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Read P, Tang BZH, Silins E, Doab A, Cornelisse VJ, Gilliver R. Hepatitis C (HCV) Reinfection and Risk Factors among Clients of a Low-Threshold Primary Healthcare Service for People Who Inject Drugs in Sydney, Australia. Viruses 2024; 16:957. [PMID: 38932249 PMCID: PMC11209512 DOI: 10.3390/v16060957] [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: 04/23/2024] [Revised: 05/29/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
Hepatitis C (HCV) reinfection studies have not focused on primary healthcare services in Australia, where priority populations including people who inject drugs (PWID) typically engage in healthcare. We aimed to describe the incidence of HCV reinfection and associated risk factors in a cohort of people most at risk of reinfection in a real-world community setting. We conducted a secondary analysis of routinely collected HCV testing and treatment data from treatment episodes initiated with direct-acting antiviral (DAA) therapy between October 2015 and June 2021. The overall proportion of clients (N = 413) reinfected was 9% (N = 37), and the overall incidence rate of HCV reinfection was 9.5/100PY (95% CI: 6.3-14.3). Reinfection incidence rates varied by sub-group and were highest for Aboriginal and/or Torres Strait Islander people (20.4/100PY; 95% CI: 12.1-34.4). Among PWID (N= 321), only Aboriginality was significantly associated with reinfection (AOR: 2.73, 95% CI: 1.33-5.60, p = 0.006). High rates of HCV reinfection in populations with multiple vulnerabilities and continued drug use, especially among Aboriginal and Torres Strait Islander people, highlight the need for ongoing regular HCV testing and retreatment in order to achieve HCV elimination. A priority is resourcing testing and treatment for Aboriginal and/or Torres Strait Islander people. Our findings support the need for novel and holistic healthcare strategies for PWID and the upscaling of Indigenous cultural approaches and interventions.
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Affiliation(s)
- Phillip Read
- Kirketon Road Centre, Kings Cross, P.O. Box 22, Sydney, NSW 1340, Australia; (E.S.); (A.D.); (R.G.)
- Kirby Institute, UNSW Australia, Sydney, NSW 2032, Australia
| | | | - Edmund Silins
- Kirketon Road Centre, Kings Cross, P.O. Box 22, Sydney, NSW 1340, Australia; (E.S.); (A.D.); (R.G.)
- National Drug and Alcohol Research Centre (NDARC), UNSW Australia, Sydney, NSW 2052, Australia
| | - Anna Doab
- Kirketon Road Centre, Kings Cross, P.O. Box 22, Sydney, NSW 1340, Australia; (E.S.); (A.D.); (R.G.)
| | - Vincent J. Cornelisse
- Kirketon Road Centre, Kings Cross, P.O. Box 22, Sydney, NSW 1340, Australia; (E.S.); (A.D.); (R.G.)
- Kirby Institute, UNSW Australia, Sydney, NSW 2032, Australia
| | - Rosie Gilliver
- Kirketon Road Centre, Kings Cross, P.O. Box 22, Sydney, NSW 1340, Australia; (E.S.); (A.D.); (R.G.)
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Eisa M, Gomez-Escobar E, Bédard N, Abdeltawab NF, Flores N, Mazouz S, Fieffé-Bédard A, Sakayan P, Gridley J, Abdel-Hakeem MS, Bruneau J, Grakoui A, Shoukry NH. Coordinated expansion of memory T follicular helper and B cells mediates spontaneous clearance of HCV reinfection. Front Immunol 2024; 15:1403769. [PMID: 38947319 PMCID: PMC11211980 DOI: 10.3389/fimmu.2024.1403769] [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: 03/19/2024] [Accepted: 05/15/2024] [Indexed: 07/02/2024] Open
Abstract
Introduction Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs. Methods We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, n = 14) or chronic infection (SR/CI, n = 8). Results Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4+CXCR5+PD-1+ICOS+FoxP3-) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19+CD27+IgM-E2-Tet+) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3+CCR6-) subset correlated with the neutralization breadth and potency of NAbs. Conclusion These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection.
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Affiliation(s)
- Mohamed Eisa
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Elsa Gomez-Escobar
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
- Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC, Canada
| | - Nathalie Bédard
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Nourtan F. Abdeltawab
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
- School of Pharmacy, Newgiza University, Giza, Egypt
| | - Nicol Flores
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
- Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC, Canada
| | - Sabrina Mazouz
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
- Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC, Canada
| | - Alizée Fieffé-Bédard
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Patrick Sakayan
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - John Gridley
- Department of Medicine, Emory University, Atlanta, GA, United States
| | - Mohamed S. Abdel-Hakeem
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
- Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, QC, Canada
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Julie Bruneau
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
- Département de Médecine familiale et département d’urgence, Université de Montréal, Montréal, QC, Canada
| | - Arash Grakoui
- Department of Medicine, Emory University, Atlanta, GA, United States
| | - Naglaa H. Shoukry
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada
- Département de Médecine, Université de Montréal, Montréal, QC, Canada
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Dröse S, Øvrehus ALH, Holm DK, Madsen LW, Mössner BK, Søholm J, Hansen JF, Røge BT, Christensen PB. A multi-level intervention to eliminate hepatitis C from the Region of Southern Denmark: the C-Free-South project. BMC Infect Dis 2022; 22:202. [PMID: 35232372 PMCID: PMC8889755 DOI: 10.1186/s12879-022-07196-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 02/22/2022] [Indexed: 11/16/2022] Open
Abstract
Denmark has signed the WHO strategy to eliminate hepatitis C virus (HCV). In the absence of a national strategy for elimination, a local action plan was developed in the Region of Southern Denmark (RSD). The aim of the strategy is to diagnose 90% of HCV-infected persons and treat 80% of those diagnosed by 2025. The strategy was developed by reviewing Danish data on HCV epidemiology and drug use to identify key populations for screening, linkage to care, and treatment. Based on available published data from 2016, an estimated 3028 persons in the RSD were HCV-RNA positive (population prevalence 0.21%). Of these, 1002 were attending clinical care, 1299 were diagnosed but not in clinical care, and 727 were undiagnosed. Three different interventions targeting the HCV-infected population and two interventions for HCV surveillance are planned to achieve elimination. The “C-Free-South” strategy aims to eliminate HCV in our region by identifying (90%) and treating (80%) of infected persons by the end of 2025, 5 years earlier than the WHO elimination target date.
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Affiliation(s)
- Sandra Dröse
- Department of Infectious Diseases, Odense University Hospital, J. B. Winsloews Vej 4, Indgang 18 Penthouse 2. sal, 5000, Odense C, Denmark. .,Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Winsløwparken 19, 3. sal, 5000, Odense, Denmark.
| | - Anne Lindebo Holm Øvrehus
- Department of Infectious Diseases, Odense University Hospital, J. B. Winsloews Vej 4, Indgang 18 Penthouse 2. sal, 5000, Odense C, Denmark.,Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Winsløwparken 19, 3. sal, 5000, Odense, Denmark
| | - Dorte Kinggaard Holm
- Department of Clinical Immunology, Odense University Hospital, 29 J. B. Winsloews Vej 4, Indgang 8, Odense C, 5000, Odense, Denmark
| | - Lone Wulff Madsen
- Department of Infectious Diseases, Odense University Hospital, J. B. Winsloews Vej 4, Indgang 18 Penthouse 2. sal, 5000, Odense C, Denmark.,Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Winsløwparken 19, 3. sal, 5000, Odense, Denmark
| | - Belinda Klemmensen Mössner
- Department of Infectious Diseases, Odense University Hospital, J. B. Winsloews Vej 4, Indgang 18 Penthouse 2. sal, 5000, Odense C, Denmark.,Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Winsløwparken 19, 3. sal, 5000, Odense, Denmark
| | - Jacob Søholm
- Department of Infectious Diseases, Odense University Hospital, J. B. Winsloews Vej 4, Indgang 18 Penthouse 2. sal, 5000, Odense C, Denmark
| | - Janne Fuglsang Hansen
- Department of Infectious Diseases, Odense University Hospital, J. B. Winsloews Vej 4, Indgang 18 Penthouse 2. sal, 5000, Odense C, Denmark
| | - Birgit Thorup Røge
- Department of Medicine, Lillebaelt Hospital, Sygehusvej 24, 6000, Kolding, Denmark
| | - Peer Brehm Christensen
- Department of Infectious Diseases, Odense University Hospital, J. B. Winsloews Vej 4, Indgang 18 Penthouse 2. sal, 5000, Odense C, Denmark. .,Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Winsløwparken 19, 3. sal, 5000, Odense, Denmark.
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Primary Care Associated With Follow Up Viral Load Testing in Patients Cured of Hepatitis C Infection With Direct Acting Antivirals at a Multidisciplinary Addiction Treatment Program: Insights From a Real-World Setting. J Addict Med 2022; 16:333-339. [PMID: 34483278 PMCID: PMC9033626 DOI: 10.1097/adm.0000000000000910] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVES Treatment of hepatitis C virus infection (HCV) with direct acting antiviral therapy is encouraged regardless of substance use status. Patients with substance use disorder are at risk of HCV reinfection after cure. Follow up viral load testing (FUVL) with HCV RNA is recommended. We investigated factors associated with adoption of FUVL in real-world clinical settings. METHODS Medical records of all patients with SUD who achieved HCV cure with direct acting antivirals at a multidisciplinary addiction treatment program between 2014 and 2019 were reviewed as part of a quality improvement initiative. Demographic and clinical characteristics including SUD treatment, urine toxicology results, and medical service use were collected. Factors associated with FUVL were analyzed and the rate of HCV reinfection was determined. RESULTS Among 149 patients, 58.4% received FUVL. Receipt of FUVL was associated with engagement in ongoing primary medical care after cure (AOR 4.39, 95% CI [1.67, 11.49]). The HCV reinfection rate among those who received FUVL was 1.95 per 100 person-years of follow up (95% CI [0.64, 5.98]). There was no significant difference in the percentage of negative urine toxicology results before and after cure. CONCLUSIONS Over half of a cohort of patients with substance use disorder cured of HCV received FUVL. The relationship between FUVL and engagement in primary medical and substance use treatment highlights the importance of integrated systems in providing longitudinal care for patients cured of HCV. Standardized interventions that facilitate FUVL testing and management of infectious complications of SUD in addiction treatment settings are needed.
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Conway B, Smyth D, Thomas R, Wong A, Sebastiani G, Cooper C, Shah H, Kumar R, Deutsch G, Watson T. Characterizing risk behaviour and reinfection rates for successful programs to engage core transmitters in HCV elimination (C-RESPECT). CANADIAN LIVER JOURNAL 2021; 4:346-359. [PMID: 35989890 PMCID: PMC9235128 DOI: 10.3138/canlivj-2021-0005] [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: 03/14/2021] [Accepted: 03/14/2021] [Indexed: 10/21/2024]
Abstract
BACKGROUND Development of robust treatment programs among core transmitters (CT) of hepatitis C virus (HCV) are needed, including strategies to address reinfection risk. The aim of this study was to describe the effectiveness of direct-acting antiviral (DAA) treatment in CT versus non-CT populations and assess reinfection rates after successful treatment. METHODS Characterizing Risk Behaviour and Reinfection Rates for Successful Programs to Engage Core Transmitters in HCV Elimination (C-RESPECT) was a prospective, observational study of HCV-infected Canadian adult patients (genotypes 1, 3, and 4) treated with DAAs between 2017 and 2020. RESULTS The full analysis set included 429 participants (259 CT, 170 non-CT). Key differences were observed in baseline profiles: CT participants were younger (mean 42.3 [SD 11.2] y versus 55.0 [SD 11.1] y, respectively) and reported higher rates of social assistance (35.7% versus 14.8%), smoking (83.7% versus 52.4%), low socioeconomic status (yearly income <$15,000: 69.6% versus 43.9%), illicit drug use (83.7% versus 34.3%), and previous incarcerations (62.7% versus 36.9%). DAA treatment adherence was similar; 93 .5% versus 98.3% of CT versus non-CT participants completed the assigned treatment duration. Cure rates (sustained virologic response) were comparable, ranging from 94.9% to 98.1%. All reinfections were among CT participants, with a rate of 13.8/100 person-years (95% CI 9.2-20.8) with mean time to reinfection of 24.6 (SD 0.6) months. CONCLUSIONS CT and non-CT participants respond equally well to DAA treatment; however, with some reinfections among CT participants. Innovative multidisciplinary programs must be developed to mitigate this risk in this key population.
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Affiliation(s)
- Brian Conway
- Vancouver Infectious Diseases Centre, Vancouver, British Columbia, Canada
| | - Dan Smyth
- Centre for Research, Education and Clinical Care of At-Risk Populations (RECAP), Moncton, New Brunswick, Canada
| | | | - Alex Wong
- Saskatchewan Health Authority, Regina, Saskatchewan, Canada
| | | | - Curtis Cooper
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Hemant Shah
- University Health Network, Toronto, Ontario, Canada
| | | | | | - Ted Watson
- Merck Canada Inc., Kirkland, Quebec, Canada
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Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, Marra F, Puoti M, Wedemeyer H. EASL recommendations on treatment of hepatitis C: Final update of the series ☆. J Hepatol 2020; 73:1170-1218. [PMID: 32956768 DOI: 10.1016/j.jhep.2020.08.018] [Citation(s) in RCA: 758] [Impact Index Per Article: 151.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 08/18/2020] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Clinical care for patients with HCV-related liver disease has advanced considerably thanks to an enhanced understanding of the pathophysiology of the disease, as well as developments in diagnostic procedures and improvements in therapy and prevention. These therapies make it possible to eliminate hepatitis C as a major public health threat, as per the World Health Organization target, although the timeline and feasibility vary from region to region. These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.
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Hajarizadeh B, Cunningham EB, Valerio H, Martinello M, Law M, Janjua NZ, Midgard H, Dalgard O, Dillon J, Hickman M, Bruneau J, Dore GJ, Grebely J. Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: A meta-analysis. J Hepatol 2020; 72:643-657. [PMID: 31785345 DOI: 10.1016/j.jhep.2019.11.012] [Citation(s) in RCA: 119] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/30/2019] [Accepted: 11/05/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT). METHODS We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies. RESULTS Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1-8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3-9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5-5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1-9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5-5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8-2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0-8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4-12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio [aRR] per year increase in mean/median follow-up 0.77; 95% CI 0.69-0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62-7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82-8.59) had higher reinfection rates. CONCLUSION HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment. LAY SUMMARY Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population - reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment.
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Affiliation(s)
| | | | | | | | - Matthew Law
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
| | - Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Håvard Midgard
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | | | - John Dillon
- Ninewells Hospital and Medical School, University of Dundee, Dundee, The United Kingdom
| | - Matthew Hickman
- Population Health Sciences, University of Bristol, Bristol, The United Kingdom
| | - Julie Bruneau
- Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada
| | - Gregory J Dore
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
| | - Jason Grebely
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
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Liu Y, Zhang H, Zhang L, Zou X, Ling L. Economic Evaluation of Hepatitis C Treatment Extension to Acute Infection and Early-Stage Fibrosis Among Patients Who Inject Drugs in Developing Countries: A Case of China. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17030800. [PMID: 32012839 PMCID: PMC7037788 DOI: 10.3390/ijerph17030800] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 01/22/2020] [Accepted: 01/24/2020] [Indexed: 12/20/2022]
Abstract
We aimed to assess the cost-effectiveness of (1) treating acute hepatitis C virus (HCV) vs. deferring treatment until the chronic phase and (2) treating all chronic patients vs. only those with advanced fibrosis; among Chinese genotype 1b treatment-naïve patients who injected drugs (PWID), using a combination Daclatasvir (DCV) plus Asunaprevir (ASV) regimen and a Peg-interferon (PegIFN)-based regimen, respectively. A decision-analytical model including the risk of HCV reinfection simulated lifetime costs and quality-adjusted life-years (QALYs) of three treatment timings, under the DCV+ASV and PegIFN regimen, respectively: Treating acute infection (“Treat at acute”), treating chronic patients of all fibrosis stages (“Treat at F0 (no fibrosis)”), treating only advanced-stage fibrosis patients (“Treat at F3 (numerous septa without cirrhosis)”). Incremental cost-effectiveness ratios (ICERs) were used to compare scenarios. “Treat at acute” compared with “Treat at F0” was cost-saving (cost: DCV+ASV regimen—US$14,486.975 vs. US$16,224.250; PegIFN-based regimen—US$19,734.794 vs. US$22,101.584) and more effective (QALY: DCV+ASV regimen—14.573 vs. 14.566; PegIFN-based regimen—14.148 vs. 14.116). Compared with “Treat at F3”; “Treat at F0” exhibited an ICER of US$3780.20/QALY and US$15,145.98/QALY under the DCV+ASV regimen and PegIFN-based regimen; respectively. Treatment of acute HCV infection was highly cost-effective and cost-saving compared with deferring treatment to the chronic stage; for both DCV+ASV and PegIFN-based regimens. Early treatment for chronic patients with DCV+ASV regimen was highly cost-effective.
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Affiliation(s)
- Yin Liu
- Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (Y.L.); (X.Z.)
- Sun Yat-sen Center for Migrant Health Policy, Sun Yat-Sen University, Guangzhou 510080, China
| | - Hui Zhang
- Department of Health Policy and Management, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China;
| | - Lei Zhang
- China-Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710000, China;
- Melbourne Sexual Health Center, Alfred Health, Melbourne VIC 3053, Australia
- Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3800, Australia
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
| | - Xia Zou
- Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (Y.L.); (X.Z.)
- Sun Yat-sen Center for Migrant Health Policy, Sun Yat-Sen University, Guangzhou 510080, China
| | - Li Ling
- Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; (Y.L.); (X.Z.)
- Sun Yat-sen Center for Migrant Health Policy, Sun Yat-Sen University, Guangzhou 510080, China
- Correspondence: ; Tel.: +86-020-873-3319
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Liu Y, Zou X, Chen W, Gong C, Ling L. Hepatitis C Virus Treatment Status and Barriers among Patients in Methadone Maintenance Treatment Clinics in Guangdong Province, China: A Cross-Sectional, Observational Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16224436. [PMID: 31726750 PMCID: PMC6888391 DOI: 10.3390/ijerph16224436] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/31/2019] [Accepted: 11/08/2019] [Indexed: 12/13/2022]
Abstract
We aimed to evaluate the status and barriers related to hepatitis C virus (HCV) treatment among Chinese methadone maintenance treatment (MMT) clients, and the willingness and barriers of patients to accept directly observed treatment (DOT) service and oral direct-acting antivirals (DAAs). We conducted a cross-sectional survey from July to October 2017 in Guangdong Province, China, involving 678 HCV antibody-positive MMT patients. If they reported being infected with HCV, then their HCV treatment experience, willingness to use DOT and DAAs, along with any barriers, were collected. Logistic regression analysis was used to identify the correlates of initiating HCV treatment. Among those reporting HCV infection (54%, 366/678), 39% (144/366) initiated treatment; however, 38% (55/144) interrupted and 55% (79/135) delayed treatment for 15 months. Seventy-five percent (273/366) and 53% (195/366) were willing to use DOT and DAAs, respectively. Unaffordable medical costs and insignificant symptoms were the major barriers to HCV treatment and accepting DOT or DAAs. The lack of a stable residence, being a woman, and having ever injected drugs were all associated with a low probability of initiating treatment (p < 0.05). This study highlights a limited uptake of HCV treatment among MMT patients, and a need to strengthen the popularity of DOT and DAAs and integrate them into Chinese MMT clinics.
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Affiliation(s)
| | | | | | | | - Li Ling
- Correspondence: ; Tel.: +86-020-873-3319
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Verna EC, Schluger A, Brown RS. Opioid epidemic and liver disease. JHEP Rep 2019; 1:240-255. [PMID: 32039374 PMCID: PMC7001546 DOI: 10.1016/j.jhepr.2019.06.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 06/27/2019] [Accepted: 06/29/2019] [Indexed: 12/12/2022] Open
Abstract
Opioid use in the United States and in many parts of the world has reached epidemic proportions. This has led to excess mortality as well as significant changes in the epidemiology of liver disease. Herein, we review the impact of the opioid epidemic on liver disease, focusing on the multifaceted impact this epidemic has had on liver disease and liver transplantation. In particular, the opioid crisis has led to a significant shift in incident hepatitis C virus infection to younger populations and to women, leading to changes in screening recommendations. Less well characterized are the potential direct and indirect hepatotoxic effects of opioids, as well as the changes in the incidence of hepatitis B virus infection and alcohol abuse that are likely rising in this population as well. Finally, the opioid epidemic has led to a significant rise in the proportion of organ donors who died due to overdose. These donors have led to an overall increase in donor numbers, but also to new considerations about the better use of donors with perceived or actual risk of disease transmission, especially hepatitis C. Clearly, additional efforts are needed to combat the opioid epidemic. Moreover, better understanding of the epidemiology and underlying pathophysiology will help to identify and treat liver disease in this high-risk population.
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Affiliation(s)
- Elizabeth C. Verna
- Center for Liver Disease and Transplantation, Columbia University Vagelos College of Physicians and Surgeons, New York, NY
| | - Aaron Schluger
- Columbia University Vagelos College of Physicians and Surgeons, New York, NY
| | - Robert S. Brown
- Center for Liver Disease and Transplantation, Columbia University Vagelos College of Physicians and Surgeons, New York, NY
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY
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11
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Marco A, Guerrero RA, Vergara M, Gallego C, Solé C, Planella R, Vaz ME, Teixidó N, Sastre A, Touzón C, da Silva A, Almada G, Ruíz A, Caylà JA, Turu E. Reinfection in a large cohort of prison inmates with sustained virological response after treatment of chronic hepatitis C in Catalonia (Spain), 2002-2016. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2019; 72:189-194. [PMID: 31160156 DOI: 10.1016/j.drugpo.2019.05.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Revised: 04/08/2019] [Accepted: 05/15/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Prisoners and other high-risk patients who show a sustained virological response (SVR) after treatment for hepatitis C virus (HCV) can become reinfected. We aimed to calculate the rate of HCV reinfection in a large cohort of inmates with SVR and to determine factors that predict reinfection. METHODS We included all inmates treated for hepatitis C in Catalonia (Spain) from January 2002 to December 2016 who achieved SVR and in whom viral load was subsequently determined. The incidence rate was calculated per 100 person-years (100 py) of follow up. Risk factors associated with reinfection were evaluated by bivariate log-rank test and multivariate Cox regression. Hazard ratio (HR) and their 95% confidence intervals (CI) were calculated. RESULTS 602 patients were included, with a mean age of 37.9 years: 95% were men, 74.1% had a history of intravenous drug use (IDU) and 28.7% were HIV-infected. Patients were followed for a total of 2154.9 years (average 3.58 ± 3.1 years). 63 (10.5%) had HCV reinfection. 41 (65.1%) presented different genotype/subgenotype, 8 the initial genotype/subgenotype, and in 14 (22.2%) the genotype could not be determined. Of the 21 reinfected patients who were interviewed, 20 (95.2%) reported IDU after antiviral treatment, and 7 (33.3%) during treatment. The overall incidence of reinfection was 2.9 cases per 100 py. All reinfections occurred in patients with IDU history. At multivariate level, HIV infection was associated with reinfection (HR = 3.03; CI:1.82-5.04). CONCLUSION In HIV-infected inmates with IDU history, the rate of reinfection of HCV post-SVR is very high. Prisons play a key role in the detection and treatment of infection and reinfection by HCV and in the post-treatment monitoring in these patients, which should be combined with counseling and the optimization of the harm reduction programs. Effective control of these vulnerable groups favours the elimination of the HCV infection.
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Affiliation(s)
- Andrés Marco
- Prison Health Program, Catalan Institute of Health, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
| | | | - Mercedes Vergara
- Hepatology Unit, Digestive Disease Department, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain; CIBERehd, Instituto Carlos III, Madrid, Spain.
| | - Carlos Gallego
- Health Services of Quatre Camins Penitentiary Centre, Barcelona, Spain.
| | - Concepció Solé
- Health Services of Puig de les Basses Penitentiary Centre, Girona, Spain.
| | - Ramón Planella
- Health Services of Ponent Penitentiary Centre, Lleida, Spain.
| | - M Elisa Vaz
- Health Services of Mas d'Enric Penitentiary Centre, Tarragona, Spain.
| | - Núria Teixidó
- Health Services of Brians-1 Penitentiary Centre, Barcelona, Spain.
| | - Ana Sastre
- Health Services of Brians-2 Penitentiary Centre, Barcelona, Spain.
| | - Carlos Touzón
- Health Services of Lledoners Penitentiary Centre, Barcelona, Spain.
| | - Antonio da Silva
- Health Services of Quatre Camins Penitentiary Centre, Barcelona, Spain.
| | - Guido Almada
- Health Services of Brians-1 Penitentiary Centre, Barcelona, Spain
| | - Ana Ruíz
- Health Services of Brians-2 Penitentiary Centre, Barcelona, Spain.
| | - Joan A Caylà
- Foundation of Tuberculosis Research Unit of Barcelona, Spain.
| | - Elisabet Turu
- Prison Health Program, Catalan Institute of Health, Spain.
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12
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Schulkind J, Stephens B, Ahmad F, Johnston L, Hutchinson S, Thain D, Ward Z, Vickerman P, Hickman M, Dillon JF. High response and re-infection rates among people who inject drugs treated for hepatitis C in a community needle and syringe programme. J Viral Hepat 2019; 26:519-528. [PMID: 30422370 DOI: 10.1111/jvh.13035] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 10/11/2018] [Indexed: 12/12/2022]
Abstract
To achieve WHO hepatitis C virus (HCV) elimination targets by 2030, mathematical models suggest there needs to be significant scale-up of treatment among people who inject drugs (PWID). We tested whether people who actively inject drugs can be recruited and treated successfully through a community needle and syringe programme (NSP), and assessed rates of re-infection. 105 HCV RNA positive participants were enrolled prospectively. Participants were recruited from the largest NSP in Dundee over 42 months. 94/105 individuals commenced treatment. Genotype 1 (G1) individuals (n = 37) were treated with peg-interferon+ribavirin+Simepravir/Telaprevir. Genotype 2/3 (G2/3) (n = 57) received peg-interferon+ribavirin. Weekly study visits took place within the NSP. Mean age of participants was 34.0 years (SD 6.9), 71.3% (61/94) were male. One in five (20/94) participants were homeless. 68.1% (64/94) were on OST (opiate substitution therapy) at enrolment; participants injected median 6.5 times/wk. In terms of clinical outcomes, >80% treatment adherence was 71.3% (67/94). There was no difference in SVR-12 rates by genotype: 81.0% (30/37) for G1 and 82.5% (47/55) for G2/3. At 18 months post-treatment, 15/77 participants were reinfected, followed up over 69.8 person-years, yielding a re-infection rate of 21.5/100 person-years (95% CI 13.00-35.65). This trial demonstrates that HCV treatment can be delivered successfully to the target population of treatment as prevention strategies. We report higher rates of re-infection than existing estimates among PWID. Scale-up of HCV treatment should be pursued alongside a comprehensive programme of harm reduction interventions to help minimize re-infection and reduce HCV transmission.
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Affiliation(s)
| | - Brian Stephens
- Department of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
| | - Farsana Ahmad
- Department of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
| | - Linda Johnston
- Department of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
| | - Sharon Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
| | - Donna Thain
- NHS Tayside, Ninewells Hospital and Medical School, Dundee, UK
| | - Zoe Ward
- Population Health Sciences, University of Bristol, Bristol, UK
| | - Peter Vickerman
- Population Health Sciences, University of Bristol, Bristol, UK
| | - Matt Hickman
- Population Health Sciences, University of Bristol, Bristol, UK
| | - John F Dillon
- Department of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
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13
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Martinello M, Dore GJ, Matthews GV, Grebely J. Strategies to Reduce Hepatitis C Virus Reinfection in People Who Inject Drugs. Infect Dis Clin North Am 2019; 32:371-393. [PMID: 29778261 DOI: 10.1016/j.idc.2018.02.003] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Reinfection after direct-acting antiviral therapy may pose a challenge to hepatitis C virus elimination efforts. Reinfection risk is cited as a reason for not offering treatment to people who inject drugs. As treatment scale-up expands among populations with risks for reacquisition, acknowledgment that reinfection can and will occur is essential. Efforts to prevent and manage reinfection should be incorporated into individual- and population-level strategies. The risk of reinfection after successful treatment emphasises the need for education, harm reduction, and posttreatment surveillance. Reinfection must not be considered an impediment to treatment, if hepatitis C virus elimination is to be achieved.
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Affiliation(s)
- Marianne Martinello
- Viral Hepatitis Clinical Research Program, Kirby Institute, Level 5, Wallace Wurth Building, High Street, UNSW Sydney, Kensington NSW 2052, Australia.
| | - Gregory J Dore
- Viral Hepatitis Clinical Research Program, Kirby Institute, Level 5, Wallace Wurth Building, High Street, UNSW Sydney, Kensington NSW 2052, Australia
| | - Gail V Matthews
- Viral Hepatitis Clinical Research Program, Kirby Institute, Level 5, Wallace Wurth Building, High Street, UNSW Sydney, Kensington NSW 2052, Australia
| | - Jason Grebely
- Viral Hepatitis Clinical Research Program, Kirby Institute, Level 5, Wallace Wurth Building, High Street, UNSW Sydney, Kensington NSW 2052, Australia
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14
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Abstract
This commentary reviews the core principals of cost-effectiveness and applies them to the rapidly evolving context of hepatitis C virus treatment in the United States. The article provides a foundation of evidence that hepatitis C virus treatment provides good economic value, even though it is expensive, and even when treating people who inject drugs who are at high risk for hepatitis C virus reinfection. The price of medications has decreased, but the high price continues to limit access to care. This wedge between cost effectiveness and affordability stands front and center as one of the leading obstacles to elimination.
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Affiliation(s)
- Benjamin P Linas
- Section of Infectious Diseases, Boston Medical Center, Boston, MA, USA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
| | - Shayla Nolen
- Section of Infectious Diseases, Boston Medical Center, Boston, MA, USA
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15
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Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, Marra F, Puoti M, Wedemeyer H. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol 2018; 69:461-511. [PMID: 29650333 DOI: 10.1016/j.jhep.2018.03.026] [Citation(s) in RCA: 1206] [Impact Index Per Article: 172.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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16
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The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2017.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
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17
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Aiza-Haddad I, Ballesteros-Amozurrutia A, Borjas-Almaguer OD, Castillo-Barradas M, Castro-Narro G, Chávez-Tapia N, Chirino-Sprung RA, Cisneros-Garza L, Dehesa-Violante M, Flores-Calderón J, Flores-Gaxiola A, García-Juárez I, González-Huezo MS, González-Moreno EI, Higuera-de la Tijera F, Kershenobich-Stalnikowitz D, López-Méndez E, Malé-Velázquez R, Marín-López E, Mata-Marín JA, Méndez-Sánchez N, Monreal-Robles R, Moreno-Alcántar R, Muñoz-Espinosa L, Navarro-Alvarez S, Pavia-Ruz N, Pérez-Ríos AM, Poo-Ramírez JL, Rizo-Robles MT, Sánchez-Ávila JF, Sandoval-Salas R, Torre A, Torres-Ibarra R, Trejo-Estrada R, Velarde-Ruiz Velasco JA, Wolpert-Barraza E, Bosques-Padilla F. The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2018; 83:275-324. [PMID: 29803325 DOI: 10.1016/j.rgmx.2017.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 10/17/2017] [Accepted: 11/02/2017] [Indexed: 12/12/2022]
Abstract
The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.
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Affiliation(s)
| | | | - O D Borjas-Almaguer
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - G Castro-Narro
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | | | - L Cisneros-Garza
- Centro de Enfermedades Hepáticas del Hospital San José, Monterrey, Nuevo León, México
| | | | - J Flores-Calderón
- Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Ciudad de México, México
| | | | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - E I González-Moreno
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | | | - E López-Méndez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática, Guadalajara, Jalisco, México
| | | | - J A Mata-Marín
- Hospital de Infectología del Centro Médico Nacional «La Raza», Ciudad de México, México
| | | | - R Monreal-Robles
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - L Muñoz-Espinosa
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - N Pavia-Ruz
- Hospital Infantil de México «Federico Gómez», Ciudad de México, México
| | - A M Pérez-Ríos
- Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - J L Poo-Ramírez
- Clínica San Jerónimo de Salud Hepática y Digestiva, Ciudad de México, México
| | | | - J F Sánchez-Ávila
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - A Torre
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
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18
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Hayashi K, Ishigami M, Yasuda S, Ishizu Y, Kuzuya T, Honda T, Ishikawa T, Hirooka Y, Goto H. Occurrence of late relapse of hepatitis C virus confirmed by molecular analysis after sustained virologic response to interferon-ribavirin-based therapy. Hepatol Res 2018. [PMID: 28643404 DOI: 10.1111/hepr.12929] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM The optimal duration of follow-up for patients who achieve sustained virologic responses (SVR) has become an important issue. Reports on long-term follow-up of SVR have indicated that 99% of patients maintained SVR. However, the limitations of a majority of studies include small patient numbers, short study periods, and lack of molecular analysis of hepatitis C virus (HCV) genome. The present study sought to evaluate the late relapse rate in long-term follow-up of patients who achieved SVR, with molecular analysis of HCV. METHODS A total of 224 patients with chronic hepatitis C who were treated by interferon and ribavirin-based therapy and achieved SVR were enrolled. All patients were recommended for follow-up every 6 or 12 months. RESULTS The mean follow-up period was 6.0 years (range, 1.0-13.6 years). Cumulative 5- and 10-year follow-up rates of the patients after SVR were 87.8% and 78.8%, respectively. Cumulative 5- and 10-year follow-up rates of serum HCV RNA after SVR were 85.5% and 52.6%, respectively. Two patients had detectable serum HCV RNA at 20 and 30 months, respectively, after SVR. Phylogenetic analyses of core, non-structural protein 3, and 5A regions of HCV strains from late relapse patients confirmed the same strain was present at baseline and late relapse. CONCLUSIONS Two of 224 patients developed late relapse of HCV by the original strain, which was confirmed by direct sequencing analysis. Although few patients may develop late relapse, SVR achieved with interferon and ribavirin-based therapy is durable for prolonged periods.
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Affiliation(s)
- Kazuhiko Hayashi
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tetsuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshiki Hirooka
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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19
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Torresi J. The Rationale for a Preventative HCV Virus-Like Particle (VLP) Vaccine. Front Microbiol 2017; 8:2163. [PMID: 29163442 PMCID: PMC5674006 DOI: 10.3389/fmicb.2017.02163] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Accepted: 10/20/2017] [Indexed: 12/16/2022] Open
Abstract
HCV represents a global health problem with ~200 million individuals currently infected, worldwide. With the high cost of antiviral therapies, the global burden of chronic hepatitis C infection (CHCV) infection will be substantially reduced by the development of an effective vaccine for HCV. The field of HCV vaccines is generally divided into proponents of strategies to induce neutralizing antibodies (NAb) and those who propose to elicit cell mediated immunity (CMI). However, for a hepatitis C virus (HCV) vaccine to be effective in preventing infection, it must be capable of generating cross-reactive CD4+, CD8+ T cell, and NAb responses that will cover the major viral genotypes. Simulation models of hepatitis C have predicted that a vaccine of even modest efficacy and coverage will significantly reduce the incidence of hepatitis C. A HCV virus like particle (VLP) based vaccine would fulfill the requirement of delivering critical conformational neutralizing epitopes in addition to providing HCV specific CD4+ and CD8+ epitopes. Several approaches have been reported including insect cell-derived genotype 1b HCV VLPs; a human liver-derived quadrivalent genotype 1a, 1b, 2, and 3a vaccine; a genotype 1a HCV E1 and E2 glycoprotein/MLV Gag pseudotype VLP vaccine; and chimeric HBs-HCV VLP vaccines. All to result in the production of cross-NAb and/or T cell responses against HCV. This paper summarizes the evidence supporting the development of a HCV VLP based vaccine.
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Affiliation(s)
- Joseph Torresi
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, Australia
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20
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Martinello M, Hajarizadeh B, Grebely J, Dore GJ, Matthews GV. HCV Cure and Reinfection Among People With HIV/HCV Coinfection and People Who Inject Drugs. Curr HIV/AIDS Rep 2017; 14:110-121. [PMID: 28432579 DOI: 10.1007/s11904-017-0358-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE OF REVIEW Highly effective, well-tolerated interferon-free direct-acting antivirals (DAA) have revolutionised hepatitis C virus (HCV) therapeutics, with the opportunity for broad treatment scale-up among marginalised or "high-risk" populations, including people who inject drugs (PWID) and people with HIV/HCV coinfection. RECENT FINDINGS Concern that HCV reinfection may compromise HCV treatment outcomes is sometimes cited as a reason for not offering treatment to current and former PWID. However, the incidence of reinfection following interferon-based treatment for chronic HCV is low among PWID. Reinfection rates in HIV-positive men-who-have-sex-with-men (MSM) are varied, with high incidence reported in some cohorts. Mathematical modelling suggests that substantial reductions in HCV incidence and prevalence could be achieved with targeted DAA therapy among those at the highest risk of ongoing transmission. This review will summarise the recent literature on DAA efficacy in PWID and people with HIV/HCV coinfection, discuss the individual- and population-level impact of DAA treatment scale-up and reinfection, and highlight ongoing and future research questions in expanding HCV care and treatment to those populations at high risk of ongoing HCV transmission.
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Affiliation(s)
- Marianne Martinello
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, NSW, 2052, Australia.
| | - Behzad Hajarizadeh
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, NSW, 2052, Australia
| | - Jason Grebely
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, NSW, 2052, Australia
| | - Gregory J Dore
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, NSW, 2052, Australia.,St Vincent's Hospital, Sydney, NSW, Australia
| | - Gail V Matthews
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Wallace Wurth Building, Sydney, NSW, 2052, Australia.,St Vincent's Hospital, Sydney, NSW, Australia
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21
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Metzig C, Surey J, Francis M, Conneely J, Abubakar I, White PJ. Impact of Hepatitis C Treatment as Prevention for People Who Inject Drugs is sensitive to contact network structure. Sci Rep 2017; 7:1833. [PMID: 28500290 PMCID: PMC5431870 DOI: 10.1038/s41598-017-01862-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Accepted: 03/17/2017] [Indexed: 12/14/2022] Open
Abstract
Treatment as Prevention (TasP) using directly-acting antivirals has been advocated for Hepatitis C Virus (HCV) in people who inject drugs (PWID), but treatment is expensive and TasP’s effectiveness is uncertain. Previous modelling has assumed a homogeneously-mixed population or a static network lacking turnover in the population and injecting partnerships. We developed a transmission-dynamic model on a dynamic network of injecting partnerships using data from survey of injecting behaviour carried out in London, UK. We studied transmission on a novel exponential-clustered network, as well as on two simpler networks for comparison, an exponential unclustered and a random network, and found that TasP’s effectiveness differs markedly. With respect to an exponential-clustered network, the random network (and homogeneously-mixed population) overestimate TasP’s effectiveness, whereas the exponential-unclustered network underestimates it. For all network types TasP’s effectiveness depends on whether treated patients change risk behaviour, and on treatment coverage: higher coverage requires fewer total treatments for the same health gain. Whilst TasP can greatly reduce HCV prevalence, incidence of infection, and incidence of reinfection in PWID, assessment of TasP’s effectiveness needs to take account of the injecting-partnership network structure and post-treatment behaviour change, and further empirical study is required.
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Affiliation(s)
- Cornelia Metzig
- MRC Centre for Outbreak Analysis and Modelling and NIHR Health Protection Research Unit in Modelling Methodology, Imperial College London School of Public Health, London, W2 1PG, UK. .,Department of Mathematics, Imperial College London, London, SW7 2AZ, UK.
| | - Julian Surey
- Research Department of Infection and Population Health, University College London, London, WC1E 6JB, UK
| | - Marie Francis
- Research Department of Infection and Population Health, University College London, London, WC1E 6JB, UK
| | - Jim Conneely
- Hepatitis C Trust, 27 Crosby Row, London, SE1 3YD, UK
| | - Ibrahim Abubakar
- Research Department of Infection and Population Health, University College London, London, WC1E 6JB, UK.,TB Section, National Infection Service, Public Health England, London, NW9 5EQ, UK.,MRC Clinical Trials Unit, University College London, London, WC2B 6NH, UK
| | - Peter J White
- MRC Centre for Outbreak Analysis and Modelling and NIHR Health Protection Research Unit in Modelling Methodology, Imperial College London School of Public Health, London, W2 1PG, UK. .,Modelling and Economics Unit, National Infection Service, Public Health England, London, NW9 5EQ, UK.
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张 莹, 颜 学. 后DAA时代抗HCV治疗的现状及存在问题. Shijie Huaren Xiaohua Zazhi 2017; 25:1135-1142. [DOI: 10.11569/wcjd.v25.i13.1135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
近年来, 由于直接抗病毒药物(direct-acting antiviral agents, DAAs)具有高效、使用方便、不良反应小、疗程短、临床治愈率高的优点, 使其在临床的应用越来越广泛. 许多著名的制药公司对其研究不断, 其上市及更新的速度未减. 随着DAAs的广泛应用及指南更新, 抗丙型肝炎病毒(hepatitis C virus, HCV)的治疗已经步入全口服药物时期, 即已经步入后DAA时代. 但在使用DAAs抗HCV治疗过程中存在许多问题, 使用时需谨慎.
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Martinello M, Grebely J, Petoumenos K, Gane E, Hellard M, Shaw D, Sasadeusz J, Applegate TL, Dore GJ, Matthews GV. HCV reinfection incidence among individuals treated for recent infection. J Viral Hepat 2017; 24:359-370. [PMID: 28027424 PMCID: PMC5400730 DOI: 10.1111/jvh.12666] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Accepted: 11/29/2016] [Indexed: 12/15/2022]
Abstract
One challenge to HCV elimination through therapeutic intervention is reinfection. The aim of this analysis was to calculate the incidence of HCV reinfection among both HIV-positive and HIV-negative individuals treated for recent HCV infection (estimated infection duration <18 months). Individuals with recent HCV infection who achieved an end-of-treatment response in four open-label studies between 2004 and 2015 in Australia and New Zealand were assessed for HCV reinfection, confirmed by sequencing of the Core-E2 and/or NS5B regions. Reinfection incidence was calculated using person-time of observation. Exact Poisson regression analysis was used to assess factors associated with HCV reinfection. The cohort at risk for reinfection (n=120; 83% male; median age 36 years) was composed of HIV-positive men-who-have-sex-with-men (53%) and people who inject drugs (current 49%, ever 69%). Total follow-up time at risk was 135 person-years (median 1.08 years, range 0.17, 2.53). Ten cases of HCV reinfection were identified, for an incidence of 7.4 per 100 py (95% CI 4.0, 13.8). Reinfection incidence was significantly higher among participants who reported injection drug use at end of or post-treatment, irrespective of HIV status (15.5 per 100 py, 95% CI 7.8, 31.1). In adjusted analysis, factors associated with reinfection were older age (aIRR 5.3, 95% CI 1.15, 51.5, P=.042) and injection drug use at end of or post-treatment (aIRR 7.9, 95% CI 1.6, 77.2, P=.008). High reinfection incidence following treatment for recent HCV infection in individuals with ongoing risk behaviour emphasizes the need for post-treatment surveillance, harm reduction strategies and education in at-risk populations.
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Affiliation(s)
- Marianne Martinello
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Sydney, NSW, Australia
| | - Jason Grebely
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Sydney, NSW, Australia
| | - Kathy Petoumenos
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Sydney, NSW, Australia
| | | | - Margaret Hellard
- Centre for Population Health, Burnet Institute, Melbourne, VIC, Australia,Infectious Diseases Unit, Alfred Hospital, Melbourne, VIC, Australia,Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, VIC, Australia
| | - David Shaw
- Infectious Diseases Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Joe Sasadeusz
- Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, VIC, Australia
| | - Tanya L Applegate
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Sydney, NSW, Australia
| | - Gregory J Dore
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Sydney, NSW, Australia,Department of Infectious Disease and Immunology, St Vincent’s Hospital, Sydney, NSW, Australia
| | - Gail V Matthews
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Australia, Sydney, NSW, Australia,Department of Infectious Disease and Immunology, St Vincent’s Hospital, Sydney, NSW, Australia
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Islam N, Krajden M, Shoveller J, Gustafson P, Gilbert M, Buxton JA, Wong J, Tyndall MW, Janjua NZ. Incidence, risk factors, and prevention of hepatitis C reinfection: a population-based cohort study. Lancet Gastroenterol Hepatol 2017; 2:200-210. [DOI: 10.1016/s2468-1253(16)30182-0] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Revised: 11/17/2016] [Accepted: 11/17/2016] [Indexed: 02/06/2023]
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The effects of needle-sharing and opioid substitution therapy on incidence of hepatitis C virus infection and reinfection in people who inject drugs. Epidemiol Infect 2016; 145:796-801. [PMID: 27927256 DOI: 10.1017/s0950268816002892] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Although high hepatitis C virus (HCV) prevalence has been observed in people who inject drugs (PWID) for decades, research suggests incidence is falling. We examined whether PWIDs' use of opioid substitution therapy (OST) and their needle-and-syringe sharing behaviour explained HCV incidence. We assessed HCV incidence in 235 PWID in Melbourne, Australia, and performed discrete-time survival with needle-sharing and OST status as independent variables. HCV infection, reinfection and combined infection/reinfection incidences were 7·6 [95% confidence interval (CI) 4·8-11·9], 12·4 (95% CI 9·1-17·0) and 9·7 (95% CI 7·4-12·6) per 100 person-years, respectively. Needle-sharing was significantly associated with higher incidence of naive HCV infection [hazard ratio (HR) 4·9, 95% CI 1·3-17·7] but not reinfection (HR 1·85, 95% CI 0·79-4·32); however, a cross-model test suggested this difference was sample specific. Past month use of OST had non-significant protective effects against naive HCV infection and reinfection. Our data confirm previous evidence of greatly reduced HCV incidence in PWID, but not the significant protective effect of OST on HCV incidence detected in recent studies. Our findings reinforce the need for greater access to HCV testing and prevention services to accelerate the decline in incidence, and HCV treatment, management and support to limit reinfection.
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Midgard H, Weir A, Palmateer N, Lo Re V, Pineda JA, Macías J, Dalgard O. HCV epidemiology in high-risk groups and the risk of reinfection. J Hepatol 2016; 65:S33-S45. [PMID: 27641987 DOI: 10.1016/j.jhep.2016.07.012] [Citation(s) in RCA: 136] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 07/08/2016] [Accepted: 07/12/2016] [Indexed: 12/18/2022]
Abstract
Injecting risk behaviours among people who inject drugs (PWID) and high-risk sexual practices among men who have sex with men (MSM) are important routes of hepatitis C virus (HCV) transmission. Current direct-acting antiviral treatment offers unique opportunities for reductions in HCV-related liver disease burden and epidemic control in high-risk groups, but these prospects could be counteracted by HCV reinfection due to on-going risk behaviours after successful treatment. Based on existing data from small and heterogeneous studies of interferon-based treatment, the incidence of reinfection after sustained virological response range from 2-6/100 person years among PWID to 10-15/100 person years among human immunodeficiency virus-infected MSM. These differences mainly reflect heterogeneity in study populations with regards to risk behaviours, but also reflect variations in study designs and applied virological methods. Increasing levels of reinfection are to be expected as we enter the interferon-free treatment era. Individual- and population-level efforts to address and prevent reinfection should therefore be undertaken when providing HCV care for people with on-going risk behaviour. Constructive strategies include acknowledgement, education and counselling, harm reduction optimization, scaled-up treatment including treatment of injecting networks, post-treatment screening, and rapid retreatment of reinfections.
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Affiliation(s)
- Håvard Midgard
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway; Institute for Clinical Medicine, University of Oslo, Norway; Department of Gastroenterology, Oslo University Hospital, Norway.
| | - Amanda Weir
- School of Health and Life Sciences, Glasgow Caledonian University, United Kingdom; NHS National Services Scotland, Health Protection Scotland, Glasgow, United Kingdom
| | - Norah Palmateer
- School of Health and Life Sciences, Glasgow Caledonian University, United Kingdom; NHS National Services Scotland, Health Protection Scotland, Glasgow, United Kingdom
| | - Vincent Lo Re
- Division of Infectious Diseases, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, United States
| | - Juan A Pineda
- Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, Spain
| | - Juan Macías
- Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, Spain
| | - Olav Dalgard
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway; Institute for Clinical Medicine, University of Oslo, Norway
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Weir A, McLeod A, Innes H, Valerio H, Aspinall EJ, Goldberg DJ, Barclay ST, Dillon JF, Fox R, Fraser A, Hayes PC, Kennedy N, Mills PR, Stanley AJ, Aitken C, Gunson R, Templeton K, Hunt A, McIntyre P, Hutchinson SJ. Hepatitis C reinfection following treatment induced viral clearance among people who have injected drugs. Drug Alcohol Depend 2016; 165:53-60. [PMID: 27268294 DOI: 10.1016/j.drugalcdep.2016.05.012] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Revised: 05/17/2016] [Accepted: 05/17/2016] [Indexed: 12/29/2022]
Abstract
BACKGROUND Although people who inject drugs (PWID) are an important group to receive Hepatitis C Virus (HCV) antiviral therapy, initiation onto treatment remains low. Concerns over reinfection may make clinicians reluctant to treat this group. We examined the risk of HCV reinfection among a cohort of PWID (encompassing all those reporting a history of injecting drug use) from Scotland who achieved a sustained virological response (SVR). METHODS Clinical and laboratory data were used to monitor RNA testing among PWID who attained SVR following therapy between 2000 and 2009. Data were linked to morbidity and mortality records. Follow-up began one year after completion of therapy, ending on 31st December, 2012. Frequency of RNA testing during follow-up was calculated and the incidence of HCV reinfection estimated. Cox proportional hazards regression was used to examine factors associated with HCV reinfection. RESULTS Among 448 PWID with a SVR, 277 (61.8%) were tested during follow-up, median 4.5 years; 191 (69%) received one RNA test and 86 (31%) received at least two RNA tests. There were seven reinfections over 410 person years generating a reinfection rate of 1.7/100py (95% CI 0.7-3.5). For PWID who have been hospitalised for an opiate or injection related cause post SVR (11%), the risk of HCV reinfection was greater [AHR=12.9, 95% CI 2.2-76.0, p=0.002] and the reinfection rate was 5.7/100py (95% CI 1.8-13.3). CONCLUSION PWID who have been tested, following SVR, for HCV in Scotland appear to be at a low risk of reinfection. Follow-up and monitoring of this population are warranted as treatment is offered more widely.
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Affiliation(s)
- Amanda Weir
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK.
| | | | - Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK.
| | - Heather Valerio
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK.
| | - Esther J Aspinall
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK.
| | - David J Goldberg
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK.
| | | | | | - Ray Fox
- Gartnavel General Hospital, Glasgow, UK.
| | | | | | | | | | | | - Celia Aitken
- West of Scotland Specialist Virology Centre, Glasgow, UK.
| | - Rory Gunson
- West of Scotland Specialist Virology Centre, Glasgow, UK.
| | - Kate Templeton
- East of Scotland Specialist Virology Centre, Edinburgh, UK.
| | | | | | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Health Protection Scotland, Glasgow, UK.
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Asher AK, Portillo CJ, Cooper BA, Dawson-Rose C, Vlahov D, Page KA. Clinicians' Views of Hepatitis C Virus Treatment Candidacy With Direct-Acting Antiviral Regimens for People Who Inject Drugs. Subst Use Misuse 2016; 51:1218-23. [PMID: 27219274 PMCID: PMC6907073 DOI: 10.3109/10826084.2016.1161054] [Citation(s) in RCA: 112] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) are curative in most persons with chronic hepatitis C virus (HCV) infection. However, high cost and concerns about adherence and reinfection may present continued barriers to treatment, particularly for people who inject drugs (PWID). OBJECTIVE To understand changes in assessments of treatment candidacy, given advances in treatment. METHODS Clinicians attending the Liver Meeting® in 2014 who reported prescribing HCV treatment in the past three years were invited to complete a survey regarding HCV treatment decisions. Participants assessed their likelihood to treat HCV in PWID in association with time of abstinence from injection drug use and what impacts their decision to provide treatment using interferon and DAAs. RESULTS 108 clinicians completed the survey; 10% were willing to treat an active PWID (last injection within 30 days) using interferon-containing regimens, and 15% with all-oral regimens. For each increasing time interval of injection abstinence, there was an increase in the odds of a clinician reporting willingness to treat with DAAs (Odds Ratio (OR) 2.57, 95% CI 2.18, 3.03) and with interferon-based treatment (OR 2.22 (95% CI 1.90, 2.61), Reinfection and medication cost were cited as most important concerns when determining candidacy. CONCLUSIONS A cure is now the norm in HCV treatment, and there is an increasing need to address the barriers to treating PWID, the population with the highest burden of infection. Understanding treatment candidacy assessments is essential to improving uptake. This study provides insight into how clinicians view treatment candidacy in this era of DAAs and can help identify supportive treatment environments and concurrent programs.
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Affiliation(s)
- Alice K Asher
- a School of Nursing , University of California, San Francisco , San Francisco , California , USA.,b Institute for Global Health , University of California, San Francisco , San Francisco , California , USA
| | - Carmen J Portillo
- a School of Nursing , University of California, San Francisco , San Francisco , California , USA
| | - Bruce A Cooper
- a School of Nursing , University of California, San Francisco , San Francisco , California , USA
| | - Carol Dawson-Rose
- a School of Nursing , University of California, San Francisco , San Francisco , California , USA
| | - David Vlahov
- a School of Nursing , University of California, San Francisco , San Francisco , California , USA
| | - Kimberly A Page
- c Biostatistics & Preventive Medicine , University of New Mexico Health Sciences Center , Albuquerque , New Mexico , USA
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Midgard H, Bjøro B, Mæland A, Konopski Z, Kileng H, Damås JK, Paulsen J, Heggelund L, Sandvei PK, Ringstad JO, Karlsen LN, Stene-Johansen K, Pettersson JHO, Dorenberg DH, Dalgard O. Hepatitis C reinfection after sustained virological response. J Hepatol 2016; 64:1020-1026. [PMID: 26780289 DOI: 10.1016/j.jhep.2016.01.001] [Citation(s) in RCA: 112] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 12/04/2015] [Accepted: 01/04/2016] [Indexed: 01/17/2023]
Abstract
BACKGROUND & AIMS On-going risk behaviour can lead to hepatitis C virus (HCV) reinfection following successful treatment. We aimed to assess the incidence of persistent HCV reinfection in a population of people who inject drugs (PWID) who had achieved sustained virological response (SVR) seven years earlier. METHODS In 2004-2006 we conducted a multicentre treatment trial comprising HCV genotype 2 or 3 patients in Sweden, Norway and Denmark (NORTH-C). Six months of abstinence from injecting drug use (IDU) was required before treatment. All Norwegian patients who had obtained SVR (n=161) were eligible for participation in this long-term follow-up study assessing virological and behavioural characteristics. RESULTS Follow-up data were available in 138 of 161 (86%) individuals. Persistent reinfection was identified in 10 of 94 (11%) individuals with a history of IDU prior to treatment (incidence rate 1.7/100 person-years (PY); 95% CI 0.8-3.1) and in 10 of 37 (27%) individuals who had relapsed to IDU after treatment (incidence rate 4.9/100 PY; 95% CI 2.3-8.9). Although relapse to IDU perfectly predicted reinfection, no baseline factor was associated with reinfection. Relapse to IDU was associated with age <30 years (vs. ⩾40 years) at treatment (adjusted odds ratio [aOR] 7.03; 95% CI 1.78-27.8) and low education level (aOR 3.64; 95% CI 1.44-9.18). CONCLUSIONS Over time, persistent HCV reinfection was common among individuals who had relapsed to IDU after treatment. Reinfection should be systematically addressed and prevented when providing HCV care for PWID.
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Affiliation(s)
- Håvard Midgard
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Benedikte Bjøro
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Arild Mæland
- Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway
| | - Zbigniew Konopski
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
| | - Hege Kileng
- Section of Gastroenterology, University Hospital of North Norway, Tromsø, Norway
| | - Jan K Damås
- Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Infectious Diseases, St. Olav's Hospital, Trondheim, Norway
| | - Jørn Paulsen
- Section of Gastroenterology, Telemark Hospital Trust, Skien, Norway
| | - Lars Heggelund
- Section of Infectious Diseases, Vestre Viken Hospital Trust, Drammen, Norway
| | - Per K Sandvei
- Department of Medicine, Østfold Hospital Trust, Grålum, Norway
| | | | - Lars N Karlsen
- Department of Medicine, Stavanger University Hospital, Stavanger, Norway
| | | | - John H-O Pettersson
- Department of Virology, The Norwegian Institute for Public Health, Oslo, Norway
| | - Dagny H Dorenberg
- Department of Virology, The Norwegian Institute for Public Health, Oslo, Norway
| | - Olav Dalgard
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2016; 22:76-139. [PMID: 27044763 PMCID: PMC4825161 DOI: 10.3350/cmh.2016.22.1.76] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 02/22/2016] [Indexed: 12/11/2022] Open
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Rozada I, Coombs D, Lima VD. Conditions for eradicating hepatitis C in people who inject drugs: A fibrosis aware model of hepatitis C virus transmission. J Theor Biol 2016; 395:31-39. [PMID: 26845310 DOI: 10.1016/j.jtbi.2016.01.030] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2015] [Revised: 12/17/2015] [Accepted: 01/19/2016] [Indexed: 12/26/2022]
Abstract
It is estimated that 80% of new hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). Eradicating HCV from this population is key for the complete eradication of the disease, and the advent of simple to use, high efficacy treatments could conceivably make this scenario possible. This paper presents a mathematical model where transmission of HCV is studied in a simulated population of PWID where fibrosis progression is explicitly tracked. The stability thresholds that determine whether HCV will remain endemic or become eradicated were established numerically, and analytically on a reduced version of the model. Conditions on testing and treatment rates for eradication to occur were determined, within the context of the new high efficacy therapies. The results show that HCV eradication in the PWID population of the Vancouver, BC test scenario is achievable, but testing and especially treatment rates will need to increase significantly from current rates. Parameter estimates were drawn from published data.
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Affiliation(s)
- Ignacio Rozada
- British Columbia Centre for Excellence in HIV/AIDS, St. Paul׳s Hospital, Vancouver, BC, Canada V6Z 1Y6.
| | - Daniel Coombs
- Department of Mathematics and Institute of Applied Mathematics, University of British Columbia, Vancouver, BC, Canada V6T 1Z2.
| | - Viviane D Lima
- British Columbia Centre for Excellence in HIV/AIDS, St. Paul׳s Hospital, Vancouver, BC, Canada V6Z 1Y6; Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
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Genetic characterization of multiple hepatitis C virus infections following acute infection in HIV-infected men who have sex with men. AIDS 2015; 29:2287-95. [PMID: 26258527 DOI: 10.1097/qad.0000000000000838] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVE High rates of hepatitis C virus (HCV) reinfections among HIV-infected men who have sex with men (MSM) following clearance of a primary infection suggest absence of protective immunity. Here, we investigated the incidence of HCV super and reinfections in 85 HIV-infected MSM with incident HCV infection. DESIGN AND METHODS Serial sequencing of a fragment of NS5B and the HCV envelope was used to longitudinally characterize the virus. If the primary genotype was still present at the most recent viremic time point, as indicated by the NS5B sequence analysis, serial envelope 2/hypervariable region 1 (E2/HRV1) sequence analysis was performed to distinguish a new infection with the same genotype (clade switch) from intrahost evolution. Incidence rate and cumulative incidence of secondary infections were estimated, and the effect of the primary genotype (1a versus non1) on the risk of acquiring a second infection with the same genotype was determined using Cox proportional-hazards analysis. RESULTS Among 85 patients with a median follow-up of 4.8 years, incidence rate of secondary infections was 5.39 cases/100 person-years (95% confidence interval 3.34-8.26). Cumulative incidence of genotype switches was markedly higher than the cumulative incidence of clade switches (26.7 versus 4.8% at 5 years, respectively). In patients with HCV-1a as primary infection, the risk for acquiring another HCV-1a infection was reduced compared to those with a primary non-HCV-1a subsequently acquiring HCV-1a (hazard ratio 0.25, 95% confidence interval 0.07-0.93). CONCLUSION Risk of acquiring a secondary infection with the primary genotype was strikingly reduced compared with the risk of acquiring a secondary infection with a different genotype.
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Ruta S, Cernescu C. Injecting drug use: A vector for the introduction of new hepatitis C virus genotypes. World J Gastroenterol 2015; 21:10811-10823. [PMID: 26478672 PMCID: PMC4600582 DOI: 10.3748/wjg.v21.i38.10811] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 06/19/2015] [Accepted: 09/15/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) genotypes' monitoring allows real-time insight into the dynamic changes that occur in the global epidemiological picture of HCV infection. Intravenous drug use is currently the primary driver for HCV transmission in developed and developing countries. The distribution of HCV genotypes/subtypes differs significantly between people who inject drugs (PWID) and the general population. HCV genotypes that previously exhibited a limited geographical distribution (3a, 4) are becoming more prevalent in this high-risk group. Immigration from HCV-endemic countries and the evolving networks of HCV transmission in PWID influence HCV genotypes distribution in Europe. Social vulnerabilities (e.g., unemployment, homelessness, and limited access to social and healthcare insurances systems) are important triggers for illicit drug use, which increases the associated risks of HCV infection and the frequent emergence of less prevalent genotypes. Genotype/subtype determination bears important clinical consequences in the progression of liver disease, susceptibility to antiviral therapies and the emergence of resistance-associated variants. An estimated half of the chronically HCV-infected PWID are unaware of their infection, and only one in ten of those diagnosed enter treatment. Nevertheless, PWID exhibit high response rates to new antiviral regimens, and the level of HCV reinfection is unexpectedly low. The focus of the healthcare system must be on the early detection and treatment of infection, to avoid late presentations that are associated with high levels of viremia and liver fibrosis, which may diminish the therapeutic success rate.
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Valerio H, Goldberg DJ, Lewsey J, Weir A, Allen S, Aspinall EJ, Barclay ST, Bramley P, Dillon JF, Fox R, Fraser A, Hayes PC, Innes H, Kennedy N, Mills PR, Stanley AJ, Hutchinson SJ. Evidence of continued injecting drug use after attaining sustained treatment-induced clearance of the hepatitis C virus: Implications for reinfection. Drug Alcohol Depend 2015; 154:125-131. [PMID: 26183402 DOI: 10.1016/j.drugalcdep.2015.06.032] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 06/15/2015] [Accepted: 06/16/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND People who inject drugs (PWID) are at the greatest risk of hepatitis C virus (HCV) infection, yet are often denied immediate treatment due to fears of on-going risk behaviour. Our principal objective was to examine evidence of continued injecting drug use among PWID following successful treatment for HCV and attainment of a sustained viral response (SVR). METHODS PWID who attained SVR between 1992 and June 2012 were selected from the National Scottish Hepatitis C Clinical Database. Hospitalisation and mortality records were sourced for these patients using record linkage techniques. Our primary outcome variable was any hospitalisation or death, which was indicative of injecting drugs post-SVR. RESULTS The cohort comprised 1170 PWID (mean age at SVR 39.6y; 76% male). The Kaplan Meier estimate of incurring the primary outcome after three years of SVR was 10.59% (95% CI, 8.75-12.79) After adjusting for confounding, the risk of an injection related hospital episode or death post-SVR was significantly increased with advancing year of SVR: AHR:1.07 per year (95% CI, 1.01-1.14), having a pre-SVR acute alcohol intoxication-related hospital episode: AHR:1.83 (95% CI, 1.29-2.60), and having a pre-SVR opiate or injection-related hospital episode: AHR:2.59 (95% CI, 1.84-3.64). CONCLUSION Despite attaining the optimal treatment outcome, these data indicate that an increasing significant minority of PWID continue to inject post-SVR at an intensity which leads to either hospitalisation or death and increased risk of reinfection.
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Affiliation(s)
- Heather Valerio
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Blood-borne Viruses and Sexually Transmitted Infections Section, Health Protection Scotland, Glasgow, UK.
| | - David J Goldberg
- Blood-borne Viruses and Sexually Transmitted Infections Section, Health Protection Scotland, Glasgow, UK; School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
| | - James Lewsey
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Amanda Weir
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Blood-borne Viruses and Sexually Transmitted Infections Section, Health Protection Scotland, Glasgow, UK
| | | | - Esther J Aspinall
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Blood-borne Viruses and Sexually Transmitted Infections Section, Health Protection Scotland, Glasgow, UK
| | | | | | | | - Ray Fox
- Gartnavel General Hospital, Glasgow, UK
| | | | | | - Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Blood-borne Viruses and Sexually Transmitted Infections Section, Health Protection Scotland, Glasgow, UK
| | | | | | | | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK; Blood-borne Viruses and Sexually Transmitted Infections Section, Health Protection Scotland, Glasgow, UK
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McCance-Katz EF, Valdiserri RO. Hepatitis C Virus Treatment and Injection Drug Users: It Is Time to Separate Fact From Fiction. Ann Intern Med 2015; 163:224-5. [PMID: 26120801 DOI: 10.7326/m15-0007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Elinore F. McCance-Katz
- From Substance Abuse and Mental Health Services Administration, U.S. Departments of Health and Human Services, Rockville, Maryland, and Office of HIV/AIDS and Infectious Disease Policy, U.S. Department of Health and Human Services, Washington, DC
| | - Ronald O. Valdiserri
- From Substance Abuse and Mental Health Services Administration, U.S. Departments of Health and Human Services, Rockville, Maryland, and Office of HIV/AIDS and Infectious Disease Policy, U.S. Department of Health and Human Services, Washington, DC
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Hauser P, Kern S. Psychiatric and substance use disorders co-morbidities and hepatitis C: Diagnostic and treatment implications. World J Hepatol 2015; 7:1921-1935. [PMID: 26244067 PMCID: PMC4517152 DOI: 10.4254/wjh.v7.i15.1921] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2015] [Revised: 04/01/2015] [Accepted: 07/02/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) viral infection is the most common blood-borne viral infection and approximately 2%-3% of the world’s population or 170-200 million people are infected. In the United States as many as 3-5 million people may have HCV. Psychiatric and substance use disorders (SUDs) are common co-morbid conditions found in people with HCV and are factors in predisposing people to HCV infection. Also, these co-morbidities are reasons that clinicians exclude people from antiviral therapy in spite of evidence that people with HCV and co-morbid psychiatric and SUD can be safely and effectively treated. Furthermore, the neuropsychiatric side effects of interferon (IFN), until recently the mainstay of antiviral therapy, have necessitated an appreciation and assessment of psychiatric co-morbidities present in people with HCV. The availability of new medications and IFN-free antiviral therapy medication combinations will shorten the duration of treatment and exposure to IFN and thus decrease the risk of neuropsychiatric side effects. This will have the consequence of dramatically altering the clinical landscape of HCV care and will increase the number of eligible treatment candidates as treatment of people with HCV and co-morbid psychiatric and SUDs will become increasingly viable. While economically developed countries will rely on expensive IFN-free antiviral therapy, less developed countries will likely continue to use IFN-based therapies at least until such time as IFN-free antiviral medications become generic. The current manuscript discusses the efficacy and viability of treating HCV in people with psychiatric and SUDs comorbidities, the treatment of the neuropsychiatric side effects of IFN -based therapies and the impact of new medications and new treatment options for HCV that offer the promise of increasing the availability of antiviral therapy in this vulnerable population.
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Pineda JA, Núñez-Torres R, Téllez F, Mancebo M, García F, Merchante N, Pérez-Pérez M, Neukam K, Macías J, Real LM. Hepatitis C virus reinfection after sustained virological response in HIV-infected patients with chronic hepatitis C. J Infect 2015. [PMID: 26212868 DOI: 10.1016/j.jinf.2015.07.006] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To assess the incidence of hepatitis C virus (HCV) reinfections after therapy-induced clearance in HIV-coinfected patients with prior chronic hepatitis C. METHODS Eighty-four HIV-infected subjects, who had previously achieved sustained virological response (SVR) after being treated of chronic hepatitis C, were analyzed. In all of them, at least yearly HCV RNA determinations were carried out during a median (range) of 34 (12-146) months. RESULTS Seventy-two (86%) subjects had been people who inject drugs (PWID), of whom 11 (15%) continued to use snorted or injected drugs during the follow-up. Four (4.76%) patients showed HCV reinfection (incidence 1.21 [95% confidence interval: 0.3-3.09] cases per 100 person-years). These patients maintained risk factors for HCV infection. In three cases, HCV genotype switched. Phylogenetic analysis of the remaining case suggested reinfection from his sexual partner. CONCLUSION The incidence of HCV reinfection in the overall population of HIV-coinfected patients who achieved SVR after being treated against chronic hepatitis C is low. A low frequency of risk behavior is the main factor accounting for this modest rate of reinfection. The possibility of reinfection should not be considered a reason against treatment of HCV infection with direct acting antivirals in PWID.
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Affiliation(s)
- Juan A Pineda
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Avda. de Bellavista s/n, 41014 Sevilla, Spain.
| | - Rocio Núñez-Torres
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Avda. de Bellavista s/n, 41014 Sevilla, Spain
| | - Francisco Téllez
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital La Línea, AGS Campo de Gibraltar, Avda. Menéndez Pelayo 103, 11300 La Línea de la Concepción, Cádiz, Spain
| | - María Mancebo
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Avda. de Bellavista s/n, 41014 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS), Campus Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain
| | - Federico García
- Servicio de Microbiología, Complejo Hospitalario Universitario de Granada, Centro San Cecilio-PTS, C. Dr. Oloriz, 18012 Granada, Spain
| | - Nicolás Merchante
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Avda. de Bellavista s/n, 41014 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS), Campus Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain
| | - Montserrat Pérez-Pérez
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital La Línea, AGS Campo de Gibraltar, Avda. Menéndez Pelayo 103, 11300 La Línea de la Concepción, Cádiz, Spain
| | - Karin Neukam
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Avda. de Bellavista s/n, 41014 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS), Campus Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain
| | - Juan Macías
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Avda. de Bellavista s/n, 41014 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS), Campus Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain
| | - Luis M Real
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Avda. de Bellavista s/n, 41014 Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBiS), Campus Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain
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40
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Abstract
The majority of new and existing cases of HCV infection in high-income countries occur among people who inject drugs (PWID). Ongoing high-risk behaviours can lead to HCV re-exposure, resulting in mixed HCV infection and reinfection. Assays used to screen for mixed infection vary widely in sensitivity, particularly with respect to their capacity for detecting minor variants (<20% of the viral population). The prevalence of mixed infection among PWID ranges from 14% to 39% when sensitive assays are used. Mixed infection compromises HCV treatment outcomes with interferon-based regimens. HCV reinfection can also occur after successful interferon-based treatment among PWID, but the rate of reinfection is low (0-5 cases per 100 person-years). A revolution in HCV therapeutic development has occurred in the past few years, with the advent of interferon-free, but still genotype-specific regiments based on direct acting antiviral agents. However, little is known about whether mixed infection and reinfection has an effect on HCV treatment outcomes in the setting of new direct-acting antiviral agents. This Review characterizes the epidemiology and natural history of mixed infection and reinfection among PWID, methodologies for detection, the potential implications for HCV treatment and considerations for the design of future studies.
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41
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42
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KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2014; 20:89-136. [PMID: 25032178 PMCID: PMC4099340 DOI: 10.3350/cmh.2014.20.2.89] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 05/20/2014] [Indexed: 12/16/2022] Open
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Aspinall EJ, Corson S, Doyle JS, Grebely J, Hutchinson SJ, Dore GJ, Goldberg DJ, Hellard ME. Treatment of hepatitis C virus infection among people who are actively injecting drugs: a systematic review and meta-analysis. Clin Infect Dis 2014; 57 Suppl 2:S80-9. [PMID: 23884071 DOI: 10.1093/cid/cit306] [Citation(s) in RCA: 261] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Although guidelines recommend that people who inject drugs (PWID) should not be excluded from hepatitis C (HCV) treatment, some services remain reluctant to treat PWID. The aim of this review was to investigate sustained virologic response (SVR), adherence, discontinuation, and HCV reinfection among PWID. METHODS A search of Medline, Embase, and Cochrane databases (between 2002 and January 2012) was conducted for primary articles/conference abstracts examining HCV treatment outcomes in PWID. Meta-analysis was used to obtain pooled estimates of SVR, adherence, discontinuation, and HCV reinfection. RESULTS Ten primary articles and 1 conference abstract met the inclusion criteria. Across 6 studies (comprising 314 drug users, of whom 141 [45%] were PWID), pooled SVR was 56% (95% confidence interval [CI], 50%-61%) for all genotypes, 37% (95% CI, 26%-48%) for genotypes 1/4, and 67% (95% CI, 56%-78%) for genotypes 2/3. Pooled 80/80/80 adherence was 82% (95% CI, 74%-89%) across 2 studies, and pooled treatment discontinuation was 22% (95% CI, 16%-27%) across 4 studies. Across 5 studies (comprising 131 drug users) examining reinfection, pooled risk was 2.4 (95% CI, .9-6.1) per 100 person-years. CONCLUSIONS HCV treatment outcomes are acceptable in PWID, supporting treatment guidelines. The pooled estimate of HCV reinfection risk was low, but there was considerable uncertainty around this estimate. Further studies on the risk of reinfection are needed to assess the long-term effectiveness of HCV treatment in PWID.
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Affiliation(s)
- Esther J Aspinall
- Health Protection Scotland, National Services Scotland, Glasgow, Scotland, UK.
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44
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Grady BP, Schinkel J, Thomas XV, Dalgard O. Hepatitis C virus reinfection following treatment among people who use drugs. Clin Infect Dis 2014; 57 Suppl 2:S105-10. [PMID: 23884057 DOI: 10.1093/cid/cit301] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Most new cases of hepatitis C virus (HCV) infections in the developed world are associated with injection drug use. However, treatment for people who inject drugs (PWID) is controversial, as successful treatment risks being followed by new infection. Reinfection after sustained virologic response has been reported, but is the risk so great that treatment should be withheld from this large HCV population? Preliminary evidence suggests that the reinfection incidence is low, but studies to date have been limited by small sample size and few cases of reinfection. In this review, we assess data from studies among PWID of HCV reinfection following treatment to give a reasonable estimate on how frequently reinfection appears and try to characterize those most at risk, The observation that spontaneous clearance of HCV reinfection following treatment occurs is suggestive of a partial protective immunity against persistent infection.
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Affiliation(s)
- Bart P Grady
- Department of Infectious Diseases, Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, the Netherlands
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45
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EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2014; 60:392-420. [PMID: 24331294 DOI: 10.1016/j.jhep.2013.11.003] [Citation(s) in RCA: 655] [Impact Index Per Article: 59.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023]
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High rates of hepatitis C virus reinfection and spontaneous clearance of reinfection in people who inject drugs: a prospective cohort study. PLoS One 2013; 8:e80216. [PMID: 24244654 PMCID: PMC3820644 DOI: 10.1371/journal.pone.0080216] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Accepted: 10/01/2013] [Indexed: 12/26/2022] Open
Abstract
Hepatitis C virus reinfection and spontaneous clearance of reinfection were examined in a highly characterised cohort of 188 people who inject drugs over a five-year period. Nine confirmed reinfections and 17 possible reinfections were identified (confirmed reinfections were those genetically distinct from the previous infection and possible reinfections were used to define instances where genetic differences between infections could not be assessed due to lack of availability of hepatitis C virus sequence data). The incidence of confirmed reinfection was 28.8 per 100 person-years (PY), 95%CI: 15.0-55.4; the combined incidence of confirmed and possible reinfection was 24.6 per 100 PY (95%CI: 16.8-36.1). The hazard of hepatitis C reinfection was approximately double that of primary hepatitis C infection; it did not reach statistical significance in confirmed reinfections alone (hazard ratio [HR]: 2.45, 95%CI: 0.87-6.86, p=0.089), but did in confirmed and possible hepatitis C reinfections combined (HR: 1.93, 95%CI: 1.01-3.69, p=0.047) and after adjustment for the number of recent injecting partners and duration of injecting. In multivariable analysis, shorter duration of injection (HR: 0.91; 95%CI: 0.83-0.98; p=0.019) and multiple recent injecting partners (HR: 3.12; 95%CI: 1.08-9.00, p=0.035) were independent predictors of possible and confirmed reinfection. Time to spontaneous clearance was shorter in confirmed reinfection (HR: 5.34, 95%CI: 1.67-17.03, p=0.005) and confirmed and possible reinfection (HR: 3.10, 95%CI: 1.10-8.76, p-value=0.033) than primary infection. Nonetheless, 50% of confirmed reinfections and 41% of confirmed or possible reinfections did not spontaneously clear. Conclusions: Hepatitis C reinfection and spontaneous clearance of hepatitis C reinfection were observed at high rates, suggesting partial acquired natural immunity to hepatitis C virus. Public health campaigns about the risks of hepatitis C reinfection are required.
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Hepatitis C transmission and treatment in contact networks of people who inject drugs. PLoS One 2013; 8:e78286. [PMID: 24223787 PMCID: PMC3815209 DOI: 10.1371/journal.pone.0078286] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2013] [Accepted: 09/10/2013] [Indexed: 12/29/2022] Open
Abstract
Hepatitis C virus (HCV) chronically infects over 180 million people worldwide, with over 350,000 estimated deaths attributed yearly to HCV-related liver diseases. It disproportionally affects people who inject drugs (PWID). Currently there is no preventative vaccine and interventions feature long treatment durations with severe side-effects. Upcoming treatments will improve this situation, making possible large-scale treatment interventions. How these strategies should target HCV-infected PWID remains an important unanswered question. Previous models of HCV have lacked empirically grounded contact models of PWID. Here we report results on HCV transmission and treatment using simulated contact networks generated from an empirically grounded network model using recently developed statistical approaches in social network analysis. Our HCV transmission model is a detailed, stochastic, individual-based model including spontaneously clearing nodes. On transmission we investigate the role of number of contacts and injecting frequency on time to primary infection and the role of spontaneously clearing nodes on incidence rates. On treatment we investigate the effect of nine network-based treatment strategies on chronic prevalence and incidence rates of primary infection and re-infection. Both numbers of contacts and injecting frequency play key roles in reducing time to primary infection. The change from "less-" to "more-frequent" injector is roughly similar to having one additional network contact. Nodes that spontaneously clear their HCV infection have a local effect on infection risk and the total number of such nodes (but not their locations) has a network wide effect on the incidence of both primary and re-infection with HCV. Re-infection plays a large role in the effectiveness of treatment interventions. Strategies that choose PWID and treat all their contacts (analogous to ring vaccination) are most effective in reducing the incidence rates of re-infection and combined infection. A strategy targeting infected PWID with the most contacts (analogous to targeted vaccination) is the least effective.
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Abstract
We are entering an important new chapter in the story of hepatitis C virus (HCV) infection. There are clear challenges and opportunities. On the one hand, new HCV infections are still occurring, and an estimated 185 million people are or have previously been infected worldwide. Most HCV-infected persons are unaware of their status yet are at risk for life-threatening diseases such as cirrhosis and hepatocellular carcinoma (HCC), whose incidences are predicted to rise in the coming decade. On the other hand, new HCV infections can be prevented, and those that have already occurred can be detected and treated--viral eradication is even possible. How the story ends will largely be determined by the extent to which these rapidly advancing opportunities overcome the growing challenges and by the vigor of the public health response.
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Rhodes T, Harris M, Martin A. Negotiating access to medical treatment and the making of patient citizenship: the case of hepatitis C treatment. SOCIOLOGY OF HEALTH & ILLNESS 2013; 35:1023-1044. [PMID: 23701040 DOI: 10.1111/1467-9566.12018] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
Drawing on qualitative interview accounts with people who have injected drugs, we deploy ideas of biological and therapeutic citizenship to explore how the negotiation of access to hepatitis C treatment enacts patient citizenship potential. We find that the patient citizenship made through hepatitis C treatment divides those who are deserving from those who are not, largely in relation to their presentations of self-control, responsibility and recovery regarding drug use. Accessing treatment requires that patients negotiate their entitlement by reflexively producing the patient citizen role expected of them. In this context of rationed treatment expectation, access to treatment is constructed in relation to gratitude rather than entitlement. Rationed treatment expectation also interplays with a utilitarian approach to hepatitis C expertise. Accounts of the bio-effects of hepatitis C and its treatment as uncertain further weaken the potential for shared illness identity and biosocial membership as well as contributing to treatment delay. We conclude that the construction of hepatitis C treatment as a negotiation of 'recovery towards normality' positions people who continue to use or inject drugs as beyond patient citizenship. Our findings underscore the situated limits of therapeutic and biological citizenship, emphasising that these processes are unavoidably forces of governance.
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Affiliation(s)
- Tim Rhodes
- Centre for Research on Drugs and Health Behaviour, London School of Hygiene and Tropical Medicine, London, UK; National Center for HIV Social Research, University of New South Wales, Australia
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50
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Marco A, Esteban JI, Solé C, da Silva A, Ortiz J, Roget M, Sarriera C, Teixidó N, Guerrero RA, Caylà JA. Hepatitis C virus reinfection among prisoners with sustained virological response after treatment for chronic hepatitis C. J Hepatol 2013; 59:45-51. [PMID: 23523577 DOI: 10.1016/j.jhep.2013.03.008] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2012] [Revised: 01/25/2013] [Accepted: 03/12/2013] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS We estimated HCV reinfection rate and its associated risk factors in inmates with chronic hepatitis C who had achieved sustained virological response (SVR) after completing combination therapy while in prison. METHODS Individuals who had achieved an SVR after treatment provided from January 2003 to December 2009 at four prisons in Catalonia, had been tested annually for HCV RNA and were in prison during 2010, were invited to complete a questionnaire regarding risk factors for reinfection. Incidence rate was calculated as 100 person-years of follow-up. Risk factors potentially associated with reinfection were evaluated by bivariate log-rank test and multivariate Cox regression analysis. RESULTS One hundred and nineteen subjects who had achieved an SVR agreed to participate. 98% were male, with a median age of 33.3 ± 6.3 years and 81% had a history of injection drug use (IDU). After a mean follow-up of 1.4 years, HCV reinfection was identified in nine former IDUs, seven with HCV genotype switch, for an overall reinfection rate of 5.27 cases per 100 person-years. Reinfection incidence was significantly higher among active drug users (HR=12.47; 95% CI: 2.90-53.71), HIV co-infected (HR=9.95; 95% CI: 1.73-57.34), and those engaging in more than one risk behaviors after treatment (HR=7.47; 95% CI: 1.19-46.89). CONCLUSIONS HCV reinfection among inmates after successful treatment is high especially in those with ongoing IDU. Preventative interventions at diagnosis and during and after HCV treatment should be strongly reinforced.
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Affiliation(s)
- A Marco
- Health Services of Barcelona Men's Penitentiary Centre, Barcelona, Spain.
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