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1
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Pearce ME, Bartlett SR, Yu A, Lamb J, Reitz C, Wong S, Alvarez M, Binka M, Velásquez Garcia H, Jeong D, Clementi E, Adu P, Samji H, Wong J, Buxton J, Yoshida E, Elwood C, Sauve L, Pick N, Krajden M, Janjua NZ. Women in the 2019 hepatitis C cascade of care: findings from the British Columbia Hepatitis Testers cohort study. BMC Womens Health 2021; 21:330. [PMID: 34511082 PMCID: PMC8436483 DOI: 10.1186/s12905-021-01470-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 08/31/2021] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Women living with hepatitis C virus (HCV) are rarely addressed in research and may be overrepresented within key populations requiring additional support to access HCV care and treatment. We constructed the HCV care cascade among people diagnosed with HCV in British Columbia, Canada, as of 2019 to compare progress in care and treatment and to assess sex/gender gaps in HCV treatment access. METHODS The BC Hepatitis Testers Cohort includes 1.7 million people who tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 2000 to 2019. Test results were linked to medical visits, hospitalizations, cancers, prescription drugs, and mortality data. Six HCV care cascade stages were identified: (1) antibody diagnosed; (2) RNA tested; (3) RNA positive; (4) genotyped; (5) initiated treatment; and (6) achieved sustained virologic response (SVR). HCV care cascade results were assessed for women, and an 'inverse' cascade was created to assess gaps, including not being RNA tested, genotyped, or treatment initiated, stratified by sex. RESULTS In 2019, 52,638 people with known sex were anti-HCV positive in BC; 37% (19,522) were women. Confirmatory RNA tests were received by 86% (16,797/19,522) of anti-HCV positive women and 83% (27,353/33,116) of men. Among people who had been genotyped, 68% (6756/10,008) of women and 67% (12,640/18,828) of men initiated treatment, with 94% (5023/5364) of women and 92% (9147/9897) of men achieving SVR. Among the 3252 women and 6188 men not yet treated, higher proportions of women compared to men were born after 1975 (30% vs. 21%), had a mental health diagnosis (42% vs. 34%) and had used injection drugs (50% vs. 45%). Among 1619 women and 2780 men who had used injection drugs and were not yet treated, higher proportions of women than men used stimulants (64% vs. 57%), and opiates (67% vs. 60%). CONCLUSIONS Women and men appear to be equally engaged into the HCV care cascade; however, women with concurrent social and health conditions are being left behind. Treatment access may be improved with approaches that meet the needs of younger women, those with mental health diagnoses, and women who use drugs.
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Affiliation(s)
- Margo E Pearce
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.
- School of Population and Public Health, University of British Columbia (UBC), Vancouver, BC, Canada.
| | - Sofia R Bartlett
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, UBC, Vancouver, BC, Canada
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Jess Lamb
- AIDS Network Kootenay Outreach and Support Society, Kimberly, BC, Canada
| | - Cheryl Reitz
- East Kootenay Network of People who Use Drugs, Kimberly, BC, Canada
- British Columbia Hepatitis Network Society, Vancouver, BC, Canada
| | - Stanley Wong
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Mawuena Binka
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | | | - Dahn Jeong
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
- School of Population and Public Health, University of British Columbia (UBC), Vancouver, BC, Canada
| | - Emilia Clementi
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
- School of Population and Public Health, University of British Columbia (UBC), Vancouver, BC, Canada
| | - Prince Adu
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
- School of Population and Public Health, University of British Columbia (UBC), Vancouver, BC, Canada
| | - Hasina Samji
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Jason Wong
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
- School of Population and Public Health, University of British Columbia (UBC), Vancouver, BC, Canada
| | - Jane Buxton
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
- School of Population and Public Health, University of British Columbia (UBC), Vancouver, BC, Canada
| | - Eric Yoshida
- Division of Gastroenterology, Department of Medicine, UBC, Vancouver, BC, Canada
- Vancouver General Hospital, Vancouver, BC, Canada
| | - Chelsea Elwood
- Department of Obstetrics and Gynecology, UBC, Vancouver, Canada
- BC Women's Hospital Research Institute, Vancouver, BC, Canada
| | - Laura Sauve
- BC Women's Hospital Research Institute, Vancouver, BC, Canada
- Division of Infectious Diseases, Department of Pediatrics, UBC, Vancouver, Canada
- BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Neora Pick
- BC Women's Hospital Research Institute, Vancouver, BC, Canada
- Division of Infectious Diseases, Department of Medicine, UBC, Vancouver, BC, Canada
| | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
- Department of Pathology and Laboratory Medicine, UBC, Vancouver, BC, Canada
| | - Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
- School of Population and Public Health, University of British Columbia (UBC), Vancouver, BC, Canada
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2
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Pérez-Latorre L, Berenguer J, Micán R, Montero M, Cifuentes C, Puig T, Sanz J, Ferrero OL, De La Fuente B, Rodríguez C, Reus S, Hernández-Quero J, Gaspar G, Pérez-Martínez L, García C, Force L, Veloso S, De Miguel M, Jarrín I, González-García J. HIV/HBV coinfection: temporal trends and patient characteristics, Spain, 2002 to 2018. ACTA ACUST UNITED AC 2021; 26. [PMID: 34169818 PMCID: PMC8229377 DOI: 10.2807/1560-7917.es.2021.26.25.2000236] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Background Recent and reliable estimates on the prevalence of coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in Europe are lacking. Aim Leveraged on a study designed to assess HIV/HCV coinfection prevalence, we assessed the prevalence of HIV/HBV coinfection in Spain in 2018 and compared the results with five similar studies performed since 2002. Methods This cross-sectional prevalence study was carried out in 43 centres, and patients were selected using simple random sampling. The reference population comprised 40,322 patients and the sample size were 1,690 patients. Results The prevalence of HIV/HBV coinfection in Spain at the end of 2018 was 3.2%. The prevalence in 2002, 2009, 2015, 2016 and 2017 was 4.9%, 3.4%, 3%, 3.9% and 3%, respectively. Among the HIV/HBV-coinfected patients identified in 2018, 16.7% had cirrhosis according to transient elastography and 26.3% tested positive for antibodies against hepatitis D virus. All HIV/HBV-coinfected patients were receiving drugs with activity against HBV, and 97% of those tested for HBV DNA had an HBV DNA load < 80 IU/mL. Conclusions The prevalence of HIV/HBV coinfection in Spain remained stable at around 3% for a decade. Our data could facilitate the design of national programmes to control HBV infection and help identify areas of patient management that need improvement.
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Affiliation(s)
| | - Juan Berenguer
- Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | | | | | - Teresa Puig
- Hospital Universitari Arnau de Vilanova, Lleida, Spain
| | - José Sanz
- Hospital Príncipe de Asturias, Alcalá de Henares, Spain
| | | | | | | | - Sergio Reus
- Hospital General Universitario de Alicante, Alicante, Spain
| | | | | | | | - Coral García
- Hospital Universitario Virgen de las Nieves, Granada, Spain
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- The members of the GeSIDA 8514 Study Group have been listed under Investigators
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3
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Legrand N, David G, Rodallec A, Gaultier A, Salmon D, Cesbron A, Wittkop L, Raffi F, Gendzekhadze K, Retière C, Allavena C, Gagne K. Influence of HLA-C environment on the spontaneous clearance of hepatitis C in European HIV-HCV co-infected individuals. Clin Exp Immunol 2021; 204:107-124. [PMID: 33314121 DOI: 10.1111/cei.13562] [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] [Received: 08/05/2020] [Revised: 12/07/2020] [Accepted: 12/07/2020] [Indexed: 12/17/2022] Open
Abstract
Natural killer (NK) cell functions are regulated by diverse inhibitory and activating receptors, including killer cell immunoglobulin-like receptors (KIR), which interact with human leukocyte antigen (HLA) class I molecules. Some KIR/HLA genetic combinations were reported associated with spontaneous clearance (SC) of hepatitis C virus (HCV) but with discordant results, possibly reflecting KIR and/or HLA gene polymorphism according to populations. KIR/HLA genetic combinations associated with both an exhaustive NK and T cell repertoire were investigated in a cohort of HIV-HCV co-infected individuals with either SC (n = 68) or chronic infection (CI, n = 163) compared to uninfected blood donors [controls (Ctrl), n = 100]. Multivariate analysis showed that the HLA C2C2 environment was associated with SC only in European HIV-HCV co-infected individuals [odds ratio (OR) = 4·30, 95% confidence interval = 1·57-12·25, P = 0·005]. KIR2D+ NK cell repertoire and potential of degranulation of KIR2DL1/S1+ NK cells were similar in the SC European cohort compared to uninfected individuals. In contrast, decreased frequencies of KIR2DS1+ and KIR2DL2+ NK cells were detected in the CI group of Europeans compared to SC and a decreased frequency of KIR2DL1/S1+ NK cells compared to controls. Regarding T cells, higher frequencies of DNAX accessory molecule-1 (DNAM-1)+ and CD57+ T cells were observed in SC in comparison to controls. Interestingly, SC subjects emphasized increased frequencies of KIR2DL2/L3/S2+ T cells compared to CI subjects. Our study underlines that the C2 environment may activate efficient KIR2DL1+ NK cells in a viral context and maintain a KIR2DL2/L3/S2+ mature T cell response in the absence of KIR2DL2 engagement with its cognate ligands in SC group of HCV-HIV co-infected European patients.
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Affiliation(s)
- N Legrand
- Etablissement Français du Sang (EFS), Nantes, France.,Université de Nantes, INSERM U1232 CNRS, CRCINA, Nantes, France
| | - G David
- Etablissement Français du Sang (EFS), Nantes, France.,Université de Nantes, INSERM U1232 CNRS, CRCINA, Nantes, France
| | - A Rodallec
- Department of Virology, CHU Nantes Hotel Dieu, Nantes, France
| | - A Gaultier
- Department of Biostatistics, CHU Hotel Dieu, Nantes, France
| | - D Salmon
- AP-HP Department of Infectious Diseases, Université Paris Descartes, Paris, France
| | | | - L Wittkop
- INSERM UMR1219, Université de Bordeaux ISPED, Bordeaux, France
| | - F Raffi
- Department of Infectious Diseases, Nantes, France
| | - K Gendzekhadze
- Division of Hematology and Bone Marrow Transplantation, Duarte, CA, USA
| | - C Retière
- Etablissement Français du Sang (EFS), Nantes, France.,Université de Nantes, INSERM U1232 CNRS, CRCINA, Nantes, France.,LabEx IGO, Nantes, France
| | - C Allavena
- Department of Infectious Diseases, Nantes, France
| | - K Gagne
- Etablissement Français du Sang (EFS), Nantes, France.,Université de Nantes, INSERM U1232 CNRS, CRCINA, Nantes, France.,LabEx IGO, Nantes, France.,LabEx Transplantex, Université de Strasbourg, Strasbourg, France
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4
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Bartlett SR, Yu A, Chapinal N, Rossi C, Butt Z, Wong S, Darvishian M, Gilbert M, Wong J, Binka M, Alvarez M, Tyndall M, Krajden M, Janjua NZ. The population level care cascade for hepatitis C in British Columbia, Canada as of 2018: Impact of direct acting antivirals. Liver Int 2019; 39:2261-2272. [PMID: 31444846 DOI: 10.1111/liv.14227] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 08/14/2019] [Accepted: 08/19/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Population-level monitoring of hepatitis C virus (HCV) infected people across cascades of care identifies gaps in access and engagement in care and treatment. We characterized the population-level care cascade for HCV in British Columbia (BC), Canada before and after introduction of Direct Acting Antiviral (DAA) treatment. METHODS BC Hepatitis Testers Cohort (BC-HTC) includes 1.7 million individuals tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 1990 to 2018 linked to medical visits, hospitalizations, cancers, prescription drugs and mortality data. We defined six HCV care cascade stages: (a) antibody diagnosed; (b) RNA tested; (c) RNA positive; (d) genotyped; (e) initiated treatment; and (f) achieved sustained virologic response (SVR). RESULTS We estimated 61 127 people were HCV antibody positive in BC in 2018 (undiagnosed: 7686, 13%; diagnosed: 53 441, 87%). Of those diagnosed, 83% (44 507) had HCV RNA testing, and of those RNA positive, 90% (28 716) were genotyped. Of those genotyped, 61% (17 441) received therapy, with 90% (15 672) reaching SVR. Individuals from older birth cohorts had lower progression to HCV RNA testing. While people who currently inject drugs had the highest proportional progression to RNA testing, this group had the lowest proportional treatment uptake. CONCLUSIONS Although gaps in HCV RNA and genotype testing after antibody diagnosis exist, the largest gap in the care cascade is treatment initiation, despite introduction of DAA treatment and removal of treatment eligibility restrictions. Further interventions are required to ensure testing and treatment is equitably accessible in BC.
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Affiliation(s)
- Sofia R Bartlett
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.,Kirby Institute, University of New South Wales Australia, Sydney, NSW, Australia
| | - Amanda Yu
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada
| | - Nuria Chapinal
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada
| | - Carmine Rossi
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Zahid Butt
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Stanley Wong
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada
| | - Maryam Darvishian
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Mark Gilbert
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Jason Wong
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Mawuena Binka
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada
| | - Mark Tyndall
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Mel Krajden
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Naveed Z Janjua
- British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
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5
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What is killing people with hepatitis C virus infection? Analysis of a population-based cohort in Canada. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2019; 72:114-122. [PMID: 31229445 DOI: 10.1016/j.drugpo.2019.06.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 05/23/2019] [Accepted: 06/06/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Persons with hepatitis C virus (HCV) infection are at risk of mortality from both chronic liver disease and HCV acquisition risk activities. We compared causes of death among HCV positive and negative individuals to characterize contributions of acquisition risks and viral sequelae. METHODS The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) includes all individuals tested for HCV or reported as a HCV case since 1992, linked to health administrative data. ICD-10 codes were used to classify deaths as: 1) liver-related (LR); 2) HCV acquisition risk-related (AR); and 3) other causes. Mortality proportions and trends were assessed among HCV positive and negative individuals overall and by birth cohort (born <1945, 1945-64 and ≥1965). RESULTS As of December 31, 2018, of 1,300,204 HCV-tested individuals, 20,049 (27.5%) HCV positive and 132,999 (10.2%) HCV negative individuals had died (median age at death: 56.4 vs. 74.5 years, respectively). HCV positive individuals were more likely than negatives to die from both AR (24.7%/4.2%) and LR (23.4%/6.2%) causes. Deaths among older HCV positive individuals were more likely to be LR while younger individuals were more likely AR: 1) birth cohort <1945 (25.3%/2.7%); 2) 1945-64 (26.5%/23.7%) and ≥1965 (7.7%/59.9%). Among HCV positives, LR mortality increased from 1992 to 2014, then declined sharply, coinciding with the introduction and uptake of direct-acting antiviral drugs. AR mortality increased from 1992 to 2000, declined slowly until 2013, then rapidly increased, coinciding with the recent surge in opioid overdose deaths. CONCLUSIONS Curative HCV treatments reduce LR mortality, but typically will not impact AR mortality. This will need to be addressed if the World Health Organization 2030 HCV mortality reduction goals are to be achieved.
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6
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Darvishian M, Janjua NZ, Chong M, Cook D, Samji H, Butt ZA, Yu A, Alvarez M, Yoshida E, Ramji A, Wong J, Woods R, Tyndall M, Krajden M. Estimating the impact of early hepatitis C virus clearance on hepatocellular carcinoma risk. J Viral Hepat 2018; 25:1481-1492. [PMID: 30047609 DOI: 10.1111/jvh.12977] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 06/04/2018] [Accepted: 07/03/2018] [Indexed: 12/15/2022]
Abstract
Although achieving sustained virological response (SVR) through antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) attributable to hepatitis C virus (HCV) infection, the impact of early viral clearance on HCC is not well defined. In this study, we compared the risk of HCC among individuals who spontaneously cleared HCV (SC), the referent population, with the risk in untreated chronic HCV (UCHC), those achieved SVR, and those who failed interferon-based treatment (TF). The BC Hepatitis Testers Cohort (BC-HTC) includes individuals tested for HCV between 1990-2013, integrated with medical visits, hospitalizations, cancers, prescription drugs and mortality data. This analysis included all HCV-positive patients with at least one valid HCV RNA by PCR on or after HCV diagnosis. Of 46 666 HCV-infected individuals, there were 12 527 (26.8%) SC; 24 794 (53.1%) UCHC; 5355 (11.5%) SVR and 3990 (8.5%) TF. HCC incidence was lowest (0.3/1000 person-years (PY)) in the SC group and highest in the TF group (7.7/1000 PY). In a multivariable model, compared to SC, TF had the highest HCC risk (hazard ratio (HR):14.52, 95% confidence interval (CI): 9.83-21.47), followed by UCHC (HR: 5.85; 95% CI: 4.07-8.41). Earlier treatment-based viral clearance similar to SC could decrease HCC incidence by 69.4% (95% CI: 57.5-78.0), 30% (95% CI: 10.8-45.1) and 77.5% (95% CI: 69.4-83.5) among UCHC, SVR and TF patients, respectively. In conclusion, using SC as a real-world comparator group, it showed that substantial reduction in HCC risk could be achieved with earlier treatment initiation. These analyses should be replicated in patients who have been treated with direct acting antiviral therapies.
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Affiliation(s)
- Maryam Darvishian
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mei Chong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Darrel Cook
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Hasina Samji
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Zahid A Butt
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Eric Yoshida
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Alnoor Ramji
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.,GI Research Institute, Vancouver, British Columbia, Canada
| | - Jason Wong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Ryan Woods
- British Columbia Cancer Agency, Vancouver, British Columbia, Canada
| | - Mark Tyndall
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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7
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Hepatitis C cross-genotype immunity and implications for vaccine development. Sci Rep 2017; 7:12326. [PMID: 28951612 PMCID: PMC5615075 DOI: 10.1038/s41598-017-10190-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 08/02/2017] [Indexed: 01/03/2023] Open
Abstract
While about a quarter of individuals clear their primary hepatitis C (HCV) infections spontaneously, clearance (spontaneous or treatment-induced) does not confer sterilizing immunity against a future infection. Since successful treatment does not prevent future infections either, an effective vaccine is highly desirable in preventing HCV (re)infection. However, development of an effective vaccine has been complicated by the diversity of HCV genotypes, and complexities in HCV immunological responses. Smaller studies on humans and chimpanzees reported seemingly opposing results regarding cross-neutralizing antibodies. We report a lack of cross-genotype immunity in the largest cohort of people to date. In the adjusted Cox proportional hazards model, reinfection with a heterologous HCV genotype (adjusted Hazard Ratio [aHR]: 0.45, 95% CI: 0.25–0.84) was associated with a 55% lower likelihood of re-clearance. Among those who cleared their first infection spontaneously, the likelihood of re-clearance was 49% lower (aHR: 0.51, 95% CI: 0.27–0.94) when reinfected with a heterologous HCV genotype. These findings indicate that immunity against a particular HCV genotype does not offer expanded immunity to protect against subsequent infections with a different HCV genotype. A prophylactic HCV vaccine boosted with multiple HCV genotype may offer a broader and more effective protection.
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8
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Janjua NZ, Islam N, Wong J, Yoshida EM, Ramji A, Samji H, Butt ZA, Chong M, Cook D, Alvarez M, Darvishian M, Tyndall M, Krajden M. Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study. J Viral Hepat 2017; 24:624-630. [PMID: 28130810 DOI: 10.1111/jvh.12684] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 12/22/2016] [Indexed: 12/15/2022]
Abstract
We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.
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Affiliation(s)
- N Z Janjua
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - N Islam
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - J Wong
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - E M Yoshida
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - A Ramji
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - H Samji
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Z A Butt
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - M Chong
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - D Cook
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - M Alvarez
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - M Darvishian
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - M Tyndall
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - M Krajden
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
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