infections (ICMR- NIRBI, formerly ICMR-NICED), P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, West Bengal, 700010, India
| | - Provash Chandra Sadhukhan
- Division of ICMR-NICED Virus Laboratory, Indian Council of Medical Research- National Institute for Research in Bacterial Infections (ICMR- NIRBI, formerly ICMR-NICED), P-33, Scheme XM, CIT Road, Beliaghata, Kolkata, West Bengal, 700010, India.
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Caudai C, Pierotti P, Rossetti B, Blanc P, Zazzi M. Genotyping and treatment issues with 'unusual' HCV 1 subtypes. Eur J Clin Microbiol Infect Dis 2025; 44:1265-1271. [PMID: 40011316 DOI: 10.1007/s10096-025-05038-3] [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: 10/08/2024] [Accepted: 01/08/2025] [Indexed: 02/28/2025]
Abstract
Unusual non 1a/1b HCV 1 subtypes are mostly prevalent in Sub-Saharan Africa. These variants harbour resistance associated substitutions as natural polymorphisms in the NS5A region and are difficult to characterize and treat. We report the HCV genome sequences from two African subjects with unusual subtype 1 g and 1e treated with the pangenotypic regimen sofosbuvir/velpatasvir with failure in the latter. Sequence analysis of different regions of the HCV genome in a subtype 1 reference panel and use of multiple subtyping tools showed that the NS5A region is the most suitable to detect these unusual HCV subtypes and assist treatment choices.
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Affiliation(s)
- Cinzia Caudai
- Microbiology and Virology Unit, Siena University Hospital, Viale M. Bracci, 16, 53100, Siena, Italy.
| | - Piera Pierotti
- Infectious Diseases Unit, S. Maria Annunziata Hospital, Florence, Italy
| | - Barbara Rossetti
- Infectious Diseases Unit, Siena University Hospital, Siena, Italy
| | - Pierluigi Blanc
- Infectious Diseases Unit, S. Maria Annunziata Hospital, Florence, Italy
| | - Maurizio Zazzi
- Department of Medical Biotechnologies, University of Siena, Siena, Italy
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Vo-Quang E, Pawlotsky JM. 'Unusual' HCV genotype subtypes: origin, distribution, sensitivity to direct-acting antiviral drugs and behaviour on antiviral treatment and retreatment. Gut 2024; 73:1570-1582. [PMID: 38782565 PMCID: PMC11347264 DOI: 10.1136/gutjnl-2024-332177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 04/30/2024] [Indexed: 05/25/2024]
Abstract
The high genetic diversity of hepatitis C virus (HCV) has led to the emergence of eight genotypes and a large number of subtypes in limited geographical areas. Currently approved pangenotypic DAA regimens have been designed and developed to be effective against the most common subtypes (1a, 1b, 2a, 2b, 2c, 3a, 4a, 5a and 6a). However, large populations living in Africa and Asia, or who have migrated from these regions to industrialised countries, are infected with 'unusual', non-epidemic HCV subtypes, including some that are inherently resistant to currently available direct-acting antiviral (DAA) drugs due to the presence of natural polymorphisms at resistance-associated substitution positions. In this review article, we describe the origin and subsequent global spread of HCV genotypes and subtypes, the current global distribution of common and unusual HCV subtypes, the polymorphisms naturally present in the genome sequences of unusual HCV subtypes that may confer inherently reduced susceptibility to DAA drugs and the available data on the response of unusual HCV subtypes to first-line HCV therapy and retreatment. We conclude that the problem of unusual HCV subtypes that are inherently resistant to DAAs and its threat to the global efforts to eliminate viral hepatitis are largely underestimated and warrant vigorous action.
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Affiliation(s)
- Erwan Vo-Quang
- National Reference Centre for Viral Hepatitis B, C and D, Department of Virology, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Institut Mondor de Recherche Biomédicale (INSERM U955), Créteil, France
- Department of Hepatology, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
| | - Jean-Michel Pawlotsky
- National Reference Centre for Viral Hepatitis B, C and D, Department of Virology, Hôpital Henri Mondor (AP-HP), Université Paris-Est, Créteil, France
- Institut Mondor de Recherche Biomédicale (INSERM U955), Créteil, France
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Loarec A, Gutierrez AG, Muvale G, Couto A, Nguyen A, Yerly S, Pinto Y, Madeira N, Gonzales A, Molfino L, Ciglenecki I, Antabak NT. Hepatitis C treatment program in Maputo, Mozambique, the challenge of genotypes and key populations: A 5-year retrospective analysis of routine programmatic data. Health Sci Rep 2023; 6:e1165. [PMID: 37008813 PMCID: PMC10061494 DOI: 10.1002/hsr2.1165] [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: 11/08/2022] [Revised: 03/10/2023] [Accepted: 03/13/2023] [Indexed: 04/04/2023] Open
Abstract
Background and Aims Hepatitis C (HCV) programs face challenges, especially linked to key populations to achieve World Health Organization (WHO) goals of eliminating hepatitis. Médecins Sans Frontières and Mozambique's Ministry of Health first implemented HCV treatment in Maputo, in 2016 and harm reduction activities in 2017. Methods We retrospectively analyzed routine data of patients enrolled between December 2016 and July 2021. Genotyping was systematically requested up to 2018 and subsequently in cases of treatment failure. Sustainable virological response was assessed 12 weeks after the end of treatment by sofosbuvir-daclatasvir or sofosbuvir-velpatasvir. Results Two hundred and two patients were enrolled, with 159 (78.71%) males (median age: 41 years [interquartile range (IQR): 37.10, 47.00]). Risk factors included drug use (142/202; 70.29%). One hundred and eleven genotyping results indicated genotype 1 predominant (87/111; 78.37%). Sixteen patients presented genotype 4, with various subtypes. The people who used drugs and HIV coinfected patients were found more likely to present a genotype 1. Intention-to-treat analysis showed 68.99% (89/129) cure rate among the patients initiated and per-protocol analysis, 88.12% (89/101) cure rate. Nineteen patients received treatment integrated with opioid substitution therapy, with a 100% cure rate versus 59.37% (38/64) for initiated ones without substitution therapy (p < 0.001). Among the resistance testing performed, NS5A resistance-associated substitutions were found in seven patients among the nine tested patients and NS5B ones in one patient. Conclusion We found varied genotypes, including some identified as difficult-to-treat subtypes. People who used drugs were more likely to present genotype 1. In addition, opioid substitution therapy was key for these patients to achieve cure. Access to second-generation direct-acting antivirals (DAAs) and integration of HCV care with harm reduction are crucial to program effectiveness.
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Affiliation(s)
- Anne Loarec
- Médecins Sans Frontières (MSF)MaputoMozambique
| | | | | | | | - Aude Nguyen
- Service des Maladies InfectieusesHôpitaux Universitaires de GenèveGenèveSwitzerland
| | - Sabine Yerly
- Laboratory of VirologyHôpitaux Universitaires de GenèveGenevaSwitzerland
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Adeboyejo K, King BJ, Tsoleridis T, Tarr AW, McLauchlan J, Irving WL, Ball JK, McClure CP. Hepatitis C subtyping assay failure in UK patients born in sub-Saharan Africa: Implications for global treatment and elimination. J Med Virol 2023; 95:e28178. [PMID: 36168235 PMCID: PMC10092547 DOI: 10.1002/jmv.28178] [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: 08/01/2022] [Revised: 09/21/2022] [Accepted: 09/26/2022] [Indexed: 01/11/2023]
Abstract
UNLABELLED BACKGROUND AND AIMS: The newly developed direct-acting antivirals have revolutionized the treatment of chronic hepatitis C virus (HCV), with cure rates as high as 98% in some cohorts. Although genome sequencing has demonstrated that some subtypes of HCV naturally harbor drug resistance associated substitutions (RAS), these are often overlooked as "rarities." Furthermore, commercial subtyping assays and associated epidemiological findings are skewed towards Western cohorts and whole-genome sequencing can be problematic to deploy without significant infrastructure and training support. We thus aimed to develop a simple, robust and accurate HCV subtyping pipeline, to optimize and streamline molecular detection and sequence-based typing of diverse RAS-containing subtypes. METHODS HCV serum derived from 146 individuals, whose likely source of infection was from sub-Saharan Africa (SSA) was investigated with a novel panel of single round polymerase chain reaction (PCR) assays targeting NS5B and NS5A genomic regions. Virus subtype assignments were determined by pairwise-distance analysis and compared to both diagnostic laboratory assignments and free-to-use online typing tools. RESULTS Partial NS5A and NS5B sequences were respectively obtained from 131 to 135 HCV-positive patients born in 19 different countries from SSA but attending clinics in the UK. We determined that routine clinical diagnostic methods incorrectly subtyped 59.0% of samples, with a further 6.8% incorrectly genotyped. Of five commonly used online tools, Geno2Pheno performed most effectively in determining a subtype in agreement with pairwise distance analysis. CONCLUSION This study provides a simple low-cost pathway to accurately subtype in SSA, guide regional therapeutic choice and assist global surveillance and elimination initiatives.
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Affiliation(s)
- Kazeem Adeboyejo
- School of Life SciencesUniversity of NottinghamNottinghamUK
- National Institute for Health Research Nottingham Biomedical Research CentreNottinghamUK
- Wolfson Centre for Global Virus ResearchNottinghamUK
| | - Barnabas J. King
- School of Life SciencesUniversity of NottinghamNottinghamUK
- National Institute for Health Research Nottingham Biomedical Research CentreNottinghamUK
- Wolfson Centre for Global Virus ResearchNottinghamUK
| | - Theocharis Tsoleridis
- School of Life SciencesUniversity of NottinghamNottinghamUK
- National Institute for Health Research Nottingham Biomedical Research CentreNottinghamUK
- Wolfson Centre for Global Virus ResearchNottinghamUK
| | - Alexander W. Tarr
- School of Life SciencesUniversity of NottinghamNottinghamUK
- National Institute for Health Research Nottingham Biomedical Research CentreNottinghamUK
- Wolfson Centre for Global Virus ResearchNottinghamUK
| | - John McLauchlan
- MRC–University of Glasgow Centre for Virus ResearchGlasgowUK
| | - William L. Irving
- School of Life SciencesUniversity of NottinghamNottinghamUK
- National Institute for Health Research Nottingham Biomedical Research CentreNottinghamUK
- Wolfson Centre for Global Virus ResearchNottinghamUK
- Clinical Microbiology, Nottingham University HospitalsNottinghamUK
- Nottingham University HospitalsNottinghamUK
| | - Jonathan K. Ball
- School of Life SciencesUniversity of NottinghamNottinghamUK
- National Institute for Health Research Nottingham Biomedical Research CentreNottinghamUK
- Wolfson Centre for Global Virus ResearchNottinghamUK
| | - C. Patrick McClure
- School of Life SciencesUniversity of NottinghamNottinghamUK
- National Institute for Health Research Nottingham Biomedical Research CentreNottinghamUK
- Wolfson Centre for Global Virus ResearchNottinghamUK
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Isfordink C, Boyd A, Mocroft A, Kusejko K, Smit C, de Wit S, Mahungu T, Falconer K, Wandeler G, Cavassini M, Stöckle M, Schinkel J, Rauch A, Peters L, van der Valk M, for EuroSIDA, the Swiss HIV Cohort Study, and the ATHENA Observational Cohort. Low Risk of Failing Direct-Acting Antivirals in People With Human Immunodeficiency Virus/Hepatitis C Virus From Sub-Saharan Africa or Southeastern Asia: A European Cross-Sectional Study. Open Forum Infect Dis 2022; 9:ofac508. [PMID: 36320198 PMCID: PMC9605702 DOI: 10.1093/ofid/ofac508] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 09/28/2022] [Indexed: 11/21/2022] Open
Abstract
Background Several studies have reported suboptimal efficacy of direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) subtypes endemic to sub-Saharan Africa (SSA) and Southeastern Asia (SEA). The extent of this issue in individuals with human immunodeficiency virus (HIV)/HCV from SSA or SEA residing in Europe is unknown. Methods We retrospectively analyzed data from several prospective European cohorts of people living with HIV. We included individuals with HIV/HCV who originated from SSA or SEA, were treated with interferon-free DAAs, and had an available HCV RNA result ≥12 weeks after the end of treatment. The primary outcome was sustained virological response at least 12 weeks after the end of treatment (SVR12). Results Of the 3293 individuals with HIV/HCV treated with DAA and with available SVR12 data, 142 were from SSA (n = 64) and SEA (n = 78). SVR12 was achieved by 60 (94% [95% confidence interval {CI}, 86%-98%]) individuals from SSA and 76 (97% [95% CI, 92%-99%]) from SEA. The genotypes of the 6 individuals failing DAA treatment were 2, 3a, 3h, 4a, 4c, and 6j. For 2 of the 4 unsuccessfully treated individuals with available sequence data at treatment failure, NS5A resistance-associated substitutions were present (30R/93S in an individual with genotype 4c and 31M in an individual with genotype 6j). Conclusions SVR12 rates were high in individuals with HIV/HCV residing in Europe and originating from regions where intrinsically NS5A-resistant HCV strains are endemic. HCV elimination for this population in Europe is unlikely to be hampered by suboptimal DAA efficacy.
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Affiliation(s)
- Cas Isfordink
- Division of Infectious Diseases, Department of Internal Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Anders Boyd
- Stichting HIV Monitoring, Amsterdam, The Netherlands
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, The Netherlands
| | - Amanda Mocroft
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, London, United Kingdom
- Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Katharina Kusejko
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Colette Smit
- Stichting HIV Monitoring, Amsterdam, The Netherlands
| | - Stephane de Wit
- Division of Infectious Diseases, St Pierre Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Tabitha Mahungu
- Department of Infectious Diseases, Royal Free Hospital London NHS Foundation Trust, London, United Kingdom
| | - Karolin Falconer
- Department of Infectious Diseases/Venhälsan, Södersjukhuset, Stockholm, Sweden
| | - Gilles Wandeler
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Matthias Cavassini
- Division of Infectious Diseases, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Marcel Stöckle
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Janke Schinkel
- Section of Clinical Virology, Department of Medical Microbiology and Infection Prevention, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Andri Rauch
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Lars Peters
- Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Marc van der Valk
- Division of Infectious Diseases, Department of Internal Medicine, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- Stichting HIV Monitoring, Amsterdam, The Netherlands
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Gupta N, Manirambona L, Shumbusho F, Kabihizi J, Murangwa A, Serumondo J, Makuza JD, Nsanzimana S, Muvunyi CM, Mukabatsinda C, Musabeyezu E, Camus G, Grant PM, Kateera F. Safety and efficacy of sofosbuvir–velpatasvir–voxilaprevir for re-treatment of chronic hepatitis C virus infection in patients with previous direct-acting antiviral treatment failure in Rwanda (SHARED-3): a single-arm trial. Lancet Gastroenterol Hepatol 2022; 7:542-551. [DOI: 10.1016/s2468-1253(21)00399-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/25/2021] [Accepted: 10/26/2021] [Indexed: 12/13/2022]
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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Ouoba S, Ouedraogo JCRP, Lingani M, E B, Hussain MRA, Ko K, Nagashima S, Sugiyama A, Akita T, Tinto H, Tanaka J. Epidemiologic profile of hepatitis C virus infection and genotype distribution in Burkina Faso: a systematic review with meta-analysis. BMC Infect Dis 2021; 21:1126. [PMID: 34724902 PMCID: PMC8561994 DOI: 10.1186/s12879-021-06817-x] [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: 07/08/2021] [Accepted: 10/25/2021] [Indexed: 11/29/2022] Open
Abstract
Background Detailed characteristics of Hepatitis C virus (HCV) infection in Burkina Faso are scarce. The main aim of this study was to assess HCV seroprevalence in various settings and populations at risk in Burkina Faso between 1990 and 2020. Secondary objectives included the prevalence of HCV Ribonucleic acid (RNA) and the distribution of HCV genotypes. Methods A systematic database search, supplemented by a manual search, was conducted in PubMed, Web of Science, Scopus, and African Index Medicus. Studies reporting HCV seroprevalence data in low and high-risk populations in Burkina Faso were included, and a random-effects meta-analysis was applied. Risk of bias was assessed using the Joanna Briggs institute checklist. Results Low-risk populations were examined in 31 studies involving a total of 168,151 subjects, of whom 8330 were positive for HCV antibodies. Six studies included a total of 1484 high-risk persons, and 96 had antibodies to HCV. The pooled seroprevalence in low-risk populations was 3.72% (95% CI: 3.20–4.28) and 4.75% (95% CI: 1.79–8.94) in high-risk groups. A non-significant decreasing trend was observed over the study period. Seven studies tested HCV RNA in a total of 4759 individuals at low risk for HCV infection, and 81 were positive. The meta-analysis of HCV RNA yielded a pooled prevalence of 1.65% (95% CI: 0.74–2.89%) in low-risk populations, which is assumed to be indicative of HCV prevalence in the general population of Burkina Faso and suggests that about 301,174 people are active HCV carriers in the country. Genotypes 2 and 1 were the most frequent, with 60.3% and 25.0%, respectively. Conclusions HCV seroprevalence is intermediate in Burkina Faso and indicates the need to implement effective control strategies. There is a paucity of data at the national level and for rural and high-risk populations. General population screening and linkage to care are recommended, with special attention to rural and high-risk populations. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06817-x.
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Affiliation(s)
- Serge Ouoba
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.,Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | | | - Moussa Lingani
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Bunthen E
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.,Payment Certification Agency (PCA), Ministry of Health, Phnom Penh, Cambodia
| | - Md Razeen Ashraf Hussain
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Ko Ko
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shintaro Nagashima
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Aya Sugiyama
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Halidou Tinto
- Unité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Science de la Santé (IRSS), Nanoro, Burkina Faso
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
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Guntipalli P, Pakala R, Kumari Gara S, Ahmed F, Bhatnagar A, Endaya Coronel MK, Razzack AA, Solimando AG, Thompson A, Andrews K, Enebong Nya G, Ahmad S, Ranaldo R, Cozzolongo R, Shahini E. Worldwide prevalence, genotype distribution and management of hepatitis C. Acta Gastroenterol Belg 2021; 84:637-656. [PMID: 34965046 DOI: 10.51821/84.4.015] [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] [Indexed: 12/09/2022]
Abstract
Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma, resulting in major global public health concerns. The HCV infection is unevenly distributed worldwide, with variations in prevalence across and within countries. The studies on molecular epidemiology conducted in several countries provide an essential supplement for a comprehensive knowledge of HCV epidemiology, genotypes, and subtypes, along with providing information on the impact of current and earlier migratory flows. HCV is phylogenetically classified into 8 major genotypes and 57 subtypes. HCV genotype and subtype distribution differ according to geographic origin and transmission risk category. Unless people with HCV infection are detected and treated appropriately, the number of deaths due to the disease will continue to increase. In 2015, 1.75 million new viral infections were mostly due to unsafe healthcare procedures and drug use injections. In the same year, access to direct-acting antivirals was challenging and varied in developing and developed countries, affecting HCV cure rates based on their availability. The World Health Assembly, in 2016, approved a global strategy to achieve the elimination of the HCV public health threat by 2030 (by reducing new infections by 90% and deaths by 65%). Globally, countries are implementing policies and measures to eliminate HCV risk based on their distribution of genotypes and prevalence.
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Affiliation(s)
- P Guntipalli
- Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, Florida, United States of America
| | - R Pakala
- Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, Florida, United States of America
| | - S Kumari Gara
- Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, Florida, United States of America
| | - F Ahmed
- Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, Florida, United States of America
| | - A Bhatnagar
- Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, Florida, United States of America
| | - M-K Endaya Coronel
- Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, Florida, United States of America
| | - A A Razzack
- Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, Florida, United States of America
| | - A G Solimando
- Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari "Aldo Moro", 70124 Bari, Italy
| | - A Thompson
- Department of Family Medicine, Mississauga Health Centre, Mississauga, Ontario, Canada
| | - K Andrews
- Department of Mathematics and Natural Sciences, Prince Mohammad Bin Fahad University, Al Khobar, Saudi Arabia
| | - G Enebong Nya
- Department of Gastroenterology, John Hopkins Hospital, Baltimore, Maryland, USA
| | - S Ahmad
- Advent Health Cancer Institute, Division of Oncology, Orlando, FL 32804, USA
| | - R Ranaldo
- Digestive Endoscopy, Department of Internal Medicine, "Mazzolani-Vandini" Hospital, Via Nazionale Ponente, 7, Argenta (Ferrara), Italy
| | - R Cozzolongo
- National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy
| | - E Shahini
- National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy
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11
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Ridruejo E, Pereson MJ, Flichman DM, Di Lello FA. Hepatitis C virus treatment failure: Clinical utility for testing resistance-associated substitutions. World J Hepatol 2021; 13:1069-1078. [PMID: 34630875 PMCID: PMC8473504 DOI: 10.4254/wjh.v13.i9.1069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/12/2021] [Accepted: 08/10/2021] [Indexed: 02/06/2023] Open
Abstract
The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions (RAS). However, the consequence of resistance selection during new direct-acting antiviral drug (DAA) treatment is not necessarily the therapeutic failure. In fact, DAA treatment has shown a high rate (> 95%) of sustained virological response even when high baseline RAS prevalence has been reported. In the context of RAS emergence and high rates of sustained viral response, the clinical relevance of variants harboring RAS is still controversial. Therefore, in order to summarize the data available in international guidelines, we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.
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Affiliation(s)
- Ezequiel Ridruejo
- Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Ciudad Autónoma de Buenos Aires C1425AS, Unspecified, Argentina
| | - Matías Javier Pereson
- Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1113, Argentina
| | - Diego M Flichman
- Instituto de Investigaciones Biomédicas en Retrovirus y Síndrome de Inmunodeficiencia Adquirida (INBIRS), Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1113, Argentina
| | - Federico Alejandro Di Lello
- Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1113, Argentina.
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12
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Howe AY, Ceccherini-Silberstein F, Dietz J, Popping S, Grebely J, Rodrigo C, Lennerstrand J, Douglas MW, Parczewsk M, Harrigan PR, Pawlotsky JM, Garcia F, Collaborators SHARED. SHARED: An International Collaboration to Unravel Hepatitis C Resistance. Viruses 2021; 13:1580. [PMID: 34452444 PMCID: PMC8402898 DOI: 10.3390/v13081580] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 07/28/2021] [Indexed: 02/07/2023] Open
Abstract
The advent of direct-acting antivirals (DAAs) has transformed the treatment landscape of hepatitis C [...].
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Affiliation(s)
- Anita Y.M. Howe
- British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada
| | | | - Julia Dietz
- Department of Internal Medicine 1, University Hospital, Goethe University, 65926 Frankfurt, Germany;
| | | | - Jason Grebely
- The Kirby Institute, UNSW Sydney, Sydney, NSW 2006, Australia;
| | - Chaturaka Rodrigo
- Department of Pathology, University of New South Wales, Sydney, NSW 2006, Australia;
| | - Johan Lennerstrand
- Department of Medical Sciences, Clinical Microbiology, Uppsala University, 75121 Uppsala, Sweden;
| | - Mark W. Douglas
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney at Westmead Hospital, Westmead, NSW 2145, Australia;
| | - Milosz Parczewsk
- Department of Infectious Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, 70-507 Szczecin, Poland;
| | - P. Richard Harrigan
- Department of Medicine, University of British Columbia, Vancouver, BC V5Z 4R4, Canada;
| | - Jean-Michel Pawlotsky
- National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Henri Mondor Hospital & INSERM U955, 94000 Créteil, France;
| | - Federico Garcia
- Microbiology Department, University Hospital San Cecilio, Instituto de Investigacion Ibs.Granada, 18012 Granada, Spain;
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13
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Cochard J, Bull-Maurer A, Tauber C, Burlaud-Gaillard J, Mazurier F, Meunier JC, Roingeard P, Chouteau P. Differentiated Cells in Prolonged Hypoxia Produce Highly Infectious Native-Like Hepatitis C Virus Particles. Hepatology 2021; 74:627-640. [PMID: 33665810 DOI: 10.1002/hep.31788] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 01/28/2021] [Accepted: 02/05/2021] [Indexed: 01/20/2023]
Abstract
BACKGROUND AND AIMS Standard hepatitis C virus (HCV) cell-culture models present an altered lipid metabolism and thus produce lipid-poor lipoviral particles (LVPs). These models are thereby weakly adapted to explore the complete natural viral life cycle. APPROACH AND RESULTS To overcome these limitations, we used an HCV cell-culture model based on both cellular differentiation and sustained hypoxia to better mimic the host-cell environment. The long-term exposure of Huh7.5 cells to DMSO and hypoxia (1% O2 ) significantly enhanced the expression of major differentiation markers and the cellular hypoxia adaptive response by contrast with undifferentiated and normoxic (21% O2 ) standard conditions. Because hepatocyte-like differentiation and hypoxia are key regulators of intracellular lipid metabolism, we characterized the distribution of lipid droplets (LDs) and demonstrated that experimental cells significantly accumulate larger and more numerous LDs relative to standard cell-culture conditions. An immunocapture (IC) and transmission electron microscopy (TEM) method showed that differentiated and hypoxic Huh7.5 cells produced lipoproteins significantly larger than those produced by standard Huh7.5 cell cultures. The experimental cell culture model is permissive to HCV-Japanese fulminant hepatitis (JFH1) infection and produces very-low-buoyant-density LVPs that are 6-fold more infectious than LVPs formed by standard JFH1-infected Huh7.5 cells. Finally, the IC-TEM approach and antibody-neutralization experiments revealed that LVPs were highly lipidated, had a global ultrastructure and a conformation of the envelope glycoprotein complex E1E2 close to that of the ones circulating in infected individuals. CONCLUSIONS This relevant HCV cell culture model thus mimics the complete native intracellular HCV life cycle and, by extension, can be proposed as a model of choice for studies of other hepatotropic viruses.
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Affiliation(s)
- Jade Cochard
- INSERM U1259Université de Tours and CHRU de ToursToursFrance
| | | | - Clovis Tauber
- UMRS INSERM U1253 Imagerie et cerveauUniversité de ToursToursFrance
| | | | - Frédéric Mazurier
- Université de ToursEquipe Associée 5501CNRS Equipe de Recherche Labellisée 7001LNOx TeamToursFrance
| | | | - Philippe Roingeard
- INSERM U1259Université de Tours and CHRU de ToursToursFrance.,Plate-Forme IBiSA des MicroscopiesUniversité de Tours and CHRU de ToursToursFrance
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14
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Solitano V, Plaz Torres MC, Pugliese N, Aghemo A. Management and Treatment of Hepatitis C: Are There Still Unsolved Problems and Unique Populations? Viruses 2021; 13:1048. [PMID: 34205966 PMCID: PMC8228389 DOI: 10.3390/v13061048] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/27/2021] [Accepted: 05/28/2021] [Indexed: 02/07/2023] Open
Abstract
Direct-acting antivirals (DAA) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, possibly leading to HCV elimination by 2030 as endorsed by the World Health Organization (WHO). However, some patients belonging to the so-called unique or special populations are referred to as difficult-to-treat due to unreached sustained virological response, potential drug side effects or interactions or co-morbidities. Several years after the DAA introduction and on the basis of excellent findings in terms of efficacy and safety, some doubts arise around the exact meaning of the special population designation and whether this group of patients actually exists. The aim of this review is to discuss and analyze current evidence on the management and treatment of the so-called "unique populations". We placed particular emphasis on patients with decompensated cirrhosis, chronic kidney disease (CKD), coinfections, rare genotypes, and previous treatment failure, in order to provide physicians with an updated overview of the actual problems and needs in the current scenario.
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Affiliation(s)
- Virginia Solitano
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20082 Milan, Italy; (V.S.); (N.P.)
- Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Rozzano, 20089 Milan, Italy;
| | - Maria Corina Plaz Torres
- Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Rozzano, 20089 Milan, Italy;
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20082 Milan, Italy; (V.S.); (N.P.)
- Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Rozzano, 20089 Milan, Italy;
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20082 Milan, Italy; (V.S.); (N.P.)
- Division of Internal Medicine and Hepatology, Humanitas Research Hospital IRCCS, Rozzano, 20089 Milan, Italy;
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15
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Carrasco T, Barquín D, Ndarabu A, Fernández-Alonso M, Rubio-Garrido M, Carlos S, Makonda B, Holguín Á, Reina G. HCV Diagnosis and Sequencing Using Dried Blood Spots from Patients in Kinshasa (DRC): A Tool to Achieve WHO 2030 Targets. Diagnostics (Basel) 2021; 11:522. [PMID: 33804260 PMCID: PMC8002119 DOI: 10.3390/diagnostics11030522] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/09/2021] [Accepted: 03/11/2021] [Indexed: 12/11/2022] Open
Abstract
The World Health Organization has established an elimination plan for hepatitis C virus (HCV) by 2030. In Sub-Saharan Africa (SSA) access to diagnostic tools is limited, and a number of genotype 4 subtypes have been shown to be resistant to some direct-acting antivirals (DAAs). This study aims to analyze diagnostic assays for HCV based on dried blood spots (DBS) specimens collected in Kinshasa and to characterize genetic diversity of the virus within a group of mainly HIV positive patients. HCV antibody detection was performed on 107 DBS samples with Vidas® anti-HCV and Elecsys anti-HCV II, and on 31 samples with INNO-LIA HCV. Twenty-six samples were subjected to molecular detection. NS3, NS5A, and NS5B regions from 11 HCV viremic patients were sequenced. HCV seroprevalence was 12.2% (72% with detectable HCV RNA). Both Elecsys Anti-HCV and INNO-LIA HCV were highly sensitive and specific, whereas Vidas® anti-HCV lacked full sensitivity and specificity when DBS sample was used. NS5B/NS5A/NS3 sequencing revealed exclusively GT4 isolates (50% subtype 4r, 30% 4c and 20% 4k). All 4r strains harbored NS5A resistance-associated substitutions (RAS) at positions 28, 30, and 31, but no NS3 RAS was detected. Elecsys Anti-HCV and INNO-LIA HCV are reliable methods to detect HCV antibodies using DBS. HCV subtype 4r was the most prevalent among our patients. RASs found in subtype 4r in NS5A region confer unknown susceptibility to DAA.
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Affiliation(s)
- Teresa Carrasco
- Microbiology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (T.C.); (D.B.); (M.F.-A.)
| | - David Barquín
- Microbiology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (T.C.); (D.B.); (M.F.-A.)
| | - Adolphe Ndarabu
- Department of Internal Medicine, Centre Hospitalier Monkole, 4484 Kinshasa, Democratic Republic of the Congo; (A.N.); (B.M.)
| | - Mirian Fernández-Alonso
- Microbiology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (T.C.); (D.B.); (M.F.-A.)
- ISTUN, Institute of Tropical Health, Universidad de Navarra, 31008 Pamplona, Spain;
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
| | - Marina Rubio-Garrido
- HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department and Instituto Ramón y Cajal para la Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, CIBER en Epidemiología y Salud Pública (CIBERESP), Red en Investigación Translacional en Infecciones Pediátricas (RITIP), 28034 Madrid, Spain; (M.R.-G.); (Á.H.)
| | - Silvia Carlos
- ISTUN, Institute of Tropical Health, Universidad de Navarra, 31008 Pamplona, Spain;
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
- Department Preventive Medicine and Public Health, Universidad de Navarra, 31008 Pamplona, Spain
| | - Benit Makonda
- Department of Internal Medicine, Centre Hospitalier Monkole, 4484 Kinshasa, Democratic Republic of the Congo; (A.N.); (B.M.)
| | - África Holguín
- HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department and Instituto Ramón y Cajal para la Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, CIBER en Epidemiología y Salud Pública (CIBERESP), Red en Investigación Translacional en Infecciones Pediátricas (RITIP), 28034 Madrid, Spain; (M.R.-G.); (Á.H.)
| | - Gabriel Reina
- Microbiology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (T.C.); (D.B.); (M.F.-A.)
- ISTUN, Institute of Tropical Health, Universidad de Navarra, 31008 Pamplona, Spain;
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
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16
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Zakalashvili M, Zarkua J, Gish RG, Zhamutashvili M, Sartania V, Weizenegger M, Bartel J, Raabe M, Gvinjilia L, Metreveli S, Barnova M, Abramishvili N, Rtskhiladze I, Metreveli D. Assessment of treatment options for patients with hepatitis C virus recombinant form 2k/1b. Hepatol Res 2021; 51:156-165. [PMID: 33207029 DOI: 10.1111/hepr.13587] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 10/21/2020] [Accepted: 10/24/2020] [Indexed: 12/12/2022]
Abstract
AIM Hepatitis C virus (HCV) intergenotype recombinant form (RF) 2k/1b has been actively circulating in HCV-infected patients, and the prevalence of this RF virus in the Republic of Georgia is one of the highest reported worldwide. The aim of this study was to define the optimal treatment regimen for patients with RF_2k/1b. METHODS We analyzed the data of 2735 patients who started treatment at the Medical Center Mrcheveli within Georgia's hepatitis C elimination program from May 2015 through December 2019. The patients were treated with sofosbuvir (SOF)-based regimens. For identification of RF_2k/1b variants, refinement of standard (INNO-LiPA) genotyping results for all patient samples assigned the unspecific HCV genotypes (GT) 2a/2c was carried out by sequencing of core and non-structural protein 5B genes. RESULTS Overall, 444 patients, representing 66% of GT2 and 16% of the total samples, were RF_2k/1b. Treatment of patients with RF_2k/1b with SOF/ledipasvir and SOF/velpatasvir was highly effective and viral cure rates did not differ among genotypes treated with the same regimen: RF_2k/1b, 99% (343/346); GT1, 99% (876/885); GT2, 96% (156/162); and GT3, 99% (545/552). A separate comparison analysis of sustained virologic response rate, treated with SOF plus ribavirin, showed significantly higher sustained virologic response (96%) in patients with confirmed GT2 (by sequencing) compared to unspecified GT2 (by INNO-LiPA) (79%) (P < 0.05). CONCLUSION Sofosbuvir-based regimens are highly effective for treatment of RF 2k/1b patients, and with availability of new pan-genotypic direct-acting antivirals, genotyping to identify RF 2k/1b patients might not be necessary.
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Affiliation(s)
- Mamuka Zakalashvili
- Hepatology and Gastroenterology Department, Medical Center Mrcheveli, Tbilisi, Georgia
| | - Jaba Zarkua
- Hepatology and Gastroenterology Department, Medical Center Mrcheveli, Tbilisi, Georgia
| | - Robert G Gish
- Hepatitis B Foundation, Doylestown, Pennsylvania, USA
| | - Maia Zhamutashvili
- Hepatology and Gastroenterology Department, Medical Center Mrcheveli, Tbilisi, Georgia
| | - Vakhtang Sartania
- Hepatology and Gastroenterology Department, Medical Center Mrcheveli, Tbilisi, Georgia
| | | | - Jan Bartel
- Medical Service Center Dr. Limbach & colleagues, Heidelberg, Germany
| | - Monika Raabe
- Medical Service Center Dr. Limbach & colleagues, Heidelberg, Germany
| | - Lia Gvinjilia
- TEPHINET independent contractor for Georgia Hepatitis C Elimination Program, Atlanta, Georgia, USA
| | - Sophia Metreveli
- Hepatology and Gastroenterology Department, Medical Center Mrcheveli, Tbilisi, Georgia
| | - Maka Barnova
- Hepatology and Gastroenterology Department, Medical Center Mrcheveli, Tbilisi, Georgia
| | - Nikoloz Abramishvili
- Hepatology and Gastroenterology Department, Medical Center Mrcheveli, Tbilisi, Georgia
| | - Irakli Rtskhiladze
- Hepatology and Gastroenterology Department, Medical Center Mrcheveli, Tbilisi, Georgia
| | - David Metreveli
- Hepatology and Gastroenterology Department, Medical Center Mrcheveli, Tbilisi, Georgia
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17
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Soria ME, García-Crespo C, Martínez-González B, Vázquez-Sirvent L, Lobo-Vega R, de Ávila AI, Gallego I, Chen Q, García-Cehic D, Llorens-Revull M, Briones C, Gómez J, Ferrer-Orta C, Verdaguer N, Gregori J, Rodríguez-Frías F, Buti M, Esteban JI, Domingo E, Quer J, Perales C. Amino Acid Substitutions Associated with Treatment Failure for Hepatitis C Virus Infection. J Clin Microbiol 2020; 58:e01985-20. [PMID: 32999010 PMCID: PMC7685896 DOI: 10.1128/jcm.01985-20] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 09/21/2020] [Indexed: 02/07/2023] Open
Abstract
Despite the high virological response rates achieved with current directly acting antiviral agents (DAAs) against hepatitis C virus (HCV), around 2% to 5% of treated patients do not achieve a sustained viral response. The identification of amino acid substitutions associated with treatment failure requires analytical designs, such as subtype-specific ultradeep sequencing (UDS) methods, for HCV characterization and patient management. Using this procedure, we have identified six highly represented amino acid substitutions (HRSs) in NS5A and NS5B of HCV, which are not bona fide resistance-associated substitutions (RAS), from 220 patients who failed therapy. They were present frequently in basal and posttreatment virus of patients who failed different DAA-based therapies. Contrary to several RAS, HRSs belong to the acceptable subset of substitutions according to the PAM250 replacement matrix. Their mutant frequency, measured by the number of deep sequencing reads within the HCV quasispecies that encode the relevant substitutions, ranged between 90% and 100% in most cases. They also have limited predicted disruptive effects on the three-dimensional structures of the proteins harboring them. Possible mechanisms of HRS origin and dominance, as well as their potential predictive value for treatment response, are discussed.
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Affiliation(s)
- María Eugenia Soria
- Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, Madrid, Spain
- Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Carlos García-Crespo
- Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Brenda Martínez-González
- Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, Madrid, Spain
- Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Lucía Vázquez-Sirvent
- Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Rebeca Lobo-Vega
- Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, Madrid, Spain
- Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Ana Isabel de Ávila
- Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Isabel Gallego
- Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
| | - Qian Chen
- Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
| | - Damir García-Cehic
- Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
| | - Meritxell Llorens-Revull
- Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
| | - Carlos Briones
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
- Centro de Astrobiología (CAB, CSIC-INTA), Torrejón de Ardoz, Madrid, Spain
| | - Jordi Gómez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Parasitología y Biomedicina 'López-Neyra' (CSIC), Parque Tecnológico Ciencias de la Salud, Armilla, Granada, Spain
| | - Cristina Ferrer-Orta
- Structural Biology Department, Institut de Biología Molecular de Barcelona CSIC, Barcelona, Spain
| | - Nuria Verdaguer
- Structural Biology Department, Institut de Biología Molecular de Barcelona CSIC, Barcelona, Spain
| | - Josep Gregori
- Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
- Roche Diagnostics, S.L., Barcelona, Spain
| | - Francisco Rodríguez-Frías
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
- Biochemistry and Microbiology Departments, VHIR-HUVH, Barcelona, Spain
| | - María Buti
- Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
| | - Juan Ignacio Esteban
- Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
| | - Esteban Domingo
- Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
| | - Josep Quer
- Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
| | - Celia Perales
- Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, Madrid, Spain
- Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
- Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain
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Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, Marra F, Puoti M, Wedemeyer H. EASL recommendations on treatment of hepatitis C: Final update of the series ☆. J Hepatol 2020; 73:1170-1218. [PMID: 32956768 DOI: 10.1016/j.jhep.2020.08.018] [Citation(s) in RCA: 756] [Impact Index Per Article: 151.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 08/18/2020] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Clinical care for patients with HCV-related liver disease has advanced considerably thanks to an enhanced understanding of the pathophysiology of the disease, as well as developments in diagnostic procedures and improvements in therapy and prevention. These therapies make it possible to eliminate hepatitis C as a major public health threat, as per the World Health Organization target, although the timeline and feasibility vary from region to region. These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.
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