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Fasano M, Ieva F, Ciarallo M, Caccianotti B, Santantonio TA. Acute Hepatitis C: Current Status and Future Perspectives. Viruses 2024; 16:1739. [PMID: 39599853 PMCID: PMC11599108 DOI: 10.3390/v16111739] [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: 09/20/2024] [Revised: 10/30/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024] Open
Abstract
The hepatitis C virus (HCV) infection continues to represent a significant public health threat and is a leading cause of liver cirrhosis, liver cancer, and liver-related mortality. The World Health Organization (WHO) has set a goal for 2030: to eliminate HCV infection as a public health threat by reducing new HCV infections by 90% and mortality by 65%. The early phase of HCV infection represents a pivotal point in the evolution of hepatitis C. Despite a favourable course in the majority of patients, approximately 50-70% of individuals with recently acquired hepatitis C will develop a chronic infection, defined as the persistence of viremia for a period exceeding six months. The diagnosis and treatment of a recent HCV infection should facilitate engagement in multidisciplinary care, prevent the development and complications of chronic liver disease, and reduce ongoing transmission in key populations. Therefore, early treatment in the early phase of infection compared with deferring treatment until the chronic infection remains a valid approach in the era of direct antiviral agents (DAAs). This approach is supported by a cost-effectiveness analysis. The aim of this review is to synthesise the existing knowledge on the early phase of hepatitis C virus infection, with a particular focus on the current risk factors, natural history, therapeutic management, and future perspectives.
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Affiliation(s)
- Massimo Fasano
- Infectious Diseases Unit, PO Della Murgia “F. Perinei”, 70022 Altamura, Italy
| | - Francesco Ieva
- Department of Medical and Surgical Sciences, Section of Infectious Diseases, University of Foggia, 71122 Foggia, Italy; (F.I.); (M.C.); (B.C.); (T.A.S.)
| | - Marianna Ciarallo
- Department of Medical and Surgical Sciences, Section of Infectious Diseases, University of Foggia, 71122 Foggia, Italy; (F.I.); (M.C.); (B.C.); (T.A.S.)
| | - Bruno Caccianotti
- Department of Medical and Surgical Sciences, Section of Infectious Diseases, University of Foggia, 71122 Foggia, Italy; (F.I.); (M.C.); (B.C.); (T.A.S.)
| | - Teresa Antonia Santantonio
- Department of Medical and Surgical Sciences, Section of Infectious Diseases, University of Foggia, 71122 Foggia, Italy; (F.I.); (M.C.); (B.C.); (T.A.S.)
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2
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Gunsolus IL, Prostko J, Pearce S, Degaga B, Eickstead S, Taylor R, Grieshaber J, Richard K, Hoffman A, Pekalska A, Daghfal D. Comparison of a hepatitis C core antigen assay to nucleic acid amplification testing for detection of hepatitis C viremia in a US population. Microbiol Spectr 2024; 12:e0097524. [PMID: 39382335 PMCID: PMC11537050 DOI: 10.1128/spectrum.00975-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 08/31/2024] [Indexed: 10/10/2024] Open
Abstract
The prevalence of hepatitis C virus (HCV) infection in the United States has increased over the past decade despite the development of effective direct-acting antiviral treatments. To meet the World Health Organization's (WHO) goal of eliminating HCV infection by 2030, transmission events must be reduced. Currently, infection screening relies on detection of HCV antibodies, with nucleic acid amplification testing (NAAT) used to confirm HCV viremia and monitor changes in viral load. However, the seroconversion window for detection of HCV antibodies is long, averaging 6 weeks, with delayed seroconversion common in co-infected and immunosuppressed populations. Testing for HCV core antigen, which is present approximately 5 weeks before HCV antibodies, holds promise for earlier detection of HCV infection. It may also hold promise as a cheaper, more accessible, and more rapid alternative to NAAT for infection confirmation. Here, we evaluated the agreement between a research-use HCV Core Antigen Assay and NAAT among US patients receiving clinically indicated NAAT. Among 412 specimens, the overall concordance was 97.1%, with a positive percent agreement of 95.5%. Discrepancies primarily occurred among patients with chronic HCV and low viral loads; 11/12 discrepancies showed viral loads <4,000 IU/mL. Among patients being screened for HCV infection (i.e., excluding those undergoing NAAT for serial monitoring of a previously diagnosed infection), the positive percent agreement was 97.0%. Among patients undergoing serial testing, changes in HCV Core Antigen Assay signal-to-cut-off values were generally correlated with changes in the viral load. Results suggest that the research-use HCV Core Antigen Assay studied here may reliably detect and/or confirm HCV infection. IMPORTANCE A research-use HCV Core Antigen Assay showed high concordance with nucleic acid amplification testing for the detection of current hepatitis C infection. The assay may enable more rapid and lower-cost detection and/or confirmation of hepatitis C infection.
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Affiliation(s)
- Ian L. Gunsolus
- Department of Laboratory Medicine and Pathology, HealthPartners, Minneapolis, Minnesota, USA
| | - John Prostko
- Core Diagnostics, Abbott Laboratories, Abbott Park, Illinois, USA
| | - Sandra Pearce
- Core Diagnostics, Abbott Laboratories, Abbott Park, Illinois, USA
| | - Biniam Degaga
- Department of Laboratory Medicine and Pathology, HealthPartners, Minneapolis, Minnesota, USA
| | - Scott Eickstead
- Department of Laboratory Medicine and Pathology, HealthPartners, Minneapolis, Minnesota, USA
| | - Russ Taylor
- Core Diagnostics, Abbott Laboratories, Abbott Park, Illinois, USA
| | | | - Kyle Richard
- Core Diagnostics, Abbott Laboratories, Abbott Park, Illinois, USA
| | - Anne Hoffman
- Core Diagnostics, Abbott Laboratories, Abbott Park, Illinois, USA
| | - Aneta Pekalska
- Core Diagnostics, Abbott Laboratories, Abbott Park, Illinois, USA
| | - David Daghfal
- Core Diagnostics, Abbott Laboratories, Abbott Park, Illinois, USA
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3
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Jaitpal S, Ng KW, San Juan AM, Martinez C, Phillips C, Tripathy S, Mabbott S. DNA-directed formation of plasmonic core-satellite nanostructures for quantification of hepatitis C viral RNA. Chem Sci 2024; 15:8112-8126. [PMID: 38817589 PMCID: PMC11134388 DOI: 10.1039/d4sc00891j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 04/19/2024] [Indexed: 06/01/2024] Open
Abstract
Hepatitis C virus (HCV) continues to be a significant public health challenge, affecting an estimated 71 million people globally and posing risks of severe liver diseases. Despite advancements in treatments, diagnostic limitations hinder the global elimination efforts targeted by 2030. This study introduces an innovative diagnostic approach, integrating catalytic hairpin assembly (CHA) with plasmonic core-satellite gold nanoparticle (AuNP) assemblies, to enable sensitive and specific detection of HCV RNA. We optimized the stoichiometry of DNA hairpins to form highly stable three-way junctions (3WJs), minimizing non-specific reactions in an enzyme-free, isothermal amplification process. The resulting dual-transduction biosensor combines colorimetric and surface-enhanced Raman spectroscopy (SERS) techniques, utilizing the Raman reporter malachite green isothiocyanate (MGITC) for signal generation. Our system targets a conserved 23-nucleotide sequence within the HCV 5'-UTR, essential for RNA replication, facilitating pan-genotypic HCV detection that complements direct-acting antiviral strategies. We evaluated the biosensor's efficacy using fluorescence spectroscopy, native PAGE, AFM, and TEM. Findings indicate that the 60 nm core AuNPs surrounded by 20 nm satellite AuNPs achieved a ten-fold increase in sensitivity over the 10 nm satellites, detecting HCV RNA concentrations as low as 1.706 fM. This sensitivity is crucial, given the extremely low viral loads present during early infection stages. Our research demonstrates the promise of enzyme-free molecular biosensors for HCV, with the potential to provide cost-efficient, rapid, point-of-care testing, although further sensitivity enhancements are needed to address the challenges of early-stage detection.
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Affiliation(s)
- Siddhant Jaitpal
- Department of Biomedical Engineering, Texas A&M University 600 Discovery Drive College Station TX 77840-3006 USA
- Center for Remote Health Technologies & Systems, Texas A&M Engineering Experiment Station 600 Discovery Drive College Station TX 77840-3006 USA
| | - Ka Wai Ng
- Department of Biomedical Engineering, Texas A&M University 600 Discovery Drive College Station TX 77840-3006 USA
- Center for Remote Health Technologies & Systems, Texas A&M Engineering Experiment Station 600 Discovery Drive College Station TX 77840-3006 USA
| | - Angela Michelle San Juan
- Department of Biomedical Engineering, Texas A&M University 600 Discovery Drive College Station TX 77840-3006 USA
- Center for Remote Health Technologies & Systems, Texas A&M Engineering Experiment Station 600 Discovery Drive College Station TX 77840-3006 USA
| | - Cecilia Martinez
- Department of Biomedical Engineering, Texas A&M University 600 Discovery Drive College Station TX 77840-3006 USA
| | - Christian Phillips
- Department of Biomedical Engineering, Texas A&M University 600 Discovery Drive College Station TX 77840-3006 USA
| | - Sayantan Tripathy
- Department of Biomedical Engineering, Texas A&M University 600 Discovery Drive College Station TX 77840-3006 USA
- Center for Remote Health Technologies & Systems, Texas A&M Engineering Experiment Station 600 Discovery Drive College Station TX 77840-3006 USA
| | - Samuel Mabbott
- Department of Biomedical Engineering, Texas A&M University 600 Discovery Drive College Station TX 77840-3006 USA
- Center for Remote Health Technologies & Systems, Texas A&M Engineering Experiment Station 600 Discovery Drive College Station TX 77840-3006 USA
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Cartwright EJ, Patel PR. Opportunities for Enhanced Prevention and Control of Hepatitis C Through Improved Screening and Testing Efforts. J Infect Dis 2024; 229:S350-S356. [PMID: 37739791 PMCID: PMC10961945 DOI: 10.1093/infdis/jiad199] [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: 03/21/2023] [Revised: 05/11/2023] [Accepted: 05/31/2023] [Indexed: 09/24/2023] Open
Abstract
An estimated 2.4 million people in the United States are living with hepatitis C virus (HCV) infection. In 2020, the Centers for Disease Control and Prevention updated hepatitis C screening recommendations to test adults aged ≥18 years at least once in a lifetime and pregnant persons during each pregnancy. For those with ongoing exposure to HCV, periodic testing is recommended. The recommended testing sequence is to obtain an HCV antibody test and, when positive, perform an HCV RNA test. Examination of HCV care cascades has found that incomplete HCV testing occurs when a separate visit is required to obtain the HCV RNA test. Hepatitis C core antigen testing has been shown to be a useful tool for diagnosing current HCV infection in some settings. Hepatitis C testing that is completed, accurate, and efficient is necessary to achieve hepatitis C elimination goals.
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Affiliation(s)
- Emily J. Cartwright
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC
- Emory University, Atlanta Georgia
- Atlanta VA Health Care System, Decatur, Georgia
| | - Priti R. Patel
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC
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Chen B, Xu B, Cui HY, Ma ZH, Guo WH, Pei LJ, Xing WG. Comparison of effectiveness and cost of different HCV testing strategies in high-risk populations in China. J Med Virol 2024; 96:e29433. [PMID: 38293900 DOI: 10.1002/jmv.29433] [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: 09/07/2023] [Revised: 12/26/2023] [Accepted: 01/17/2024] [Indexed: 02/01/2024]
Abstract
High-risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost-effective HCV testing strategies for high-risk populations to identify potential undiagnosed HCV-infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high-risk populations. Among the 2093 samples from high-risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV-positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high-risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti-HCV screening, followed by HCV RNA testing on reactive samples.
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Affiliation(s)
- Bing Chen
- Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Anhui, China
| | - Bing Xu
- Center for Global Public Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Hai-Yan Cui
- Department of Clinical Laboratory, Zhumadian Center for Disease Control and Prevention, Henan, China
| | - Zhong-Hui Ma
- Department of Communicable and Endemic Disease Control and Prevention, Fangshan District Center for Disease Control and Prevention in Beijing, Beijing, China
| | - Wen-Hui Guo
- National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Li-Jian Pei
- National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Wen-Ge Xing
- National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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6
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Li H, Yang S, Cao D, Wang Q, Zhang S, Zhou Y, Liu D, Yang R, Cui L, Zhu Z. A new double-antigen sandwich test based on the light-initiated chemiluminescent assay for detecting anti-hepatitis C virus antibodies with high sensitivity and specificity. Front Cell Infect Microbiol 2023; 13:1222778. [PMID: 38076452 PMCID: PMC10704264 DOI: 10.3389/fcimb.2023.1222778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 10/20/2023] [Indexed: 12/18/2023] Open
Abstract
Objectives The aim of this study was to evaluate the performance of a new double-antigen sandwich test that is based on the light-initiated chemiluminescent assay (LiCA®) for detecting anti-hepatitis C virus antibodies (anti-HCV) in comparison to Architect®. Methods Analytical characteristics and diagnostic performance were tested using seroconversion panels and large pools of clinical samples. Positive results were validated by the strip immunoblot assay (RIBA) and HCV RNA. Results Repeatability and within-lab imprecision of LiCA® anti-HCV were 1.31%-3.27%. The C5-C95 interval was -5.44%-5.03% away from C50. LiCA® detected seroconversion in an average of 28.9 days and showed a mean of 3.7 (p = 0.0056) days earlier than Architect®. In a pool of 239 samples with known HCV genotypes 1 to 6, both assays correctly detected all subjects. In 16,305 clinical patient sera, LiCA® detected 4 false-negative (0.25‰) and 14 false-positive (0.86‰) anti-HCV cases, while Architect® recorded 6 false-negative (0.37‰) and 138 false-positive (8.46‰) subjects, respectively. Compared to Architect®, LiCA® presented a significantly better performance in specificity (99.91% vs. 99.14%, n = 16,018, p < 0.0001), positive predictive value (95.29% vs. 67.06%, n = 419, p < 0.0001), and overall accuracy (99.89% vs. 99.12%, n = 16,305, p < 0.0001), while no significant difference in sensitivity (98.61% vs. 97.91%, n = 287, p = 0.5217) and negative predictive value (99.98% vs. 99.96%, n = 15,886, p = 0.3021) was seen. An S/Co value of 3.28 was predicted to be the threshold with a positivity ≥95% for the LiCA® anti-HCV assay. Conclusion LiCA® anti-HCV is a precise and fully automatic chemiluminescent assay with superior sensitivity and specificity. The assay can be used as a valuable tool to supplement the diagnosis of HCV infection.
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Affiliation(s)
- Haicong Li
- Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Shanghai, China
| | - Shuo Yang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Dan Cao
- Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Shanghai, China
| | - Qianying Wang
- Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Shanghai, China
| | - Siyu Zhang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Yi Zhou
- Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Shanghai, China
| | - Di Liu
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Ruifeng Yang
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing, China
| | - Liyan Cui
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Zhaoqin Zhu
- Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Shanghai, China
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Martinello M, Solomon SS, Terrault NA, Dore GJ. Hepatitis C. Lancet 2023; 402:1085-1096. [PMID: 37741678 DOI: 10.1016/s0140-6736(23)01320-x] [Citation(s) in RCA: 66] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 05/30/2023] [Accepted: 06/22/2023] [Indexed: 09/25/2023]
Abstract
Hepatitis C virus (HCV) is a hepatotropic RNA virus that can cause acute and chronic hepatitis, with progressive liver damage resulting in cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In 2016, WHO called for the elimination of HCV infection as a public health threat by 2030. Despite some progress, an estimated 57 million people were living with HCV infection in 2020, and 300 000 HCV-related deaths occur per year. The development of direct-acting antiviral therapy has revolutionised clinical care and generated impetus for elimination, but simplified and broadened HCV screening, enhanced linkage to care, and higher coverage of treatment and primary prevention strategies are urgently required.
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Affiliation(s)
- Marianne Martinello
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia; Department of Infectious Diseases, Prince of Wales Hospital, Sydney, NSW, Australia.
| | - Sunil S Solomon
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, USA
| | - Gregory J Dore
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia; Department of Infectious Diseases, St Vincent's Hospital, Sydney, NSW, Australia
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Liu CH, Kao JH. Acute hepatitis C virus infection: clinical update and remaining challenges. Clin Mol Hepatol 2023; 29:623-642. [PMID: 36800699 PMCID: PMC10366792 DOI: 10.3350/cmh.2022.0349] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 01/27/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Acute hepatitis C virus (HCV) infection is a global health concern with substantial geographical variation in the incidence rate. People who have received unsafe medical procedures, used injection drugs, and lived with human immunodeficiency virus are reported to be most susceptible to acute HCV infection. The diagnosis of acute HCV infection is particularly challenging in immunocompromised, reinfected, and superinfected patients due to difficulty in detecting anti-HCV antibody seroconversion and HCV ribonucleic acid from a previously negative antibody response. With an excellent treatment effect on chronic HCV infection, recently, clinical trials investigating the benefit of direct-acting antivirals (DAAs) treatment for acute HCV infection have been conducted. Based on the results of cost-effectiveness analysis, DAAs should be initiated early in acute HCV infection prior to spontaneous viral clearance. Compared to the standard 8-12 week-course of DAAs for chronic HCV infection, DAAs treatment duration may be shortened to 6-8 weeks in acute HCV infection without compromising the efficacy. Standard DAA regimens provide comparable efficacy in treating HCV-reinfected patients and DAA-naïve ones. For cases contracting acute HCV infection from HCV-viremic liver transplant, a 12-week course of pangenotypic DAAs is suggested. While for cases contracting acute HCV infection from HCV-viremic non-liver solid organ transplants, a short course of prophylactic or pre-emptive DAAs is suggested. Currently, prophylactic HCV vaccines are unavailable. In addition to treatment scale-up for acute HCV infection, practice of universal precaution, harm reduction, safe sex, and vigilant surveillance after viral clearance remain critical in reducing HCV transmission.
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Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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Pedersen J, Moukandja IP, Ndidi S, Sørensen AL, Koumakpayi IH, Lekana-Douki JB, Vachon ML, Weis N, Kobinger G, Fausther-Bovendo H. An adaptable platform for in-house hepatitis C serology. J Virol Methods 2022; 308:114586. [PMID: 35850366 DOI: 10.1016/j.jviromet.2022.114586] [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: 03/14/2022] [Revised: 06/16/2022] [Accepted: 07/14/2022] [Indexed: 12/09/2022]
Abstract
Serology-based diagnosis remains one of the major tools for diagnosis and surveillance of infectious diseases. However, for many neglected diseases no or only few commercial assays are available and often with prices prohibiting large scale testing in low and middle-income countries (LMICs). We developed an adaptable enzyme-linked immunoassay (ELISA) using hepatitis C virus (HCV) as a proof-of-concept application. By combining the maltose-binding-protein with a multiepitope HCV protein, we were able to obtain a high concentration of protein suitable for downstream applications. Following optimization, the assay was verified using previously tested human samples from Canada, Denmark and Gabon in parallel with the use of a commercial protein. Sensitivity and specificity were calculated to 98 % and 97 % respectively, after accounting for non-specific binding and assay optimization. This study provides a thorough description of the development, and validation of a multiepitope ELISA-based diagnostic assay against HCV, which could be implemented at low cost. The described methodology can be readily adapted to develop novel ELISA-based diagnostic assays for other infectious pathogens with well-described immunogenic epitopes. This method could improve the diagnosis of neglected diseases for which affordable diagnostic assays are lacking.
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Affiliation(s)
- Jannie Pedersen
- Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, Canada
| | | | - Stella Ndidi
- Centre Hospitalier Universitaire de Libreville, Libreville BP2228, Gabon
| | - Anna-Louise Sørensen
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Jean-Bernard Lekana-Douki
- Unité d'Evolution Epidémiologie et Résistances Parasitaires, Centre Interdisciplinaire de Recherches Médicales de Franceville, Franceville, Gabon
| | - Marie-Louise Vachon
- Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec G1V 4G2, Canada
| | - Nina Weis
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Gary Kobinger
- Galveston National Laboratory, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
| | - Hugues Fausther-Bovendo
- Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, Canada; Global Urgent and Advanced Research and Development - GUARD, 911 Rue Principale, unit 100, Batiscan, Quebec G0X 1A0, Canada.
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Sun HY, Chiang C, Huang SH, Guo WJ, Chuang YC, Huang YC, Yang CJ, Su LH, Chen YT, Chen YW, Hsu FC, Ho SY, Liu WC, Su YC, Chang SY, Hsiao CF, Hung CC, Yu ML. Three-Stage Pooled Plasma Hepatitis C Virus RNA Testing for the Identification of Acute HCV Infections in At-Risk Populations. Microbiol Spectr 2022; 10:e0243721. [PMID: 35499354 PMCID: PMC9241589 DOI: 10.1128/spectrum.02437-21] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 04/11/2022] [Indexed: 01/26/2023] Open
Abstract
Timely diagnosis and treatment of hepatitis C virus (HCV) infection may prevent its transmission. We evaluated the performance and cost reductions of the pooled plasma HCV RNA testing strategy to identify acute HCV infections among people living with HIV (PLWH). PLWH with sexually transmitted infections, elevated aminotransferases within the past 6 months or past HCV infections (high-risk) and those without (low-risk) were enrolled prospectively. Participants underwent three-stage pooled plasma HCV RNA testing every 12 to 24 weeks until detection of HCV RNA or completion of a 48-week follow-up. The three-stage strategy combined 20 individual specimens into a stage 1 pool, 5 individual specimens from the stage 1 pool that tested positive for HCV RNA in the stage 2 mini-pool, followed by testing of individual specimens of the stage 2 mini-pool tested positive for HCV RNA. A simulation was constructed to investigate the cost reductions and pooled sensitivity and specificity under different combinations of HCV prevalence and pool/mini-pool sizes. Between June 25, 2019 and March 31, 2021, 32 cases of incident HCV viremia were identified in 760 high-risk PLWH that were enrolled 834 times, giving an incidence rate of 56.6 per 1000 person-years of follow-up (PYFU). No cases of HCV viremia were identified in 557 low-risk PLWH during a total of 269.2 PYFU. Simulation analysis suggested that this strategy could reduce HCV RNA testing cost by 50% to 86% with HCV viremia prevalence of 1% to 5% and various pooled sizes despite compromised pooled sensitivity. This pooled plasma HCV RNA testing strategy is cost-saving to identify acute HCV infections in high-risk populations with HCV viremia prevalence of 1% to 5%. IMPORTANCE Our three-stage pooled plasma HCV RNA testing successfully identified HCV viremia in high-risk PLWH with a testing cost reduction of 84.5%. Simulation analysis offered detailed information regarding the selection of pool and mini-pool sizes in settings of different HCV epidemiology and the performance of HCV RNA testing to optimize the cost reduction.
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Affiliation(s)
- Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chieh Chiang
- Department of Mathematics, Tamkang University, New Taipei City, Taiwan
| | - Sung-Hsi Huang
- Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
- Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wen-Jin Guo
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
| | - Yu-Chung Chuang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Chia Huang
- Department of Internal Medicine, National Taiwan University Hospital Biomedical Park Branch, Hsin-Chu, Taiwan
| | - Chia-Jui Yang
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Li-Hsin Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ting Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yea-Wen Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Fu-Chiang Hsu
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Laboratory Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shu-Yuan Ho
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Laboratory Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wen-Chun Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ching Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Sui-Yuan Chang
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Laboratory Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chin-Fu Hsiao
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- China Medical University, Taichung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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11
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Sun HY, Liu WD, Wang CW, Wei YJ, Lin KY, Huang YS, Su LH, Chen YT, Liu WC, Su YC, Chen YW, Chuang YC, Lu PL, Hung CC, Yu ML. Performance of Hepatitis C Virus (HCV) Core Antigen Assay in the Diagnosis of Recently Acquired HCV Infection among High-Risk Populations. Microbiol Spectr 2022; 10:e0034522. [PMID: 35579445 PMCID: PMC9241744 DOI: 10.1128/spectrum.00345-22] [Citation(s) in RCA: 6] [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: 01/29/2022] [Accepted: 04/26/2022] [Indexed: 11/20/2022] Open
Abstract
How the hepatitis C virus (HCV) core antigen (HCVcAg) assay performs in detecting recently acquired HCV infection among people living with HIV (PLWH) and HIV-negative men who have sex with men (MSM) is rarely assessed in the Asia-Pacific region. High-risk participants, including PLWH with sexually transmitted infections (STIs), HCV clearance by antivirals or spontaneously, or elevated aminotransferases, HIV-negative MSM with STIs or on HIV preexposure prophylaxis, and low-risk PLWH were enrolled. Blood samples were subjected to 3-stage pooled-plasma HCV RNA testing every 3 to 6 months until detection of HCV viremia or completion of the 1-year follow-up. The samples at enrollment and all of the archived samples preceding the detection of HCV RNA during follow-up were tested for HCVcAg. During June 2019 and February 2021, 1,639 blood samples from 744 high-risk and 727 low-risk PLWH and 86 HIV-negative participants were tested for both HCV RNA and HCVcAg. Of 62 samples positive for HCV RNA, 54 (87.1%) were positive for HCVcAg. Of 1,577 samples negative for HCV RNA, 1,568 (99.4%) were negative for HCVcAg. The mean HCV RNA load of the 8 individual samples positive for HCV RNA but negative for HCVcAg was 3.2 (range, 2.5 to 3.9) log10 IU/mL, and that of the remaining 54 samples with concordant results was 6.2 (range, 1.3 to 8.5) log10 IU/mL. The positive predictive value (PPV) and negative predictive value (NPV) of HCVcAg were 85.7% and 99.5%, respectively. In at-risk populations, HCVcAg has a high specificity and NPV but lower sensitivity and PPV, particularly in individuals with low HCV RNA loads. IMPORTANCE The HCV core antigen assay has a high specificity of 99.4% and negative predictive value of 99.5% but a lower sensitivity of 87.1% and positive predictive value of 85.7% in the diagnosis of recently acquired HCV infection in high-risk populations. Our findings are informative for many countries confronted with limited resources to timely identify acute HCV infections and provide effective direct-acting antivirals to halt onward transmission.
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Affiliation(s)
- Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wang-Da Liu
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Chih-Wen Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Ju Wei
- Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuan-Yin Lin
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yu-Shan Huang
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Li-Hsin Su
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ting Chen
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wen-Chun Liu
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Chin Su
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yea-Wen Chen
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yu-Chung Chuang
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Po-Liang Lu
- Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospitalgrid.412094.a and National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- China Medical University, Taichung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
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12
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O'Shea J, Oliver N, Cartwright EJ. Diagnosis and Clinical Manifestations of Acute Hepatitis C Infection in People Living with HIV. AIDS Patient Care STDS 2022; 36:172-177. [PMID: 35507325 DOI: 10.1089/apc.2022.0021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
HIV/hepatitis C virus (HCV) coinfection is a global health problem with overlapping modes of transmission. We performed a single-center retrospective case series of acute HCV infections at the Atlanta Veterans Affairs Health Care System between January 2001 and June 2020 to better characterize the presentation and clinical course of acute HCV among veterans with HIV. Cases were discovered through routine clinical care. We identified 29 cases of acute HCV: all men. Risk for HCV acquisition included men who have sex with men (MSM; 93%) and injection drug use (17%). Thirteen (45%) had a concurrent sexually transmitted infection (STI). Symptoms were seen in 76% of acute HCV cases and resulted in hospitalization in 59% of symptomatic cases. Seven (24%) presented as HCV antibody seronegative. Three never seroconverted, all with CD4 T cell counts <200. Spontaneous HCV clearance occurred in 21% (n = 6) and was more common in those who developed jaundice (p = 0.01). Time to treatment was significantly reduced in the direct-acting antivirals (DAAs) era versus the interferon era (300 vs. 1631 days, p < 0.01). Of those who did not spontaneously clear, 87% were treated (n = 20/23) and 95% (n = 19/20) achieved sustained virological response. Three patients died before HCV treatment, all in the pre-DAA period (one death was liver related). In this case series of acute HCV infection in persons with HIV, many were symptomatic MSM who had a concurrent STI, suggesting sexual HCV transmission. Some presented as HCV antibody negative, highlighting the role of enhanced HCV screening and treatment in MSM with HIV to prevent HCV transmission in sexual networks.
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Affiliation(s)
- Jesse O'Shea
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Nora Oliver
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
- Infectious Diseases, Atlanta VA Health Care System, Decatur, Georgia, USA
| | - Emily J. Cartwright
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
- Infectious Diseases, Atlanta VA Health Care System, Decatur, Georgia, USA
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13
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Ji Q, Chu X, Zhou Y, Liu X, Zhao W, Ye W. Safety and efficacy of grazoprevir/elbasvir in the treatment of acute hepatitis C in hemodialysis patients. J Med Virol 2022; 94:675-682. [PMID: 34599755 PMCID: PMC9298284 DOI: 10.1002/jmv.27374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 09/07/2021] [Accepted: 09/30/2021] [Indexed: 11/18/2022]
Abstract
Treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents (DAAs) in hemodialysis patients requires extensive consideration. At present, studies regarding DAAs for acute HCV infection in such patients are limited. The present study aims to evaluate the efficacy and safety of grazoprevir (GZR) plus elbasvir (EBR) treatment in acute hepatitis C (AHC) patients undergoing hemodialysis. Patients undergoing hemodialysis who had a nosocomial acute HCV infection were enrolled. All patients received GZR 100 mg/EBR 50 mg once daily for 12 weeks and were followed up for 12 weeks. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and HCV RNA levels were monitored during treatment and follow-up periods. Sustained virologic response at 12 weeks after treatment cessation and treatment-emergent adverse events (AEs) were assessed. A total of 68 AHC patients were enrolled. All patients were infected with HCV genotype 1b and achieved SVR12. Decreasing ALT, AST, and TBIL were observed over time in the first 4 weeks and became steady thereafter. Forty-eight (70.59%) patients reported at least one AEs. The most common AEs were fatigue, headache, and nausea. Two AHC patients discontinued treatment due to serious but drug-unrelated AEs. In conclusion, GZR/EBR has a high efficacy and safety profile in hemodialysis-dependent patients with genotype 1b AHC.
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Affiliation(s)
- Qinghua Ji
- Department of Infectious Disease, School of MedicineSoutheast UniversityNanjingJiangsuChina
| | - Xudong Chu
- Department of Infectious DiseasesThe Affiliated Dongtai Hospital of Nantong UniversityDongtaiJiangsuChina
| | - Yugui Zhou
- Department of Clinical LaboratoryThe Affiliated Dongtai Hospital of Nantong UniversityDongtaiJiangsuChina
| | - Xuan Liu
- Department of Clinical LaboratoryThe Second Hospital of NanjingNanjingJiangsuChina
| | - Wei Zhao
- Department of Infectious Disease, School of MedicineSoutheast UniversityNanjingJiangsuChina
| | - Wei Ye
- Department of Liver DiseaseThe Second Hospital of Nanjing, Southeast UniversityNanjingJiangsuChina
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14
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Ogega CO, Skinner NE, Flyak AI, Clark KE, Board NL, Bjorkman PJ, Crowe JE, Cox AL, Ray SC, Bailey JR. B cell overexpression of FCRL5 and PD-1 is associated with low antibody titers in HCV infection. PLoS Pathog 2022; 18:e1010179. [PMID: 34990486 PMCID: PMC8769295 DOI: 10.1371/journal.ppat.1010179] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/19/2022] [Accepted: 12/07/2021] [Indexed: 11/25/2022] Open
Abstract
Antibodies targeting the hepatitis C virus (HCV) envelope glycoprotein E2 are associated with delayed disease progression, and these antibodies can also facilitate spontaneous clearance of infection in some individuals. However, many infected people demonstrate low titer and delayed anti-E2 antibody responses. Since a goal of HCV vaccine development is induction of high titers of anti-E2 antibodies, it is important to define the mechanisms underlying these suboptimal antibody responses. By staining lymphocytes with a cocktail of soluble E2 (sE2) glycoproteins, we detected HCV E2-specific (sE2+) B cells directly ex vivo at multiple acute infection timepoints in 29 HCV-infected subjects with a wide range of anti-E2 IgG titers, including 17 persistently infected subjects and 12 subjects with spontaneous clearance of infection. We performed multi-dimensional flow cytometric analysis of sE2+ and E2-nonspecific (sE2-) class-switched B cells (csBC). In sE2+ csBC from both persistence and clearance subjects, frequencies of resting memory B cells (rMBC) were reduced, frequencies of activated MBC (actMBC) and tissue-like MBC (tlMBC) were increased, and expression of FCRL5, an IgG receptor, was significantly upregulated. Across all subjects, plasma anti-E2 IgG levels were positively correlated with frequencies of sE2+ rMBC and sE2+ actMBC, while anti-E2 IgG levels were negatively correlated with levels of FCRL5 expression on sE2+ rMBC and PD-1 expression on sE2+ actMBC. Upregulation of FCRL5 on sE2+ rMBC and upregulation of PD-1 on sE2+ actMBC may limit anti-E2 antibody production in vivo. Strategies that limit upregulation of these molecules could potentially generate higher titers of protective antibodies against HCV or other pathogens. Antiviral immunity relies on production of protective immunoglobulin G (IgG) by B cells, but many hepatitis C virus (HCV)-infected individuals have very low levels of HCV-specific IgG in their serum. Elucidating mechanisms underlying this suboptimal IgG expression remains paramount in guiding therapeutic and vaccine strategies. In this study, we developed a highly specific method to capture HCV-specific B cells and characterized their surface protein expression. Two proteins analyzed were Fc receptor-like protein 5 (FCRL5), a cell surface receptor for IgG, and programmed cell death protein-1 (PD-1), a marker of lymphocyte activation and exhaustion. We measured serum levels of anti-HCV IgG in these subjects and demonstrated that overexpression of FCRL5 and PD-1 on memory B cells was associated with reduced anti-E2 IgG levels. This study uses HCV as a viral model, but the findings may be applicable to many viral infections, and they offer new potential targets to enhance antiviral IgG production.
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Affiliation(s)
- Clinton O. Ogega
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, Maryland, United States of America
| | - Nicole E. Skinner
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, Maryland, United States of America
| | - Andrew I. Flyak
- Division of Biology and Biological Engineering, California Institute of Technology; Pasadena, California, United States of America
| | - Kaitlyn E. Clark
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, Maryland, United States of America
| | - Nathan L. Board
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, Maryland, United States of America
| | - Pamela J. Bjorkman
- Division of Biology and Biological Engineering, California Institute of Technology; Pasadena, California, United States of America
| | - James E. Crowe
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center; Nashville, Tennessee, United States of America
- Department of Pediatrics, Vanderbilt University Medical Center; Nashville, Tennessee, United States of America
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center; Nashville, Tennessee, United States of America
| | - Andrea L. Cox
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, Maryland, United States of America
| | - Stuart C. Ray
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, Maryland, United States of America
| | - Justin R. Bailey
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine; Baltimore, Maryland, United States of America
- * E-mail:
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15
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Paper microfluidic implementation of loop mediated isothermal amplification for early diagnosis of hepatitis C virus. Nat Commun 2021; 12:6994. [PMID: 34848705 PMCID: PMC8632961 DOI: 10.1038/s41467-021-27076-z] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 10/27/2021] [Indexed: 12/26/2022] Open
Abstract
The early diagnosis of active hepatitis C virus (HCV) infection remains a significant barrier to the treatment of the disease and to preventing the associated significant morbidity and mortality seen, worldwide. Current testing is delayed due to the high cost, long turnaround times and high expertise needed in centralised diagnostic laboratories. Here we demonstrate a user-friendly, low-cost pan-genotypic assay, based upon reverse transcriptase loop mediated isothermal amplification (RT-LAMP). We developed a prototype device for point-of-care use, comprising a LAMP amplification chamber and lateral flow nucleic acid detection strips, giving a visually-read, user-friendly result in <40 min. The developed assay fulfils the current guidelines recommended by World Health Organisation and is manufactured at minimal cost using simple, portable equipment. Further development of the diagnostic test will facilitate linkage between disease diagnosis and treatment, greatly improving patient care pathways and reducing loss to follow-up, so assisting in the global elimination strategy. Current HCV nucleic acid-based diagnosis is largely performed in centralised laboratories. Here, the authors present a pan-genotypic RNA assay, based on reverse transcriptase loop mediated isothermal amplification and develop a low-cost prototype paper-based lateral flow device for point-of-care use, providing a visually read result within 40 min.
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16
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Sadeghimehr M, Bertisch B, Negro F, Butsashvili M, Shilton S, Tskhomelidze I, Tsereteli M, Keiser O, Estill J. Hepatitis C core antigen test as an alternative for diagnosing HCV infection: mathematical model and cost-effectiveness analysis. PeerJ 2021; 9:e11895. [PMID: 34595063 PMCID: PMC8436958 DOI: 10.7717/peerj.11895] [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: 12/23/2020] [Accepted: 07/12/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND The cost and complexity of the polymerase chain reaction (PCR) test are barriers to diagnosis and treatment of hepatitis C virus (HCV) infection. We investigated the cost-effectiveness of testing strategies using antigen instead of PCR testing. METHODS We developed a mathematical model for HCV to estimate the number of diagnoses and cases of liver disease. We compared the following testing strategies: antibody test followed by PCR in case of positive antibody (baseline strategy); antibody test followed by HCV-antigen test (antibody-antigen); antigen test alone; PCR test alone. We conducted cost-effectiveness analyses considering either the costs of HCV testing of infected and uninfected individuals alone (A1), HCV testing and liver-related complications (A2), or all costs including HCV treatment (A3). The model was parameterized for the country of Georgia. We conducted several sensitivity analyses. RESULTS The baseline scenario could detect 89% of infected individuals. Antibody-antigen detected 86% and antigen alone 88% of infected individuals. PCR testing alone detected 91% of the infected individuals: the remaining 9% either died or spontaneously recovered before testing. In analysis A1, the baseline strategy was not essentially more expensive than antibody-antigen. In analysis A2, strategies using PCR became cheaper than antigen-based strategies. In analysis A3, antibody-antigen was again the cheapest strategy, followed by the baseline strategy, and PCR testing alone. CONCLUSIONS Antigen testing, either following a positive antibody test or alone, performed almost as well as the current practice of HCV testing. The cost-effectiveness of these strategies depends on the inclusion of treatment costs.
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Affiliation(s)
| | - Barbara Bertisch
- Institute of Global Health, University of Geneva, Geneva, Switzerland
- Checkin Helvetiaplatz, Zürich, Switzerland
| | - Francesco Negro
- Divisions of Gastroenterology and Hepatology and of Clinical Pathology, Geneva University Hospitals, Geneva, Switzerland
| | | | | | - Irina Tskhomelidze
- TEPHINET for Georgia Hepatitis C Elimination Program, I. Javakhishvili Tbilisi State University, Tbilisi, Georgia
| | - Maia Tsereteli
- Department of HIV/AIDS, Hepatitis, STI and TB, National Center for Disease Control and Public Health, Tbilisi, Georgia
| | - Olivia Keiser
- Institute of Global Health, University of Geneva, Geneva, Switzerland
| | - Janne Estill
- Institute of Global Health, University of Geneva, Geneva, Switzerland
- Institute of Mathematical Statistics and Actuarial Science, University of Bern, Bern, Switzerland
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17
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Baeka GB, Oloke JK, Opaleye OO. Detection of hepatitis C virus among HIV patients in Port Harcourt, Rivers State. Afr Health Sci 2021; 21:1010-1015. [PMID: 35222562 PMCID: PMC8843266 DOI: 10.4314/ahs.v21i3.8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background Hepatitis C virus (HCV) a major human pathogen infecting millions of individuals worldwide, thereby increasing the risks for chronic liver diseases and has been discovered that HIV/HCV co-infected patients have a greater risk. Objective To determine the prevalence of HCV infection among HIV infected people in Port Harcourt, Rivers State. Methodology The patients were from the ages of 18 and above attending the antiretroviral clinic for over 6 months. The mean age of the participants was 36.91±8.38. Data were gotten from the 550 patients using a modified questionnaire and 5mls of blood samples were collected through venepuncture into EDTA bottles and spun at 3000rpm for 10 minutes separating the plasma from the whole blood. The CD4+ count was gotten from the patients' file and the samples kept at -700C till analized. HCV antibody was detected using a commercially available third generation kit manufactured by Melsin Medical Co and statistical analysis was done using a Stata version 16. P value was determined using ANOVA Result Total number positive to the HCV antibody was 24(4.4%) of which 8(33.3%) were males, while 16(66.7%) were females. Prevalence (29.2%) was among patients in the 31–35 age range. The CD4+ count ranged from 22–864 cells/µl with a mean value of 303.08±194. Conclusion From this study HIV/HCV co-infection occurs among HIV infected people in Port Harcourt. The CD4+ count was discovered to be low and was not age, nor gender dependent. HIV infected people should therefore be routinely screened for HCV.
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Affiliation(s)
- Glory Barinuaka Baeka
- Department of Pure and Applied Biology (Microbiology/Virology Unit), Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.,Department of Microbiology, Rivers State University, Port Harcourt, Rivers State
| | - Julius Kola Oloke
- Department of Pure and Applied Biology (Microbiology/Virology Unit), Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
| | - Oluyinka Oladele Opaleye
- Department of Pure and Applied Biology (Microbiology/Virology Unit), Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.,Department of Medical Microbiology and Parasitology, College of Health Sciences, Ladoke Akintola University of Technology, Nigeria
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18
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Castry M, Cousien A, Supervie V, Velter A, Ghosn J, Paltiel AD, Yazdanpanah Y, Deuffic-Burban S. Impact of test-and-treat and risk reduction strategies on HCV transmission among MSM living with HIV in France: a modelling approach. Gut 2021; 70:1561-1569. [PMID: 33109688 DOI: 10.1136/gutjnl-2020-321744] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 09/24/2020] [Accepted: 10/02/2020] [Indexed: 01/09/2023]
Abstract
OBJECTIVE Since the early 2000s, there has been an epidemic of HCV occurring among men who have sex with men (MSM) living with HIV, mainly associated with high-risk sexual and drug-related behaviours. Early HCV diagnosis and treatment, and behavioural risk-reduction, may be effective to eliminate HCV among MSM living with HIV. DESIGN We developed a deterministic dynamic compartmental model to simulate the impact of test-and-treat and risk-reduction strategies on HCV epidemic (particularly on incidence and prevalence) among MSM living with HIV in France. We accounted for HIV and HCV cascades of care, HCV natural history and heterogeneity in HCV risk behaviours. The model was calibrated to primary HCV incidence observed between 2014 and 2017 among MSM living with HIV in care (ANRS CO4-French hospital database on HIV (FHDH)). RESULTS With current French practices (annual HCV screening and immediate treatment), total HCV incidence would fall by 70%, from 0.82/100 person-years in 2015 to 0.24/100 person-years in 2030. It would decrease to 0.19/100 person-years in 2030 with more frequent screening and to 0.19 (0.12)/100 person-years in 2030 with a 20% (50%) risk-reduction. When combining screening every 3 months with a 50% risk-reduction, HCV incidence would be 0.11/100 person-years in 2030, allowing to get close to the WHO target (90% reduction from 2015 to 2030). Similarly, HCV prevalence would decrease from 2.79% in 2015 to 0.48% in 2030 (vs 0.71% with current practices). CONCLUSION Combining test-and-treat and risk-reduction strategies could have a marked impact on the HCV epidemic, paving the way to HCV elimination among MSM living with HIV.
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Affiliation(s)
- Mathieu Castry
- Université de Paris, Inserm, IAME, F-75006 Paris, France
| | | | - Virginie Supervie
- Sorbonne Université, Inserm, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France
| | - Annie Velter
- Department of Infectious Diseases, Santé Publique France, French national public health agency, Saint-Maurice, France
| | - Jade Ghosn
- Université de Paris, Inserm, IAME, F-75006 Paris, France.,Service de Maladies Infectieuses et Tropicales, Hôpital Bichat Claude-Bernard, F-75018 Paris, France
| | - A David Paltiel
- Department of Health Policy and Management, Yale University School of Public Health, New Haven, Connecticut, USA
| | - Yazdan Yazdanpanah
- Université de Paris, Inserm, IAME, F-75006 Paris, France.,Service de Maladies Infectieuses et Tropicales, Hôpital Bichat Claude-Bernard, F-75018 Paris, France
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19
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Rockstroh JK, Boesecke C. Hepatitis C Virus Treatment as Prevention: Challenges and Opportunities in Men Who Have Sex With Men. J Infect Dis 2021; 222:S782-S788. [PMID: 33245348 DOI: 10.1093/infdis/jiaa096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Since 2002, a global epidemic of acute hepatitis C virus (HCV) infection has been noted in men who have sex with men (MSM). Transmission of HCV, particularly in the context of traumatic sex practices that increase the risk of blood-blood contacts (eg, anal sex and fisting), was initially found in human immunodeficiency virus (HIV)-coinfected and more recently in HIV-uninfected MSM, especially those receiving pre-exposure prophylaxis (PrEP). Early HCV treatment with all-oral direct-acting antiviral combination therapy has been associated with very high HCV cure rates of up to 100%. Indeed, immediate treatment of recently acquired HCV directly after new HCV diagnosis, or after 4 weeks if no 2-log10 drop in HCV RNA level occurs, promises rapid HCV elimination. Reports from the Netherlands, Switzerland, and the United Kingdom all show that with increased treatment uptake in this particular patient group, dramatic reductions in new HCV infections can be achieved. A general consensus on how to best screen for and manage acute HCV infections, along with broad access to rapid HCV therapy initiation, is crucial to attaining HCV elimination, a goal that is challenged by high HCV reinfection rates among MSM.
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Affiliation(s)
- Jürgen Kurt Rockstroh
- Department of Medicine I, University Hospital Bonn, Germany.,German Centre for Infection Research, partner site Bonn-Cologne, Bonn, Germany
| | - Christoph Boesecke
- Department of Medicine I, University Hospital Bonn, Germany.,German Centre for Infection Research, partner site Bonn-Cologne, Bonn, Germany
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20
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Abstract
PURPOSE OF REVIEW The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets. RECENT FINDINGS With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM. Recent evidence demonstrates that treatment in early infection is well tolerated, cost effective and may reduce the risk of onward transmission. Modelling studies suggest that to reduce incidence, a combination approach including behavioural interventions and access to early treatment, targeting both HIV+ and negative high-risk groups, will be required. HCV vaccine trials have not yet demonstrated efficacy in human studies, however phase one and two studies are ongoing. SUMMARY Some progress towards the WHO HCV elimination targets has been reported. Achieving sustained HCV elimination is likely to require a combination approach including early access to DAAs in acute infection and reinfection, validated and reproducible behavioural interventions and an efficacious HCV vaccine.
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Ang LW, Choy CY, Ng OT, Leo YS, Wong CS. Hepatitis C virus infection in HIV-infected men in Singapore, 2006-2018: incidence and associated factors. Sex Health 2021; 18:221-231. [PMID: 34148565 DOI: 10.1071/sh20197] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Accepted: 02/23/2021] [Indexed: 11/23/2022]
Abstract
Background The epidemiology of hepatitis C virus (HCV) infection in people living with HIV has been evolving, with increasing evidence of permucosal (sexual) transmission identified predominantly in HIV-positive men who have sex with men (MSM). The aim of this study was to estimate the incidence rate and elucidate epidemiological factors associated with HCV infection among HIV-infected men in Singapore from 2006 to 2018. METHODS A retrospective cohort study was conducted using a clinical database maintained by the Clinical HIV Program at the National Centre for Infectious Diseases, Singapore. Factors associated with incident HCV infections were identified using Cox proportional hazards regression analyses. RESULTS Among 1348 HIV-infected male patients who were HCV seronegative at baseline, 64 (4.7%) subsequently tested positive for HCV, giving an incidence of 0.88 per 100 person-years of follow-up (PYFU) (95% confidence interval (CI) 0.69-1.13). The incidence rate of HCV seroconversion increased from 0.33 (95% CI 0.12-0.71) per 100 PYFU in 2010-2012 to 1.93 (95% CI 1.36-2.67) in 2016-2018. Independent factors associated with incident HCV infection were younger age groups at HIV diagnosis versus ≥45 years, HIV acquisition via MSM or via both sexual contact and intravenous drug use versus heterosexual transmission, HIV diagnosis in later periods versus 2006-2009, and recent syphilis acquisition. CONCLUSIONS An increasing trend of incident HCV infection was seen in HIV-infected men, particularly for MSM. Preventive and behavioural interventions should be targeted at HIV-infected individuals engaged in high-risk sexual behaviour.
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Affiliation(s)
- Li Wei Ang
- National Public Health and Epidemiology Unit, National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, 308442, Singapore; and Corresponding author.
| | - Chiaw Yee Choy
- Department of Infectious Diseases, National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, 308442, Singapore
| | - Oon Tek Ng
- Department of Infectious Diseases, National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, 308442, Singapore; and Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore; and Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, 308232, Singapore
| | - Yee Sin Leo
- Department of Infectious Diseases, National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, 308442, Singapore; and Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore; and Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, 308232, Singapore; and Saw Swee Hock School of Public Health, National University of Singapore, 16 Medical Drive, 117597, Singapore; and Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, 117597, Singapore
| | - Chen Seong Wong
- Department of Infectious Diseases, National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, 308442, Singapore; and Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore; and Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, 308232, Singapore
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22
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The Latest Achievements in the Construction of Influenza Virus Detection Aptasensors. Viruses 2020; 12:v12121365. [PMID: 33265901 PMCID: PMC7760490 DOI: 10.3390/v12121365] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 11/14/2020] [Accepted: 11/23/2020] [Indexed: 12/14/2022] Open
Abstract
Aptamers are short fragments of nucleic acids, DNA or RNA that have the ability to bind selected proteins with high specificity and affinity. These properties allow them to be used as an element of biosensors for the detection of specific proteins, including viral ones, which makes it possible to design valuable diagnostic tools. The influenza virus causes a huge number of human and animal deaths worldwide every year, and contributes to remarkable economic losses. In addition, in 2020, a new threat appeared-the SARS-Cov-2 pandemic. Both disease entities, especially in the initial stage of infection, are almost identical in terms of signs and symptoms. Therefore, a diagnostic solution is needed that will allow distinguishing between both pathogens, with high sensitivity and specificity; it should be cheap, quick and possible to use in the field, for example, in a doctor's office. All the mentioned properties are met by aptasensors in which the detection elements are specific aptamers. We present here the latest developments in the construction of various types of aptasensors for the detection of influenza virus. Aptasensor operation is based on the measurement of changes in electric impedance, fluorescence or electric signal (impedimetric, fluorescence and electrochemical aptasensors, respectively); it allows both qualitative and quantitative determinations. The particularly high advancement for detecting of influenza virus concerns impedimetric aptasensors.
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23
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Chen YC, Thio CL, Kamangar F, Cox AL, Wiberg KJ. Evolving trends in the prevalence of hepatitis C virus antibody positivity among HIV-infected men in a community-based primary care setting. J Viral Hepat 2020; 27:1202-1213. [PMID: 32579777 PMCID: PMC7544680 DOI: 10.1111/jvh.13354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 05/04/2020] [Accepted: 05/20/2020] [Indexed: 12/09/2022]
Abstract
Hepatitis C virus (HCV) infections in the United States occurred mostly among those born between 1945 and 1965. However, new infections continue to increase in recent years. To understand the changes in the prevalence and risk factors of HCV infection in different age and risk groups among men living with HIV, we performed a retrospective cross-sectional analyses of 1948 HIV-infected men at a multisite community health centre in urban/suburban and rural Maryland from 2003 through 2014. We used multivariate logistic regression to determine factors associated with HCV antibody (anti-HCV) positivity and restricted cubic spline method to model trends in anti-HCV prevalence over time. The overall anti-HCV prevalence was 24.2%. The annual prevalence declined in the full cohort, from 38% in 2003 to 24% in 2014, and among those ≥ 40 years old. However, the annual prevalence increased initially and then stabilized in the groups of men who were younger (<40 years old) or had injection-drug use and/or sex with men. Among the younger injection-drug users, the prevalence rose from 33% in 2003 to 79% in 2009 and then stabilized. The independent predictors for anti-HCV positivity differed between the men with and without injection-drug use and between those < 40 and ≥ 40 years old. Notably, a high prevalence of anti-HCV was observed among the younger, white injection-drug users residing in rural areas. Thus, the HCV epidemic continued unabated among high-risk individuals in this diverse population of HIV-infected men. The ongoing HCV transmission among young HIV-infected men poses a challenge en route to HCV eradication.
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Affiliation(s)
- Yun-Chi Chen
- Department of Biology, Morgan State University, Baltimore, MD,Corresponding author: Yun-Chi Chen, D.Phil (Oxon). Department of Biology, Morgan State University, 1700 Cold Spring Lane, Baltimore, 21251 MD, Phone: 1-443-885-1997,
| | - Chloe L Thio
- Department of Medicine, Johns Hopkins University, Baltimore, MD
| | - Farin Kamangar
- Department of Biology, Morgan State University, Baltimore, MD
| | - Andrea L Cox
- Department of Medicine, Johns Hopkins University, Baltimore, MD
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24
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Recently acquired and early chronic hepatitis C in MSM: Recommendations from the European treatment network for HIV, hepatitis and global infectious diseases consensus panel. AIDS 2020; 34:1699-1711. [PMID: 32694411 DOI: 10.1097/qad.0000000000002622] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
: In response to growing evidence of an expanding epidemic of sexually acquired hepatitis C virus (HCV) infection in HIV-positive MSM, the European AIDS Treatment Network (NEAT) acute hepatitis C consensus panel developed their first recommendations for HCV prevention and care during a consensus conference in May 2010 in Paris, France. As then, two major breakthroughs have changed the landscape. First, directly acting antivirals (DAA) with high levels of tolerability and HCV cure rates of over 95% are now widely available and will play a large role in the goal of elimination of HCV by 2030 (WHO sector strategy). Second, landmark studies demonstrated that universal test and treatment (UTT) approach as well as the demonstration that HIV cannot be sexually transmitted from a person living with HIV with an undetectable viraemia [undetectable = untransmittable (U = U) campaign] and HIV preexposure prophylaxis (PrEP) are very effective HIV biomedical prevention strategies for MSM. The scale-up of these interventions has reduced HIV incidence in MSM and also changed patterns of sexual networks and behaviour, which has contributed to increased HCV incidence among HIV-negative MSM who were eligible for or on PrEP. These recent developments, together with new clinical and scientific insights, underscore the importance of updating the statements and recommendations for acute HCV in both HIV-positive and HIV-negative MSM. In June 2019, experts from different disciplines and organizations including community representatives participated at the second acute HCV consensus conference of NEAT Infectious Diseases (ID) in Amsterdam, the Netherlands.
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25
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Boon D, Bruce V, Patel EU, Quinn J, Srikrishnan AK, Shanmugam S, Iqbal S, Balakrishnan P, Sievers M, Kirk GD, Thomas DL, Quinn TC, Cox AL, Page KA, Solomon SS, Mehta SH, Laeyendecker O. Antibody avidity-based approach to estimate population-level incidence of hepatitis C. J Hepatol 2020; 73:294-302. [PMID: 32240715 PMCID: PMC7458132 DOI: 10.1016/j.jhep.2020.03.028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 03/11/2020] [Accepted: 03/15/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Accurate HCV incidence estimates are critical for monitoring progress towards HCV elimination goals, including an 80% reduction in HCV incidence by 2030. Moreover, incidence estimates can help guide prevention and treatment programming, particularly in the context of the US opioid epidemic. METHODS An inexpensive, Genedia-based HCV IgG antibody avidity assay was evaluated as a platform to estimate cross-sectional, population-level primary HCV incidence using 1,840 HCV antibody and RNA-positive samples from 875 individuals enrolled in 5 cohort studies in the US and India. Using samples collected <2 years following HCV seroconversion, the mean duration of recent infection (MDRI) was calculated by fitting a maximum likelihood binomial regression model to the probability of appearing recent. Among samples collected ≥2 years post-HCV seroconversion, an individual-level false recent ratio (FRR) was calculated by estimating the probability of appearing recent using an exact binomial test. Factors associated with falsely appearing recent among samples collected ≥2 years post seroconversion were determined by Poisson regression with generalized estimating equations and robust variance estimators. RESULTS An avidity index cut-off of <40% resulted in an MDRI of 113 days (95% CI 84-146), and FRRs of 0.4% (95% CI 0.0-1.2), 4.6% (95% CI 2.2-8.3), and 9.5% (95% CI 3.6-19.6) among individuals who were HIV-uninfected, HIV-infected, and HIV-infected with a CD4 count <200/μl, respectively. No variation was seen between HCV genotypes 1 and 3. In hypothetical scenarios of high-risk settings, a sample size of <1,000 individuals could reliably estimate primary HCV incidence. CONCLUSIONS This cross-sectional approach can estimate primary HCV incidence for the most common genotypes. This tool can serve as a valuable resource for program and policy planners seeking to monitor and reduce HCV burden. LAY SUMMARY Determining the rate of new hepatitis C virus (HCV) infections in a population is critical to monitoring progress toward HCV elimination and to appropriately guide control efforts. However, since HCV infections are most often initially asymptomatic, it is difficult to estimate the rate of new HCV infections without following HCV-uninfected people over time and repeatedly testing them for HCV infection. Here, we present a novel, resource-efficient method to estimate the rate of new HCV infections in a population using data from a single timepoint.
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Affiliation(s)
- Denali Boon
- Johns Hopkins University, Baltimore, Maryland, USA.
| | | | | | | | | | | | - Syed Iqbal
- YR Gaitonde Centre for AIDS Research and Education, Chennai, India
| | | | | | | | | | - Thomas C Quinn
- Johns Hopkins University, Baltimore, Maryland, USA; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Andrea L Cox
- Johns Hopkins University, Baltimore, Maryland, USA
| | | | - Sunil S Solomon
- Johns Hopkins University, Baltimore, Maryland, USA; YR Gaitonde Centre for AIDS Research and Education, Chennai, India
| | | | - Oliver Laeyendecker
- Johns Hopkins University, Baltimore, Maryland, USA; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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26
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Moorman AC, de Perio MA, Goldschmidt R, Chu C, Kuhar D, Henderson DK, Naggie S, Kamili S, Spradling PR, Gordon SC, Russi MB, Teshale EH. Testing and Clinical Management of Health Care Personnel Potentially Exposed to Hepatitis C Virus - CDC Guidance, United States, 2020. MMWR Recomm Rep 2020; 69:1-8. [PMID: 32701942 PMCID: PMC8631757 DOI: 10.15585/mmwr.rr6906a1] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Exposure to hepatitis viruses is a recognized occupational risk for health care personnel (HCP). This report establishes new CDC guidance that includes recommendations for a testing algorithm and clinical management for HCP with potential occupational exposure to hepatitis C virus (HCV). Baseline testing of the source patient and HCP should be performed as soon as possible (preferably within 48 hours) after the exposure. A source patient refers to any person receiving health care services whose blood or other potentially infectious material is the source of the HCP's exposure. Two options are recommended for testing the source patient. The first option is to test the source patient with a nucleic acid test (NAT) for HCV RNA. This option is preferred, particularly if the source patient is known or suspected to have recent behaviors that increase risk for HCV acquisition (e.g., injection drug use within the previous 4 months) or if risk cannot be reliably assessed. The second option is to test the source patient for antibodies to hepatitis C virus (anti-HCV), then if positive, test for HCV RNA. For HCP, baseline testing for anti-HCV with reflex to a NAT for HCV RNA if positive should be conducted as soon as possible (preferably within 48 hours) after the exposure and may be simultaneous with source-patient testing. If follow-up testing is recommended based on the source patient's status (e.g., HCV RNA positive or anti-HCV positive with unavailable HCV RNA or if the HCV infection status is unknown), HCP should be tested with a NAT for HCV RNA at 3-6 weeks postexposure. If HCV RNA is negative at 3-6 weeks postexposure, a final test for anti-HCV at 4-6 months postexposure is recommended. A source patient or HCP found to be positive for HCV RNA should be referred to care. Postexposure prophylaxis of hepatitis C is not recommended for HCP who have occupational exposure to blood and other body fluids. This guidance was developed based on expert opinion (CDC. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recommend Rep 2001;50[No. RR-11]; Supplementary Figure, https://stacks.cdc.gov/view/cdc/90288) and reflects updated guidance from professional organizations that recommend treatment for acute HCV infection. Health care providers can use this guidance to update their procedures for postexposure testing and clinical management of HCP potentially exposed to hepatitis C virus.
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27
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Yaroslavtseva NG, Tikhomirov DS, Nikolaeva LI, Dedova AV, Ovchinnikova EN, Misko ON, Romanova TY, Makhnovskiy PI, Grishechkin AE, Tupoleva TA. [Low concentrations of hepatitis C virus RNA in serologically mild infection.]. Vopr Virusol 2020; 64:30-35. [PMID: 30893527 DOI: 10.18821/0507-4088-2019-64-1-30-35] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Accepted: 03/06/2018] [Indexed: 11/17/2022]
Abstract
Occult HCV infection (OCI) provides significant interest recently. HCV RNA in this case can be detected not in plasma, but in blood cells and/or in liver tissue. In case of antibody genesis impairment anti-HCV detection may lead to negative or "uncertain" result. The aim of the study was to estimate infection type in blood donors and patients with hematological diseases by exploration of samples with uncertain anti-HCV detection results. Blood samples of 30 180 potential blood donors' and 4322 patients with hematological diseases were tested. Comparative analysis of wide pattern of HCV markers was performed. 33 blood donors and 42 patients were enrolled in follow-up examination. Uncertain results of Anti-HCV detection in donors' samples were in 0.18% of cases. Follow-up examination of 33 donors provided discordant results using immunochemiluminescence assay and ELISA. 15.2% donors' samples contained HCV RNA in low concentration. Follow-up observation of 42 patients with incomplete antiviral antibody pattern showed HCV RNA presence in 40.5% cases (21.4% high viremia and 19.0% low viremia). Samples with low RNA concentration contained low titers of anti-core antibodies. Samples with high titers of anti-core antibodies contained high HCV RNA level. Uncertain results of anti-HCV in 15.2% of potential blood donors' samples were confirmed by detection of HCV RNA in low concentration. It proved OCI presence in these individuals and called for testing for wide pattern of HCV markers in addition to routine screening. Patients with hematological diseases showed low level of HCV RNA along with low titers of antibodies against one or two viral antigens.
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Affiliation(s)
- N G Yaroslavtseva
- National Medical Research Center of Hematology, 125167, Moscow, Russian Federation
| | - D S Tikhomirov
- National Medical Research Center of Hematology, 125167, Moscow, Russian Federation
| | - L I Nikolaeva
- D.I. Ivanovsky Institute of Virology «National Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya», 123098, Moscow, Russian Federation
| | - A V Dedova
- D.I. Ivanovsky Institute of Virology «National Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya», 123098, Moscow, Russian Federation
| | - E N Ovchinnikova
- National Medical Research Center of Hematology, 125167, Moscow, Russian Federation
| | - O N Misko
- National Medical Research Center of Hematology, 125167, Moscow, Russian Federation
| | - T Yu Romanova
- National Medical Research Center of Hematology, 125167, Moscow, Russian Federation
| | - P I Makhnovskiy
- D.I. Ivanovsky Institute of Virology «National Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya», 123098, Moscow, Russian Federation
| | - A E Grishechkin
- D.I. Ivanovsky Institute of Virology «National Research Center of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya», 123098, Moscow, Russian Federation
| | - T A Tupoleva
- National Medical Research Center of Hematology, 125167, Moscow, Russian Federation
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28
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Bradshaw D, Vasylyeva TI, Davis C, Pybus OG, Thézé J, Thomson EC, Martinello M, Matthews GV, Burholt R, Gilleece Y, Cooke GS, Page EE, Waters L, Nelson M. Transmission of hepatitis C virus in HIV-positive and PrEP-using MSM in England. J Viral Hepat 2020; 27:721-730. [PMID: 32115809 DOI: 10.1111/jvh.13286] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 12/12/2019] [Accepted: 02/18/2020] [Indexed: 12/14/2022]
Abstract
We sought to characterize risk factors and patterns of HCV transmission amongst men who have sex with men (MSM). MSM with recently acquired HCV (AHCV) were prospectively recruited ('clinic cohort') between January and September 2017. Clinical data and risk behaviours were identified and blood obtained for HCV whole genome sequencing. Phylogenetic analyses were performed, using sequences from this cohort and two other AHCV cohorts, to identify transmission clusters. Sixteen (40.0%) men in the clinic cohort were HIV-negative MSM. HIV-negative MSM were younger than HIV-positive MSM; most (81.3%) had taken HIV PrEP in the preceding year. Eighteen men (45.0%) reported injection drug use; most (34, 85.0%) reported noninjection drug use in the last year. Most in both groups reported condomless anal sex, fisting and sex in a group environment. Few (7, 17.5%) men thought partners may have had HCV. There were 52 sequences in the HCV genotype 1a phylogeny, 18 from the clinic cohort and 34 from other AHCV cohorts; 47 (90.4%) clustered with ≥1 other sequence. There were 7 clusters of 2-27 sequences; 6 clusters contained HIV-negative and HIV-positive MSM and 1 cluster only HIV-positive MSM. Four of these clusters were part of larger clusters first described in 2007. PrEP-using MSM are at risk of HCV, sharing similar risk factors to HIV-positive MSM. Phylogenetics highlights that PrEP-using and HIV-positive MSM are involved in the same HCV transmission networks. Few men demonstrated HCV awareness and risk reduction strategies should be expanded.
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Affiliation(s)
- Daniel Bradshaw
- Department of HIV and Sexual Health, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | | | - Chris Davis
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
| | | | - Julien Thézé
- Department of Zoology, University of Oxford, Oxford, UK
| | - Emma C Thomson
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
| | | | - Gail V Matthews
- Kirby Institute, University of New South Wales, Sydney, Australia
| | - Ruth Burholt
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
| | - Yvonne Gilleece
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
| | | | - Emma E Page
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | | | - Mark Nelson
- Department of HIV and Sexual Health, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
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29
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Eshetu A, Hauser A, An der Heiden M, Schmidt D, Meixenberger K, Ross S, Obermeier M, Ehret R, Bock CT, Bartmeyer B, Bremer V, Bannert N. Establishment of an anti-hepatitis C virus IgG avidity test for dried serum/plasma spots. J Immunol Methods 2020; 479:112744. [PMID: 31958450 DOI: 10.1016/j.jim.2020.112744] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 11/18/2019] [Accepted: 01/14/2020] [Indexed: 11/22/2022]
Abstract
Monitoring recency of infection helps to identify current transmission in vulnerable populations for effective disease control. We have established an in-house avidity based hepatitis C virus (HCV) recency assay based on the Monolisa Anti-HCV PLUS Version 3 ELISA kit for use of dried serum/plasma spots (DS/PS) in order to distinguish recent and long-term infections. A first panel of DS/PS (n = 218; genotype 1 n = 170 and non-genotype 1 n = 48) consisting of primary and at least one follow up sample was used to analyze the temporal changes of the Avidity Index (AI) over time. Sub-panels of longitudinal DS/PS (n = 66) and acute cases (<26 weeks; n = 34) were taken to calculate the Mean Duration of Recent Infection (MDRI) and the False Long-term Rate (FLTR), respectively. A second panel of DS/PS >104 weeks (n = 132) and a third panel of DS/PS prepared from resolved infections (≥180 days since last positive; n = 32) were used to calculate the False Recent Rate (FRR). For all genotypes, the optimal AI cut-off was determined to be 40% resulting in an MDRI of 364 days (95% CI: 223-485). FLTR was 5.9% (95% CI: 0.7-19.7), 8.3% (95% CI: 1-27), and 0% (-) and FRR was 13.6% (95% CI: 8.3-20.7), 11.7% (95% CI: 6.6-19), and 30.6% (95% CI: 9.1-61.4) for all genotypes, genotype 1, and non-genotype 1 infections, respectively. For resolved infections, the FRR was 53.1% (95% CI: 35.8-70.4). Thus, this assay performs particularly well for genotype 1 reaching a high rate of correct discriminations between infections acquired less than a year before diagnosis and those acquired earlier by applying an AI cut-off of 40%. Due to a rapid decline in avidity post resolution of an HCV infection this assay is not recommended to be used in HCV RNA negative patients.
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Affiliation(s)
- Amare Eshetu
- HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany
| | - Andrea Hauser
- HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany; Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | | | - Daniel Schmidt
- HIV/AIDS, STI and Blood-borne Infections, Robert Koch Institute, Berlin, Germany
| | | | - Stefan Ross
- Institute of Virology, Universität Duisburg-Essen, Essen, Germany
| | | | - Robert Ehret
- Medizinisches Infektiologiezentrum Berlin, Berlin, Germany
| | - Claus-Thomas Bock
- Division for Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Robert Koch Institute, Berlin, Germany
| | - Barbara Bartmeyer
- HIV/AIDS, STI and Blood-borne Infections, Robert Koch Institute, Berlin, Germany
| | - Viviane Bremer
- HIV/AIDS, STI and Blood-borne Infections, Robert Koch Institute, Berlin, Germany
| | - Norbert Bannert
- HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany; Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany.
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30
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Fierer DS, Wyles DL. Re-treatment of Hepatitis C Infection After Multiple Failures of Direct-Acting Antiviral Therapy. Open Forum Infect Dis 2020; 7:ofaa095. [PMID: 32296728 PMCID: PMC7148001 DOI: 10.1093/ofid/ofaa095] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 03/12/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) result in initial cure rates of 95% to 99% and re-treatment cure rates of 95%. Nevertheless, given the sheer magnitude of infected persons, some will ultimately fail multiple DAA therapies, and re-treatment of these persons has not been adequately studied. METHODS We evaluated treated an HIV-infected man with cirrhosis from genotype 1b HCV who had failed 3 DAA regimens. RESULTS We treated and cured our "particularly difficult-to-cure" patient with sofosbuvir plus glecaprevir/pibrentasvir plus ribavirin for 24 weeks. We discuss the literature on potential biological factors behind his treatment failures such as lack of HCV seroconversion during his infection course, and multiple failures of hepatitis B seroconversion after vaccination, and the rationale for choosing his curative salvage regimen. DISCUSSION There are no clinical trials-proven re-treatment regimens for "particularly difficult-to-cure" patients. Multiple patient- and virus-related factors that do not affect cure rates in treatment-naive patients may need to be considered in choosing a re-treatment regimen for these patients. These regimens may need to include combinations drugs that are not available in single-tablet form, addition of ribavirin, and longer durations of treatment than standard.
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Affiliation(s)
- Daniel S Fierer
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - David L Wyles
- Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado, USA
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31
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Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71:686-721. [PMID: 31816111 PMCID: PMC9710295 DOI: 10.1002/hep.31060] [Citation(s) in RCA: 513] [Impact Index Per Article: 102.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023]
Affiliation(s)
| | - Timothy R. Morgan
- Chief of Hepatology Veterans Affairs Long Beach Healthcare System Long Beach CA
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Rossotti R, Puoti M. Sexually Transmitted Hepatitis. Sex Transm Infect 2020. [DOI: 10.1007/978-3-030-02200-6_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Popping S, Nichols B, Rijnders B, van Kampen J, Verbon A, Boucher C, van de Vijver D. Targeted HCV core antigen monitoring among HIV-positive men who have sex with men is cost-saving. J Virus Erad 2019; 5:179-190. [PMID: 31754441 PMCID: PMC6844408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
INTRODUCTION The World Health Organization declared the goal of hepatitis C virus (HCV) elimination by 2030. Micro-elimination, which is the reduction of incidence to zero in targeted populations, is less complex and costly and may be the first step to prove whether elimination is feasible. A suitable target group are HIV-positive men who have sex with men (MSM) because of their high-risk behaviour and high incidence rates. Moreover, HCV monitoring is integrated in HIV care. The current HCV monitoring approach is suboptimal and complex and may miss new HCV infections. Alternative monitoring strategies, based on alanine aminotransferase, HCV-PCR and HCV-core antigen (HCV-cAg), combined with immediate direct-acting antiviral (DAA) treatment, may be more effective in reducing new HCV infections. METHODS A deterministic mathematical transmission model was constructed representing the Dutch HCV epidemic among HIV-positive MSM to compare different HCV monitoring strategies from 2018 onwards. We evaluated the epidemiological impact of alternative and intensified monitoring in MSM with HCV. In addition, the cost-effectiveness was calculated over a lifetime horizon. RESULTS Current HCV monitoring and treatment is projected to result in an incidence of 1.1/1000 person-years, 0.24% prevalence, at a cost of €61.8 million (interquartile range 52.2-73.9). Compared with current monitoring, intensified monitoring will result in a maximum 27% reduction of incidence and 33% in prevalence at an increased cost. Conversely, compared with current monitoring, targeted HCV-cAg monitoring will result in a comparable incidence (1.1/1000 person-years) and prevalence (0.23%) but will be €1 million cheaper with increased quality-adjusted life year. CONCLUSION Targeted monitoring reduces the HCV epidemic in a cost-saving manner; however, micro-elimination may not be obtained by 2030, highlighting the need for harm-reduction programmes.
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Affiliation(s)
| | - Brooke Nichols
- Department of Viroscience,
Erasmus MC,
Rotterdam,
the Netherlands
- Department of Global Health,
Boston University,
Boston,
United States
| | - Bart Rijnders
- Department of Medical Microbiology and Infectious Diseases,
Erasmus MC,
Rotterdam,
The Netherlands
| | | | - Annelies Verbon
- Department of Medical Microbiology and Infectious Diseases,
Erasmus MC,
Rotterdam,
The Netherlands
| | - Charles Boucher
- Department of Viroscience,
Erasmus MC,
Rotterdam,
the Netherlands
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Popping S, Nichols B, Rijnders B, van Kampen J, Verbon A, Boucher C, van de Vijver D. Targeted HCV core antigen monitoring among HIV-positive men who have sex with men is cost-saving. J Virus Erad 2019. [DOI: 10.1016/s2055-6640(20)30031-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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35
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Nijmeijer BM, Koopsen J, Schinkel J, Prins M, Geijtenbeek TBH. Sexually transmitted hepatitis C virus infections: current trends, and recent advances in understanding the spread in men who have sex with men. J Int AIDS Soc 2019; 22 Suppl 6:e25348. [PMID: 31468692 PMCID: PMC6715947 DOI: 10.1002/jia2.25348] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 06/21/2019] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) is a major public health threat. Although the recent availability of highly effective directly acting antivirals created optimism towards HCV elimination, there is ongoing transmission of HCV in men who have sex with men (MSM). We here report current epidemiological trends and synthesise evidence on behavioural, network, cellular and molecular host factors associated with sexual transmission of HCV, in particular the role of HIV-1 co-infection. We discuss prevention opportunities focusing on the potential of HCV treatment. METHODS We searched MEDLINE, fact sheets from health professional bodies and conference abstracts using appropriate keywords to identify and select relevant reports. RESULTS AND DISCUSSION Recent studies strongly suggest that HCV is transmitted via sexual contact in HIV-positive MSM and more recently in HIV-negative MSM eligible for or on pre-exposure prophylaxis. The reinfection risk following clearance is about 10 times the risk of primary infection. International connectedness of MSM transmission networks might contribute to ongoing reinfection. Some of these networks might overlap with networks of people who inject drugs. Although, the precise mechanisms facilitating sexual transmission remain unclear, damage to the mucosal barrier in the rectum could increase susceptibility. Mucosal dendritic cell subsets could increase HCV susceptibility by retaining HCV and transmitting the virus to other cells, allowing egress into blood and liver. Early identification of new HCV infections is important to prevent onward transmission, but early diagnosis of acute HCV infection and prompt treatment is hampered by the slow rate of HCV antibody seroconversion, which in rare cases may take more than a year. Novel tests such as testing for HCV core antigen might facilitate early diagnosis. CONCLUSIONS High-risk sexual behaviour, network characteristics, co-infection with sexually transmitted infections like HIV-1 and other concomitant bacterial and viral sexually transmitted infections are important factors that lead to HCV spread. Targeted and combined prevention efforts including effective behavioural interventions and scale-up of HCV testing and treatment are required to halt HCV transmission in MSM.
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Affiliation(s)
- Bernadien M Nijmeijer
- Department of Experimental ImmunologyAmsterdam Infection and Immunity InstituteAmsterdam University Medical CentersUniversity of AmsterdamAmsterdamThe Netherlands
| | - Jelle Koopsen
- Department of Medical MicrobiologyLaboratory of Clinical VirologyAmsterdam Infection and Immunity InstituteAmsterdam University Medical CentersUniversity of AmsterdamAmsterdamThe Netherlands
| | - Janke Schinkel
- Department of Medical MicrobiologyLaboratory of Clinical VirologyAmsterdam Infection and Immunity InstituteAmsterdam University Medical CentersUniversity of AmsterdamAmsterdamThe Netherlands
| | - Maria Prins
- Department of Infectious Diseases, Research and PreventionPublic Health Service of AmsterdamAmsterdamThe Netherlands
| | - Teunis BH Geijtenbeek
- Department of Experimental ImmunologyAmsterdam Infection and Immunity InstituteAmsterdam University Medical CentersUniversity of AmsterdamAmsterdamThe Netherlands
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Abstract
Many microbes, toxins, autoimmune diseases, and neoplastic diseases may cause liver inflammation; however, 5 viruses whose main pathogenesis is liver disease are referred to as hepatitis A, B, C, D, and E viruses. These viruses cause a significant burden of global illness. With the exception of hepatitis A virus, all may cause chronic infection potentially leading to cirrhosis and hepatocellular carcinoma. Excellent serologic and nucleic acid detection methods are available for determining the precise cause and, in some cases, the duration of infection. Diagnostics are critical for identifying individuals needing treatment and for monitoring the treatment success.
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Affiliation(s)
- Kunatum Prasidthrathsint
- Division of Infectious Diseases, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Division of Clinical Microbiology, Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, USA; University of Iowa Hospitals and Clinics, SW54, GH, 200 Hawkins Drive, Iowa City, IA 52242, USA; Medicine and Research Services, Iowa City Veterans Administration Health Care Center, Iowa City, IA, USA
| | - Jack T Stapleton
- Division of Infectious Diseases, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA, USA; University of Iowa Hospitals and Clinics, SW54, GH, 200 Hawkins Drive, Iowa City, IA 52242, USA; Medicine and Research Services, Iowa City Veterans Administration Health Care Center, Iowa City, IA, USA.
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Sun HY, Uemura H, Wong NS, Chan DPC, Wong BCK, Lin PH, Su LH, Hung CC, Oka S, Chang SY, Lee SS. Molecular epidemiology of acute HCV infection in HIV-positive patients from Hong Kong, Taipei, Tokyo. Liver Int 2019; 39:1044-1051. [PMID: 30770636 DOI: 10.1111/liv.14073] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 01/02/2019] [Accepted: 02/11/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Acute hepatitis C virus (HCV) infections have been increasingly reported among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) in the Asia-Pacific region. It remains unknown whether international network of HCV transmission has occurred in this region. METHODS HIV-positive patients with acute HCV infection, defined as HCV seroconversion within a year or documented acute hepatitis with seroconversion, diagnosed in Hong Kong, Taipei and Tokyo during 2010-2016 were included in this molecular epidemiology study. The NS5B region of the HCV genome (365 bp) was amplified using nested polymerase chain reaction and sequenced. RESULTS Of 234 HIV-positive patients with acute HCV infection, all were male with 94% being MSM. At the diagnosis of acute HCV infection, 73.5% had concurrent sexually transmitted diseases and 88.0% were receiving combination antiretroviral therapy. The most prevalent HCV genotype was 3a, 2a and 1b in Hong Kong, Taipei and Tokyo respectively. Nine independent clusters belonging to five genotypes (1b, 2a, 2c, 3a and 6a) were identified, each of which occurred in one city without overlapping except for one 3a sequence from Taipei that was closely related genetically to the Hong Kong cluster. CONCLUSIONS No international network of HCV transmission was identified among HIV-positive patients in the three Asia-Pacific cities. The transmission dynamics of sexually acquired HCV differed by city, but the risk of intercity clustering should not be ignored.
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Affiliation(s)
- Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Haruka Uemura
- National Center for Global Health and Medicine, AIDS Clinical Center, Tokyo, Japan
| | - Ngai-Sze Wong
- Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Denise P-C Chan
- Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Bonnie C-K Wong
- Special Prevention Programme, Department of Health, Centre for Health Protection, Hong Kong Special Administrative Region Government, Hong Kong, China
| | - Pi-Han Lin
- Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Li-Hsin Su
- Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shinichi Oka
- National Center for Global Health and Medicine, AIDS Clinical Center, Tokyo, Japan
| | - Sui-Yuan Chang
- Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shui-Shan Lee
- Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, China
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Gómez Outomuro A, Fraile M, Torner M. Acute seronegative hepatitis C: two case reports. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2019; 111:406. [PMID: 30896958 DOI: 10.17235/reed.2019.5921/2018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
We present two cases of immunosuppressed patients diagnosed with acute hepatitis C (AHC) HCV-antibody negative by HCV-RNA testing. Delayed seroconversion in immunosuppressed patients may result in retarded diagnosis and treatment. Therefore, HCV-RNA testing should be part of the initial evaluation.
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Affiliation(s)
| | - Miguel Fraile
- Aparato Digestivo, Hospital Universitario Central de Asturias, España
| | - María Torner
- Digestivo, Hospital Universitario Central de Asturias
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39
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Chaillon A, Sun X, Cachay ER, Looney D, Wyles D, Garfein RS, Martin TCS, Jain S, Mehta SR, Smith DM, Little SJ, Martin NK. Primary Incidence of Hepatitis C Virus Infection Among HIV-Infected Men Who Have Sex With Men in San Diego, 2000-2015. Open Forum Infect Dis 2019; 6:ofz160. [PMID: 31041355 PMCID: PMC6483132 DOI: 10.1093/ofid/ofz160] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 03/29/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Little is known about the hepatitis C virus (HCV) epidemic among HIV-infected men who have sex with men (HIV+ MSM) in the United States. In this study, we aimed to determine the incidence of primary HCV infection among HIV+ MSM in San Diego, California. METHODS We performed a retrospective cohort analysis of HCV infection among HIV+ MSM attending 2 of the largest HIV clinics in San Diego. Incident HCV infection was assessed among HIV+ MSM with a negative anti-HCV test and subsequent HCV test between 2000 and 2017, with data censored to 2015. HCV reinfection was assessed among HIV+ MSM successfully treated for HCV between 2008 and 2015. Infection/reinfection rates were calculated using person-time methods. RESULTS Among 3068 initially HCV-seronegative HIV+ MSM, 178 new infections occurred over 15 796 person-years, giving an incidence of 1.13 per 100 person-years (/100py; 95% confidence interval [CI], 0.97-1.31). Incidence was stable from 2000 to 2014 (0.83/100py; 95% CI, 0.41-1.48), with an increase to 3.01/100py (95% CI, 1.97-4.42) in 2015 (P = .02). Among 43 successfully treated patients, 3 were reinfected. CONCLUSIONS HCV incidence is high among HIV+ MSM in San Diego, with evidence suggesting a recent increase in 2015. Strong HCV testing guidelines and active prevention efforts among HIV+ MSM are urgently needed that include rapid diagnosis, treatment, and risk reduction.
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Affiliation(s)
- Antoine Chaillon
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California
| | - Xiaoying Sun
- Biostatistics Research Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California
| | - Edward R Cachay
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California
| | - David Looney
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California
- VA San Diego Healthcare System, San Diego, California
| | - David Wyles
- Division of Infectious Diseases, Denver Health Medical Center, Denver, Colorado
| | - Richard S Garfein
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California
| | - Thomas C S Martin
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California
| | - Sonia Jain
- Biostatistics Research Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California
| | - Sanjay R Mehta
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California
- VA San Diego Healthcare System, San Diego, California
| | - Davey M Smith
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California
- VA San Diego Healthcare System, San Diego, California
| | - Susan J Little
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California
| | - Natasha K Martin
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California
- School of Social and Community Medicine, University of Bristol, Bristol, UK
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40
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Shenge JA, Odaibo GN, Olaleye DO. Phylogenetic analysis of hepatitis C virus among HIV/ HCV co-infected patients in Nigeria. PLoS One 2019; 14:e0210724. [PMID: 30726229 PMCID: PMC6364902 DOI: 10.1371/journal.pone.0210724] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 12/31/2018] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) infection has been associated with liver disease including liver cirrhosis and hepatocellular carcinoma (HCC) in chronically-infected persons. However, in HIV/HCV co-infected patients, increased rate of progression to cirrhosis and HCC has been reported. Limited information exists regarding genetic variants of HCV circulating among co-infected patients, which could be important in the design of broadly protective vaccine and management of the disease. Here, we determined the genotypes of HCV isolates circulating among HIV/HCV co-infected patients in Ibadan, southwestern Nigeria. One hundred and twenty-five HIV/HCV IgM positive samples obtained from HIV laboratory, University of Ibadan were used for this study. HCV NS5B gene was amplified using polymerase chain reaction (PCR). The amplified NS5B gene was sequenced using gene specific primers. Twenty isolates were amplified, out of which 13 were successfully sequenced. Phylogenetic analysis of the 13 sequenced isolates showed three HCV subtypes 1a, 3a and 5a belonging to genotypes 1, 3 and 5 respectively. Ten isolates (77%) belong to subtype 5a, followed by 2 isolates (15%) subtype 1a and 1 isolate (8%) was subtype 3a. The predominant HCV genotype was 5, followed by genotype 1 (subtype 1a). The findings, as well as the observed mutations in NS5B gene, indicate the need for screening and monitoring of HIV/HCV co-infected patients. Further study to determine the phylogeny of isolates circulating in other parts of Nigeria will be carried out.
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Affiliation(s)
- Juliet A. Shenge
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Georgina N. Odaibo
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - David O. Olaleye
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
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41
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Popping S, Hullegie SJ, Boerekamps A, Rijnders BJA, de Knegt RJ, Rockstroh JK, Verbon A, Boucher CAB, Nichols BE, van de Vijver DAMC. Early treatment of acute hepatitis C infection is cost-effective in HIV-infected men-who-have-sex-with-men. PLoS One 2019; 14:e0210179. [PMID: 30629662 PMCID: PMC6328146 DOI: 10.1371/journal.pone.0210179] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 12/18/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Treatment of hepatitis C virus infections (HCV) with direct acting antivirals (DAA) can prevent new infections since cured individuals cannot transmit HCV. However, as DAAs are expensive, many countries defer treatment to advances stages of fibrosis, which results in ongoing transmission. We assessed the epidemiological impact and cost-effectiveness of treatment initiation in different stages of infection in the Netherlands where the epidemic is mainly concentrated among HIV-infected MSMs. METHODS We calibrated a deterministic mathematical model to the Dutch HCV epidemic among HIV-infected MSM to compare three different DAA treatment scenarios: 1) immediate treatment, 2) treatment delayed to chronic infection allowing spontaneous clearance to occur, 3) treatment delayed until F2 fibrosis stage. All scenarios are simulated from 2015 onwards. Total costs, quality adjusted life years (QALY), incremental cost-effectiveness ratios (ICERs), and epidemiological impact were calculated from a providers perspective over a lifetime horizon. We used a DAA price of €35,000 and 3% discounting rates for cost and QALYs. RESULTS Immediate DAA treatment lowers the incidence from 1.2/100 person-years to 0.2/100 person-years (interquartile range 0.1-0.2) and the prevalence from 5.0/100 person-years to 0.5/100 person-years (0.4-0.6) after 20 years. Delayed treatment awaiting spontaneous clearance will result in a similar reduction. However, further delayed treatment to F2 will increases the incidence and prevalence. Earlier treatment will cost society €68.3 and €75.1 million over a lifetime for immediate and awaiting until the chronic stage, respectively. The cost will increase if treatment is further delayed until F2 to €98.4 million. Immediate treatment will prevent 7070 new infections and gains 3419 (3019-3854) QALYs compared to F2 treatment resulting in a cost saving ICER. Treatment in the chronic stage is however dominated. CONCLUSIONS Early DAA treatment for HIV-infected MSM is an excellent and sustainable tool to meet the WHO goal of eliminating HCV in 2030.
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Affiliation(s)
| | - Sebastiaan J. Hullegie
- Department of Internal Medicine and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands
| | - Anne Boerekamps
- Department of Internal Medicine and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands
| | - Bart J. A. Rijnders
- Department of Internal Medicine and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands
| | - Robert J. de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
| | | | - Annelies Verbon
- Department of Internal Medicine and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands
| | | | - Brooke E. Nichols
- Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands
- Department of Global Health, Boston University, Boston, United States
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42
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[HCV healing also in HIV infected patients]. MMW Fortschr Med 2018; 159:56-60. [PMID: 28597261 DOI: 10.1007/s15006-017-9739-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Martinello M, Hajarizadeh B, Grebely J, Dore GJ, Matthews GV. Management of acute HCV infection in the era of direct-acting antiviral therapy. Nat Rev Gastroenterol Hepatol 2018; 15:412-424. [PMID: 29773899 DOI: 10.1038/s41575-018-0026-5] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The management of acute HCV infection has not been standardized following the availability of direct-acting antiviral agents (DAAs) for chronic HCV infection, and substantial uncertainty exists regarding the optimal treatment regimen and duration. Despite the lack of direct evidence, the 2016 American Association for the Study of Liver Diseases (AASLD)-Infectious Diseases Society of America (IDSA) guidelines supported "the same regimens for acute HCV as recommended for chronic HCV infection … owing to high efficacy and safety", whereas the 2016 European Association for the Study of the Liver (EASL) guidelines recommended sofosbuvir-ledipasvir, sofosbuvir-velpatasvir or sofosbuvir plus daclatasvir for 8 weeks in acute HCV infection, with a longer duration of 12 weeks recommended for those infected with HIV and/or baseline HCV RNA levels >1,000,000 IU/ml. This Review outlines the epidemiology, natural history and diagnosis of acute HCV infection and provides contemporary information on DAAs for acute and recent HCV infection. The Review also discusses the 2016 AASLD-IDSA and EASL recommendations for acute HCV infection management in light of available evidence and highlights key differences in study populations and design that influence interpretation. We focus on populations at high risk of HCV transmission and acquisition, including people who inject drugs and HIV-positive men who have sex with men, and highlight the potential effects of diagnosis and treatment of acute HCV infection in contributing to HCV elimination.
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Affiliation(s)
- Marianne Martinello
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia.
| | - Behzad Hajarizadeh
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia
| | - Jason Grebely
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia
| | - Gregory J Dore
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia
| | - Gail V Matthews
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia
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Sacks-Davis R, Pedrana AE, Scott N, Doyle JS, Hellard ME. Eliminating HIV/HCV co-infection in gay and bisexual men: is it achievable through scaling up treatment? Expert Rev Anti Infect Ther 2018; 16:411-422. [PMID: 29722275 DOI: 10.1080/14787210.2018.1471355] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Broad availability of direct-acting antiviral therapy for hepatitis C virus (HCV) raises the possibility that HCV prevalence and incidence can be reduced through scaling-up treatment, leading to the elimination of HCV. High rates of linkage to HIV care among HIV-infected gay and bisexual men may facilitate high uptake of HCV treatment, possibly making HCV elimination more achievable in this group. Areas covered: This review covers HCV elimination in HIV-infected gay and bisexual men, including epidemiology, spontaneous clearance and long term sequelae in the absence of direct-acting antiviral therapy; direct-acting antiviral therapy uptake and effectiveness in this group; HCV reinfection following successful treatment; and areas for further research. Expert commentary: Early data from the direct-acting antiviral era suggest that treatment uptake is increasing among HIV infected GBM, and SVR rates are very promising. However, in order to sustain current treatment rates, additional interventions at the behavioral, physician, and structural levels may be required to increase HCV diagnosis, including prompt detection of HCV reinfection. Timely consideration of these issues is required to maximize the population-level impact of HCV direct-acting antiviral therapy. Potential HCV transmissions from HIV-uninfected GBM, across international borders, and from those who are not GBM also warrant consideration.
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Affiliation(s)
- Rachel Sacks-Davis
- a Disease Elimination Program , Burnet Institute , Melbourne , Australia.,b Department of Medicine , University of Melbourne , Parkville , Australia
| | - Alisa E Pedrana
- a Disease Elimination Program , Burnet Institute , Melbourne , Australia.,c Department of Epidemiology and Preventive Medicine , Monash University , Melbourne , Australia
| | - Nick Scott
- a Disease Elimination Program , Burnet Institute , Melbourne , Australia.,c Department of Epidemiology and Preventive Medicine , Monash University , Melbourne , Australia
| | - Joseph S Doyle
- a Disease Elimination Program , Burnet Institute , Melbourne , Australia.,d Central Clinical School , Monash University , Melbourne , Australia
| | - Margaret E Hellard
- a Disease Elimination Program , Burnet Institute , Melbourne , Australia.,c Department of Epidemiology and Preventive Medicine , Monash University , Melbourne , Australia
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Brook G, Brockmeyer N, van de Laar T, Schellberg S, Winter AJ. 2017 European guideline for the screening, prevention and initial management of hepatitis B and C infections in sexual health settings. Int J STD AIDS 2018; 29:949-967. [PMID: 29716442 DOI: 10.1177/0956462418767576] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This guideline updates the 2010 European guideline for the management of hepatitis B and C virus infections. It is primarily intended to provide advice on testing, prevention and initial management of viral hepatitis B and C for clinicians working in sexual health clinical settings in European countries. The guideline is in a new question and answer format based on clinical situations, from which population/intervention/comparison/outcome questions were formulated. Updates cover areas such as epidemiology, point-of-care tests for hepatitis B, hepatitis C risk and 'chemsex', and HIV pre-exposure prophylaxis and hepatitis B. We have also included a short paragraph on hepatitis E noting there is no evidence for sexual transmission. The guideline has been prepared in accordance with the Europe protocol for production available at http://www.iusti.org/regions/europe/pdf/2017/ProtocolForProduction2017.pdf.
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Affiliation(s)
- Gary Brook
- 1 Genitourinary Medicine, London North West Healthcare NHS Trust, London, UK
| | - Norbert Brockmeyer
- 2 Klinik für Dermatologie, Venerologie und Allergologie, Ruhr-Universität Bochum, Bochum, Germany
| | - Thijs van de Laar
- 3 Department of Bloodborne Infections, Sanquin Blood Supply, Amsterdam, Netherlands
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Dehghani-Dehej F, Sarvari J, Esghaei M, Hosseini SY, Garshasbi S, Kalantari S, Monavari SH, Fakhim A, Keyvani H, Bokharaei-Salim F. Presence of different hepatitis C virus genotypes in plasma and peripheral blood mononuclear cell samples of Iranian patients with HIV infection. J Med Virol 2018; 90:1343-1351. [DOI: 10.1002/jmv.24925] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 07/31/2017] [Indexed: 01/05/2023]
Affiliation(s)
- Farzaneh Dehghani-Dehej
- Department of Bacteriology and Virology; School of Medicine; Shiraz University of Medical Sciences; Shiraz Iran
| | - Jamal Sarvari
- Department of Bacteriology and Virology; School of Medicine; Shiraz University of Medical Sciences; Shiraz Iran
- Gastroenterohepatology Research Center; Shiraz University of Medical Sciences; Shiraz Iran
| | - Maryam Esghaei
- Department of Virology; School of Medicine; Iran University of Medical Sciences; Tehran Iran
| | - Seyed Y. Hosseini
- Department of Bacteriology and Virology; School of Medicine; Shiraz University of Medical Sciences; Shiraz Iran
| | - Saba Garshasbi
- HIV Laboratory of National Center; Deputy of Health; Iran University of Medical Sciences; Tehran Iran
| | - Saeed Kalantari
- Departments of Infectious Diseases and Tropical Medicine; Iran University of Medical Sciences; Tehran Iran
| | - Seyed H. Monavari
- Department of Virology; School of Medicine; Iran University of Medical Sciences; Tehran Iran
| | - Atousa Fakhim
- Department of Architectural Engineering; Faculty of Engineering; Islamic Azad University; South Tehran Branch; Tehran Iran
| | - Hossein Keyvani
- Department of Virology; School of Medicine; Iran University of Medical Sciences; Tehran Iran
| | - Farah Bokharaei-Salim
- Department of Virology; School of Medicine; Iran University of Medical Sciences; Tehran Iran
- HIV Laboratory of National Center; Deputy of Health; Iran University of Medical Sciences; Tehran Iran
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47
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Aebi-Popp K, Wandeler G, Salazar-Vizcaya L, Metzner K, Stöckle M, Cavassini M, Hoffmann M, Lüthi A, Suter F, Bernasconi E, Fehr J, Furrer H, Rauch A. Rapid decline of anti-hepatitis C virus (HCV) antibodies following early treatment of incident HCV infections in HIV-infected men who have sex with men. HIV Med 2018; 19:420-425. [PMID: 29573533 DOI: 10.1111/hiv.12602] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2018] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Following clearance of incident hepatitis C virus (HCV) infections, HCV antibody levels may decline, resulting in seroreversion. It is unclear to what extent HCV antibody level trajectories differ between patients with treatment-induced sustained virological response (SVR), those with spontaneous clearance and those with untreated replicating HCV infection. We investigated HCV antibody level dynamics in HIV-infected MSM with different clinical outcomes. METHODS We investigated anti-HCV antibody level dynamics following an incident HCV infection in 67 HIV-infected men who have sex with men (MSM) with different clinical outcomes: SVR (n = 33), spontaneous clearance (n = 12), and untreated replicating infection (n = 22). Antibody levels were measured at the time of HCV diagnosis, and at yearly intervals for 3 years thereafter. RESULTS At baseline, median HCV antibody levels were similar in the three groups: 13.4, 13.8 and 13.5 sample to cut-off (S/CO) for SVR, spontaneous clearance and untreated infection, respectively. Over 3 years of follow-up, SVR was associated with a more pronounced decrease in anti-HCV levels compared with spontaneous clearance and untreated infection [median decline 71% [interquartile range (IQR: 43-87%), 38% (IQR: 29-60%) and 12% (IQR: 9-22%), respectively; P < 0.001]. Seroreversions occurred in five of 33 (15%) patients with SVR and in one of 12 (8%) with spontaneous clearance. A shorter delay between time of infection and treatment start correlated with higher rates of decline in antibody levels. Seven patients experienced a reinfection. CONCLUSIONS Treatment-induced HCV clearance was associated with a more pronounced decline in anti-HCV antibody levels and with higher rates of seroreversion compared with spontaneous clearance or untreated replicating HCV infection among HIV-infected MSM with incident HCV infections. Rapid clearance of HCV RNA following early HCV treatment might impair the development of persistent antibody titres.
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Affiliation(s)
- K Aebi-Popp
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | - G Wandeler
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | - L Salazar-Vizcaya
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | - K Metzner
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.,Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - M Stöckle
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - M Cavassini
- Division of Infectious Diseases, University Hospital Lausanne, Lausanne, Switzerland
| | - M Hoffmann
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St Gallen, St Gallen, Switzerland
| | - A Lüthi
- Institute for Infectious Diseases, University of Bern, Bern, Switzerland
| | - F Suter
- Institute for Infectious Diseases, University of Bern, Bern, Switzerland
| | - E Bernasconi
- Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland
| | - J Fehr
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - H Furrer
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | - A Rauch
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
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48
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Newsum AM, Stolte IG, van der Meer JT, Schinkel J, van der Valk M, Vanhommerig JW, Buvé A, Danta M, Hogewoning A, Prins M. Development and validation of the HCV-MOSAIC risk score to assist testing for acute hepatitis C virus (HCV) infection in HIV-infected men who have sex with men (MSM). ACTA ACUST UNITED AC 2018; 22:30540. [PMID: 28597832 PMCID: PMC5479984 DOI: 10.2807/1560-7917.es.2017.22.21.30540] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 12/22/2016] [Indexed: 12/26/2022]
Abstract
Current guidelines recommend hepatitis C virus (HCV) testing for HIV-infected men who have sex with men (MSM) with ongoing risk behaviour, without specifying the type of risk behaviour. We developed and validated the HCV-MOSAIC risk score to assist HCV testing in HIV-infected MSM. The risk score consisted of six self-reported risk factors identified using multivariable logistic regression using data from the Dutch MOSAIC study (n = 213, 2009–2013). Area under the ROC curve (AUC), sensitivity, specificity, post-test-probability-of-disease and diagnostic gain were calculated. The risk score was validated in case–control studies from Belgium (n = 142, 2010–2013) and the United Kingdom (n = 190, 2003–2005) and in cross-sectional surveys at a Dutch sexually transmitted infections clinic (n = 284, 2007–2009). The AUC was 0.82; sensitivity 78.0% and specificity 78.6%. In the validation studies sensitivity ranged from 73.1% to 100% and specificity from 56.2% to 65.6%. The post-test-probability-of-disease ranged from 5.9% to 20.0% given acute HCV prevalence of 1.7% to 6.4%, yielding a diagnostic gain of 4.2% to 13.6%. The HCV-MOSAIC risk score can successfully identify HIV-infected MSM at risk for acute HCV infection. It could be a promising tool to improve HCV testing strategies in various settings.
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Affiliation(s)
- Astrid M Newsum
- Department of Infectious Diseases Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands.,Department of Internal Medicine, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Netherlands
| | - Ineke G Stolte
- Department of Infectious Diseases Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands
| | - Jan Tm van der Meer
- Department of Internal Medicine, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Netherlands
| | - Janke Schinkel
- Department of Medical Microbiology, Academic Medical Center, Amsterdam, the Netherlands
| | - Marc van der Valk
- Department of Internal Medicine, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Netherlands
| | - Joost W Vanhommerig
- Department of Infectious Diseases Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands.,Department of Medical Microbiology, Academic Medical Center, Amsterdam, the Netherlands
| | - Anne Buvé
- Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium
| | - Mark Danta
- St Vincent's Clinical School, University of New South Wales, Sydney, Australia
| | - Arjan Hogewoning
- STI Outpatient Clinic, Public Health Service of Amsterdam, Amsterdam, the Netherlands
| | - Maria Prins
- Department of Infectious Diseases Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands.,Department of Internal Medicine, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, the Netherlands
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- The members of the group are listed at the end of the article
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49
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Benito R, Arribas J, Algarate S, Cebollada R, Gude MJ. Hepatitis C virus core antigen for screening organ donors and recipients. Diagn Microbiol Infect Dis 2018; 91:126-129. [PMID: 29477273 DOI: 10.1016/j.diagmicrobio.2018.01.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 01/25/2018] [Accepted: 01/28/2018] [Indexed: 02/07/2023]
Abstract
Organ donors and recipients are routinely screened for hepatitis C virus (HCV) infection, typically via anti-HCV detection. We analyze the utility of an alternative HCV core antigen (HCV-Ag) quantification system, the ARCHITECT HCV Ag Assay, in this setting. We simultaneously tested 315 samples from potential organ donors and recipients using two chemiluminescent microparticle immunoassays: ARCHITECT Anti-HCV and HCV Ag (Abbott, Germany). HCV-Ag was detected in 81 of the serum samples (25.71%) and anti-HCV in 87 (27.62%). Seventy-five of the HCV-Ag-positive samples were positive for anti-HCV (92.59%). Overall concordance between the two assays was 94.29%. Of the six HCV-Ag-positive/anti-HCV-negative patients, five had HCV-Ag values <32 fmol/L, and the sixth had a concentration of 477.50 fmol/L (viral load, 137,000 IU/mL). The HCV AG Assay detects HCV infections missed by the Anti-HCV Assay. Both markers should be used to screen for HCV infection in potential organ donors and recipients.
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Affiliation(s)
- Rafael Benito
- Department of Microbiology, University of Zaragoza, Pedro Cerbuna, 12, 50009, Zaragoza, Spain; Service of Microbiology, Hospital Clínico Universitario Lozano Blesa, Pedro Cerbuna, 12, 50009, Zaragoza, Spain.
| | - Jorge Arribas
- Service of Microbiology, Hospital Clínico Universitario Lozano Blesa, San Juan Bosco, 15, 50009, Zaragoza, Spain
| | - Sonia Algarate
- Department of Microbiology, University of Zaragoza, Pedro Cerbuna, 12, 50009, Zaragoza, Spain; Service of Microbiology, Hospital Clínico Universitario Lozano Blesa, Pedro Cerbuna, 12, 50009, Zaragoza, Spain
| | - Rocío Cebollada
- Service of Microbiology, Hospital Clínico Universitario Lozano Blesa, San Juan Bosco, 15, 50009, Zaragoza, Spain
| | - M José Gude
- Service of Microbiology, Hospital Clínico Universitario Lozano Blesa, San Juan Bosco, 15, 50009, Zaragoza, Spain
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50
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Earlier Detection of Hepatitis C Virus Infection Through Routine Hepatitis C Virus Antibody Screening of Human Immunodeficiency Virus-Positive Men Who Have Sex With Men Attending A Sexually Transmitted Infection Outpatient Clinic: A Longitudinal Study. Sex Transm Dis 2017; 43:560-5. [PMID: 27513382 DOI: 10.1097/olq.0000000000000497] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND In 2007, routine hepatitis C virus (HCV) antibody testing was introduced for men who have sex with men (MSM) with a human immunodeficiency virus (HIV)-positive or unknown status attending a Dutch sexually transmitted infection (STI) outpatient clinic. We evaluated whether this screening resulted in additional and earlier HCV diagnoses among MSM who also attend HIV clinics. METHODS At first STI consultation, HIV-positive MSM and MSM opting-out of HIV testing (HIV-status-unknown) were tested for HCV antibodies (anti-HCV). During follow-up consultations, only previously HCV-negative men were tested. Retrospectively, STI clinic and HIV clinic HCV diagnosis dates were compared. RESULTS One hundred twelve (6.4%) of 1742 (95% confidence interval [CI], 5.3-7.6%) HIV-positive and 3 (0.7%) of 446 (95% CI, 0.2-2.0%) HIV-status-unknown MSM tested anti-HCV-positive at first consultation. During follow-up consultations, 32 HIV-positive (incidence HCV-positive: 2.35/100 person years (PY) (95% CI, 1.66-3.33)) and 0 (1-sided, 97.5% CI, 0.0-3.76) HIV-status-unknown MSM became anti-HCV-positive. Four (11.8%) of 34 HIV-positive MSM notified by their sexual partner of HCV tested anti-HCV-positive.Of 163 HIV-positive MSM with HCV antibodies, 78 reported a history of HCV. HCV diagnosis data at the HIV clinic was requested for the remaining 85 MSM and available for 54 MSM. Of these 54 MSM, 28 (51.9%) had their first HCV diagnosis at the STI clinic, of whom 7 concurrently with HIV. At their next scheduled HIV clinic consultation, 3 HCV cases probably would have been missed. CONCLUSIONS The introduction of routine anti-HCV testing at the STI outpatient clinic resulted in additional and earlier HCV detection among HIV-positive MSM. Testing should be continued among HIV-positive MSM, at least for those not (yet) under the care of an HIV clinic and those notified of HCV by their sexual partner.
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