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Elbadry M, Badawi M, Youssef N, Duracinsky M, Saleh SA, Funk A, Elessawy H, Rumpler E, Sayed K, Vasiliu A, Madec Y, Fontanet A, El-Kassas M. Impact of treating chronic hepatitis C with direct acting antivirals on health-related quality of life: a real-life Egyptian experience. EGYPTIAN LIVER JOURNAL 2024; 14:14. [DOI: 10.1186/s43066-024-00317-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 02/14/2024] [Indexed: 04/03/2025] Open
Abstract
Abstract
Background
Chronic hepatitis C virus (HCV) infection negatively impacts health-related quality of life (HRQL). We aimed to assess patient-reported outcomes (PROs) to evaluate the impact of treating chronic HCV with directly acting antivirals (DAAs) on HRQL.
Methods
PROs were assessed prospectively using the PROQOL-HCV questionnaire before (week 0), at the end (week 12), and after DAA treatment at week 24. HRQL was measured in six different dimensions: physical health, emotional health, future uncertainty, intimate relationships, social health, and cognitive functions.
Results
A total of 500 HCV patients receiving DAAs were enrolled; of them, 399 were included in the analysis (median age 57 years, 59% females). HRQL increased significantly between baseline, end of treatment, and week 24 for all dimensions (P < 0.001), more often for physical health in females compared to males (OR = 1.69, 95% CI = 1.1–2.5), for future uncertainty among people with diabetes (1.75, 95% CI = 1.05–2.9), and for cognitive functions among obese patients (OR = 1.98; 95% CI = 1.1–3.3). Improvement in HRQL was less common for intimate relations among females (OR = 0.47; 95% CI = 0.3–0.7) and in patients with cirrhosis (OR = 0.35, 95% CI = 0.1–0.7). Improvement in HRQL was consistently higher in < 60 years compared to ≥ 60 years patients, with a significant difference in social health (P < 0.001) and future uncertainty (P < 0.049) HRQL domains.
Conclusion
HRQL improved with DAA therapy, a relation consistent across all HRQL dimensions up to 12 weeks after the end of treatment.
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Tronina O, Brzdęk M, Zarębska-Michaluk D, Dybowska D, Lorenc B, Janczewska E, Mazur W, Parfieniuk-Kowerda A, Piekarska A, Krygier R, Klapaczyński J, Berak H, Jaroszewicz J, Garlicki A, Tomasiewicz K, Citko J, Flisiak R. Rescue Therapy after Failure of HCV Antiviral Treatment with Interferon-Free Regimens. Viruses 2023; 15:677. [PMID: 36992388 PMCID: PMC10055110 DOI: 10.3390/v15030677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/01/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
Direct-acting antivirals (DAA) regimens have provided hope for eliminating hepatitis C virus (HCV) infection. Patients following ineffective therapy with DAA, especially those previously treated with inhibitors of non-structural protein 5A (NS5A), remain a challenge. The study aimed to assess the effectiveness of DAA pangenotypic options in patients after failure of NS5A containing genotype-specific regimens. The analysis included 120 patients selected from the EpiTer-2 database with data on 15675 HCV-infected individuals treated with IFN-free therapies from 1 July 2015 to 30 June 2022 at 22 Polish hepatology centres. The majority of them were infected with genotype (GT) 1b (85.8%) and one-third was diagnosed with fibrosis F4. Among the rescue pangenotypic regimens, the most commonly used was the sofosbuvir/velpatasvir (SOF/VEL) ± ribavirin (RBV) combination. The sustained virologic response, which was a measure of treatment effectiveness, was achieved by 102 patients, resulting in cure rate of 90.3% in the per protocol analysis. All 11 non-responders were infected with GT1b, 7 were diagnosed with cirrhosis, and 9 were treated with SOF/VEL±RBV. We demonstrated the high effectiveness of the pangenotypic rescue options in patients after genotype specific NS5A-containing regimens failures, identifying cirrhosis as a negative prognostic factor of treatment effectiveness.
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Affiliation(s)
- Olga Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, 25-317 Kielce, Poland
| | - Dorota Zarębska-Michaluk
- Collegium Medicum, Jan Kochanowski University, 25-317 Kielce, Poland
- Department of Infectious Diseases, Voivodship Hospital, 25-317 Kielce, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Ewa Janczewska
- Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, 40-055 Katowice, Poland
- ID Clinic, Hepatology Outpatient Department, 41-400 Bytom, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Medical University of Silesia, 41-500 Chorzów, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, 90-419 Łódź, Poland
| | - Rafał Krygier
- Outpatients Hepatology Department, State University of Applied Sciences, 62-510 Konin, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, 02-241 Warszawa, Poland
| | - Hanna Berak
- Outpatient Clinic, Hospital for Infectious Diseases, 02-091 Warsaw, Poland
| | - Jerzy Jaroszewicz
- Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, 41-902 Bytom, Poland
| | - Aleksander Garlicki
- Department of Infectious and Tropical Diseases, Jagiellonian University Collegium Medicum, 30-252 Kraków, Poland
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland
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Santos EM, Silva JDM, Barbosa AN, Pontes GS. Clinico-epidemiological and sociodemographic profile of patients with hemophilia in the Brazilian Amazon: High prevalence of hepatitis C infection and its possible corrrelation with inhibitor development. Front Public Health 2022; 10:963790. [PMID: 36159250 PMCID: PMC9493701 DOI: 10.3389/fpubh.2022.963790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 08/19/2022] [Indexed: 01/24/2023] Open
Abstract
Hemophilia is a recessive genetic disease caused by a mutation on the X chromosome that has been linked to a high risk of transfusion-transmitted infections, especially sexually transmitted infections. The purpose of this retrospective study was to characterize the clinical and epidemiological profile and describe the prevalence of sexually transmitted viral infections in patients with hemophilia in the Northern Brazilian state of Amazonas. We assessed clinical, laboratory and sociodemographic data of hemophiliac patients (n = 311) for the period 2011-2019. The majority of the study population was composed of people with a low level of education aged 21-30 years old. The prevalence of HCV, HBV, and HTLV-1/2 infections among the study population were 10.52, 0.52, and 1.05%, respectively. No HIV infection was found among the patients. Between 2011 and 2015 the prevalence of HCV increased by over 100% and the incidence peaked in 2013. The severe hemophilia was associated with the presence of inhibitor factor (Odds Ratio [OD] 9.83; 95% IC: 3.41-27.62, p < 0.0001) or target joint (OD 6.59; 95% IC: 3.27-13.34, p < 0.0001). The presence of inhibitor was positive and significantly correlated with HCV infection (r = 1.00, p < 0.0001). Our results showed that HCV infection is highly prevalent in patients with hemophilia and might be involved in the development of inhibitors. Thus, these data provide new insights into the clinical and epidemiological profile of patients suffering from hemophilia in the Northern Brazilian state of Amazonas.
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Affiliation(s)
- Enzo Miranda Santos
- Programa de Pós-Graduação em Hematologia, Universidade Do Estado Do Amazonas (UEA), Manaus, Amazonas, Brazil
| | - Jean de Melo Silva
- Programa de Pós-Graduação em Imunologia Básica e Aplicada—PPGIBA, Instituto de Ciências Biológicas, Universidade Federal Do Amazonas—UFAM, Manaus, Amazonas, Brazil
| | - Anderson Nogueira Barbosa
- Laboratório de Virologia e e Imunologia, Institituto Nacional de Pesquisa da Amazônia (INPA), Manaus, Amazonas, Brazil
| | - Gemilson Soares Pontes
- Programa de Pós-Graduação em Hematologia, Universidade Do Estado Do Amazonas (UEA), Manaus, Amazonas, Brazil,Programa de Pós-Graduação em Imunologia Básica e Aplicada—PPGIBA, Instituto de Ciências Biológicas, Universidade Federal Do Amazonas—UFAM, Manaus, Amazonas, Brazil,Laboratório de Virologia e e Imunologia, Institituto Nacional de Pesquisa da Amazônia (INPA), Manaus, Amazonas, Brazil,*Correspondence: Gemilson Soares Pontes
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Efficacy and Safety of a Botanical Formula Fuzheng Huayu for Hepatic Fibrosis in Patients with CHC: Results of a Phase 2 Clinical Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:4494099. [PMID: 35873630 PMCID: PMC9307334 DOI: 10.1155/2022/4494099] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 06/15/2022] [Indexed: 12/09/2022]
Abstract
Background. Hepatitis C virus (HCV) is a common cause of progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma worldwide. Despite the availability of effective direct-acting antivirals, patients often have significant hepatic fibrosis at the time of diagnosis due to delay in diagnosis and comorbidities which promote fibrogenesis. Thus, antifibrotic agents represent an attractive adjunctive therapy. Fuzheng Huayu (FZHY), a traditional Chinese medicine botanical formulation, has been used as an antifibrotic agent in chronic HBV infection. Our aim was to assess FZHY in patients with HCV infection and active viremia. Method. We randomized 118 patients with active viremia from 8 liver centers in the U.S. to receive oral FZHY (n = 59) or placebo (n = 59) for 48 weeks. Efficacy was assessed by histopathologic changes at the end of therapy. A subset of biopsies was further analyzed using qFibrosis to detect subtle changes in fibrosis in different zones of the hepatic lobules. Results. FZHY was well tolerated and safe. Patients with baseline Ishak fibrosis stages F3 and F4 had better response rates to FZHY than patients with baseline F0–F2 (
). qFibrosis zonal analysis showed significant improvement in fibrosis in all zones in patients with regression of the fibrosis stage. Conclusions. FZHY produced antifibrotic effects in patients with baseline Ishak F3 and F4 fibrosis stages. Reduction in fibrosis severity was zonal and correlated with the severity of inflammation. Based on its tolerability, safety, and efficacy, FZHY should be further investigated as a therapy in chronic liver diseases because of its dual anti-inflammatory and antiibrotic properties. Lay Summary. This is the first US-based, multicenter and placebo-controlled clinical trial that shows statistically significant reduction in fibrosis in patients with active HCV using an antifibrotic botanical formula. This has important implications as there is an immediate need for effective antifibrotic agents in treating many chronic diseases including NASH that lead to scarring of the liver. With artificial intelligence-based methodology, qFibrosis, we may provide a more reliable way to assess the FZHY as a therapy in chronic liver diseases because of its dual anti-inflammatory and antifibrotic properties.
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Tergast TL, Blach S, Tacke F, Berg T, Cornberg M, Kautz A, Manns M, Razavi H, Sarrazin C, Serfert Y, van Thiel I, Zeuzem S, Wedemeyer H. Updated epidemiology of hepatitis C virus infections and implications for hepatitis C virus elimination in Germany. J Viral Hepat 2022; 29:536-542. [PMID: 35357770 DOI: 10.1111/jvh.13680] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 02/24/2022] [Accepted: 03/08/2022] [Indexed: 12/09/2022]
Abstract
In 2014, an analysis was conducted to evaluate the hepatitis C virus (HCV) epidemiology and disease burden in Germany. Since then, there have been considerable developments in HCV management such as the implementation of direct acting antivirals. The aim of this analysis was to assess the recent data available for Germany, establish an updated 2020 HCV prevalence and cascade of care and evaluate the impact of what-if scenarios on the future burden of disease using modelling analysis. A dynamic Markov model was used to forecast the HCV disease burden in Germany. Model inputs were retrieved through literature review, unpublished sources and expert input. Next, three "what-if" scenarios were developed to evaluate the status quo, COVID-19 pandemic, and steps needed to achieve the WHO targets for elimination. At the beginning of 2020, there were 189,000 (95% UI: 76,700-295,000) viremic infections in Germany, a decline of more than 85,000 viremic infections since 2012. Annual treatment starts went down since 2015. Compared with 2019, the COVID-19 pandemic resulted in a further 11% decline in 2020. If this continues for two years, it could result in 110 excess HCC cases and 200 excess liver related deaths by 2030. To achieve the WHO targets, 81,200 people need to be diagnosed, with 118,600 initiated on treatment by 2030. This could also avert 1,020 deaths and 720 HCC cases between 2021 and 2030. Germany has made strides towards HCV elimination, but more efforts are needed to achieve the WHO targets by 2030.
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Affiliation(s)
- Tammo L Tergast
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | | | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Leberstiftungs-GmbH Deutschland, Hannover, Germany
| | | | - Michael Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Leberstiftungs-GmbH Deutschland, Hannover, Germany
| | | | - Christoph Sarrazin
- Department of Internal Medicine and Liver Center, St. Josefs-Hospital Wiesbaden, Wiesbaden, Germany.,Viral Hepatitis Research Group, Goethe-University Hospital Frankfurt, Frankfurt, Germany
| | | | | | - Stefan Zeuzem
- Department of Medicine, University Hospital, Frankfurt, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Leberstiftungs-GmbH Deutschland, Hannover, Germany
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6
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Abstract
The development of direct-acting antivirals (DAA) has revolutionized the treatment of chronic hepatitis C, enabling cure of hepatitis C virus (HCV) infection in more than 95% of cases. There are essentially no contraindications, so almost any patient can now be successfully treated. The result is the prevention or amelioration of cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Consequently, the 2020 Nobel Prize in Medicine and Physiology was awarded for the discovery of HCV. Due to the high efficacy of therapy, even global HCV elimination is conceivable even without a vaccine. Here, we would like to venture a SWOT analysis of current HCV therapies aimed at HCV elimination.
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Affiliation(s)
- Markus Cornberg
- Department of Gastroenterology, Hepatology, and Endocrinology, 9177Hannover Medical School Hannover, Hannover, Germany.,Centre for Individualised Infection Medicine (CiiM), a joint venture of Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner-Site Hannover-Braunschweig, Hannover, Germany
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7
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Abstract
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
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Affiliation(s)
- Michael P. Manns
- grid.10423.340000 0000 9529 9877Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- grid.10423.340000 0000 9529 9877Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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8
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Ullah N, Kakakhel MA, Bai Y, Xi L, Khan I, Kalra BS, Kumar T, Ahmad H, Shah M, Guanlan L, Zhang C. Prevalence of active HCV infection and genotypic distribution among the general population of district Mardan, Pakistan. BRAZ J BIOL 2021; 83:e244977. [PMID: 34287506 DOI: 10.1590/1519-6984.244977] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 12/04/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) is the serious global public health burden of liver disease. Approximately 170 million people in the world are infected with (HCV). In Pakistan, where the disease has high occurrence rate. The present study envisages an up-to-date prevalence of HCV and genotypic distribution in the general population of Mardan District, Khyber Pakhtunkhwa (KP), Pakistan. The blood samples from 6,538 individuals including 3,263 males and 3,275 females were analyzed for hepatitis C surface antigen by Immuno-chromatographic test (ICT), Enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (PCR). It was found that 396 (12.13%) out of 3263 individuals contained antibodies in their blood against HCV, while among the different age groups, the highest incidences of HCV antibodies were found in the 31-40 age group (11.01%). The ICT positive samples were further screened by nested PCR to determine the existence of active HCV-RNA. It was identified that 7.11% (3263) of the total population (6538) tested was positive, among which the 461 (14.07%) females possessed antibodies in their blood against HCV. Our data showed total HCV infection in the investigated population was 5.78%. Higher percentage of HCV prevalence was detected in males than females in the age group 31-40 and 41-50. To compare the prevalence of HCV genotypes age-wise in male and female genotype 3a was found most prevalent genotype followed by 1a, 2a and 3b, respectively.
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Affiliation(s)
- N Ullah
- Lanzhou University, School of Life Sciences, MOE Key Laboratory of Cell Activities and Stress Adaptations, Lanzhou, Gansu, China
| | - M A Kakakhel
- Lanzhou University, School of Life Sciences, MOE Key Laboratory of Cell Activities and Stress Adaptations, Lanzhou, Gansu, China
| | - Y Bai
- Lanzhou University, School of Life Sciences, MOE Key Laboratory of Cell Activities and Stress Adaptations, Lanzhou, Gansu, China
| | - L Xi
- Lanzhou University, School of Life Sciences, MOE Key Laboratory of Cell Activities and Stress Adaptations, Lanzhou, Gansu, China
| | - I Khan
- Lanzhou University, School of Life Sciences, MOE Key Laboratory of Cell Activities and Stress Adaptations, Lanzhou, Gansu, China
| | - B S Kalra
- Virtual University of Pakistan, Department of Bioinformatics and Computational Biology, Lahore, Pakistan
| | - T Kumar
- Ministry of Agriculture, Key Laboratory of Grassland Livestock Industry Innovation, State Key Laboratory of Grassland Agro-Ecosystems, Lanzhou, P.R. China.,Lanzhou University, College of Pastoral Agriculture Science and Technology, Lanzhou, P.R. China
| | - H Ahmad
- Hazara University Mansehra, Department of Genetics, Mansehra, Pakistan
| | - M Shah
- University of Swat, Centre for Animal Sciences and Fisheries, Swat, Khyber Pakhtunkhwa, Pakistan
| | - L Guanlan
- Lanzhou University, School of Life Sciences, MOE Key Laboratory of Cell Activities and Stress Adaptations, Lanzhou, Gansu, China
| | - C Zhang
- Lanzhou University, School of Life Sciences, MOE Key Laboratory of Cell Activities and Stress Adaptations, Lanzhou, Gansu, China
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Real-World Outcomes in Historically Underserved Patients with Chronic Hepatitis C Infection Treated with Glecaprevir/Pibrentasvir. Infect Dis Ther 2021; 10:2203-2222. [PMID: 34125405 PMCID: PMC8572930 DOI: 10.1007/s40121-021-00455-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 05/06/2021] [Indexed: 12/22/2022] Open
Abstract
Introduction Glecaprevir/pibrentasvir is approved for treating chronic hepatitis C virus (HCV) genotypes (GT) 1–6. We evaluated real-world effectiveness, safety, and patient-reported outcomes of glecaprevir/pibrentasvir in underserved patient populations, focusing on persons who use drugs infected with HCV. Methods Data were pooled from nine countries (13 November 2017–31 January 2020). Patients had HCV GT1–6, with or without compensated cirrhosis, with or without prior HCV treatment and received glecaprevir/pibrentasvir consistent with local label at their physician’s discretion. Patients with prior direct-acting antiviral exposure were excluded from efficacy and quality-of-life analyses. The percentage of patients achieving sustained virologic response at post-treatment week 12 (SVR12) was assessed. Mean changes from baseline to SVR12 visit in 36-Item Short-Form Health Survey mental and physical component summary scores were reported. Safety was assessed in patients receiving at least one dose of glecaprevir/pibrentasvir. Results Of 2036 patients, 1701 (83.5%) received 8-week glecaprevir/pibrentasvir. In 1684 patients with sufficient follow-up, SVR12 rates were 98.0% (1651/1684) overall, 98.1% (1432/1459) in 8-week treated patients, 97.0% (519/535) in persons who use drugs, and greater than 95% across subgroups. Mean changes from baseline in mental and physical component summary scores were 3.7 and 2.4, respectively. One glecaprevir/pibrentasvir-related serious adverse event was reported; six glecaprevir/pibrentasvir-related adverse events led to discontinuation. Conclusions Glecaprevir/pibrentasvir was highly effective, well tolerated, and improved quality of life in HCV-infected persons who use drugs and other underserved patients. Trial Registration These multinational post-marketing observational studies are registered with ClinicalTrials.gov, number NCT03303599. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00455-1.
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10
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Stvilia K, Vephkvadze N, Gamkrelidze A, Khonelidze I, Getia V, Tsereteli M, Gvinjilia L, Kuchuloria T. Hepatitis C treatment uptake among patients who have received methadone substitution treatment in the Republic of Georgia. Public Health 2021; 195:42-50. [PMID: 34051674 DOI: 10.1016/j.puhe.2021.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 03/16/2021] [Accepted: 03/21/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVES There is a dearth of research on hepatitis C virus (HCV) treatment uptake among people who inject drugs (PWIDs) and receive methadone substitution treatment (MST) in Eastern Europe and Central Asia countries. This study contributed to addressing that gap. We examined and identified factors that may affect HCV treatment uptake among PWID who received MST in the Republic of Georgia. STUDY DESIGN The design of the study is retrospective cohort study. METHODS We conducted HCV care cascade analysis by matching the data from the web-based national hepatitis C program registry (ELIM C) and the MST treatment database between January 1, 2015, and December 31, 2018. Using the World Health Organization's (WHO) Consensus HCV cascade of care (CoC) global instrument, we assessed the progress made toward the country's 2020 and WHO's 2030 hepatitis C elimination targets for the subpopulation of MST patients. RESULTS Overall, 10,498 individuals have been dispensed methadone during the study period. A total of 6828 MST beneficiaries had HCV screening, of whom 5843 (85.6%) tested positive; 5476 (93.7%) were tested for HCV viremia, and 5275 (96.3%) were confirmed with chronic HCV infection. More than 75% (n = 4000) of HCV-infected MST patients initiated HCV treatment, and 3772 (94.3%) completed the treatment. Of those eligible for sustained virologic response assessment, 71.0% (2641/3715) were evaluated, and the reported cure rate was 96.1% (2537). The study found the odds of patients starting HCV treatment differed by the type of facility they were screened at and whether they were registered as PWID at the screening sites. The patients screened at centers with integrated HCV treatment services had higher treatment uptake rates than those screened at other centers. CONCLUSIONS As the cumulative HCV treatment uptake and cure rates among MST patients with HCV infection are high (75.8% and 96.1%, respectively), the MST patients might become the first microelimination target population in which hepatitis C elimination will be achieved in Georgia. The study found the type of screening facility and whether MST patients registered themselves as PWID or not had significant effects on MST patients starting HCV treatment. At the same time, the study did not find gender and age to be significant predictors of MST patients starting HCV treatment. MST patients used different types of health facilities to get screened for HIV. Many of them did not register themselves as PWID when screened for HIV. The existence of only a few harm reduction sites with integrated HCV treatment services, a high level of stigma, and the criminalization of drug use might have incentivized MST patients to self-navigate across the HCV care continuum with the rest of the population. The implementation of focused, harm reduction, integrated HCV treatment with good peer and professional adherence support at treatment sites could help reach the hepatitis C elimination goals among MST patients.
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Affiliation(s)
- Ketevan Stvilia
- National Center for Disease Control and Public Health, Georgia.
| | | | | | - Irma Khonelidze
- National Center for Disease Control and Public Health, Georgia
| | - Vladimer Getia
- National Center for Disease Control and Public Health, Georgia
| | - Maia Tsereteli
- National Center for Disease Control and Public Health, Georgia
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11
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Bajis S, Applegate TL, Grebely J, Matthews GV, Dore GJ. Novel Hepatitic C Virus (HCV) Diagnosis and Treatment Delivery Systems: Facilitating HCV Elimination by Thinking Outside the Clinic. J Infect Dis 2021; 222:S758-S772. [PMID: 33245354 DOI: 10.1093/infdis/jiaa366] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The World Health Organization has set a goal to eliminate hepatitis C virus (HCV) infection as public health threat by 2030. Although the advent of highly effective and tolerable direct-acting antiviral therapy has paved the way for HCV elimination, most people with HCV infection remain undiagnosed and untreated globally, with striking disparities between high-income and low- to middle-income countries. Novel decentralized and cost-effective "test-and-treat" strategies are critically needed to identify the millions of people unaware of their status and link them to treatment.
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Affiliation(s)
- Sahar Bajis
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
| | - Tanya L Applegate
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
| | - Jason Grebely
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
| | - Gail V Matthews
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
| | - Gregory J Dore
- The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia
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12
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Abstract
Parenteral transmission is the major route of hepatitis C virus transmission in adults; however, vertical transmission is most common in children. There are several factors that have been shown to be associated with vertical transmission of hepatitis C virus, including hepatitis C virus RNA, human immunodeficiency virus coinfection, and peripheral blood mononuclear cell infection. As there is no effective vaccine to prevent hepatitis C virus infection, and there are no human data describing the safety of the new direct acting antiviral agents in pregnancy, the only preventive strategy for vertical transmission is to treat the hepatitis C virus infection before becoming pregnant. Direct acting antiviral agents are interferon-free, and many are also ribavirin-free. Based on animal studies, sofosbuvir plus ledipasvir may be the best safety profile during pregnancy for now; however, it is too early to recommend treating hepatitis C virus-infected pregnant women with these direct acting antiviral agents currently.
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HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection. Viruses 2020; 12:v12111241. [PMID: 33142675 PMCID: PMC7692400 DOI: 10.3390/v12111241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/19/2020] [Accepted: 10/27/2020] [Indexed: 11/25/2022] Open
Abstract
HIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, we evaluated the correlation of APD with TSI, and its ability to infer TSI via a linear model. We additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with TSI (R2 = 0.33) and could predict TSI (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to E2-NS2 further improved accuracy (ROC-AUC = 0.85, R2 = 0.54, mean absolute error = 1.38 years). Genetic diversity in HCV correlates with TSI and is a proxy for infection recency and TSI, even several years post-infection.
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Houri I, Horowitz N, Katchman H, Weksler Y, Miller O, Deutsch L, Shibolet O. Emergency department targeted screening for hepatitis C does not improve linkage to care. World J Gastroenterol 2020; 26:4878-4888. [PMID: 32921964 PMCID: PMC7459203 DOI: 10.3748/wjg.v26.i32.4878] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 06/13/2020] [Accepted: 08/09/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease worldwide. New treatments for HCV revolutionized management and prompted the world health organization to set the goal of viral elimination by 2030. These developments strengthen the need for HCV screening in order to identify asymptomatic carriers prior to development of chronic liver disease and its complications. Different screening strategies have been attempted, most targeting high-risk populations. Previous studies focusing on patients arriving at emergency departments showed a higher prevalence of HCV compared to the general population.
AIM To identify previously undiagnosed HCV carriers among high risk emergency room attendees and link them to care for anti-viral treatment.
METHODS In this single center prospective study, persons visiting the emergency department in an urban hospital were screened by a risk factor-specific questionnaire. The risk factors screened for were exposure to blood products or organ transplantation before 1992; origins from countries with high prevalence of HCV; intravenous drug use; human immunodeficiency virus carriers; men who have sex with men; those born to HCV-infected mothers; prior prison time; and chronic kidney disease. Those with at least one risk factor were tested for HCV by serum for HCV antibodies, a novel oral test from saliva (OraQuick®) or both.
RESULTS Five hundred and forty-one participants had at least one risk factor and were tested for HCV. Eighty four percent of all study participants had only one risk factor. Eighty five percent of participants underwent OraQuick® testing, 34% were tested for serum anti-HCV antibodies, and 25% had both tests. 3.1% of patients (17/541) had a positive result, compared to local population incidence of 1.96%. Of these, 82% were people who inject drugs (current or former), and 64% served time in prison. One patient had a negative HCV-RNA, and two patients died from non-HCV related reasons. On review of past medical records, 12 patients were found to have been previously diagnosed with HCV but were unaware of their carrier state. At 1-year follow-up none of the remaining 14 patients had completed HCV-RNA testing, visited a hepatology clinic or received anti-viral treatment.
CONCLUSION Targeted high-risk screening in the emergency department identified undiagnosed and untreated HCV carriers, but did not improve treatment rates. Other strategies need to be developed to improve linkage to care in high risk populations.
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Affiliation(s)
- Inbal Houri
- Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
| | - Noya Horowitz
- Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 6423906, Israel
| | - Helena Katchman
- Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
| | - Yael Weksler
- Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
| | - Ofer Miller
- Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
| | - Liat Deutsch
- Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
| | - Oren Shibolet
- Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 6423906, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
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15
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Şahin AR, Erdoğan A, Gisi K, İspiroğlu M, Ateş S, Okyay RA, Nazik S, Kantarçeken B. Can family physicians have a role in eradication of hepatitis c infection? TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:393-399. [PMID: 32519959 DOI: 10.5152/tjg.2020.19913] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND/AIMS Hepatitis C Virus (HCV) infection is an important global public health problem. The application of screening programs is important for the elimination of HCV in addition to DAA therapies. The aim of this study was to measure the knowledge, attitudes and behaviours of family physicians, who are important in screening programs for the diagnosis, natural history, and treatment of HCV infection. MATERIALS AND METHODS This cross-sectional study aimed to measure the knowledge levels in respect of HCV screening, diagnosis, natural history and treatment, of family physicians working nationwide in Turkey, through a survey. RESULTS The most common reason to perform an anti-HCV test stated by 70.9% (n:420) of the participants was the mandatory screening program before marriage. Of the participants included in the study, 29.6% (n=175) had encountered anti-HCV test positivity at least once within the last year, and of these, 15.4% (n=27) had no knowledge of whether the patient went to a higher level center for further diagnosis, while 58.9% (n=103) did not know the disease stage. In response to questions about current drug options for hepatitis C infection, 14.5% were aware of DAA and 34.8% of participitant reported interferon+ ribavirin. CONCLUSION Family physicians have gaps in their knowledge of the screening, natural history and treatment of HCV infection. The results of this study show that HCV training plans for family physicians should cover all aspects of the infection, and emphasize the necessity for the establishment of guideline-based screening recommendations.
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Affiliation(s)
- Ahmet Rıza Şahin
- Department of Infectious Diseases and Clinical Microbiology, Kahramanmaraş Sütçü İmam University School of Medicine, Kahramanmaraş, Turkey
| | - Ayşegül Erdoğan
- Department of Public Health, Kahramanmaraş Sütçü İmam University School of Medicine, Kahramanmaraş, Turkey
| | - Kadir Gisi
- Department of Gastroenterology, Kahramanmaraş Sütçü İmam University School of Medicine, Kahramanmaras, Turkey
| | - Murat İspiroğlu
- Department of Gastroenterology, Kahramanmaraş Sütçü İmam University School of Medicine, Kahramanmaras, Turkey
| | - Selma Ateş
- Department of Infectious Diseases and Clinical Microbiology, Kahramanmaraş Sütçü İmam University School of Medicine, Kahramanmaraş, Turkey
| | - Ramazan Azim Okyay
- Department of Public Health, Kahramanmaraş Sütçü İmam University School of Medicine, Kahramanmaraş, Turkey
| | - Selçuk Nazik
- Department of Infectious Diseases and Clinical Microbiology, Kahramanmaraş Sütçü İmam University School of Medicine, Kahramanmaraş, Turkey
| | - Bülent Kantarçeken
- Department of Gastroenterology, Kahramanmaraş Sütçü İmam University School of Medicine, Kahramanmaras, Turkey
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16
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Martinello M, Bajis S, Dore GJ. Progress Toward Hepatitis C Virus Elimination: Therapy and Implementation. Gastroenterol Clin North Am 2020; 49:253-277. [PMID: 32389362 DOI: 10.1016/j.gtc.2020.01.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The World Health Organization has called for the elimination of hepatitis C virus (HCV) as a public health threat by 2030. Highly effective direct-acting antiviral agents provide the therapeutic tools required for elimination. In the absence of a vaccine, HCV elimination will require enhanced primary prevention and an increase in the proportions of people diagnosed and treated. Given that globally only 20% of people with chronic HCV are diagnosed, and around 5% have initiated HCV treatment, the task ahead is enormous. But, global public health needs optimism, and countries currently on track for HCV elimination provide a pathway forward.
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Affiliation(s)
- Marianne Martinello
- Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Sydney, Sydney, Australia.
| | - Sahar Bajis
- Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Sydney, Sydney, Australia
| | - Gregory J Dore
- Viral Hepatitis Clinical Research Program, The Kirby Institute, UNSW Sydney, Sydney, Australia
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17
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Olmos-Martínez JM, Hernández JL, Fábrega E, Olmos JM, Crespo J, González-Macías J. Bone mineral density and trabecular bone score in treatment-naïve patients with non-cirrhotic hepatitis C virus infection. Arch Osteoporos 2020; 15:72. [PMID: 32399944 DOI: 10.1007/s11657-020-00752-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 05/05/2020] [Indexed: 02/03/2023]
Abstract
UNLABELLED We studied 112 treatment-naïve chronic HCV patients without cirrhosis, and we found that, especially HCV+ postmenopausal women, they had lower TBS and BMD values than healthy controls. This suggests that HCV infection is an independent risk factor for osteoporosis, and therefore, screening for osteoporosis in postmenopausal HCV+ women should be considered. PURPOSE To know whether patients in earlier stages of chronic HCV infection are at increased risk of developing low bone mass and bone microarchitectural changes and whether there is an association between bone metabolism and the severity of the liver disease. METHODS We studied 112 treatment-naïve chronic HCV outpatients and 233 healthy age- and sex-matched controls. Bone mineral density (BMD) and trabecular bone score (TBS) were assessed by DXA. Serum 25(OH)D, PTH, P1NP, and CTX were determined by electrochemiluminescence. RESULTS TBS values were significantly lower in HCV patients than in controls, both considering the population as a whole (1.337 ± 0.119 vs. 1.377 ± 0.122; p < 0.005) and after stratifying by sex (1.347 ± 0.12 vs. 1.381 ± 0.13 in men and 1.314 ± 0.10 vs. 1.369 ± 0.11 in women). The difference remained significant (p < 0.0001 in all cases) after adjusting for confounders. BMD was also lower in HCV patients (lumbar spine, 0.935 ± 0.151 vs. 0.991 ± 0.143 g/cm2, p 0.001; femoral neck, 0.764 ± 0.123 vs. 0.818 ± 0.123 g/cm2, p 0.0001; total hip, 0.926 ± 0.148 vs. 0.963 ± 0.132 g/cm2, p 0.02), although, after adjustment, differences kept a clear trend towards statistical significance in women at the lumbar spine and femoral neck. However, in men and at the total hip in women, differences were no longer significant. We find no relationship between these parameters and the severity of the disease. No significant difference was observed in PTH and 25OHD status after adjustment. Finally, serum P1NP, but not CTX, was higher in HCV patients. CONCLUSIONS Our findings suggest that HCV infection is an independent risk factor for osteoporosis, especially among postmenopausal women. Therefore, the appropriateness of screening for osteoporosis in postmenopausal HCV-positive women should be considered.
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Affiliation(s)
- José M Olmos-Martínez
- Department of Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain
| | - José L Hernández
- Bone Metabolic Unit, Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Avda. Valdecilla s/n, 39008, Santander, Spain.
| | - Emilio Fábrega
- Department of Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain
| | - José M Olmos
- Bone Metabolic Unit, Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Avda. Valdecilla s/n, 39008, Santander, Spain
| | - Javier Crespo
- Department of Gastroenterology and Hepatology, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain
| | - Jesús González-Macías
- Bone Metabolic Unit, Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Avda. Valdecilla s/n, 39008, Santander, Spain
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18
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Masarone M, Caruso R, Aglitti A, Izzo C, De Matteis G, Attianese MR, Pagano AM, Persico M. Hepatitis C virus infection in jail: Difficult-to-reach, not to-treat. Results of a point-of-care screening and treatment program. Dig Liver Dis 2020; 52:541-546. [PMID: 32234417 DOI: 10.1016/j.dld.2020.02.012] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 01/13/2020] [Accepted: 02/24/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND An unmet objective in the pursuit of HCV elimination is the creation of a simple and fast operating model to identify difficult-to-treat populations, like prisoners. Of many obstacles, the first is represented by the poor knowledge of inmates HCV-Ab prevalence. Moreover, due to the peculiar status of conviction, often their access to antiviral therapy is neglected. AIMS To evaluate the prevalence of HCV infection in a penitentiary Institution of Southern Italy through a point-of-care screening and treatment program. METHODS We conducted a prospective observational study in two phases: first, we reviewed all the prisoners' clinical records, to verify HCV-Ab execution. Subsequently, we performed a universal point-of-care screening and treatment program. RESULTS We enrolled 670 patients. Overall, 310(46.27%) were already HCV-Ab tested. At the screening initiation, 23.28% patients were discharged, whereas 8.35% refused. Of the remaining 458 subjects, 58(12.67%) were HCV-Ab positive and 46 HCVRNA positive. All these underwent DAA, obtaining 100% SVR. At the end of the program, a total of 491(73.28%) subjects had HCV-Ab available. Sixty-nine (14.05%) were positive. A total of 214(31.94%) subjects were lost to follow-up. CONCLUSIONS We revealed a prevalence of 14.05% of HCV-Ab in conviction. Antiviral treatment was safe and efficacious. More efforts are advisable to provide screening for HCV-Ab in conviction.
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Affiliation(s)
- Mario Masarone
- Internal Medicine and Hepatology Division, Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - Rosa Caruso
- Internal Medicine and Hepatology Division, Department of Medicine and Surgery, University of Salerno, Salerno, Italy; Department of Territorial Activities, Simple Departmental Operating Unit for the Protection of Adult and Minor Health, Criminal Area, ASL Salerno, Salerno, Italy
| | - Andrea Aglitti
- Internal Medicine and Hepatology Division, Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - Carmine Izzo
- Internal Medicine and Hepatology Division, Department of Medicine and Surgery, University of Salerno, Salerno, Italy; Department of Territorial Activities, Simple Departmental Operating Unit for the Protection of Adult and Minor Health, Criminal Area, ASL Salerno, Salerno, Italy
| | - Giuseppe De Matteis
- Department of Territorial Activities, Simple Departmental Operating Unit for the Protection of Adult and Minor Health, Criminal Area, ASL Salerno, Salerno, Italy
| | - Maria Rosaria Attianese
- Department of Territorial Activities, Simple Departmental Operating Unit for the Protection of Adult and Minor Health, Criminal Area, ASL Salerno, Salerno, Italy
| | - Antonio Maria Pagano
- Department of Territorial Activities, Simple Departmental Operating Unit for the Protection of Adult and Minor Health, Criminal Area, ASL Salerno, Salerno, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Division, Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
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19
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Razavi H, Sanchez Gonzalez Y, Yuen C, Cornberg M. Global timing of hepatitis C virus elimination in high-income countries. Liver Int 2020; 40:522-529. [PMID: 31815353 DOI: 10.1111/liv.14324] [Citation(s) in RCA: 146] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 10/28/2019] [Accepted: 11/29/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Introduction of highly efficacious pan-genotypic therapies for hepatitis C virus (HCV) infection has made the elimination of the disease an attainable goal. This study assessed progress made in 45 high-income countries towards meeting the World Health Organization's targets for HCV elimination by 2030. METHODS A Markov model developed to forecast annual HCV-infected population was populated with demographic and epidemiological inputs, with historical incidence calibrated to reported prevalence of chronic HCV for each country. Future incidence was assumed to be a linear function of overall prevalence (or prevalence of minimal fibrosis in countries with treatment restrictions). 2017 levels of diagnosis and treatment were assumed constant in the future. The analysis estimated the year countries would meet HCV elimination targets for 80% reduction in incidence, 65% reduction in liver-related deaths, 90% diagnosis coverage and 80% treatment among the treatment-eligible population. RESULTS Of the 45 countries analyzed, nine (Australia, France, Iceland, Italy, Japan, South Korea, Spain, Switzerland and the United Kingdom) are on track towards meeting the HCV elimination targets by 2030. While Austria, Germany and Malta could also reach the targets with expanded screening efforts, 30 countries are not projected to eliminate HCV before 2050. Incidence was the most difficult target to achieve, followed by liver-related deaths. CONCLUSIONS Even with introduction of curative therapies, 80% of high-income countries are not on track to meet HCV elimination targets by 2030, and 67% are off track by at least 20 years. Immediate action to improve HCV screening and treatment is needed globally to make HCV elimination attainable.
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Affiliation(s)
- Homie Razavi
- Center for Disease Analysis, Lafayette, CO, United States
| | | | | | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany
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20
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Carvalho-Louro DM, Soares EB, Trevizoli JE, Marra TMG, da Cunha ALR, Rodrigues MP, Carvalho-Furtado ACL, Dos Santos BTA, de Assis da Rocha Neves F. Hepatitis C screening, diagnosis, and cascade of care among people aged > 40 years in Brasilia, Brazil. BMC Infect Dis 2020; 20:114. [PMID: 32041537 PMCID: PMC7011476 DOI: 10.1186/s12879-020-4809-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 01/21/2020] [Indexed: 12/18/2022] Open
Abstract
Background Identifying patients with hepatitis C virus (HCV) infection and enhancing the cascade of care are essential for eliminating HCV infection. This study aimed to estimate the prevalence of positive anti-HCV serology in Brasilia, Brazil, and evaluate the efficiency of the cascade of care for HCV-positive individuals. Methods This cross-sectional study analyzed 57,697 rapid screening tests for hepatitis C in individuals aged > 40 years between June 2018 and June 2019. HCV-positive patients were contacted and scheduled to undergo the HCV RNA viral test, genotyping, and transient elastography. Results The prevalence of positive serology was 0.27%. Among 161 patients with positive anti-HCV serology, 124 (77%) were contacted, 109 (67.7%) were tested for HCV RNA viral load, and 69 (42.8%) had positive results. Genotype 1 (75%) was the most prevalent genotype. Among 65 patients (94.2%) who underwent transient elastography, 30 (46.2%) presented with advanced fibrosis. Additionally, of the 161 patients, 55 (34.1%) were referred for treatment, but only 39 (24.2%) complied, with 36 (22.4%) showing sustained virological response. By the end of the study, 16 patients were still awaiting to receive medication. Conclusions The prevalence of HCV-positive patients was low in Brasilia, and the gaps in the cascade of care for these patients were significantly below the targets of HCV infection elimination. This study opens new avenues for eliminating HCV infection and suggests that partnerships with clinical laboratories to conduct anti-HCV tests are a useful strategy to improve HCV diagnosis. Trial registration Research Ethics Committee of the Faculty of Health Sciences of the University of Brasília - UNB (CAAE number 77818317.2.0000.0030) and by the Ethics Committee of the Health Science Teaching and Research Foundation - FEPECS/SES/DF (CAAE number 77818317.2.3001.5553).
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Affiliation(s)
| | - Eric Bassetti Soares
- Gilead Sciences Farmacêutica do Brasil Ltd. and Liver Center at UFMG, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 04711-130, Brazil
| | - Jose Eduardo Trevizoli
- Gastroenterology Unit, Instituto Hospital de Base, Brasilia, Federal District, 70322-000, Brazil
| | - Thayna Moreira Gomes Marra
- Postgraduate Program in Health Sciences and Technologies, University of Brasilia, Brasilia, Federal District, 70919-970, Brazil
| | | | - Marcelo Palmeira Rodrigues
- Pneumology Unit, Faculty of Medicine, University of Brasilia, Brasilia, Federal District, 70673-432, Brazil
| | | | - Beatriz Taynara Araujo Dos Santos
- Subsecretaria de Atencao Integral a Saude, Secretaria do Estado de Saude do Distrito Federal, Brasilia, Federal District, 70770-200, Brazil
| | - Francisco de Assis da Rocha Neves
- Molecular Pharmacology Laboratory, Faculty of Health Sciences, University of Brasilia, Brasilia, Federal District, 70919-970, Brazil
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21
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Örmeci N, Gülşen MT, Sezgin O, Aghayeva S, Demir M, Köksal I, Güner R, Erarslan E, Asiller ÖÖ, Balkan A, Yaraş S, Kartal AÇ. Treatment of HCV infection with direct-acting antiviral agents. Real life experiences from the Euro-Asian region. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2020; 31:148-155. [PMID: 32141824 PMCID: PMC7062133 DOI: 10.5152/tjg.2020.19440] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Accepted: 10/22/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND/AIMS Hepatitis C virus (HCV) infection is a common disease that causes liver cirrhosis, hepatocellular carcinoma, and extra hepatic manifestations with high mortality and morbidity rates. This study aimed to present real-life experiences and results of treatment of HCV infection with direct-acting antiviral agents (DAAs) from the Euro-Asian region, including Turkey and Azerbaijan. MATERIALS AND METHODS A total of 1224 patients with chronic HCV infection were treated with DAAs in accordance with the international guidelines for the management of HCV infection. The mean age was 58.74±14.75 years, with 713 (58.25%) females. The genotypes of the patients were as follows: genotype 1b, 83.36% (n=1024); genotype 1a, 8.08% (n=99); genotype 2, 2.85% (n=35); genotype 3, 3.34% (n=41); genotype 4, 1.71% (n=21); and combined genotypes, 0.32% (n=4). Approximately 808 patients were treated with sofosbuvir-based DAAs with or without Ribavirin for 12 or 24 weeks, whereas 416 patients were treated with the Paritaprevir, Ombitasvir, Ritonavir.Dasabuvir (PROD) regimen with or without Ribavirin for 12 weeks or 24 weeks. RESULTS At the end of follow-up examinations, 1183 patients (97.93%) had sustained virological response (SVR), 17 (1.40%) died of reasons unrelated to the treatment regimen, 12 had recurrence after treatment, and 129 (10.67%) had adverse events like anemia, itching, and weakness. CONCLUSION In this large cohort of HCV-infected patients, treatment with DAAs yielded a high overall SVR rate of 97.93%. DAAs were safe and well-tolerated. Thus, the elimination of HCV infection is no longer a dream worldwide.
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Affiliation(s)
- Necati Örmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Murat Taner Gülşen
- Department of Gastroenterology, Gaziantep University School of Medicine, Gaziantep, Turkey
| | - Orhan Sezgin
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Sevda Aghayeva
- Department of Gastroenterology, Azerbaijan Medical University School of Medicine, Baku, Azerbaijan
| | - Mehmet Demir
- Department of Gastroenterology, Hatay Mustafa Kemal University School of Medicine, Hatay, Turkey
| | - Iftihar Köksal
- Department of Gastroenterology, Karadeniz Technical University School of Medicine, Trabzon, Turkey
| | - Rahmet Güner
- Department of Infectious Diseases and Clinical Microbiology, Yıldırım Beyazıt University School of Medicine, Ankara, Turkey
| | - Elife Erarslan
- Department of Gastroenterology, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Özgün Ömer Asiller
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ayhan Balkan
- Department of Gastroenterology, Gaziantep University School of Medicine, Gaziantep, Turkey
| | - Serkan Yaraş
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Aysun Çalışkan Kartal
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
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22
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Ali S, Ali M, Paudyal V, Rasheed F, Ullah S, Haque S, Ur-Rehman T. A Randomized Controlled Trial to Assess the Impact of Clinical Pharmacy Interventions on Treatment Outcomes, Health Related Quality of Life and Medication Adherence Among Hepatitis C Patients. Patient Prefer Adherence 2019; 13:2089-2100. [PMID: 31997877 PMCID: PMC6917610 DOI: 10.2147/ppa.s224937] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Accepted: 10/30/2019] [Indexed: 12/15/2022] Open
Abstract
PURPOSE The role of specialized pharmacy services remains unexplored in clinical practice for hepatitis C patients in Pakistan. This study aimed to evaluate the impact of clinical pharmacy interventions on treatment outcomes, health-related quality of life (HRQoL), and medication adherence among hepatitis C patients. METHODS A randomized control trial was conducted at two tertiary-care teaching hospitals in Pakistan. Hepatitis C patients who attended the outpatient clinics between October 2015 and September 2018 were randomized to two groups [usual care (UC) and pharmaceutical care (PC)] in a 1:1 ratio, applying simple envelope method. The PC group received pharmaceutical care led by a clinical pharmacist. The care that patients received included education and counseling on medication compliance, labeling of medication packs, and monitoring of adverse drug events, led by a qualified clinical pharmacist during the 15- to 20-minute monthly sessions, while the UC group received standard care at hospital, which did not involve clinical pharmacist input. Outcome measures, such as sustained virological response, HRQoL, and adherence rate (pharmacy data) were assessed at enrolment and distinct time intervals: 4 weeks, 8 weeks, and end of treatment. RESULTS A total of 931 patients were included in the study (UC 466 and PC 465), with mean age 42.35±1.9 years. Sustained virological response at 12 weeks was achieved in 86.0% patients in the PC group, significantly (p<0.001) higher than the UC (69.3%) group. Fewer patients (9.9%) in the PC group reported mobility problems, significantly fewer (p<0.001) than the UC group (11.8%). Self-care, usual activity, pain, and depression were relieved significantly in the PC group compared to the UC group. The EuroQol visual analogue scale (baseline 56.1 of UC group versus 55.2 for PC group) was raised to 71.8 and 71.9 in the UC and PC groups, respectively. Medication adherence was significantly improved (p<0.001) in the PC group (88.6%) when compared to the UC group (77.9%, 95% CI 88.9%-91.9%). CONCLUSION Pharmacist-led clinical pharmacy interventions as part of multidisciplinary care had a significant impact on improving cure rates, HRQoL, and medication adherence for hepatitis C patients. This study suggests that clinical pharmacists should be incorporated into the multidisciplinary health-care team for care of hepatitis C patients.
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Affiliation(s)
- Salamat Ali
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
- Services Institute of Medical Sciences, Lahore, Pakistan
| | - Mashhood Ali
- Department of Gastroenterology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan
| | - Vibhu Paudyal
- School of Pharmacy, University of Birmingham, Birmingham, UK
| | - Faisal Rasheed
- Pakistan Institute of Nuclear Sciences and Technology, Islamabad, Pakistan
| | - Shahan Ullah
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | - Sayeed Haque
- Institute of Applied Health Research Medical Statistics, University of Birmingham, Birmingham, UK
| | - Tofeeq Ur-Rehman
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
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23
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Kramer J, Wolffram I, Früh U, Bätz O, Berg T, Wiegand J. Laboratory reform counteracts the WHO hepatitis C elimination strategy in Germany. J Viral Hepat 2019; 26:1493-1495. [PMID: 31386783 DOI: 10.1111/jvh.13188] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 05/04/2019] [Accepted: 06/10/2019] [Indexed: 12/09/2022]
Abstract
The World Health Organization and the German government have announced an initiative to eliminate chronic hepatitis C until the year 2030. To reach this goal, one important step is adequate screening and detection of so far undiagnosed infections. The most common initial test is anti-HCV. This parameter was extra-budgetary reimbursed by statuary healthcare insurances in the past. However, this policy has changed after a nationwide laboratory reform which should reduce the laboratory costs of patients insured in the statuary healthcare insurances. We therefore analysed the impact of the laboratory reform on the order of anti-HCV tests in 510 656 anonymized patient data sets before and after the initiation of the reform. The number of anti-HCV tests declined by 9.4% in quarters I-III 2018 in comparison with the same time period of the year 2017. The number of HBsAg tests declined by 7.4%, indicating that the reduced anti-HCV laboratory orders are not parameter-specific, but most likely a surrogate of the intention of the laboratory reform to generally lower the demands of blood samples and laboratory costs. Thus, the scenario is an important example, how political decisions of the medical self-government influence the screening setting for viral hepatitis: if the current policy is not changed, the laboratory reform directly counteracts the WHO hepatitis C elimination strategy in Germany.
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Affiliation(s)
- Jan Kramer
- Accredited Laboratories in Medicine (ALM) e.V., Berlin, Germany.,LADR Laboratory Group Dr. Kramer & Colleagues, Geesthacht, Germany
| | | | - Uli Früh
- WCG Consulting, Reutlingen, Germany
| | - Olaf Bätz
- LADR Laboratory Group Dr. Kramer & Colleagues, Geesthacht, Germany
| | - Thomas Berg
- Klinik für Gastroenterologie, Universität Leipzig, Leipzig, Germany
| | - Johannes Wiegand
- Klinik für Gastroenterologie, Universität Leipzig, Leipzig, Germany
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24
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Gardini I, Bartoli M, Conforti M, Mennini FS, Marcellusi A. Estimation of the number of HCV-positive patients in Italy. PLoS One 2019; 14:e0223668. [PMID: 31671120 PMCID: PMC6822946 DOI: 10.1371/journal.pone.0223668] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 09/25/2019] [Indexed: 12/17/2022] Open
Abstract
Background HCV is one of the main causes of cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation. Aim The aim of this study was to estimate the number of living individuals diagnosed with hepatitis C in Italy. This study also aimed to stratify these subjects as diagnosed and cured, diagnosed awaiting a cure, and undiagnosed (individuals who were not diagnosed, living or lived with hepatitis C). Methods To quantify the number of ill patients in Italy, an inquiry was conducted based on questionnaires submitted to three nationally representative regions, namely, Campania, Lazio and Piemonte, as representatives of the three main areas of Italy (North, Centre and South regions). The data were collected through a questionnaire to acquire demographic and clinical information on patients in the participating hospitals. The questionnaires contained 6 questions on sex, age, region of residence, disease condition, type of exemption and category. The questionnaires were administered individually to consecutive patients through face-to-face interviews conducted by specialised personnel in each centre. Data were collected between September 2017 and January 2018. Results In total, 2,860 questionnaires were analysed. They were completed by the patients (55% male), who had an average age of 61 years (64 years for women and 59 years for men). In total, 54% of the sample declared that they were still infected with HCV (1,548 patients out of 2,860 respondents), while the remaining subjects declared that they had been cured. The inquiry showed that 46.6% of the sample had at least a 016 exemption (chronic hepatitis), while more than 51% (1,469 interviewed patients out of 2,860 respondents) had a different type of exemption. Only 2% of the respondents declared that they had no exemption. Assuming that the analysed sample is representative of the actual HCV-positive population in Italy and considering the number of 016 exempt patients in the regional data, the model estimates that there are 443,491 cured and HCV-positive living patients and 240,043 ill patients who have yet to be treated. Conclusions Although this study has limitations, it represents a considerable improvement over the previously available studies. This study can help decision-makers implement more effective strategic planning to eliminate hepatitis C.
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Affiliation(s)
- Ivan Gardini
- EpaC Onlus, Italian Liver Patient Association, Rome, Italy
| | - Marco Bartoli
- EpaC Onlus, Italian Liver Patient Association, Rome, Italy
| | | | - Francesco Saverio Mennini
- Centre for Economic and International Study (CEIS), Faculty of Economics, University of Rome "Tor Vergata", Rome, Italy
| | - Andrea Marcellusi
- Department of Accounting, Finance and Informatics, Kingston Business School, Kingston University London, London, United Kingdom
- * E-mail:
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25
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Gounder PP, Koch A, Provo G, Lovlie A, Ederth JL, Axelsson M, Archibald CP, Hanley B, Mullen A, Matheson M, Allison D, Trykker H, Hennessy TW, Kuusi M, Chulanov V, McMahon BJ. Summary of available surveillance data on hepatitis C virus infection from eight Arctic countries, 2012 to 2014. ACTA ACUST UNITED AC 2019; 23. [PMID: 30301489 PMCID: PMC6178586 DOI: 10.2807/1560-7917.es.2018.23.40.1700408] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
We summarised available hepatitis C virus (HCV) surveillance data for 2012–14 from Arctic/sub-Arctic countries/regions. We sent a HCV data collection template by email to public health authorities in all jurisdictions. Population statistics obtained from census sources for each country were used to estimate rates of reported acute and chronic/undifferentiated HCV cases. Seven countries with Arctic regions (Canada, Denmark, Finland, Greenland, Norway, Sweden and the United States, represented by the state of Alaska), including three Canadian territories and one province, as well as 11 Russian subnational Arctic regions, completed the data collection template. Data on acute HCV infection during 2014 was available from three Arctic countries and all Russian Arctic regions (rate range 0/100,000 population in Greenland, as well as Nenets and Chukotka Automous Okrugs (Russian subnational Arctic regions) to 3.7/100,000 in the Russian Republic of Komi). The rate of people with chronic/undifferentiated HCV infection in 2014 ranged from 0/100,000 in Greenland to 171.2/100,000 in Alaska. In most countries/regions, the majority of HCV-infected people were male and aged 19–64 years. Differences in surveillance methods preclude direct comparisons of HCV surveillance data between Arctic countries/regions. Our data can inform future efforts to develop standardised approaches to HCV surveillance in the Arctic countries/regions by identifying similarities/differences between the surveillance data collected.
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Affiliation(s)
- Prabhu P Gounder
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, U.S. Centers for Disease Control and Prevention (CDC), Anchorage, Alaska, USA
| | - Anders Koch
- Lisimatusarfik, University of Greenland, Nuuk, Greenland.,Statens Serum Institut, Copenhagen, Denmark
| | - Ginger Provo
- Division of Public Health, State of Alaska, Anchorage, Alaska, USA
| | - Astrid Lovlie
- Department for Infectious Disease Registries, Norwegian Institute of Public Health, Oslo, Norway
| | - Josefine Lundberg Ederth
- Department of Public Health Analysis and Data Management, Public Health Agency of Sweden, Stockholm, Sweden
| | - Maria Axelsson
- Unit for Epidemiology & Health Economic, the Public Health Agency of Sweden, Stockholm, Sweden
| | - Chris P Archibald
- Surveillance and Epidemiology Division, Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, Canada
| | - Brendan Hanley
- Chief Medical Officer of Health, Whitehorse, Yukon, Canada
| | - Angie Mullen
- Department of Health, Government of Nunavut, Iqaluit, Nunavut, Canada
| | - Myrna Matheson
- Communicable Disease Control Unit, Department of Health and Social Services, Government of the Northwest Territories, Yellowknife, Northwest Territories, Canada
| | - David Allison
- Department of Health and Community Services, St. John's, Newfoundland and Labrador, Canada
| | | | - Thomas W Hennessy
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, U.S. Centers for Disease Control and Prevention (CDC), Anchorage, Alaska, USA
| | - Markku Kuusi
- National Institute for Health and Welfare (THL), Helsinki, Finland
| | - Vladimir Chulanov
- Central Research Institute of Epidemiology, Reference Center for Viral Hepatitis, Moscow, Russia
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska, USA.,Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, U.S. Centers for Disease Control and Prevention (CDC), Anchorage, Alaska, USA
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26
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Hickman M, Dillon JF, Elliott L, De Angelis D, Vickerman P, Foster G, Donnan P, Eriksen A, Flowers P, Goldberg D, Hollingworth W, Ijaz S, Liddell D, Mandal S, Martin N, Beer LJZ, Drysdale K, Fraser H, Glass R, Graham L, Gunson RN, Hamilton E, Harris H, Harris M, Harris R, Heinsbroek E, Hope V, Horwood J, Inglis SK, Innes H, Lane A, Meadows J, McAuley A, Metcalfe C, Migchelsen S, Murray A, Myring G, Palmateer NE, Presanis A, Radley A, Ramsay M, Samartsidis P, Simmons R, Sinka K, Vojt G, Ward Z, Whiteley D, Yeung A, Hutchinson SJ. Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) - a natural experiment (protocol). BMJ Open 2019; 9:e029538. [PMID: 31551376 PMCID: PMC6773339 DOI: 10.1136/bmjopen-2019-029538] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 07/25/2019] [Accepted: 07/29/2019] [Indexed: 01/15/2023] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV 'Treatment as Prevention' (TasP) in PWID. METHODS AND ANALYSIS We plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome - chronic HCV prevalence in PWID - is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a 'virtual cohort' of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes. ETHICS AND DISSEMINATION Extending HCV community care pathways is covered by ethics (ERADICATE C, ISRCTN27564683, Super DOT C Trial clinicaltrials.gov: NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England.
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Affiliation(s)
- Matthew Hickman
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - John F Dillon
- Hepatology & Gastroenterology, Clinical & Molecular Medicine, School of Medicine, University of Dundee, Dundee, UK
| | | | - Daniela De Angelis
- MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Peter Vickerman
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Graham Foster
- Blizard Institute, Queen Mary University of London, London, UK
- Barts Health NHS Trust, London, UK
| | - Peter Donnan
- Dundee Epidemiology and Biostatistics Unit, University of Dundee, Dundee, UK
| | | | | | - David Goldberg
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
| | | | - Samreen Ijaz
- National Infection Service, Public Health England, London, UK
| | | | - Sema Mandal
- National Infection Service, Public Health England, London, UK
| | - Natasha Martin
- Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, UK
| | - Lewis J Z Beer
- Tayside Clinical Trials Unit, Tayside Medical Science Centre, University of Dundee, Dundee, UK
| | - Kate Drysdale
- Blizard Institute, Queen Mary University of London, London, UK
- Barts Health NHS Trust, London, UK
| | - Hannah Fraser
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Rachel Glass
- National Infection Service, Public Health England, London, UK
| | | | - Rory N Gunson
- West Of Scotland Specialist Virology Centre, NHS Greater Glasgow & Clyde Board, Glasgow, UK
| | | | - Helen Harris
- National Infection Service, Public Health England, London, UK
| | | | - Ross Harris
- National Infection Service, Public Health England, London, UK
| | | | - Vivian Hope
- Liverpool John Moores University, Liverpool, UK
| | - Jeremy Horwood
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Sarah Karen Inglis
- Tayside Clinical Trials Unit, Tayside Medical Science Centre, University of Dundee, Dundee, UK
| | - Hamish Innes
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
| | - Athene Lane
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Jade Meadows
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Andrew McAuley
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
| | - Chris Metcalfe
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | | | | | - Gareth Myring
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | - Norah E Palmateer
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
| | - Anne Presanis
- MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Andrew Radley
- Hepatology & Gastroenterology, Clinical & Molecular Medicine, School of Medicine, University of Dundee, Dundee, UK
- Directorate of Public Health, NHS Tayside, Dundee, UK
| | - Mary Ramsay
- National Infection Service, Public Health England, London, UK
| | - Pantelis Samartsidis
- MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK
| | - Ruth Simmons
- National Infection Service, Public Health England, London, UK
| | - Katy Sinka
- National Infection Service, Public Health England, London, UK
| | | | - Zoe Ward
- Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK
| | | | - Alan Yeung
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
| | - Sharon J Hutchinson
- Glasgow Caledonian University, Glasgow, UK
- Health Protection Scotland, Glasgow, UK
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27
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Liraglutide Inhibits Hepatitis C Virus Replication Through an AMP Activated Protein Kinase Dependent Mechanism. Int J Mol Sci 2019; 20:ijms20184569. [PMID: 31540136 PMCID: PMC6769880 DOI: 10.3390/ijms20184569] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Revised: 08/29/2019] [Accepted: 09/09/2019] [Indexed: 12/13/2022] Open
Abstract
Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 μg/mL, activated the 5′ adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.
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28
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El-Ghitany EM, Farghaly AG. Geospatial epidemiology of hepatitis C infection in Egypt 2017 by governorate. Heliyon 2019; 5:e02249. [PMID: 31463388 PMCID: PMC6709406 DOI: 10.1016/j.heliyon.2019.e02249] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 05/17/2019] [Accepted: 08/05/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Geographic Information Systems (GIS) and spatial epidemiological methods may provide a basis for disease investigation through which hotspots and disease determinants can be identified. Applying these methods for hepatitis C virus (HCV) in Egypt would support a more effective strategy to control its transmission. Therefore, this study used GIS software to draw one of the first HCV maps in Egypt elucidating and analyzing geographical and epidemiological differences in HCV distribution within the country. METHODS A cross-sectional survey of 21 governorates (n = 12169, 8080 rural, 3733 urban and 356 slums areas) was completed. All participants were interviewed regarding potential exposures to HCV. Third generation ELISA was used to test serum for HCV antibody. Quantitative real-time RT-PCR was used to test anti-HCV positive subjects for HCV-RNA. RESULTS The participants ranged in age from 14-90 years. Overall, anti-HCV sero-prevalence was 14.8%. The prevalence of HCV-RNA, was 9.5%. Proportionally, 65.8% of anti-HCV positives were positive for HCV-RNA. The map of Egyptian governorates highlighted the darkest spot of HCV infection in Menoufeya (37.8%) followed by Beni Suef (29.2%) and Minya (28.6%). Anti-HCV prevalence was higher among males and logistic regression models revealed a strong independent association with increasing age, rural residence and parenteral anti-schistosomal therapy. CONCLUSIONS Rural residences and HCV hotspots should be prioritized for HCV prevention programs. The unique age distribution first shown in this study shows that the older age groups (≥60 years old) constitutes a considerable reservoir of infection and must not be neglected.
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29
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Fraňková S, Urbánek P, Husa P, Němeček V, Razavi H, Razavi-Shearer D, Chlíbek R, Šperl J. Chronic hepatitis C in the Czech Republic: Forecasting the disease burden. Cent Eur J Public Health 2019; 27:93-98. [PMID: 31241282 DOI: 10.21101/cejph.a5350] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Accepted: 04/25/2019] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Chronic HCV infection is associated with cirrhosis of the liver, hepatocellular carcinoma (HCC), and liver transplantation. HCV disease burden and the impact of new potent direct acting antivirals (DAAs) in the Czech Republic are unknown. METHODS Using a modelling framework, HCV disease progression in the Czech Republic was predicted to 2030 under the current standard of care treatment structure. In addition, two strategies to reduce the future burden of HCV infection were modelled: an incremental increase in treatment annually and WHO targets. RESULTS The number of viremic infected individuals in the Czech Republic is estimated to peak in 2026 (n = 55,130) and to decline by 0.5% by 2030 (n = 54,840). The number of individuals with compensated cirrhosis (n = 1,400), decompensated cirrhosis (n = 80), HCC (n = 70), and liver-related deaths (n = 60) is estimated to more than double by 2030. Through aggressive increases in diagnosis and treatment, HCV related mortality may decrease by 70% by 2030. CONCLUSIONS Disease burden associated with chronic HCV infection is projected to peak in the Czech Republic in 30-40 years. Assuming that the current portion of DAAs used remains constant, a significant reduction in HCV disease burden is possible through increased diagnosis and treatment through 2030. This analysis provides evidence in order to facilitate the development of national strategies for HCV care and management in the Czech Republic.
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Affiliation(s)
- Soňa Fraňková
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Petr Urbánek
- Department of Internal Medicine, First Faculty of Medicine, Charles University and Central Military Hospital, Prague, Czech Republic
| | - Petr Husa
- Clinic of Infectious Diseases, University Hospital Brno, Masaryk University, Brno, Czech Republic
| | - Vratislav Němeček
- National Reference Laboratory for Hepatitis, National Institute of Public Health, Prague, Czech Republic
| | - Homie Razavi
- Center for Disease Analysis, Lafayette, Colorado, USA
| | | | - Roman Chlíbek
- Department of Epidemiology, Vaccination Centre, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic
| | - Jan Šperl
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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30
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Sandmann L, Manns MP, Maasoumy B. Utility of viral kinetics in HCV therapy - It is not over until it is over? Liver Int 2019; 39:815-817. [PMID: 31020775 DOI: 10.1111/liv.14047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Accepted: 01/10/2019] [Indexed: 12/23/2022]
Affiliation(s)
- Lisa Sandmann
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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31
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Gountas I, Sypsa V, Papatheodoridis G, Souliotis K, Athanasakis K, Razavi H, Hatzakis A. Economic evaluation of the hepatitis C elimination strategy in Greece in the era of affordable direct-acting antivirals. World J Gastroenterol 2019; 25:1327-1340. [PMID: 30918426 PMCID: PMC6429341 DOI: 10.3748/wjg.v25.i11.1327] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 02/20/2019] [Accepted: 02/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is a leading cause of worldwide liver-related morbidity and mortality. The World Health Organization released an integrated strategy targeting HCV-elimination by 2030. This study aims to estimate the required interventions to achieve elimination using updated information for direct-acting antiviral (DAA) treatment coverage, to compute the total costs (including indirect/societal costs) of the strategy and to identify whether the elimination strategy is cost-effective/cost-saving in Greece.
AIM To estimate the required interventions and subsequent costs to achieve HCV elimination in Greece.
METHODS A previously validated mathematical model was adapted to the Greek HCV-infected population to compare the outcomes of DAA treatment without the additional implementation of awareness or screening campaigns versus an HCV elimination strategy, which includes a sufficient number of treated patients. We estimated the total costs (direct and indirect costs), the disability-adjusted life years and the incremental cost-effectiveness ratio using two different price scenarios.
RESULTS Without the implementation of awareness or screening campaigns, approximately 20000 patients would be diagnosed and treated with DAAs by 2030. This strategy would result in a 19.6% increase in HCV-related mortality in 2030 compared to 2015. To achieve the elimination goal, 90000 patients need to be treated by 2030. Under the elimination scenario, viremic cases would decrease by 78.8% in 2030 compared to 2015. The cumulative direct costs to eliminate the disease would range from 2.1-2.3 billion euros (€) by 2030, while the indirect costs would be €1.1 billion. The total elimination cost in Greece would range from €3.2-3.4 billion by 2030. The cost per averted disability-adjusted life year is estimated between €10100 and €13380, indicating that the elimination strategy is very cost-effective. Furthermore, HCV elimination strategy would save €560-895 million by 2035.
CONCLUSION Without large screening programs, elimination of HCV cannot be achieved. The HCV elimination strategy is feasible and cost-saving despite the uncertainty of the future cost of DAAs in Greece.
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Affiliation(s)
- Ilias Gountas
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
- Hellenic Scientific Society for the Study of AIDS and Sexually Transmitted Diseases, Athens 11527, Greece
| | - Vana Sypsa
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - George Papatheodoridis
- Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece
| | - Kyriakos Souliotis
- Faculty of Social and Political Sciences, University of Peloponnese, Korinthos 20100, Greece
| | - Kostas Athanasakis
- Department of Health Economics, National School of Public Health, Athens 11521, Greece
| | - Homie Razavi
- Center for Disease Analysis, Lafayette, CO 80026, United States
| | - Angelos Hatzakis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
- Hellenic Scientific Society for the Study of AIDS and Sexually Transmitted Diseases, Athens 11527, Greece
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Kileng H, Gutteberg T, Goll R, Paulssen EJ. Screening for hepatitis C in a general adult population in a low-prevalence area: the Tromsø study. BMC Infect Dis 2019; 19:189. [PMID: 30808290 PMCID: PMC6390317 DOI: 10.1186/s12879-019-3832-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 02/19/2019] [Indexed: 12/15/2022] Open
Abstract
Background Chronic hepatitis C virus (HCV) infection can progress to cirrhosis and end-stage liver disease in a substantial proportion of patients. The infection is frequently asymptomatic, leaving many infected individuals unaware of the diagnosis until complications occur. This advocates the screening of healthy individuals. The aim of this study was to estimate the prevalence of HCV infection in the general adult population of the municipality of Tromsø, Norway, and to evaluate the efficiency of such an approach in a presumed low-prevalence area. Methods The study was part of the seventh survey of the Tromsø Study (Tromsø 7) in 2015–2016. Sera from 20,946 individuals aged 40 years and older were analysed for antibodies to HCV (anti-HCV). A positive anti-HCV test was followed up with a new blood test for HCV RNA, and the result of any previous laboratory HCV data were recorded. Samples positive for anti-HCV and negative for HCV RNA were tested with a recombinant immunoblot assay. All HCV RNA positive individuals were offered clinical evaluation. Results Among 20,946 participants, HCV RNA was detected in 33 (0.2%; 95% CI: 0.1–0.3), of whom 13 (39.4%; 95% CI: 22.7–56.1) were unaware of their infection. The anti-HCV test was confirmed positive in 134 individuals (0.6%; 95% CI: 0.5–0.7) with the highest prevalence in the age group 50–59 years. Current or treatment-recovered chronic HCV-infection was found in 85 individuals (0.4%; 95% CI: 0.3–0.5) and was associated with an unfavorable psychosocial profile. Conclusion In this population-based study, the prevalence of viraemic HCV infection was 0.2%. A substantial proportion (39%) of persons with viraemic disease was not aware of their infectious status, which suggests that the current screening strategy of individuals with high risk of infection may be an inadequate approach to identify chronic HCV infection hidden in the general population.
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Affiliation(s)
- H Kileng
- Gastroenterology and Nutrition Research Group, Department of Clinical Medicine, UiT The Arctic University of Tromsø, 9037, Tromsø, Norway. .,Department of Internal Medicine, Section of Gastroenterology, University Hospital of North Norway, Tromsø, Norway.
| | - T Gutteberg
- Research group for Host Microbe Interactions, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.,Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway
| | - R Goll
- Gastroenterology and Nutrition Research Group, Department of Clinical Medicine, UiT The Arctic University of Tromsø, 9037, Tromsø, Norway.,Department of Internal Medicine, Section of Gastroenterology, University Hospital of North Norway, Tromsø, Norway
| | - E J Paulssen
- Gastroenterology and Nutrition Research Group, Department of Clinical Medicine, UiT The Arctic University of Tromsø, 9037, Tromsø, Norway.,Department of Internal Medicine, Section of Gastroenterology, University Hospital of North Norway, Tromsø, Norway
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Petruzziello A, Sabatino R, Loquercio G, Guzzo A, Di Capua L, Labonia F, Cozzolino A, Azzaro R, Botti G. Nine-year distribution pattern of hepatitis C virus (HCV) genotypes in Southern Italy. PLoS One 2019; 14:e0212033. [PMID: 30785909 PMCID: PMC6382136 DOI: 10.1371/journal.pone.0212033] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 01/26/2019] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION It has been greatly described that different hepatitis C virus (HCV) genotypes are strictly correlated to various evolution, prognosis and response to therapy during the chronic liver disease. Aim of this study was to outline the changes in the epidemiology of Hepatitis C genotypes in Southern Italy regions from 2006 to 2014. MATERIAL/METHODS Prevalence of HCV genotypes was analyzed in 535 HCV-RNA positive patients with chronic Hepatitis C infection, selected during the period 2012-2014, and compared with our previous data, referred to periods 2006-2008 and 2009-2011. RESULTS In all the three periods analyzed, genotype 1b is predominant (51.8% in 2006-08, 48.3% in 2009-11 and 54.4% in 2012-14) while genotype 2 showed an increase in prevalence (27.9% in 2006-08, 31.7% in 2009-11 and 35.2% in 2012-14) and genotypes 3a and 1a a decrease during the same period (6.8% in 2006-08, 4.7% in 2009-11 and 3.2% in 2012-14 and 7.9% in 2006-08, 4.7% in 2009-11 and 2.6% in 2012-14, respectively). Subtype 1b seems to be equally distributed between males and females (52.7% vs 56.6%) and the prevalence in the age range 31-40 years is significantly higher in the 2012-14 period than in both previous periods (53.8% vs. 16.6% in 2009-11, p< 0.001 and 13.4% in 2006-08, p < 0.001). CONCLUSIONS Genotype 1b is still the most prevalent, even if shows a significantly increase in the under 40 years old population. Instead, genotype 3a seems to have a moderate increase among young people. Overall, the alarming finding is the "returning" role of the iatrogenic transmission as risk factor for the diffusion of Hepatitis C infection.
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Affiliation(s)
- Arnolfo Petruzziello
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Rocco Sabatino
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Giovanna Loquercio
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Annunziata Guzzo
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Lucia Di Capua
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Francesco Labonia
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Anna Cozzolino
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Rosa Azzaro
- Transfusion Service, Department of Hemathology, Istituto Nazionale Tumori—Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
| | - Gerardo Botti
- SSD Virology and Molecular Biology, Department of Diagnostic Area, Istituto Nazionale Tumori, Fondazione “G. Pascale”, IRCCS Italia, Naples, Italy
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Marshall AD, Pawlotsky JM, Lazarus JV, Aghemo A, Dore GJ, Grebely J. The removal of DAA restrictions in Europe - One step closer to eliminating HCV as a major public health threat. J Hepatol 2018; 69:1188-1196. [PMID: 29959953 DOI: 10.1016/j.jhep.2018.06.016] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 05/10/2018] [Accepted: 06/21/2018] [Indexed: 12/20/2022]
Abstract
Of ∼10.2 million people with chronic HCV infection in Europe, 6.7 million live in Eastern Europe, 2.3 million in Western Europe and 1.2 million in Central Europe. HCV transmission continues to occur in parallel with an increasing HCV-related liver disease burden, the result of an ageing population infected during peak HCV epidemics decades earlier. In 2016, the World Health Organization set targets to eliminate HCV infection as a major public health threat by 2030. Across Europe, an estimated 36% of those living with chronic HCV infection have been diagnosed and ∼5% have been treated. A major barrier to enhancing HCV treatment uptake has been restrictions set by payers, including national governments and others, in response to the initially high list prices of direct-acting antiviral (DAA) therapies. The aims of this article are to discuss DAA restrictions in Europe, why DAA restrictions are still in place, what has facilitated the removal of DAA restrictions, and what challenges remain as we attempt to eliminate HCV as a major public health threat in the region by 2030.
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Affiliation(s)
| | - Jean-Michel Pawlotsky
- National Reference Center for Viral Hepatitis B, C and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France
| | - Jeffrey V Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain; CHIP, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Humanitas Clinical and Research Center, Rozzano, Italy
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Omran D, Alboraie M, Zayed RA, Wifi MN, Naguib M, Eltabbakh M, Abdellah M, Sherief AF, Maklad S, Eldemellawy HH, Saad OK, Khamiss DM, El Kassas M. Towards hepatitis C virus elimination: Egyptian experience, achievements and limitations. World J Gastroenterol 2018; 24:4330-4340. [PMID: 30344418 PMCID: PMC6189850 DOI: 10.3748/wjg.v24.i38.4330] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 09/13/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
Worldwide, more than one million people die each year from hepatitis C virus (HCV) related diseases, and over 300 million people are chronically infected with hepatitis B or C. Egypt used to be on the top of the countries with heavy HCV burden. Some countries are making advances in elimination of HCV, yet multiple factors preventing progress; remain for the majority. These factors include lack of global funding sources for treatment, late diagnosis, poor data, and inadequate screening. Treatment of HCV in Egypt has become one of the top national priorities since 2007. Egypt started a national treatment program intending to provide cure for Egyptian HCV-infected patients. Mass HCV treatment program had started using Pegylated interferon and ribavirin between 2007 and 2014. Yet, with the development of highly-effective direct acting antivirals (DAAs) for HCV, elimination of viral hepatitis has become a real possibility. The Egyptian National Committee for the Control of Viral Hepatitis did its best to provide Egyptian HCV patients with DAAs. Egypt adopted a strategy that represents a model of care that could help other countries with high HCV prevalence rate in their battle against HCV. This review covers the effects of HCV management in Egyptian real life settings and the outcome of different treatment protocols. Also, it deals with the current and future strategies for HCV prevention and screening as well as the challenges facing HCV elimination and the prospect of future eradication of HCV.
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Affiliation(s)
- Dalia Omran
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo 11651, Egypt
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo 11651, Egypt
| | - Rania A Zayed
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo 11651, Egypt
| | - Mohamed-Naguib Wifi
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11599, Egypt
| | - Mervat Naguib
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11599, Egypt
| | - Mohamed Eltabbakh
- Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Mohamed Abdellah
- Department of Internal Medicine, Al-Azhar University, Cairo 11651, Egypt
| | - Ahmed Fouad Sherief
- Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Sahar Maklad
- National Hepatology and Tropical Medicine Research Institute, Cairo 11599, Egypt
| | - Heba Hamdy Eldemellawy
- Department of Internal Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef 62511, Egypt
| | | | - Doaa Mohamed Khamiss
- Department of Clinical and Chemical Pathology, El-monera hospital, Ministry of Health, Cairo 11562, Egypt
| | - Mohamed El Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11599, Egypt
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Abozeid M, Alsebaey A, Abdelsameea E, Othman W, Elhelbawy M, Rgab A, Elfayomy M, Abdel-Ghafar TS, Abdelkareem M, Sabry A, Fekry M, Shebl N, Rewisha E, Waked I. High efficacy of generic and brand direct acting antivirals in treatment of chronic hepatitis C. Int J Infect Dis 2018; 75:109-114. [PMID: 30077791 DOI: 10.1016/j.ijid.2018.07.025] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 07/26/2018] [Accepted: 07/27/2018] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Direct acting antivirals (DAAs) are highly effective for treatment of hepatitis C (HCV) but brand products are priced beyond the means of most low and middle income countries (LMICs). Although a few DAAs are offered at reduced prices in access programs, they are still beyond affordability in limited resource settings with a large HCV infected population. Cheap generics might fill this economic need, but studies comparing their clinical efficacy to that of original products are limited. AIM To compare efficacy of brand and generic DAAs used in the national treatment program in Egypt. METHODS HCV treatment eligible patients (n=971) were enrolled. They were treated with 12 weeks of either sofosbuvir-daclatasvir (SOF-DCV) or SOF-ledipasvir (SOF-LDV). Ribavirin (RBV) was added to patients with cirrhosis and to SOF experienced patients. Patients with cirrhosis who were RBV intolerant were treated for 24 weeks without RBV. RESULTS Most patients were males (61.4%), treatment naïve (88.6%), without cirrhosis (61.7%), and the mean age was 51.3±11.31 years. Baseline characteristics were not different in patients treated with brand or generic medications regarding age, liver tests, creatinine, platelets, MELD score, baseline HCV-RNA and transient elastography. Overall sustained virologic response (SVR) rate was 98.1%, which was similar for generic and brand drugs (98.2% vs. 98.1%; p=1), and similar with both regimens used (SOF-DCV±RBV: brand: 98.1%, generic 97.8%; p=0.729, SOF-LDV±RBV: brand 98.2%, generic 100%; p=0.729). AST and ALT decreased significantly with initiation of therapy with both generic and original drugs. CONCLUSION Generic and brand DAAs are equally effective for achieving SVR and improving aminotransferases.
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Affiliation(s)
- Mai Abozeid
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Ayman Alsebaey
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt.
| | - Eman Abdelsameea
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Warda Othman
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Mostafa Elhelbawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Amr Rgab
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Marwa Elfayomy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Tamer Samir Abdel-Ghafar
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Mervat Abdelkareem
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Alyaa Sabry
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Marwa Fekry
- Department of Public Health, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Nashwa Shebl
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Eman Rewisha
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Imam Waked
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
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Abozeid M, Alsebaey A, Abdelsameea E, Othman W, Elhelbawy M, Rgab A, Elfayomy M, Abdel-Ghafar TS, Abdelkareem M, Sabry A, Fekry M, Shebl N, Rewisha E, Waked I. High efficacy of generic and brand direct acting antivirals in treatment of chronic hepatitis C. Int J Infect Dis 2018. [DOI: https:/doi.org/10.1016/j.ijid.2018.07.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
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Abozeid M, Alsebaey A, Abdelsameea E, Othman W, Elhelbawy M, Rgab A, Elfayomy M, Abdel-Ghafar TS, Abdelkareem M, Sabry A, Fekry M, Shebl N, Rewisha E, Waked I. High efficacy of generic and brand direct acting antivirals in treatment of chronic hepatitis C. Int J Infect Dis 2018. [DOI: https://doi.org/10.1016/j.ijid.2018.07.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
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Pimpin L, Cortez-Pinto H, Negro F, Corbould E, Lazarus JV, Webber L, Sheron N. Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies. J Hepatol 2018; 69:718-735. [PMID: 29777749 DOI: 10.1016/j.jhep.2018.05.011] [Citation(s) in RCA: 467] [Impact Index Per Article: 66.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 05/04/2018] [Accepted: 05/05/2018] [Indexed: 02/06/2023]
Abstract
The burden of liver disease in Europe continues to grow. We aimed to describe the epidemiology of liver diseases and their risk factors in European countries, identifying public health interventions that could impact on these risk factors to reduce the burden of liver disease. As part of the HEPAHEALTH project we extracted information on historical and current prevalence and mortality from national and international literature and databases on liver disease in 35 countries in the World Health Organization European region, as well as historical and recent prevalence data on their main determinants; alcohol consumption, obesity and hepatitis B and C virus infections. We extracted information from peer-reviewed and grey literature to identify public health interventions targeting these risk factors. The epidemiology of liver disease is diverse, with variations in the exact composition of diseases and the trends in risk factors which drive them. Prevalence and mortality data indicate that increasing cirrhosis and liver cancer may be linked to dramatic increases in harmful alcohol consumption in Northern European countries, and viral hepatitis epidemics in Eastern and Southern European countries. Countries with historically low levels of liver disease may experience an increase in non-alcoholic fatty liver disease in the future, given the rise of obesity across most European countries. Liver disease in Europe is a serious issue, with increasing cirrhosis and liver cancer. The public health and hepatology communities are uniquely placed to implement measures aimed at reducing their causes: harmful alcohol consumption, child and adult obesity, and chronic infection with hepatitis viruses, which will in turn reduce the burden of liver disease.
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Affiliation(s)
| | - Helena Cortez-Pinto
- Departamento de Gastrenterologia, CHLN, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Portugal
| | - Francesco Negro
- Divisions of Gastroenterology and Hepatology and Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland
| | | | - Jeffrey V Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clinic, University of Barcelona, Barcelona, Spain; CHIP, Rigshospitalet, University of Copenhagen, Øster Alle 56, 5. sal, DK-2100 Copenhagen, Denmark
| | | | - Nick Sheron
- University of Southampton, Southampton SO17 1BJ, United Kingdom.
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Chung YS, Choi JY, Han MG, Park KR, Park SJ, Lee H, Jee Y, Kang C. A large healthcare-associated outbreak of hepatitis C virus genotype 1a in a clinic in Korea. J Clin Virol 2018; 106:53-57. [PMID: 30075460 DOI: 10.1016/j.jcv.2018.07.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 06/26/2018] [Accepted: 07/18/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND In November 2015, reuse of needles and syringes in conjunction with an increase in cases of HCV at a clinic in Korea was reported and investigated by public health authorities. Patients who received injections at the clinic from the first time this infection control breach may have occurred in 2008 through 2015 when the practice was stopped were offered screening for HCV and other blood-borne pathogens such as HIV, HTLV, HBV, syphilis, and malaria. OBJECTIVES The aim of this study was to assess whether an outbreak of hepatitis C had occurred among the potentially exposed clinic patients due to this infection control breach. STUDY DESIGN We performed hepatitis C viral RNA load tests and genotyping using plasma from hepatitis C antibody-positive individuals who had visited the clinic between May 2008 and November 2015. We analyzed the core-E2 and NS5B regions of the virus from RNA-positive samples by constructing a phylogenetic tree based on maximum likelihood analysis. To identify transmission risk factors and epidemiological relationships among the patients, we reviewed their medical records, assessed staff infection control practices and performed environmental inspection of the clinic. Environmental samples from medication room surfaces and medication vial contents were tested for HCV RNA. RESULTS AND CONCLUSIONS Among the 1721 patients tested, 96 were IgG-positive and 70 were viral RNA-positive. Among the 61 patients whose viral loads were greater than the detection limit, 41 (67.2%) were classified as genotype 1a, 1 (1.6%) as genotype 1b, 18 (29.5%) as genotype 1, and one (1.6%) as genotype 2. After sequencing, 12 genotype 1 cases were further classified as genotype 1a (11) or 1b (1). The sequences of the core-E2 and NS5B regions of 45 patients formed a monophyletic cluster distinct from genotype 1a. The hepatitis C virus sequences from patients and environmental specimens were well-matched in the partial E1 gene region. We detected genotype 1a RNA in environmental specimens, indicating a healthcare-associated outbreak caused by reuse of syringes and contaminated multi-dose vials. Our molecular epidemiological investigation of hepatitis C genotype 1a, rare in Korea, will aid investigations of infection sources during future pathogen outbreaks.
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Affiliation(s)
- Yoon-Seok Chung
- Division of Viral Diseases, Center for Laboratory Control and Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea
| | - Ju-Yeon Choi
- Division of Viral Diseases, Center for Laboratory Control and Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea
| | - Myung Guk Han
- Division of Viral Diseases Research, Center for Research of Infectious Diseases, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea
| | - Kye Ryeong Park
- Division of Viral Diseases, Center for Laboratory Control and Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea
| | - Su-Jin Park
- Division of Viral Diseases, Center for Laboratory Control and Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea
| | - Hyerim Lee
- Division of Infectious Disease Control, Center for Infectious Disease Control, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea
| | - Youngmee Jee
- Division of Viral Diseases Research, Center for Research of Infectious Diseases, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea
| | - Chun Kang
- Division of Viral Diseases, Center for Laboratory Control and Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea.
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Cipriano LE, Goldhaber-Fiebert JD. Population Health and Cost-Effectiveness Implications of a "Treat All" Recommendation for HCV: A Review of the Model-Based Evidence. MDM Policy Pract 2018; 3:2381468318776634. [PMID: 30288448 PMCID: PMC6157435 DOI: 10.1177/2381468318776634] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 04/20/2018] [Indexed: 12/15/2022] Open
Abstract
The World Health Organization HCV Guideline Development Group is considering a "treat all" recommendation for persons infected with hepatitis C virus (HCV). We reviewed the model-based evidence of cost-effectiveness and population health impacts comparing expanded treatment policies to more limited treatment access policies, focusing primarily on evaluations of all-oral directly acting antivirals published after 2012. Searching PubMed, we identified 2,917 unique titles. Sequentially reviewing titles and abstracts identified 226 potentially relevant articles for full-text review. Sixty-nine articles met all inclusion criteria-42 cost-effectiveness analyses and 30 models of population-health impacts, with 3 articles presenting both types of analysis. Cost-effectiveness studies for many countries concluded that expanding treatment to people with mild liver fibrosis, who inject drugs (PWID), or who are incarcerated is generally cost-effective compared to more restrictive treatment access policies at country-specific prices. For certain patient subpopulations in some countries-for example, elderly individuals without fibrosis-treatment is only cost-effective at lower prices. A frequent limitation is the omission of benefits and consequences of HCV transmission (i.e., treatment as prevention; risks of reinfection), which may underestimate or overestimate the cost-effectiveness of a "treat all" policy. Epidemiologic modeling studies project that through a combination of prevention, aggressive screening and diagnosis, and prompt treatment for all fibrosis stages, it may be possible to virtually eliminate HCV in many countries. Studies show that if resources are not available to diagnose and treat all HCV-infected individuals, treatment prioritization may be needed, with alternative prioritization strategies resulting in tradeoffs between reducing mortality or reducing incidence. Notably, because most new HCV infections are among PWID in many settings, HCV elimination requires unrestricted treatment access combined with injection transmission disruption strategies. The model-based evidence suggests that a properly constructed strategy that substantially expands HCV treatment could achieve cost-effective improvements in population health in many countries.
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Affiliation(s)
- Lauren E Cipriano
- Ivey Business School and the Department of Biostatistics and Epidemiology, Western University, London, Ontario, Canada
| | - Jeremy D Goldhaber-Fiebert
- Center for Health Policy and Center for Primary Care and Outcomes Research, Department of Medicine, Stanford University, Stanford, California
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Elsharkawy A, El-Raziky M, El-Akel W, El-Saeed K, Eletreby R, Hassany M, El-Sayed MH, Kabil K, Ismail SA, El-Serafy M, Abdelaziz AO, Shaker MK, Yosry A, Doss W, El-Shazly Y, Esmat G, Waked I. Planning and prioritizing direct-acting antivirals treatment for HCV patients in countries with limited resources: Lessons from the Egyptian experience. J Hepatol 2018; 68:691-698. [PMID: 29223371 DOI: 10.1016/j.jhep.2017.11.034] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2017] [Revised: 11/16/2017] [Accepted: 11/20/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS The introduction of direct-acting antivirals for hepatitis C virus (HCV) in Egypt led to massive treatment uptake, with Egypt's national HCV treatment program becoming the largest in the world. The aim of this paper is to present the Egyptian experience in planning and prioritizing mass treatment for patients with HCV, highlighting the difficulties and limitations of the program, as a guide for other countries of similarly limited resources. METHODS Baseline data of 337,042 patients, treated between October 2014 to March 2016 in specialized viral hepatitis treatment centers, were grouped into three equal time intervals of six months each. Patients were treated with different combinations of direct-acting antivirals, with or without ribavirin and pegylated interferon. Baseline data, percentage of patients with known outcome, and sustained virological response at week 12 (SVR12) were analyzed for the three cohorts. The outcomes of 94,258 patients treated in the subsequent two months are also included. RESULTS For cohort-1, treatment was prioritized for patients with advanced fibrosis (F3-F4 fibrosis, liver stiffness ≥9.5 kPa, or Fibrosis-4 ≥3.25). Starting cohort-2, all stages of fibrosis were included (F0-F4). The prioritization strategy in the initial phase caused delays in enrollment and massive backlogs. Cohort-1 patients were significantly older, and more had advanced fibrosis compared to subsequent cohorts. The percentage of patients with known SVR12 results were low initially, and increased with each cohort, as several methods to capture patient results were adopted. Sofosbuvir-ribavirin therapy for 24 weeks had the lowest SVR12 rate (82.7%); while other therapies were associated with SVR12 rates between 94% and 98%. CONCLUSION Prioritization based on fibrosis stage was not effective and enrollment increased greatly only after including all stages of fibrosis. The availability of generic drugs reduced costs, and helped massively increase uptake of the program. Post-treatment follow-up was initially very low, and although this has increased, further improvement is still needed. LAY SUMMARY We are presenting the largest national program for HCV treatment in the world. We clearly demonstrate that hepatitis C can be cured efficiently in large scale real-life programs. This is a clear statement that global HCV eradication is foreseeable, providing a model for other countries with limited resources and prevalent HCV. Moreover, the availability of generic products has influenced the success of this program.
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Affiliation(s)
- Aisha Elsharkawy
- Endemic Medicine and Hepatogastroentrology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Maissa El-Raziky
- Endemic Medicine and Hepatogastroentrology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Wafaa El-Akel
- Endemic Medicine and Hepatogastroentrology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Kadry El-Saeed
- Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Rasha Eletreby
- Endemic Medicine and Hepatogastroentrology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Hassany
- Tropical Medicine Department, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt
| | | | - Khaled Kabil
- New Pediatric Children Hospital, Cairo University, Cairo, Egypt
| | - Sohier A Ismail
- Tropical Medicine Department, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt
| | - Magdy El-Serafy
- Endemic Medicine and Hepatogastroentrology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ashraf Omar Abdelaziz
- Endemic Medicine and Hepatogastroentrology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Kamal Shaker
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ayman Yosry
- Endemic Medicine and Hepatogastroentrology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Wahid Doss
- Endemic Medicine and Hepatogastroentrology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Yehia El-Shazly
- Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatogastroentrology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Imam Waked
- Department of Hepatology, National Liver Institute, Menoufiya University, Menoufiya, Egypt
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[Personalized treatment of viral hepatitis of the present and the future : Hepatitis B, C, delta, and E]. Internist (Berl) 2018. [PMID: 28631044 DOI: 10.1007/s00108-017-0262-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Precision medicine is also possible for infectious diseases as shown for the treatment of chronic viral hepatitis, especially if different options are available. In hepatitis B virus (HBV) infection, treatment indication as well as the choice of treatment and the decisions to stop treatment are based on viral markers and alanine aminotransferase (ALT) level. Future therapies for HBV infection aiming for functional cure or even virus elimination may be even more personalized and have to take into account the immune status of a given patient. Such treatment modalities might also increase the chance for successful treatment of chronic hepatitis delta where treatment options are still very limited. Some new therapeutic concepts targeting host receptors or host enzymes are promising, but may require individualized approaches. Chronic hepatitis C is a good example for precision medicine based on viral and host factors. However, the main reason for individualized direct-acting antiviral (DAA) treatment is to save costs. As DAAs are effective in more than 95% of patients, elimination of HCV seems to be possible at the level of a given country or even on a global scale. However, owing to high reinfection rates in high-risk groups and limited availability of antiviral therapy in many high endemic countries, it must still be decided whether an HCV vaccine or pre-exposure prophylaxis is required to achieve this goal. Hepatitis E is an emerging topic as this is the most frequent acute hepatitis virus infection. It can result in a chronic infection in immunosuppressed individuals. Treatment options are still limited and individualized management is based on tailoring immunosuppressive therapy and therapy with ribavirin. Thus, personalized therapy of hepatitis E virus infection is still limited.
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Bethea E, Chen Q, Hur C, Chung RT, Chhatwal J. Should we treat acute hepatitis C? A decision and cost-effectiveness analysis. Hepatology 2018; 67:837-846. [PMID: 29059461 PMCID: PMC5826841 DOI: 10.1002/hep.29611] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 10/12/2017] [Accepted: 10/19/2017] [Indexed: 12/20/2022]
Abstract
It is not standard practice to treat patients with acute hepatitis C virus (HCV) infection. However, as the incidence of HCV in the United States continues to rise, it may be time to re-evaluate acute HCV management in the era of direct-acting antiviral (DAA) agents. In this study, a microsimulation model was developed to analyze the trade-offs between initiating HCV therapy in the acute versus chronic phase of infection. By simulating the lifetime clinical course of patients with acute HCV infection, we were able to project long-term outcomes such as quality-adjusted life years (QALYs) and costs. We found that treating acute HCV versus deferring treatment until the chronic phase increased QALYs by 0.02 and increased costs by $483 in patients not at risk of transmitting HCV. The resulting incremental cost-effectiveness ratio was $19,991 per QALY, demonstrating that treatment of acute HCV was cost-effective using a willingness-to-pay threshold of $100,000 per QALY. In patients at risk of transmitting HCV, treating acute HCV became cost-saving, increasing QALYs by 0.03 and decreasing costs by $3,655. CONCLUSION Immediate treatment of acute HCV with DAAs can improve clinical outcomes and be highly cost-effective or cost-saving compared with deferring treatment until the chronic phase of infection. If future studies continue to demonstrate effective HCV cure with shorter 6-week treatment duration, then it may be time to revisit current HCV guidelines to incorporate recommendations that account for the clinical and economic benefits of treating acute HCV in the era of DAAs. (Hepatology 2018;67:837-846).
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Affiliation(s)
- Emily Bethea
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA
- Harvard Medical School, Boston, MA
- Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Qiushi Chen
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA
- Harvard Medical School, Boston, MA
| | - Chin Hur
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA
- Harvard Medical School, Boston, MA
- Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Raymond T. Chung
- Harvard Medical School, Boston, MA
- Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Jagpreet Chhatwal
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA
- Harvard Medical School, Boston, MA
- Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
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Linkage to care of HbsAg-positive and anti-HCV-positive patients after a systematic screening approach in the German primary care setting. Eur J Gastroenterol Hepatol 2018; 30:280-283. [PMID: 29324587 DOI: 10.1097/meg.0000000000001052] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Identification of previously unknown cases is important to lower the burden of chronic hepatitis B and C infection. However, a screening program in the primary care setting has not yet been established. Therefore, a systematic screening project was conducted in 21 008 patients (Wolffram and colleagues). Here, we describe linkage to care of identified HbsAg-positive and anti-hepatitis C virus (HCV)-positive patients. METHODS General practitioners characterized further medical care by a standardized questionnaire. Data of 48/110 HbsAg-positive and 114/199 anti-HCV-positive patients were available. An APRI index more than 2 or up to 0.5 indicated the presence of cirrhosis or the absence of fibrosis. RESULTS APRI was calculated in 32/48 hepatitis B virus (HBV) patients (>2: n=1; ≤0.5: n=29) and 34/114 HCV patients (>2: n=4; ≤0.5: n=23). The general practitioners were already aware of the positive HBsAg and anti-HCV-test in 13/48 and 59/114 patients, respectively.For 29/35 newly diagnosed HBV patients and 26/55 HCV patients, further diagnostics were initiated: ultrasound 77 versus 38%, liver biopsy 20 versus 4%, and gastroscopy 20 versus 7%.Antiviral treatment was initiated in 5/35 HBV cases and in 10/55 HCV patients.A family screening was initiated in 22/35 HBV versus 13/55 HCV index patients and showed one additional HbsAg-positive and two anti-HCV-positive cases.Diagnostic procedures differed significantly between anti-HCV-positive and HbsAg-positive patients (P<0.001 for APRI, ultrasound, and family screening; P=0.03 for liver biopsy). CONCLUSION Diagnostic procedures should be improved for hepatitis C-infected patients. The APRI index was only of limited value in the primary care setting.
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Béguelin C, Suter A, Bernasconi E, Fehr J, Kovari H, Bucher HC, Stoeckle M, Cavassini M, Rougemont M, Schmid P, Wandeler G, Rauch A. Trends in HCV treatment uptake, efficacy and impact on liver fibrosis in the Swiss HIV Cohort Study. Liver Int 2018; 38:424-431. [PMID: 28741901 DOI: 10.1111/liv.13528] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Accepted: 07/20/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) therapies with interferon-free second-generation direct-acting antivirals (DAAs) are highly effective and well tolerated. They have the potential to increase treatment eligibility and efficacy in HIV-infected patients. We assessed the impact of DAAs on treatment uptake and efficacy, as well as its impact on the burden of liver disease in the Swiss HIV Cohort Study (SHCS). METHODS We describe clinical and virological characteristics of patients treated with second-generation DAAs. We compared treatment incidence, sustained virological response (SVR)12 and liver fibrosis stages between three time periods: period 1, 01/2009-08/2011 (prior to the availability of DAAs); period 2, 09/2011-03/2014 (first generation DAAs); period 3, 04/2014-12/2015 (second generation DAAs). RESULTS At the beginning of the third period, 876 SHCS participants had a chronic HCV infection of whom 180 (20%) started treatment with a second-generation DAA. Three-quarters of them had advanced liver fibrosis (Metavir ≥ F3) of whom 80% were cirrhotics. SVR12 was achieved in 173/180 (96%) patients, three patients died and four experienced a virological failure. Over the three time periods, treatment uptake (4.5/100 py, 5.7/100 py, 22.4/100 py) and efficacy (54%, 70%, 96% SVR12) continuously increased. The proportion of cirrhotic patients with replicating HCV infection in the SHCS declined from 25% at the beginning to 12% at the end of the last period. CONCLUSIONS After the introduction of second-generation DAAs, we observed an increase in treatment uptake and efficacy which resulted in a significant reduction in the number of cirrhotic patients with a replicating HCV infection in the SHCS.
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Affiliation(s)
- Charles Béguelin
- Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Annatina Suter
- Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Enos Bernasconi
- Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland
| | - Jan Fehr
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Helen Kovari
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Heiner C Bucher
- Basel Institute for Clinical Epidemiology & Biostatistics, University Hospital Basel and University of Basel, Basel, Switzerland.,Department of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Marcel Stoeckle
- Department of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Mathias Cavassini
- Division of Infectious Diseases, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland
| | - Mathieu Rougemont
- Division of Infectious Diseases, University Hospital Geneva, University of Geneva, Geneva, Switzerland
| | - Patrick Schmid
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St.Gallen, St.Gallen, Switzerland
| | - Gilles Wandeler
- Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland.,Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Andri Rauch
- Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland
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Fraser H, Martin NK, Brummer-Korvenkontio H, Carrieri P, Dalgard O, Dillon J, Goldberg D, Hutchinson S, Jauffret-Roustide M, Kåberg M, Matser AA, Matičič M, Midgard H, Mravcik V, Øvrehus A, Prins M, Reimer J, Robaeys G, Schulte B, van Santen DK, Zimmermann R, Vickerman P, Hickman M. Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe. J Hepatol 2018; 68:402-411. [PMID: 29080808 PMCID: PMC5841161 DOI: 10.1016/j.jhep.2017.10.010] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2016] [Revised: 10/02/2017] [Accepted: 10/08/2017] [Indexed: 12/31/2022]
Abstract
BACKGROUND & AIMS Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. METHODS We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. RESULTS At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%. CONCLUSIONS The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. LAY SUMMARY Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment).
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Affiliation(s)
- Hannah Fraser
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
| | - Natasha K Martin
- Division of Global Public Health, University of California, San Diego, San Diego, CA, USA; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | | | - Patrizia Carrieri
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Marseille, France; ORS PACA, Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur, Marseille, France
| | - Olav Dalgard
- University of Oslo, Oslo, Norway; Akershus University Hospital, Lørenskog, Norway
| | | | | | - Sharon Hutchinson
- Glasgow Caledonian University, Glasgow, Scotland, UK; Health Protection Scotland, Glasgow, Scotland, UK
| | - Marie Jauffret-Roustide
- French Institute for Public Health Surveillance, St. Maurice, France; CERMES3 (Inserm U988/UMR CNRS 8211/EHESS/Paris Descartes University), Paris, France
| | - Martin Kåberg
- Department of Medicine, Huddinge, Division of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Amy A Matser
- Public Health Service of Amsterdam, Amsterdam, The Netherlands; University Medical Center Utrecht, Utrecht, The Netherlands
| | - Mojca Matičič
- University of Ljubljana, Ljubljana, Slovenia; University Medical Centre Ljubljana, Ljubljana, Slovenia
| | | | - Viktor Mravcik
- National Monitoring Centre for Drugs and Drug Addiction, Prague, Czech Republic; Charles University and General University Hospital in Prague, Prague, Czech Republic; National Institute of Mental Health, Klecany, Czech Republic
| | | | - Maria Prins
- Public Health Service of Amsterdam, Amsterdam, The Netherlands; Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Jens Reimer
- HealthNorth, Bremen, Germany; University of Hamburg, Hamburg, Germany
| | - Geert Robaeys
- Ziekenhuis Oost-Limburg, Genk, Belgium; Hasselt University, Diepenbeek, Belgium; University Hospital Leuven, Leuven, Belgium
| | | | | | | | - Peter Vickerman
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Matthew Hickman
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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Hashim A, O’Sullivan M, Williams H, Verma S. Developing a community HCV service: project ITTREAT (integrated community-based test - stage - TREAT) service for people who inject drugs. Prim Health Care Res Dev 2018; 19:110-120. [PMID: 29199921 PMCID: PMC6452958 DOI: 10.1017/s1463423617000731] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 09/05/2017] [Accepted: 10/08/2017] [Indexed: 12/19/2022] Open
Abstract
Background and aims Majority of the individuals with hepatitis C virus (HCV) infection in England are people who inject drugs, a vulnerable and disenfranchised cohort with poor engagement with secondary care. Our aim is to describe our experiences in setting up a successful nurse led HCV service at a substance misuse service (SMS). METHODS We justify the need for a community HCV service and review the different community based models. Our experiences in engaging with stakeholders, obtaining funding, service set up, challenges faced and key recommendations are discussed. Finally, a summary of interim clinical outcomes is presented. RESULTS A successful community based "one-stop" nurse led HCV service was set up in Dec 2013 at a large SMS. It provides all aspects of care (blood borne virus screening, non-invasive assessment of hepatic fibrosis, Hepatology input, HCV treatment, peer mentor, social and psychiatrist support, and opiod substitution) at one site. Interim clinical data indicate high service uptake with HCV treatment outcomes comparable to secondary care. CONCLUSIONS The advent of direct acting antivirals provides a unique opportunity for HCV elimination in England by 2030. Our "one-stop" integrated and multidisciplinary community HCV model suggests that HCV care can be successfully delivered outside of a hospital setting and warrants national adoption.
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Affiliation(s)
- Ahmed Hashim
- Department of Medicine, Brighton and Sussex Medical School, Brighton, UK
- Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospital, Brighton, UK
| | - Margaret O’Sullivan
- Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospital, Brighton, UK
- Pavilions Drug & Alcohol Services, Richmond House, Brighton, UK
| | - Hugh Williams
- Pavilions Drug & Alcohol Services, Richmond House, Brighton, UK
- Surrey and Borders Partnership NHS foundation trust
| | - Sumita Verma
- Department of Medicine, Brighton and Sussex Medical School, Brighton, UK
- Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospital, Brighton, UK
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Falla AM, Hofstraat SHI, Duffell E, Hahné SJM, Tavoschi L, Veldhuijzen IK. Hepatitis B/C in the countries of the EU/EEA: a systematic review of the prevalence among at-risk groups. BMC Infect Dis 2018; 18:79. [PMID: 29433454 PMCID: PMC5809955 DOI: 10.1186/s12879-018-2988-x] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Accepted: 01/31/2018] [Indexed: 12/22/2022] Open
Abstract
Background In 2016, the World Health Organisation set a goal to eliminate viral hepatitis by 2030. Robust epidemiological information underpins all efforts to achieve elimination and this systematic review provides estimates of HBsAg and anti-HCV prevalence in the European Union/European Economic Area (EU/EEA) among three at-risk populations: people in prison, men who have sex with men (MSM), and people who inject drugs (PWID). Methods Estimates of the prevalence among the three risk groups included in our study were derived from multiple sources. A systematic search of literature published during 2005–2015 was conducted without linguistic restrictions to identify studies among people in prison and HIV negative/HIV sero-status unknown MSM. National surveillance focal points were contacted to validate the search results. Studies were assessed for risk of bias and high quality estimates were pooled at country level. PWID data were extracted from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) repository. Results Despite gaps, we report 68 single study/pooled HBsAg/anti-HCV prevalence estimates covering 23/31 EU/EEA countries, 42 of which were of intermediate/high prevalence using the WHO endemicity threshold (of ≥2%). This includes 20 of the 23 estimates among PWID, 20 of the 28 high quality estimates among people in prison, and four of the 17 estimates among MSM. In general terms, the highest HBsAg prevalence was found among people in prison (range of 0.3% - 25.2%) followed by PWID (0.5% - 6.1%) and MSM (0.0% - 1.4%). The highest prevalence of anti-HCV was also found among people in prison (4.3% - 86.3%) and PWID (13.8% - 84.3%) followed by MSM (0.0% - 4.7%). Conclusions Our results suggest prioritisation of PWID and the prison population as the key populations for HBV/HCV screening and treatment given their dynamic interaction and high prevalence. The findings of this study do not seem to strongly support the continued classification of MSM as a high risk group for chronic hepatitis B infection. However, we still consider MSM a key population for targeted action given the emerging evidence of viral hepatitis transmission within this risk group together with the complex interaction of HBV/HCV and HIV. Electronic supplementary material The online version of this article (10.1186/s12879-018-2988-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Abby May Falla
- Division of Infectious Disease Control, Municipal Public Health Service Rotterdam-Rijnmond, Rotterdam, the Netherlands. .,Department of Public Health, Erasmus MC, University Medical Centre Rotterdam, Box 70032, 3000 LP, Rotterdam, The Netherlands.
| | - Sanne Henrietta Ina Hofstraat
- National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, Postbus 1, 3720 BA, Bilthoven, the Netherlands
| | - Erika Duffell
- European Centre for Disease Prevention and Control, Granits väg 8, 171 65, Solna, Sweden
| | - Susan Josien Maria Hahné
- National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, Postbus 1, 3720 BA, Bilthoven, the Netherlands
| | - Lara Tavoschi
- European Centre for Disease Prevention and Control, Granits väg 8, 171 65, Solna, Sweden
| | - Irene Karen Veldhuijzen
- Division of Infectious Disease Control, Municipal Public Health Service Rotterdam-Rijnmond, Rotterdam, the Netherlands.,National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, Postbus 1, 3720 BA, Bilthoven, the Netherlands
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Balasubramanian K, Patil VM. Quantum molecular modeling of hepatitis C virus inhibition through non-structural protein 5B polymerase receptor binding of C 5-arylidene rhodanines. Comput Biol Chem 2018; 73:147-158. [PMID: 29486389 DOI: 10.1016/j.compbiolchem.2018.01.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 01/09/2018] [Accepted: 01/23/2018] [Indexed: 11/25/2022]
Abstract
We have carried out high-level quantum chemical computations followed by molecular docking studies on a set of 17C5-arylidene rhodanine isomers to provide insights into the binding modes with different reported binding pockets of the nonstructural protein 5B (NS5B) polymerase that contribute to the hepatitis C virus (HCV) inhibition. We optimized the multi-target profile of the selected rhodanine analogs to investigate potential non-nucleotide inhibitors (NNIs) by quantum chemical optimization of the 18 isomers followed by docking with quantum chemically optimized structures of each isomer with NS5B polymerase at multiple binding pockets. The binding affinities of the PP-I, PP-II and TP-II pockets of NS5B polymerase were analyzed for all the 17 isomers of 2-[(5Z)-5-(2,4-dichlorobenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid. On the basis of binding propensity at the different pockets and inhibitor constants, we ranked these isomers as potential candidates for the HCV inhibition. We have identified four isomers as promising NNIs of NS5B polymerase with comparable binding and inhibition to the standard (1,3) dichloro substituted isomer that exhibits in vitro activity and several other isomers as candidates in a "multi-targeted drug" approach.
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Affiliation(s)
| | - Vaishali M Patil
- Department of Pharmaceutical Chemistry, KIET School of Pharmacy, KIET Group of Institutions, Ghaziabad, Uttar Pradesh, India.
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