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Bal T, Dirican E. A potential new way to facilitate HCV elimination: The prediction of viremia in anti-HCV seropositive patients using machine learning algorithms. Arab J Gastroenterol 2024; 25:223-229. [PMID: 38705815 DOI: 10.1016/j.ajg.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 01/19/2024] [Accepted: 03/20/2024] [Indexed: 05/07/2024]
Abstract
BACKGROUND AND STUDY AIMS The present study was undertaken to design a new machine learning (ML) model that can predict the presence of viremia in hepatitis C virus (HCV) antibody (anti-HCV) seropositive cases. PATIENTS AND METHODS This retrospective study was conducted between January 2012-January 2022 with 812 patients who were referred for anti-HCV positivity and were examined for HCV ribonucleic acid (HCV RNA). Models were constructed with 11 features with a predictor (presence and absence of viremia) to predict HCV viremia. To build an optimal model, this current study also examined and compared the three classifier data mining approaches: RF, SVM and XGBoost. RESULTS The highest performance was achieved with XGBoost (90%), which was followed by RF (89%), SVM Linear (85%) and SVM Radial (83%) algorithms, respectively. The four most important key features contributing to the models were: alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) and anti-HCV levels, respectively, while "ALB" was replaced by the "AGE" only in the XGBoost model. CONCLUSION This study has shown that XGBoost and RF based ML models, incorporating anti-HCV levels and routine laboratory tests (ALT, AST, ALB), and age are capable of providing HCV viremia diagnosis with 90% and 89% accuracy, respectively. These findings highlight the potential of ML models in the early diagnosis of HCV viremia, which may be helpful in optimizing HCV elimination programs.
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Affiliation(s)
- Tayibe Bal
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey.
| | - Emre Dirican
- Department of Biostatistics, Faculty of Medicine, Hatay Mustafa Kemal University, Hatay, Turkey
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Li H, Yang S, Cao D, Wang Q, Zhang S, Zhou Y, Liu D, Yang R, Cui L, Zhu Z. A new double-antigen sandwich test based on the light-initiated chemiluminescent assay for detecting anti-hepatitis C virus antibodies with high sensitivity and specificity. Front Cell Infect Microbiol 2023; 13:1222778. [PMID: 38076452 PMCID: PMC10704264 DOI: 10.3389/fcimb.2023.1222778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 10/20/2023] [Indexed: 12/18/2023] Open
Abstract
Objectives The aim of this study was to evaluate the performance of a new double-antigen sandwich test that is based on the light-initiated chemiluminescent assay (LiCA®) for detecting anti-hepatitis C virus antibodies (anti-HCV) in comparison to Architect®. Methods Analytical characteristics and diagnostic performance were tested using seroconversion panels and large pools of clinical samples. Positive results were validated by the strip immunoblot assay (RIBA) and HCV RNA. Results Repeatability and within-lab imprecision of LiCA® anti-HCV were 1.31%-3.27%. The C5-C95 interval was -5.44%-5.03% away from C50. LiCA® detected seroconversion in an average of 28.9 days and showed a mean of 3.7 (p = 0.0056) days earlier than Architect®. In a pool of 239 samples with known HCV genotypes 1 to 6, both assays correctly detected all subjects. In 16,305 clinical patient sera, LiCA® detected 4 false-negative (0.25‰) and 14 false-positive (0.86‰) anti-HCV cases, while Architect® recorded 6 false-negative (0.37‰) and 138 false-positive (8.46‰) subjects, respectively. Compared to Architect®, LiCA® presented a significantly better performance in specificity (99.91% vs. 99.14%, n = 16,018, p < 0.0001), positive predictive value (95.29% vs. 67.06%, n = 419, p < 0.0001), and overall accuracy (99.89% vs. 99.12%, n = 16,305, p < 0.0001), while no significant difference in sensitivity (98.61% vs. 97.91%, n = 287, p = 0.5217) and negative predictive value (99.98% vs. 99.96%, n = 15,886, p = 0.3021) was seen. An S/Co value of 3.28 was predicted to be the threshold with a positivity ≥95% for the LiCA® anti-HCV assay. Conclusion LiCA® anti-HCV is a precise and fully automatic chemiluminescent assay with superior sensitivity and specificity. The assay can be used as a valuable tool to supplement the diagnosis of HCV infection.
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Affiliation(s)
- Haicong Li
- Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Shanghai, China
| | - Shuo Yang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Dan Cao
- Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Shanghai, China
| | - Qianying Wang
- Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Shanghai, China
| | - Siyu Zhang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Yi Zhou
- Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Shanghai, China
| | - Di Liu
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Ruifeng Yang
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing, China
| | - Liyan Cui
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Zhaoqin Zhu
- Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Shanghai, China
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Abstract
Hepatitis C virus (HCV) infection contributes significantly to liver cirrhosis and hepatocellular carcinoma (HCC), often requiring liver transplantation. Introducing direct-acting antiviral agents (DAAs) has radically changed HCV treatment. DAAs achieve high rates of sustained virological response (>98%). Even then, resistant-associated substitution and HCC during or after treatment have become prominent clinical concerns. Further, several clinically significant issues remain unresolved after successful HCV eradication by DAAs, including treating patients with chronic kidney disease or decompensated liver cirrhosis. Extensive and large-scale screening and treatment implementation programs are needed to make DAA therapies effective at the population level.
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Tilmon S, Aronsohn A, Boodram B, Canary L, Goel S, Hamlish T, Kemble S, Lauderdale DS, Layden J, Lee K, Millman AJ, Nelson N, Ritger K, Rodriguez I, Shurupova N, Wolf J, Johnson D. HepCCATT: a multilevel intervention for hepatitis C among vulnerable populations in Chicago. J Public Health (Oxf) 2022; 44:891-899. [PMID: 34156077 PMCID: PMC8692481 DOI: 10.1093/pubmed/fdab190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 05/07/2021] [Accepted: 05/20/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Hepatitis C infection could be eliminated. Underdiagnosis and lack of treatment are the barriers to cure, especially for vulnerable populations (i.e. unable to pay for health care). METHODS A multilevel intervention from September 2014 to September 2019 focused on the providers and organizations in 'the safety net' (providing health care to populations unable to pay), including: (i) public education, (ii) training for primary care providers (PCPs) and case managers, (iii) case management for high-risk populations, (iv) policy advice and (v) a registry (Registry) for 13 health centers contributing data. The project tracked the number of PCPs trained and, among Registry sites, the number of people screened, engaged in care (i.e. clinical follow-up after diagnosis), treated and/or cured. RESULTS In Chicago, 215 prescribing PCPs and 56 other health professionals, 86% of whom work in the safety net, were trained to manage hepatitis C. Among Registry sites, there was a 137% increase in antibody screening and a 32% increase in current hepatitis C diagnoses. Engagement in care rose by 18%. CONCLUSIONS Hepatitis C Community Alliance to Test and Treat (HepCCATT) successfully targeted safety net providers and organizations with a comprehensive care approach. While there were challenges, HepCCATT observed increased hepatitis C screening, diagnosis and engagement in care in the Chicago community.
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Affiliation(s)
- Sandra Tilmon
- Academic Pediatrics, University of Chicago Medicine, Chicago, IL 60637, USA
| | - A Aronsohn
- Gastroenterology, University of Chicago Medicine, Chicago, IL 60637, USA
| | - B Boodram
- Department of Public Health, University of Illinois at Chicago, Chicago, IL 60607, USA
| | - L Canary
- CDC: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, GA 30329, USA
| | - S Goel
- Division of General Internal Medicine and Geriatrics, Northwestern University (Medicine), Chicago, IL 60611 USA
| | - T Hamlish
- Cancer Center, University of Illinois at Chicago, Chicago, IL 60612 USA
| | - S Kemble
- Hawaii Department of Health, Honolulu, HI 96813, USA
| | - D S Lauderdale
- Public Health Sciences, University of Chicago Medicine, Chicago, IL 60637
| | - J Layden
- Illinois Department of Public Health, West Chicago, IL 60185, USA
| | - K Lee
- Academic Pediatrics, University of Chicago Medicine, Chicago, IL 60637, USA
| | - A J Millman
- CDC: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, GA 30329, USA
| | - N Nelson
- CDC: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, GA 30329, USA
| | - K Ritger
- Chicago Department of Public Health, Chicago, IL 60604, USA
| | - I Rodriguez
- Academic Pediatrics, University of Chicago Medicine, Chicago, IL 60637, USA
| | - N Shurupova
- Medical Research Analytics and Informatics Alliance (MRAIA), Chicago, IL 60606, USA
| | - J Wolf
- Caring Ambassadors Program, Oregon City, OR 97045, USA
| | - D Johnson
- Academic Pediatrics, University of Chicago Medicine, Chicago, IL 60637, USA
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Muacevic A, Adler JR. Direct-Acting Antiviral Treatment in Albanian Patients With Chronic Hepatitis C and Advanced Liver Fibrosis. Cureus 2022; 14:e32646. [PMID: 36540321 PMCID: PMC9759809 DOI: 10.7759/cureus.32646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2022] [Indexed: 12/23/2022] Open
Abstract
Background Treating chronic hepatitis C (CHC) with direct-acting antiviral (DAA) is very effective at clearing the infection. In Albania treatment with DAA is limited to patients with liver stiffness F3-F4, and with other co-infections. The objective of this study was to evaluate the efficacy of DAA in Albanian patients with genotypes 1-5, who mostly suffer from advanced liver fibrosis. Material and Methods This is a retrospective study carried out at the University Hospital Center "Mother Teresa", Tirana, during 2014-2019, including treatment-naïve and treatment-experienced patients with genotypes 1-5. All patients were evaluated with elastography and most of them were F3-F4. The primary endpoint involved the patients achieving SVR-12, or undetectable hepatitis C virus/ribonucleic acid (HCV RNA) 12 weeks after the end of treatment. In patients without a genotype, we have used a pangenotypic regimen. Results This study included 207 patients with a mean age of 48.9 ± 13.1 years, 56% male and 44% female; 152 (73%) were genotype 1, 24 were (11.5%) genotype 2, nine were (4.3%) genotype 3, 14 were (6.7%) genotype 4, one was (0.4%) genotype 5, and seven (3.8%) unassigned genotypes. The sustained virologic response (SVR) percentage according to genotype is discussed in the article. The overall SVR score of all the patients in our study was >93%. According to elastography, 127 (66%) were F3-F4, and 80 (38.6%) were F1-F2. Conclusion Treatment with DAA proved to be very effective in our patients; most of them had advanced liver fibrosis as well as compensated or decompensated liver cirrhosis. The overall SVR score of the patients in our study was >93%. Our country needs to treat all patients with chronic hepatitis C without limitations to attain the WHO objective of eradicating this disease by 2030.
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Torres HA, Angelidakis G, Jiang Y, Economides M, Mustafayev K, Yibirin M, Orlowski R, Champlin R, Verstovsek S, Raad I. Serologic versus molecular testing for screening for hepatitis C virus infection in patients with hematologic malignancies. Medicine (Baltimore) 2022; 101:e30608. [PMID: 36123927 PMCID: PMC9478288 DOI: 10.1097/md.0000000000030608] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 08/16/2022] [Indexed: 11/26/2022] Open
Abstract
Testing for antibody against hepatitis C virus (anti-HCV) is a low-cost diagnostic method worldwide; however, an optimal screening test for HCV in patients with cancer has not been established. We sought to identify an appropriate screening test for HCV infection in patients with hematologic malignancies and/or hematopoietic cell transplants (HCT). Patients in our center were simultaneously screened using serological (anti-HCV) and molecular (HCV RNA) assays (February 2019-November 2019). In total, 214 patients were enrolled in this study. Three patients (1.4%) were positive for anti-HCV, and 2 (0.9%) were positive for HCV RNA. The overall percentage agreement was 99.5% (95% CI: 97.4-99.9). There were no cases of seronegative HCV virus infection. The positive percentage agreement was 66.7% (95% CI: 20.8-93.9), and the negative percentage agreement was 100.0% (95% CI: 98.2-100.0). Cohen kappa coefficient was 0.80 (95% CI: 0.41-1.00, P < .0001). The diagnostic yield of screening for chronic HCV infection in patients with cancer is similar for serologic and molecular testing.
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Affiliation(s)
- Harrys A. Torres
- Department of Infectious Diseases, Infection Control and Employee Health, the University of Texas MD Anderson Cancer Center, Houston, TX
- Department of Gastroenterology, Hepatology and Nutrition, the University of Texas MD Anderson Cancer Center, Houston, TX
| | - Georgios Angelidakis
- Department of Infectious Diseases, Infection Control and Employee Health, the University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ying Jiang
- Department of Infectious Diseases, Infection Control and Employee Health, the University of Texas MD Anderson Cancer Center, Houston, TX
| | - Minas Economides
- Department of Infectious Diseases, Infection Control and Employee Health, the University of Texas MD Anderson Cancer Center, Houston, TX
| | - Khalis Mustafayev
- Department of Infectious Diseases, Infection Control and Employee Health, the University of Texas MD Anderson Cancer Center, Houston, TX
| | - Marcel Yibirin
- Department of Infectious Diseases, Infection Control and Employee Health, the University of Texas MD Anderson Cancer Center, Houston, TX
| | - Robert Orlowski
- Department of Lymphoma/Myeloma, the University of Texas MD Anderson Cancer Center, Houston, TX
| | - Richard Champlin
- Department of Stem Cell Transplantation, the University of Texas MD Anderson Cancer Center, Houston, TX
| | - Srdan Verstovsek
- Department of Leukemia, the University of Texas MD Anderson Cancer Center, Houston, TX
| | - Issam Raad
- Department of Infectious Diseases, Infection Control and Employee Health, the University of Texas MD Anderson Cancer Center, Houston, TX
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Yeung A, Palmateer NE, Dillon JF, McDonald SA, Smith S, Barclay S, Hayes PC, Gunson RN, Templeton K, Goldberg DJ, Hickman M, Hutchinson SJ. Population-level estimates of hepatitis C reinfection post scale-up of direct-acting antivirals among people who inject drugs. J Hepatol 2022; 76:549-557. [PMID: 34634387 PMCID: PMC8852744 DOI: 10.1016/j.jhep.2021.09.038] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 09/08/2021] [Accepted: 09/27/2021] [Indexed: 12/26/2022]
Abstract
BACKGROUND & AIMS Scale-up of highly effective direct-acting antivirals (DAAs) for HCV among people who inject drugs (PWID) in Scotland has led to a reduction in the prevalence of viraemia in this population. However, the extent of reinfection among those treated with DAAs remains uncertain. We estimated HCV reinfection rates among PWID in Scotland by treatment setting, pre- and post-introduction of DAAs, and the potential number of undiagnosed reinfections resulting from incomplete follow-up testing. METHODS Through linkage of national clinical and laboratory HCV data, a retrospective cohort of PWID who commenced treatment between 2000-2018 and achieved a sustained virological response (SVR) were followed up for reinfection to December 2019. Reinfection was defined as a positive HCV antigen or RNA test. RESULTS Of 5,686 SVRs among 5,592 PWID, 4,126 (73%) had an HCV RNA or antigen test post-SVR. Of those retested, we identified 361 reinfections (3.9/100 person-years [PY]). The reinfection rate increased from 1.5/100 PY among PWID treated in 2000-2009 to 8.8/100 PY in 2017-2018. The highest reinfection rates were observed among those treated in prison (14.3/100 PY) and community settings (9.5/100 PY). Among those treated in the DAA era (2015-2018), 68% were tested within the first year post-SVR but only 30% in the second year; while 169 reinfections were diagnosed in follow-up, an estimated 200 reinfections (54% of the estimated total) had gone undetected. CONCLUSIONS HCV reinfection rates among PWID in Scotland have risen alongside the scale-up of DAAs and broadened access to treatment for those at highest risk, through delivery in community drug services. Promotion of HCV testing post-SVR among PWID is essential to ensure those reinfected are identified and retreated promptly. LAY SUMMARY Increased rates of hepatitis C reinfection in Scotland were observed following the rapid scale-up of highly effective direct-acting antiviral (DAA) treatments among people who inject drugs. This demonstrates that community-based treatment pathways are reaching high-risk groups, regarded vital in efforts to eliminate the virus. However, we estimate that less than half of reinfections have been detected in the DAA era because of inadequate levels of retesting beyond the first year following successful treatment. Sustained efforts that involve high coverage of harm reduction measures and high uptake of annual testing are required to ensure prompt diagnosis and treatment of those reinfected if the goals of elimination are to be met.
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Affiliation(s)
- Alan Yeung
- Glasgow Caledonian University, Glasgow, United Kingdom; Public Health Scotland, Edinburgh, United Kingdom.
| | - Norah E Palmateer
- Glasgow Caledonian University, Glasgow, United Kingdom; Public Health Scotland, Edinburgh, United Kingdom
| | | | - Scott A McDonald
- Glasgow Caledonian University, Glasgow, United Kingdom; Public Health Scotland, Edinburgh, United Kingdom
| | - Shanley Smith
- Glasgow Caledonian University, Glasgow, United Kingdom; Public Health Scotland, Edinburgh, United Kingdom
| | | | - Peter C Hayes
- Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Rory N Gunson
- West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Kate Templeton
- Royal Infirmary of Edinburgh, Specialist Virology Centre, Edinburgh, United Kingdom
| | - David J Goldberg
- Public Health Scotland, Edinburgh, United Kingdom; Glasgow Caledonian University, Glasgow, United Kingdom
| | - Matthew Hickman
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; NIHR Health Protection Research Unit in Behavioural Science and Evaluation, Bristol, United Kingdom
| | - Sharon J Hutchinson
- Glasgow Caledonian University, Glasgow, United Kingdom; Public Health Scotland, Edinburgh, United Kingdom
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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9
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Reported Barriers to Hepatitis C Treatment among Pregnant and Early-Parenting Mothers Undergoing Substance Use Disorder Treatment in One U.S. State. Infect Dis Rep 2021; 14:1-11. [PMID: 35076528 PMCID: PMC8788261 DOI: 10.3390/idr14010001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/15/2021] [Accepted: 12/15/2021] [Indexed: 11/16/2022] Open
Abstract
Nationwide, the prevalence of the hepatitis C virus (HCV) has risen in recent years. At least 90% of infected persons must be treated to achieve global elimination targets. The current study aimed to explore barriers to, and facilitators of, direct-acting antiviral (DAA) HCV treatment uptake amongst pregnant and early-parenting women undergoing comprehensive substance use treatment. Twenty participants with documented HCV antibody positivity were recruited from two substance use treatment centers in central Kentucky. Semi-structured interviews were conducted to explore knowledge about HCV, previous experiences, and intentions to seek care. Themes were extracted using an inductive analytical approach. Most participants were aware of the dangers posed by HCV infection. However, there was a high degree of misinformation about transmission mechanisms and treatment eligibility requirements. Low priority for HCV treatment also surfaced as a barrier to treatment uptake. Participants reported being unable to seek care due to time and resource limitations in the presence of a highly demanding treatment process. Findings from the current study suggest that more work is needed to eliminate residual barriers that limit access to HCV treatment among pregnant and early-parenting women in treatment for substance use disorder.
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Calvaruso V, Petta S, Cacciola I, Cabibbo G, Cartabellotta F, Distefano M, Scifo G, Di Rosolini MA, Russello M, Prestileo T, Madonia S, Malizia G, Montineri A, Digiacomo A, Licata A, Benanti F, Bertino G, Enea M, Battaglia S, Squadrito G, Raimondo G, Cammà C, Craxì A, Di Marco V, Rete Sicilia Selezione Terapia ‐ HCV (RESIST‐HCV). Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort. J Viral Hepat 2021; 28:1190-1199. [PMID: 33896097 PMCID: PMC8359835 DOI: 10.1111/jvh.13523] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/11/2021] [Accepted: 04/13/2021] [Indexed: 01/06/2023]
Abstract
Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16-152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA-positive at last follow-up. Sixty-three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio,HR0.09, beta -2.37, p < .001). Also, platelet count (HR 0.99, beta-0.01, p = .007) and albumin value (HR 0.26, beta -1.36 p = .001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta-2.67, p < .001). Presence of diabetes (HR 3.45, beta 1.24, p = .014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease.
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Affiliation(s)
- Vincenza Calvaruso
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Salvatore Petta
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Irene Cacciola
- UOC Epatologia Clinica e BiomolecolareMessinaItaly
- AOUP G. MartinoDipartimento di Medicina Interna e SperimentaleUniversity of MessinaMessinaItaly
| | - Giuseppe Cabibbo
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | | | - Marco Distefano
- UOC Malattie InfettiveOspedale Umberto I di SiracusaASP SiracusaSiracusaItaly
| | - Gaetano Scifo
- UOC Malattie InfettiveOspedale Umberto I di SiracusaASP SiracusaSiracusaItaly
| | | | | | - Tullio Prestileo
- UOC Malattie InfettiveARNAS Civico‐Di Cristina‐BenefratelliPalermoItaly
| | | | | | - Arturo Montineri
- UOC Malattie infettiveAO Universitaria V. Emanuele di CataniaCataniaItaly
| | | | - Anna Licata
- UOC Medicina InternaAOUP Paolo GiacconePalermoItaly
| | | | - Gaetano Bertino
- UOC Medicina InternaAO Universitaria V. Emanuele di CataniaCataniaItaly
| | - Marco Enea
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Salvatore Battaglia
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Giovanni Squadrito
- UOC Epatologia Clinica e BiomolecolareMessinaItaly
- AOUP G. MartinoDipartimento di Medicina Interna e SperimentaleUniversity of MessinaMessinaItaly
| | - Giovanni Raimondo
- UOC Epatologia Clinica e BiomolecolareMessinaItaly
- AOUP G. MartinoDipartimento di Medicina Interna e SperimentaleUniversity of MessinaMessinaItaly
| | - Calogero Cammà
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Antonio Craxì
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
| | - Vito Di Marco
- Gastroenterology and Hepatology UnitDepartment of Health Promotion Sciences Maternal and Infantile CareInternal Medicine and Medical SpecialitiesPROMISEUniversity of PalermoPalermoItaly
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Tran L, Feldman R, Riley T, Jung J. Association of the Extension for Community Healthcare Outcomes Project With Use of Direct-Acting Antiviral Treatment Among US Adults With Hepatitis C. JAMA Netw Open 2021; 4:e2115523. [PMID: 34213557 PMCID: PMC8254131 DOI: 10.1001/jamanetworkopen.2021.15523] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
IMPORTANCE Direct-acting antiviral (DAA) medications are highly effective in treating hepatitis C virus (HCV) infection. However, use of DAAs in rural and underserved areas is low owing to limited access to specialist physicians with experience in care of HCV infection. Project ECHO (Extension for Community Healthcare Outcomes) is a distance education model that trains primary care physicians to improve access to care for underserved populations with complex diseases such as HCV infection. Evidence on whether Project ECHO is associated with increased DAA use is limited. OBJECTIVE To examine the association between Project ECHO and use of DAA treatment in patients with HCV infection. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from Medicare beneficiaries who newly sought care for HCV infection between January 1, 2014, and December 31, 2017. Data were analyzed between September and December 2020. EXPOSURES Project ECHO. MAIN OUTCOMES AND MEASURES Use of DAA treatment. Discrete-time hazard models with state and year fixed effects were used to examine the association between Project ECHO and DAA use in rural areas and areas with low specialist density. RESULTS A total of 267 908 patients (mean [SD] age, 60.7 [11.5] years; 57.9% male; 66.6% White patients) were included in the analysis. For every 100 clinicians attending a Project ECHO training, the odds of DAA treatment initiation among patients with HCV infection increased by 9% (adjusted odds ratio [OR], 1.09; 95% CI, 1.07-1.11; P < .001) in nonrural areas with specialist density equaling 0. The association between DAA use and Project ECHO was stronger in areas with lower vs higher specialist density. For every additional 100 Project ECHO participants, the odds of DAA use decreased by 1% as specialist density in the area increased (adjusted OR, 0.99; 95% CI, 0.98-1.00; P = .03). There was no association between Project ECHO and the odds of receiving DAAs among patients in rural vs urban areas (adjusted OR, 1.01; 95% CI, 0.99-1.02; P = .49). CONCLUSIONS AND RELEVANCE In this cohort study, implementation of Project ECHO was associated with increased DAA use in areas with few specialist physicians, suggesting that Project ECHO may enhance access to DAA treatment through expanding the capacity of primary care physicians to treat HCV infection, especially in underserved areas.
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Affiliation(s)
- Linh Tran
- Department of Health Policy and Administration, Pennsylvania State University College of Health and Human Development, University Park, State College
| | - Roger Feldman
- Division of Health Policy and Management, University of Minnesota School of Public Health, Minneapolis
| | - Thomas Riley
- Department of Medicine, Pennsylvania State University College of Medicine, Hershey
| | - Jeah Jung
- Department of Health Policy and Administration, Pennsylvania State University College of Health and Human Development, University Park, State College
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12
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Lynch E, Falq G, Sun C, Bunchhoeung PDT, Huerga H, Loarec A, Dousset JP, Marquardt T, Paih ML, Maman D. Hepatitis C viraemic and seroprevalence and risk factors for positivity in Northwest Cambodia: a household cross-sectional serosurvey. BMC Infect Dis 2021; 21:223. [PMID: 33637051 PMCID: PMC7912833 DOI: 10.1186/s12879-021-05826-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 01/21/2021] [Indexed: 12/31/2022] Open
Abstract
Background Despite a dramatic reduction in HCV drug costs and simplified models of care, many countries lack important information on prevalence and risk factors to structure effective HCV services. Methods A cross-sectional, multi-stage cluster survey of HCV seroprevalence in adults 18 years and above was conducted, with an oversampling of those 45 years and above. One hundred forty-seven clusters of 25 households were randomly selected in two sets (set 1=24 clusters ≥18; set 2=123 clusters, ≥45). A multi-variable analysis assessed risk factors for sero-positivity among participants ≥45. The study occurred in rural Moung Ruessei Health Operational District, Battambang Province, Western Cambodia. Results A total of 5098 individuals and 3616 households participated in the survey. The overall seroprevalence was 2.6% (CI95% 2.3–3.0) for those ≥18 years, 5.1% (CI95% 4.6–5.7) for adults ≥ 45 years, and 0.6% (CI95% 0.3–0.9) for adults 18–44. Viraemic prevalence was 1.9% (CI95% 1.6–2.1), 3.6% (CI95% 3.2–4.0), and 0.5% (CI95% 0.2–0.8), respectively. Men had higher prevalence than women: ≥18 years male seroprevalence was 3.0 (CI95% 2.5–3.5) versus 2.3 (CI95% 1.9–2.7) for women. Knowledge of HCV was poor: 64.7% of all respondents and 57.0% of seropositive participants reported never having heard of HCV. Risk factor characteristics for the population ≥45 years included: advancing age (p< 0.001), low education (higher than secondary school OR 0.7 [95% CI 0.6–0.8]), any dental or gum treatment (OR 1.6 [95% CI 1.3–1.8]), historical routine medical care (medical injection after 1990 OR 0.7 [95% CI 0.6–0.9]; surgery after 1990 OR 0.7 [95% CI0.5–0.9]), and historical blood donation or transfusion (blood donation after 1980 OR 0.4 [95% CI 0.2–0.8]); blood transfusion after 1990 OR 0.7 [95% CI 0.4–1.1]). Conclusions This study provides the first large-scale general adult population prevalence data on HCV infection in Cambodia. The results confirm the link between high prevalence and age ≥45 years, lower socio-economic status and past routine medical interventions (particularly those received before 1990 and 1980). This survey suggests high HCV prevalence in certain populations in Cambodia and can be used to guide national and local HCV policy discussion.
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Affiliation(s)
- Emily Lynch
- Epicentre, 40 Rector St, New York, NY, 10006, USA.
| | | | - Chhorvy Sun
- Médecins Sans Frontières, Phnom Penh, Cambodia
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13
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Wang W, Huang X, Fan X, Yan J, Luan J. Progress in evaluating the status of hepatitis C infection based on the functional changes of hepatic stellate cells (Review). Mol Med Rep 2020; 22:4116-4124. [PMID: 33000255 DOI: 10.3892/mmr.2020.11516] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 08/18/2020] [Indexed: 11/06/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a global public health problem. Cirrhosis and hepatocellular carcinoma are the main causes of death in patients with chronic hepatitis C (CHC) infection. Liver fibrosis is an important cause of cirrhosis and end‑stage liver disease after CHC infection. Along with the course of infection, liver fibrosis exhibits a progressive exacerbation. Hepatic stellate cells (HSCs) are involved in both physiological and pathological processes of the liver. During the chronic liver injury process, the activated HSCs transform into myofibroblasts, which are important cells in the development of liver fibrosis. At present, HCV infection still lacks specific markers for the accurate detection of the disease condition and progression. Therefore, the present review focused on HSCs, which are closely related to HCV‑infected liver fibrosis, and analyzed the changes in the HSCs, including their surface‑specific markers, cytokine production, activation, cell function and morphological structure. The present review aimed to propose novel diagnostic markers, at both the cellular and molecular level, which would be of great significance for the timely diagnosis of the disease. According to this aim, the characteristic changes of HSCs during HCV infection were reviewed in the present article.
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Affiliation(s)
- Wei Wang
- Department of Blood Transfusion Medicine, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Xuelian Huang
- Department of Blood Transfusion Medicine, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Xuzhou Fan
- Department of Blood Transfusion Medicine, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Jingmei Yan
- Department of Blood Transfusion Medicine, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Jianfeng Luan
- Department of Blood Transfusion Medicine, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, Jiangsu 210002, P.R. China
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14
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Beaumont E, Joël Clément B, Guérin V, Chopin L, Roch E, Gomez-Escobar E, Roingeard P. Mixing particles from various HCV genotypes increases the HBV-HCV vaccine ability to elicit broadly cross-neutralizing antibodies. Liver Int 2020; 40:1865-1871. [PMID: 32458507 DOI: 10.1111/liv.14541] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 05/06/2020] [Accepted: 05/19/2020] [Indexed: 12/13/2022]
Abstract
The development of a safe, effective and affordable prophylactic vaccine against hepatitis C virus (HCV) remains a medical priority. Hepatitis B-C subviral envelope particles, which could be produced by industrial procedures adapted from those established for the hepatitis B virus vaccine, appear promising for use for this purpose. The prototype HBV-HCV bivalent vaccine-bearing genotype 1a HCV envelopes can induce neutralizing antibodies against this genotype, but is less effective against other genotypes. We show here, in a small animal model, that the use of a set of vaccine particles harbouring envelopes from different HCV genotypes in various association strategies can induce broad neutralizing protection or an optimized protection against a particular genotype prevalent in a given region, such as genotype 4 in Egypt. This vaccine could help to control the hepatitis C epidemic worldwide.
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Affiliation(s)
- Elodie Beaumont
- INSERM U1259, Université de Tours and CHRU de Tours, Tours, France
| | | | - Vanessa Guérin
- INSERM U1259, Université de Tours and CHRU de Tours, Tours, France
| | - Lucie Chopin
- INSERM U1259, Université de Tours and CHRU de Tours, Tours, France
| | - Emmanuelle Roch
- INSERM U1259, Université de Tours and CHRU de Tours, Tours, France
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15
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Roingeard P, Beaumont E. Hepatitis C Vaccine: 10 Good Reasons for Continuing. Hepatology 2020; 71:1845-1850. [PMID: 32060946 DOI: 10.1002/hep.31182] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 02/11/2020] [Indexed: 12/12/2022]
Affiliation(s)
- Philippe Roingeard
- Faculté de Médecine, INSERM U1259, Université de Tours and CHRU de Tours, Tours, France
| | - Elodie Beaumont
- Faculté de Médecine, INSERM U1259, Université de Tours and CHRU de Tours, Tours, France
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Human genetics of HCV infection phenotypes in the era of direct-acting antivirals. Hum Genet 2020; 139:855-863. [PMID: 32100095 DOI: 10.1007/s00439-020-02136-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 02/10/2020] [Indexed: 12/14/2022]
Abstract
The recent introduction of direct-acting antivirals (DAAs) has revolutionized hepatitis C virus (HCV) therapy by improving virus eradication rates to over 90% in most patient groups. However, the impact of DAAs on global disease burden is currently limited, and a large number of chronically infected individuals remain at risk of developing liver complications, such as liver cirrhosis and hepatocellular carcinoma (HCC). The identification of patients at risk of liver complications and a greater understanding of the biological mechanisms involved in HCV disease progression might improve disease control. Recent genome-wide association and exome sequencing studies have identified several host genetic variants influencing the progression of liver fibrosis and the development of HCC associated with HCV infection and are reviewed here. Interestingly, some of the genetic variants associated with those HCV-associated liver complications were also associated with the clinical course of non-viral chronic hepatitis. Future challenges include the incorporation of this genetic information into clinical risk models for personalized disease management and the study of emerging phenotypes such as liver fibrosis regression and HCC development after HCV eradication.
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Zoratti MJ, Siddiqua A, Morassut RE, Zeraatkar D, Chou R, van Holten J, Xie F, Druyts E. Pangenotypic direct acting antivirals for the treatment of chronic hepatitis C virus infection: A systematic literature review and meta-analysis. EClinicalMedicine 2020; 18:100237. [PMID: 31922124 PMCID: PMC6948236 DOI: 10.1016/j.eclinm.2019.12.007] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 12/02/2019] [Accepted: 12/05/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recent approval and adoption of pangenotypic direct acting antivirals (DAAs) necessitated a revision of the 2015 World Health Organization guidelines for the management of persons with hepatitis C virus (HCV) infection. METHODS We searched MEDLINE, EMBASE, CENTRAL, and relevant conference proceedings to identify randomized and non-randomized trials, as well as prospective observational studies of DAAs. The proportions of persons with events were pooled for sustained virological response at 12 weeks post-treatment (SVR12), discontinuations due to adverse events (DAEs), serious adverse events (SAEs), and all-cause mortality. Analyses were stratified by HCV genotype and antiviral treatment experience, with subgroup analyses based on presence of cirrhosis and HIV-HCV coinfection. FINDINGS The evidence base consisted of 238 publications describing 142 studies. In the overall analysis, which included all persons irrespective of treatment experience or comorbidities, the pooled proportion achieving SVR12 exceeded 0.94 for all pangenotypic regimens across genotypes 1, 2, and 4. Some heterogeneity may have led to lower SVR rates in persons with genotype 3 infection. High SVR12 (>0.90) was observed in persons with genotype 1 infection with cirrhosis, though evidence varied and was limited for genotypes 2-4. Evidence was sparse for persons with HIV-HCV coinfection. All regimens were associated with small proportions of persons with DAEs, SAEs, or all-cause mortality. INTERPRETATION Based on this and other supporting evidence, the WHO issued updated guidelines with a conditional recommendation, based on moderate quality evidence, for the use of pangenotypic DAA regimens for persons with chronic HCV infection aged 18 years and older (July 2018). FUNDING This study was funded by the World Health Organization.
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Affiliation(s)
- Michael J. Zoratti
- Zoratti HEOR Consulting Inc., Oakville, Ontario, Canada
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Ayesha Siddiqua
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
| | - Rita E. Morassut
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Dena Zeraatkar
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Roger Chou
- Department of Medical Informatics and Clinical Epidemiology, Division of General Internal Medicine and Geriatrics, Oregon Health and Science University, Portland, Oregon, USA
| | - Judith van Holten
- Department of HIV and Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | - Feng Xie
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Eric Druyts
- Pharmalytics Group, Vancouver, British Columbia, Canada
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