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Batsaikhan O, Chimed-Ochir O, Kubo T, Jigjidsuren C, Delgermaa V, Purevdagva A, Sarankhuu A, Nansalmaa E, Tsegmed U, Davgasuren B, Purev O, Mokdad AH, Weaver ND, Erkhembayar R, Murray CJL, Naghavi M. The burden of liver cancer in Mongolia from 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Front Oncol 2024; 14:1381173. [PMID: 39290241 PMCID: PMC11405307 DOI: 10.3389/fonc.2024.1381173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 07/22/2024] [Indexed: 09/19/2024] Open
Abstract
Background Liver cancer remains the leading cause of death and public health threat among the Mongolian population. So far, there has been no in-depth analysis to describe the burden of common attributable factors to liver cancer in Mongolia. Therefore, we aimed to explore the most prevalent causes of liver cancer and its trends from 1990 to 2019. Methods We extracted the primary liver cancer data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to examine the mortality and morbidity of liver cancer by its etiological types, which included alcohol, viral hepatitis B and C, and non-alcoholic steatohepatitis (NASH). The data was extracted by sex and 5-year age intervals from 1990 to 2019. Data included mortality, incidence, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) of liver cancer among the Mongolian population. Results Mongolia had the world's highest age-standardized DALYs for liver cancer (2558.1) in 2019. Alcohol-attributable DALYs (786.6) were 29 times higher than the global average (26.1), and liver cancer due to hepatitis C (752.6) and B (763.2) were 21.5 (35.0) and 10.9 (69.1) times higher, respectively. Over the past 30 years, there has been a steady increase in the incidence and number of deaths caused by liver cancer in Mongolia. In 2019, liver cancer incidence due to alcohol consumption was 3.1 times higher for males than females, and hepatitis B was 2.7 times higher for males than females. However, the incidence of hepatitis C and NASH were slightly higher for females. Deaths from liver cancer accounted for 9.51% (2365) of total deaths in Mongolia in 2019, with a continuously increasing trend in the fraction of death compared to 1990, which was 11 times higher than the global average (0.86%), particularly in females with a 319.6% (95% UI 234.9-435.7) increase observed during the study period. Liver cancer due to hepatitis B, C, and alcohol each shared about one-third of liver cancer deaths. Conclusion A comprehensive analysis of the burden of liver cancer in Mongolia reveals alcohol use as a primary cause of liver cancer mortality, particularly affecting men and significantly impacting the disease burden. Viral hepatitis continues to pose a major public health concern in the country. Although significant milestones have progressed, addressing the unique demographic and geographical challenges requires tailored approaches for specific target populations. The evidence generated from this analysis is crucial to support policy guidance, contribute to evidence-based decisions, guide public health prevention measures, and amplify population health promotion and disease prevention throughout Mongolia.
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Affiliation(s)
- Oyundari Batsaikhan
- Department of Public Health and Health Policy, Hiroshima University, Hiroshima, Japan
| | - Odgerel Chimed-Ochir
- Department of Public Health and Health Policy, Hiroshima University, Hiroshima, Japan
| | - Tatsuhiko Kubo
- Department of Public Health and Health Policy, Hiroshima University, Hiroshima, Japan
| | | | | | - Anuzaya Purevdagva
- Communicable Diseases, World Health Organization (WHO), Ulaanbaatar, Mongolia
| | | | | | | | - Badral Davgasuren
- Infectious Diseases Surveillance and Research Department, National Center for Communicable Diseases, Ulaanbaatar, Mongolia
| | - Oyuntsetseg Purev
- Department of Policy Planning, Ministry of Health, Ulaanbaatar, Mongolia
| | - Ali H. Mokdad
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, United States
- Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, United States
| | - Nicole Davis Weaver
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, United States
| | - Ryenchindorj Erkhembayar
- Department of International Cyber Education, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Christopher J. L. Murray
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, United States
- Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, United States
| | - Mohsen Naghavi
- Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, United States
- Department of Health Metrics Sciences, School of Medicine, University of Washington, Seattle, WA, United States
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Baptista-Leite R, Lopes H, Vandewalle B, Félix J, Franco D, Clemens T, Brand H. Epidemiological Modeling of the Impact of Public Health Policies on Hepatitis C: Protocol for a Gamification Tool Targeting Microelimination. JMIR Res Protoc 2023; 12:e38521. [PMID: 37747764 PMCID: PMC10562970 DOI: 10.2196/38521] [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: 04/05/2022] [Revised: 06/06/2023] [Accepted: 06/07/2023] [Indexed: 09/26/2023] Open
Abstract
BACKGROUND Hepatitis C is a disease with a strong social component, as its main transmission route is via blood, making it associated with lifestyle. Therefore, it is suitable to be worked on from the perspective of public health policy, which still has a lot of room to explore and improve, contrary to diagnoses and treatments, which are already very refined and effective. OBJECTIVE An interactive gamified policy tool, designated as Let's End HepC (LEHC), was created to understand the impact of policies related to hepatitis C on the disease's epidemiology on a yearly basis until 2030. METHODS To this end, an innovative epidemiological model was developed, integrating Markov chains to model the natural history of the disease and adaptive conjoint analysis to reflect the degree of application of each of the 24 public health policies included in the model. This double imputation model makes it possible to assess a set of indicators such as liver transplant, incidence, and deaths year by year until 2030 in different risk groups. Populations at a higher risk were integrated into the model to understand the specific epidemiological dynamics within the total population of each country and within segments that comprise people who have received blood products, prisoners, people who inject drugs, people infected through vertical transmission, and the remaining population. RESULTS The model has already been applied to a group of countries, and studies in 5 of these countries have already been concluded, showing results very close to those obtained through other forms of evaluation. CONCLUSIONS The LEHC model allows the simulation of different degrees of implementation of each policy and thus the verification of its epidemiological impact on each studied population. The gamification feature allows assessing the adequate fulfillment of the World Health Organization goals for the elimination of hepatitis C by 2030. LEHC supports health decision makers and people who practice patient advocacy in making decisions based on science, and because LEHC is democratically shared, it ends up contributing to the increase of citizenship in health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) RR1-10.2196/38521.
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Affiliation(s)
- Ricardo Baptista-Leite
- Department of International Health, Care and Public Health Research Institute - CAPHRI, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
- NOVA Center for Global Health - Information Management School, Universidade Nova de Lisboa, Lisbon, Portugal
| | - Henrique Lopes
- NOVA Center for Global Health - Information Management School, Universidade Nova de Lisboa, Lisbon, Portugal
| | | | | | - Diogo Franco
- NOVA Center for Global Health - Information Management School, Universidade Nova de Lisboa, Lisbon, Portugal
| | - Timo Clemens
- Department of International Health, Care and Public Health Research Institute - CAPHRI, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
| | - Helmut Brand
- Department of International Health, Care and Public Health Research Institute - CAPHRI, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
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Brooks R, Wegener M, Speers S, Nichols L, Sideleau R, Valeriano T, Buchelli M, Villanueva M. Creating a Longitudinal HCV Care Cascade for Persons With HIV/HCV Coinfection in Selected HIV Clinics Using Data to Care Methods. Health Promot Pract 2023; 24:1039-1049. [PMID: 37439600 DOI: 10.1177/15248399231169792] [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] [Indexed: 07/14/2023]
Abstract
Highly effective direct-acting antiviral (DAA) treatments for hepatitis C have led to strategic goals promoting hepatitis C virus (HCV) cure particularly in focus populations including persons with HIV/HCV coinfection. Implementing treatment more broadly requires both clinic-level and public health approaches such as those inherent in Data to Care (D2C) originally developed to improve the treatment cascade for persons with HIV (PWH). We used D2C methods to characterize and improve HCV treatment for persons with HIV/HCV coinfection among 11 HIV clinics in Connecticut cities with high PWH prevalence. Providers who were local champions in HCV treatment were recruited to participate along with clinic data staff and were key to quality improvement via practice transformation. We developed a methodology whereby clinic-generated lists of PWH receiving care from 2009 to 2018 were matched by CT Department of Public Health (DPH) against the state-wide HCV surveillance system. The resultant coinfection list was reviewed by clinical staff who designated HCV treatment status, enabling creation of individual clinic-level HCV treatment cascades. Data from DPH, especially current residency and deaths, enabled better characterization and allowed for refinement of longitudinal cascades. There were 1,496 patients with HIV/HCV coinfection. Sustained virologic response (SVR) rates varied by clinic (range, 44%-100%) with an aggregate SVR rate of 71% in September 2020. SVR rates improved during the project through a combination of increased treatment initiation/completion as well as data clean-up including serial updates of patient treatment status. Lack of treatment initiation was associated with being female (odds ratio [OR] = 2.18) and not having HIV viral suppression (OR = 3.24).
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Affiliation(s)
| | | | - Suzanne Speers
- Connecticut Department of Public Health, Hartford, CT, USA
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Country versus pharmaceutical company interests for hepatitis C treatment. Health Care Manag Sci 2022; 25:725-749. [PMID: 36001218 PMCID: PMC9399601 DOI: 10.1007/s10729-022-09607-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 07/06/2022] [Indexed: 11/04/2022]
Abstract
Hepatitis C virus (HCV) is one of the leading causes of liver disease and is responsible for massive health and economic burden worldwide. The disease is asymptomatic in its early stages, but it can progress over time to fatal end-stage liver disease. Thus, the majority of individuals infected with HCV are unaware of their chronic condition. Recent treatment options for HCV can completely cure the infection but are costly. We developed a game model between a pharmaceutical company (PC) and a country striving to maximize its citizens' utility. First, the PC determines the price of HCV treatment; then, the country responds with corresponding screening and treatment strategies. We employed an analytical framework to calculate the utility of the players for each selected strategy. Calibrated to detailed HCV data from Israel, we found that the PC will gain higher revenue by offering a quantity discount rather than using standard fixed pricing per treatment, by indirectly forcing the country to conduct more screening than it desired. By contrast, risk-sharing agreements, in which the country pays only for successful treatments are beneficial for the country. Our findings underscore that policy makers worldwide should prudently consider recent offers by PCs to increase screening either directly, via covering HCV screening, or indirectly, by providing discounts following a predetermined volume of sales. More broadly, our approach is applicable in other healthcare settings where screening is essential to determine treatment strategies.
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Matthews DW, Coleman S, Razavi H, Izaret J. The Payer License Agreement, or "Netflix model," for hepatitis C virus therapies enables universal treatment access, lowers costs and incentivizes innovation and competition. Liver Int 2022; 42:1503-1516. [PMID: 35289467 PMCID: PMC9314612 DOI: 10.1111/liv.15245] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 02/18/2022] [Accepted: 03/10/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS High unit prices of treatments limit access. For epidemics like that of hepatitis C virus (HCV), reduced treatment access increases prevalence and incidence, making the infectious disease increasingly difficult to manage. The objective of the current study was to construct and test an alternative pricing model, the Payer License Agreement (PLA), and determine whether it could improve outcomes, cut costs and incentivize innovation versus the current unit-based pricing model. METHODS We built and used computational models of hepatitis C disease progression, treatment, and pricing in historical and future scenarios and quantitatively analyzed their economic and epidemiological impact in three high-income countries. RESULTS This study had three key results regarding HCV treatment. First, if the PLA model had been implemented when interferon-free direct-acting antiviral (DAA) combinations launched, the number of patients treated and cured would have more than doubled in the first three years, while the liver-related deaths (LRDs) would have decreased by around 40%. Second, if the PLA model had been implemented beginning in 2018, the year that several Netflix-like payment models were under implementation, the number of treated and cured patients would nearly double, and the LRDs would decline by more than 55%. Third, implementing the PLA model would result in a decline in total payer costs of more than 25%, with an increase to pharmaceutical manufacturer revenues of 10%. These results were true across the three healthcare landscapes studied, the USA, the UK and Italy, and were robust against variations to critical model parameters through sensitivity analysis. CONCLUSIONS AND RELEVANCE These results suggest that implementation of the PLA model in high-income countries across a variety of health system contexts would improve patient outcomes at lower payer cost with more stable revenue for pharmaceutical manufacturers. Health policy-makers in high-income countries should consider the PLA model for application to more cost-effective management of HCV, and explore its application for other infectious diseases with curative therapies available now or soon.
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Affiliation(s)
- David W. Matthews
- The Boston Consulting GroupBostonMassachusettsUSA,The Bruce Henderson InstituteNew YorkNew YorkUSA
| | | | - Homie Razavi
- The Center for Disease Analysis (CDA)LafayetteColoradoUSA
| | - Jean‐Manuel Izaret
- The Boston Consulting GroupBostonMassachusettsUSA,The Bruce Henderson InstituteNew YorkNew YorkUSA
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Blach S, Terrault NA, Tacke F, Gamkrelidze I, Craxi A, Tanaka J, Waked I, Dore GJ, Abbas Z, Abdallah AR, Abdulla M, Aghemo A, Aho I, Akarca US, Alalwan AM, Alanko Blomé M, Al-Busafi SA, Aleman S, Alghamdi AS, Al-Hamoudi WK, Aljumah AA, Al-Naamani K, Al Serkal YM, Altraif IH, Anand AC, Anderson M, Andersson MI, Athanasakis K, Baatarkhuu O, Bakieva SR, Ben-Ari Z, Bessone F, Biondi MJ, Bizri ARN, Brandão-Mello CE, Brigida K, Brown KA, Brown, Jr RS, Bruggmann P, Brunetto MR, Busschots D, Buti M, Butsashvili M, Cabezas J, Chae C, Chaloska Ivanova V, Chan HLY, Cheinquer H, Cheng KJ, Cheon ME, Chien CH, Chien RN, Choudhuri G, Christensen PB, Chuang WL, Chulanov V, Cisneros LE, Coco B, Contreras FA, Cornberg M, Cramp ME, Crespo J, Cui F, Cunningham CW, Dagher Abou L, Dalgard O, Dao DY, De Ledinghen V, Derbala MF, Deuba K, Dhindsa K, Djauzi S, Drazilova S, Duberg AS, Elbadri M, El-Sayed MH, Esmat G, Estes C, Ezzat S, Färkkilä MA, Ferradini L, Ferraz MLG, Ferreira PRA, Filipec Kanizaj T, Flisiak R, Frankova S, Fung J, Gamkrelidze A, Gane E, Garcia V, García-Samaniego J, Gemilyan M, Genov J, Gheorghe LS, Gholam PM, Goldis A, Gottfredsson M, Gray RT, Grebely J, Gschwantler M, et alBlach S, Terrault NA, Tacke F, Gamkrelidze I, Craxi A, Tanaka J, Waked I, Dore GJ, Abbas Z, Abdallah AR, Abdulla M, Aghemo A, Aho I, Akarca US, Alalwan AM, Alanko Blomé M, Al-Busafi SA, Aleman S, Alghamdi AS, Al-Hamoudi WK, Aljumah AA, Al-Naamani K, Al Serkal YM, Altraif IH, Anand AC, Anderson M, Andersson MI, Athanasakis K, Baatarkhuu O, Bakieva SR, Ben-Ari Z, Bessone F, Biondi MJ, Bizri ARN, Brandão-Mello CE, Brigida K, Brown KA, Brown, Jr RS, Bruggmann P, Brunetto MR, Busschots D, Buti M, Butsashvili M, Cabezas J, Chae C, Chaloska Ivanova V, Chan HLY, Cheinquer H, Cheng KJ, Cheon ME, Chien CH, Chien RN, Choudhuri G, Christensen PB, Chuang WL, Chulanov V, Cisneros LE, Coco B, Contreras FA, Cornberg M, Cramp ME, Crespo J, Cui F, Cunningham CW, Dagher Abou L, Dalgard O, Dao DY, De Ledinghen V, Derbala MF, Deuba K, Dhindsa K, Djauzi S, Drazilova S, Duberg AS, Elbadri M, El-Sayed MH, Esmat G, Estes C, Ezzat S, Färkkilä MA, Ferradini L, Ferraz MLG, Ferreira PRA, Filipec Kanizaj T, Flisiak R, Frankova S, Fung J, Gamkrelidze A, Gane E, Garcia V, García-Samaniego J, Gemilyan M, Genov J, Gheorghe LS, Gholam PM, Goldis A, Gottfredsson M, Gray RT, Grebely J, Gschwantler M, Hajarizadeh B, Hamid SS, Hamoudi W, Hatzakis A, Hellard ME, Himatt S, Hofer H, Hrstic I, Hunyady B, Husa P, Husic-Selimovic A, Jafri WSM, Janicko M, Janjua N, Jarcuska P, Jaroszewicz J, Jerkeman A, Jeruma A, Jia J, Jonasson JG, Kåberg M, Kaita KDE, Kaliaskarova KS, Kao JH, Kasymov OT, Kelly-Hanku A, Khamis F, Khamis J, Khan AG, Khandu L, Khoudri I, Kielland KB, Kim DY, Kodjoh N, Kondili LA, Krajden M, Krarup HB, Kristian P, Kwon JA, Lagging M, Laleman W, Lao WC, Lavanchy D, Lázaro P, Lazarus JV, Lee AU, Lee MH, Li MKK, Liakina V, Lim YS, Löve A, Lukšić B, Machekera SM, Malu AO, Marinho RT, Maticic M, Mekonnen HD, Mendes-Correa MC, Mendez-Sanchez N, Merat S, Meshesha BR, Midgard H, Mills M, Mohamed R, Mooneyhan E, Moreno C, Muljono DH, Müllhaupt B, Musabaev E, Muyldermans G, Nartey YA, Naveira MCM, Negro F, Nersesov AV, Njouom R, Ntagirabiri R, Nurmatov ZS, Obekpa SA, Oguche S, Olafsson S, Ong JP, Opare-Sem OK, Orrego M, Øvrehus AL, Pan CQ, Papatheodoridis GV, Peck-Radosavljevic M, Pessoa MG, Phillips RO, Pimenov N, Plaseska-Karanfilska D, Prabdial-Sing NN, Puri P, Qureshi H, Rahman A, Ramji A, Razavi-Shearer DM, Razavi-Shearer K, Ridruejo E, Ríos-Hincapié CY, Rizvi SMS, Robaeys GKMM, Roberts LR, Roberts SK, Ryder SD, Sadirova S, Saeed U, Safadi R, Sagalova O, Said SS, Salupere R, Sanai FM, Sanchez-Avila JF, Saraswat VA, Sarrazin C, Sarybayeva G, Seguin-Devaux C, Sharara AI, Sheikh M, Shewaye AB, Sievert W, Simojoki K, Simonova MY, Sonderup MW, Spearman CW, Sperl J, Stauber RE, Stedman CAM, Su TH, Suleiman A, Sypsa V, Tamayo Antabak N, Tan SS, Tergast TL, Thurairajah PH, Tolmane I, Tomasiewicz K, Tsereteli M, Uzochukwu BSC, Van De Vijver DAMC, Van Santen DK, Van Vlierberghe H, Van Welzen B, Vanwolleghem T, Vélez-Möller P, Villamil F, Vince A, Waheed Y, Weis N, Wong VWS, Yaghi CG, Yesmembetov K, Yosry A, Yuen MF, Yunihastuti E, Zeuzem S, Zuckerman E, Razavi HA. Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study. Lancet Gastroenterol Hepatol 2022; 7:396-415. [PMID: 35180382 DOI: 10.1016/s2468-1253(21)00472-6] [Show More Authors] [Citation(s) in RCA: 337] [Impact Index Per Article: 112.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 12/08/2021] [Accepted: 12/09/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. METHODS This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age ≥0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. FINDINGS Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0·7% (95% UI 0·7-0·9), corresponding to 56·8 million (95% UI 55·2-67·8) infections, on Jan 1, 2020. This number represents a decrease of 6·8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63·6 million (61·8-75·8) infections (0·9% [0·8-1·0] prevalence). By the end of 2020, an estimated 12·9 million (12·5-15·4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. INTERPRETATION At the beginning of 2020, there were an estimated 56·8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. FUNDING John C Martin Foundation, Gilead Sciences, AbbVie, ZeShan Foundation, and The Hepatitis Fund.
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Butt N, Anoshia, Khan MA, Akbar A. Effectiveness of Sofosbuvir and Daclatasvir in treatment of Hepatitis-C: An experience of tertiary care hospital in Karachi. Pak J Med Sci 2021; 37:2014-2019. [PMID: 34912436 PMCID: PMC8613042 DOI: 10.12669/pjms.37.7.4627] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/31/2021] [Accepted: 09/06/2021] [Indexed: 11/25/2022] Open
Abstract
Objective: To assess the effectiveness of Sofosbuvir (SOF) and Daclatasvir (DCV) in patients with chronic hepatitis C (CHC), compensated cirrhosis (CC) and decompensated cirrhosis (DCLD) either treatment naïve or experienced. Methods: This was a prospective, observational study, conducted from January 2017 to December 2018 at Jinnah Postgraduate Medical Centre, Karachi. All patients above 12 years of age with detectable HCV RNA PCR were included. Patients were divided into three groups: CHC, CC and DCLD. SOF and DCV for 12 or 24 weeks were given. Ribavirin (RBV) was given to treatment experienced and cirrhotic patients. Primary outcome was End of Treatment Response (ETR) and secondary outcome was Sustained Virological Response (SVR) at post treatment week 12 or 24. Results: Total 300 patients with mean age of 40.49 ± 13.86 were enrolled. Majority were females 174 (58%). CHC were 200 (66.6%) while cirrhotic were 100 (33.4%). Treatment naïve patients were 267 (89%) and 33 (11%) patients were experienced. Most common genotype was 3 (83%). ETR was achieved in 292 (97.33%) and SVR in 265 (88.33%) patients respectively. Conclusion: SOF plus DCV with or without RBV is a highly effective treatment for chronic HCV and is still used in many centers of Pakistan. This regimen has excellent results for GT-3. The outcomes are mainly influenced by the presence or absence of cirrhosis.
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Affiliation(s)
- Nazish Butt
- Dr. Nazish Butt, MBBS, FCPS. Assistant Professor, Head Department of Gastroenterology, Department of Gastroenterology, Jinnah Postgraduate Medical Center, Karachi, Pakistan
| | - Anoshia
- Dr. Anoshia, MBBS, FCPS. Consultant Gastroenterologist, Department of Gastroenterology, Jinnah Postgraduate Medical Center, Karachi, Pakistan
| | - Muhammad Ali Khan
- Dr. Muhammad Ali Khan, MBBS. Department of Gastroenterology, Jinnah Postgraduate Medical Center, Karachi, Pakistan
| | - Ali Akbar
- Dr. Ali Akbar, MBBS, FCPS. Consultant Gastroenterologist, Department of Gastroenterology, Jinnah Postgraduate Medical Center, Karachi, Pakistan
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Cunha LRD, Castro MCMD, Duarte GS, Nascimento GCE, Rocha GA, Silva LD. MAJOR DEPRESSIVE DISORDER IS ASSOCIATED WITH TYPE 2 DIABETES IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:476-482. [PMID: 34909853 DOI: 10.1590/s0004-2803.202100000-86] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 06/11/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND Major depressive disorder (MDD) is commonly reported in patients with chronic hepatitis C (CHC); however, the factors behind the co-occurrence of these conditions have not been completely clarified yet. OBJECTIVE We aimed to evaluate the frequency of mental disorders in CHC patients and to investigate variables associated with MDD. METHODS CHC patients (n=151) attending a referral Centre for hepatitis were evaluated using the Mini-International Neuropsychiatry Interview and the Cut-Annoyed-Guilty-Eye (CAGE) Questionnaire. Multivariate analysis was used to evaluate independent covariates associated with current MDD. RESULTS Seventy-six (50.3%) patients had, at least, one current psychiatric diagnosis with MDD (33.1%) being the most common. Current MDD was independently associated with age (≤50 yr.) (OR=2.57; 95%CI=1.25-5.29; P=0.01) and type 2 diabetes mellitus (OR=2.80, 95%CI=1.17-6.70; P=0.02). Cirrhosis was associated with type 2 diabetes mellitus (OR=5.09; 95%CI=1.73-15.04; P=0.03) and current alcohol abuse/dependence (OR=2.54; 95%CI=1.04-6.22; P=0.04). DISCUSSION MDD is associated with type 2 diabetes in CHC patients. Even in the direct-acting antivirals (DAAs) era, characterized by great perspectives for the first ample cure of a chronic viral infection, we should ensure that the screening for psychiatric disorders takes place in the course of routine clinical care of patients chronically infected with hepatitis C virus.
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Affiliation(s)
- Luciana Rodrigues da Cunha
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil.,Universidade Federal de Minas Gerais, Programa de Pós-Graduação em Neurociências, Instituto de Ciências Biológicas, Belo Horizonte, MG, Brasil
| | - Maria Carolina Magalhães de Castro
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil
| | - Gabriela Silva Duarte
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil
| | - Graziela Cançado E Nascimento
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil
| | - Gifone Aguiar Rocha
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Laboratório de Pesquisa em Bacteriologia, Belo Horizonte, MG, Brasil
| | - Luciana Diniz Silva
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Belo Horizonte, MG, Brasil.,Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Clínica Médica, Belo Horizonte, MG, Brasil
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9
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The Netherlands Is on Track to Meet the World Health Organization Hepatitis C Elimination Targets by 2030. J Clin Med 2021; 10:jcm10194562. [PMID: 34640576 PMCID: PMC8509638 DOI: 10.3390/jcm10194562] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/22/2021] [Accepted: 09/26/2021] [Indexed: 12/24/2022] Open
Abstract
Background: The Netherlands strives for hepatitis C virus (HCV) elimination, in accordance with the World Health Organization targets. An accurate estimate when HCV elimination will be reached is elusive. We have embarked on a nationwide HCV elimination project (CELINE) that allowed us to harvest detailed data on the Dutch HCV epidemic. This study aims to provide a well-supported timeline towards HCV elimination in The Netherlands. Methods: A previously published Markov model was used, adopting published data and unpublished CELINE project data. Two main scenarios were devised. In the Status Quo scenario, 2020 diagnosis and treatment levels remained constant in subsequent years. In the Gradual Decline scenario, an annual decrease of 10% in both diagnoses and treatments was implemented, starting in 2020. WHO incidence target was disregarded, due to low HCV incidence in The Netherlands (≤5 per 100,000). Results: Following the Status Quo and Gradual Decline scenarios, The Netherlands would meet WHO’s elimination targets by 2027 and 2032, respectively. From 2015 to 2030, liver-related mortality would be reduced by 97% in the Status Quo and 93% in the Gradual Decline scenario. Compared to the Status Quo scenario, the Gradual Decline scenario would result in 12 excess cases of decompensated cirrhosis, 18 excess cases of hepatocellular carcinoma, and 20 excess cases of liver-related death from 2020–2030. Conclusions: The Netherlands is on track to reach HCV elimination by 2030. However, it is vital that HCV elimination remains high on the agenda to ensure adequate numbers of patients are being diagnosed and treated.
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10
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Bloom DE, Khoury A, Srinivasan V. Estimating the net value of treating hepatitis C virus using sofosbuvir-velpatasvir in India. PLoS One 2021; 16:e0252764. [PMID: 34292958 PMCID: PMC8297876 DOI: 10.1371/journal.pone.0252764] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 05/21/2021] [Indexed: 12/12/2022] Open
Abstract
Recently developed direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV) have been groundbreaking for their high efficacy across disease genotypes and lack of severe side effects. This study uses a cost-of-illness (COI) approach to estimate the net value conferred by this class of drugs using the cost and efficacy of one of these novel drug combinations, sofosbuvir and velpatasvir (SOF/VEL), recently licensed for generic manufacture in India. This study considers COI of lifetime earnings lost by patients and potential secondarily infected individuals due to disability and premature death from HCV infection. Expected net benefits of treatment are substantial for non-cirrhotic (NC) and compensated cirrhotic (CC) patients (ranging from 5,98,003 INR for NC women to 1,05,25,504 INR for CC men). Increased earnings are not sufficient to fully offset cost of treatment for decompensated cirrhotic individuals but treatment may still be justified on the basis of the intrinsic value of health improvements and other treatment benefits.
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Affiliation(s)
- David E. Bloom
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
- * E-mail:
| | - Alexander Khoury
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
| | - V. Srinivasan
- Stanford Graduate School of Business, Stanford, California, United States of America
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11
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Chaabna K, Dashzeveg D, Shagdarsuren T, Al-Rifai RH. Prevalence and genotype distribution of hepatitis C virus in Mongolia: Systematic review and meta-analysis. Int J Infect Dis 2021; 105:377-388. [PMID: 33601031 DOI: 10.1016/j.ijid.2021.02.040] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 02/08/2021] [Accepted: 02/10/2021] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE To characterize hepatitis C virus (HCV) infection epidemiology in Mongolia. METHOD Publications on HCV antibody (Ab) and RNA prevalence, and/or genotypes/subtypes were systematically reviewed and reported following PRISMA guidelines. Random-effects meta-analyses and age adjustments were conducted to estimate the prevalence of Mongolians exposed to HCV (pooled HCV-Ab prevalence) by time period, sex, and at-risk populations; and to estimate the prevalence of chronically-infected HCV individuals. RESULTS The national pooled HCV-Ab prevalence was 12.3% in 2000-2009 and 11.2% in 2013. Sex-specific pooled prevalence appeared higher among females than males (14.0% versus 6.8%). Age-specific pooled prevalence significantly increased from 3.7% among children (aged 0-10 years) to 34.1% among people aged ≥50 years (p < 0.001). Among the adult general population (low-risk population), the national age-adjusted prevalence was 8.1%. Age-adjusted chronic infection prevalence in adults was 6.0%. Among healthcare workers, pooled prevalence was 18.0%. Among patients with liver diseases, pooled prevalence was 53.7%. Among individuals engaging in risky sexual behaviors, pooled prevalence was 11.1%. The identified circulating genotypes/subtypes were 1b (58.0%), 2a (21.7%), and 1a (20.2%). CONCLUSION The national HCV prevalence in Mongolia appeared to be among the highest worldwide. Higher prevalence in the clinical setting indicated potential ongoing HCV iatrogenic and occupational transmission. Additionally, HCV transmission in community settings should be investigated.
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Affiliation(s)
- Karima Chaabna
- Institute for Population Health, Weill Cornell Medicine-Qatar, Doha, Qatar.
| | - Delgermaa Dashzeveg
- Global Health Entrepreneurship Department, Tokyo Medical and Dental University, Tokyo, Japan; Head of Public Health Policy Implementation and Coordination, National Centre for Public Health, Ministry of Health, Mongolia
| | - Tserendulam Shagdarsuren
- Head of Public Health Policy Implementation and Coordination, National Centre for Public Health, Ministry of Health, Mongolia; Department of Mongolia and Healthy City Network of Mongolia, Mongolia
| | - Rami H Al-Rifai
- Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates
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12
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Wiessing L, Giraudon I, Duffell E, Veldhuijzen I, Zimmermann R, Hope V. Epidemiology of Hepatitis C Virus: People Who Inject Drugs and Other Key Populations. HEPATITIS C: EPIDEMIOLOGY, PREVENTION AND ELIMINATION 2021:109-149. [DOI: 10.1007/978-3-030-64649-3_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Sood AK, Manrai M, Thareja S, Shukla R, Patel A. Epidemiology of hepatitis C virus infection in a tertiary care hospital. Med J Armed Forces India 2020; 76:443-450. [PMID: 33162654 PMCID: PMC7606104 DOI: 10.1016/j.mjafi.2019.08.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 08/25/2019] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND There are epidemiological lacunae in literature of hepatitis C virus (HCV) infection. We report a prospective observational study of asymptomatic HCV infected patients from a tertiary care Government Hospital. METHODS All consecutive asymptomatic antibodies to hepatitis C virus (anti-HCV) positive patients were studied from July 2011 to April 2016. Patients were reviewed for demographic factors including symptom profile, risk factors, family screening, and point prevalence in relation to various districts of Punjab and Haryana. RESULTS One thousand twelve patients were studied with median age of 52 years (range:13-85) with a male to female ratio of 0.87. Eight hundred (79.25%) patients were from Punjab and 110 (10.67%) from Haryana. Forty percent patients were in 40-60 age group. Six hundred seventy patients (66.21%) did not have any apparent risk factor, 274 (27.08%) had one risk factor, and 68 patients (6.72%) had > 2 risk factors. Commonest risk factor was h/o surgery in 243 patients (24.01%), 32 patients had h/o IV drug abuse and 29 among them were < 30 years. Three hundred and sixty-seven families and children were screened, and 27 spouses and 16 children were found to be anti-HCV positive. The risk factor of IV drug abuse was more common in the younger adults with age ≤ 30 years as compared with age > 30 years (p = 0.001). CONCLUSION HCV infection was common in certain districts of Punjab and common in adults of 40-60 years. This finding needs to be confirmed in larger population-based study. The IV drug abuse is the risk factor of concern among young adults.
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Affiliation(s)
| | - Manish Manrai
- Associate Professor, Department of Internal Medicine, Armed Forces Medical College, Pune 411040, India
| | | | - Rajat Shukla
- Commandant, Military Hospital Namkum, Ranchi, Jharkhand, India
| | - Amol Patel
- Classified Specialist (Medicine) & Medical Oncologist, Army Hospital (R&R), New Delhi-110010, India
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14
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Debnath P, Chandnani S, Rathi P, Nair S, Junare P, Udgirkar S, Singh A, Contractor Q. A new model to predict response to direct-acting antiviral therapy in decompensated cirrhotics due to hepatitis C virus. Clin Exp Hepatol 2020; 6:253-262. [PMID: 33145432 PMCID: PMC7592091 DOI: 10.5114/ceh.2020.99525] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 06/19/2020] [Indexed: 02/06/2023] Open
Abstract
AIM of the study: Decompensated hepatitis C virus (HCV) cirrhosis is a difficult to treat cohort, and there is no gold standard predictor of response to direct-acting antiviral (DAA) therapy. We conducted this study to look for factors responsible for improvement in post-therapy status, i.e. attainment of Child-Turcotte-Pugh (CTP) class A from B or C, and devise a new model to predict post-therapy response. MATERIAL and methods: Prospective analysis of data from decompensated HCV cirrhotics was done and association of each parameter with patient outcomes at 36 weeks after treatment was assessed. RESULTS 34 patients (54.8%) attained CTP class A after treatment. Factors that were independently associated with disease outcome included albumin (odds ratio [OR] = 4.84, 95% confidence interval [CI]: 1.43-20.15, p = 0.018), alanine transaminase (ALT) (OR = 1.02, 95% CI: 1-1.04, p = 0.049), bilirubin (OR = 0.41, 95% CI: 0.2-0.75, p = 0.007) and estimated glomerular filtration rate (eGFR) (OR = 1.03, 95% CI: 1.0-1.06, p = 0.045). On multivariate analysis, bilirubin was significantly associated with treatment outcome (OR = 0.28, 95% CI: 0.1-0.64, p = 0.006). A composite model was devised using demographic, biochemical, and clinical features, which has sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 67.86%, 79.41%, 73.08%, 75%, and 73.63% respectively in predicting response to therapy. Only 7.6% of patients with a Model for End-Stage Liver Disease (MELD) score > 15 and none of the patients with CTP class C met the primary end-point of our study. CONCLUSIONS 55% of our cohort met the primary end-point at 36 weeks. Patients with CTP class C and a MELD score > 15 should be referred for liver transplantation followed by DAA therapy. Our model was good at predicting improvement in post-therapy liver function.
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Affiliation(s)
| | | | - Pravin Rathi
- TNMC & BYL Nair Charitable Hospital, Mumbai, India
| | - Sujit Nair
- TNMC & BYL Nair Charitable Hospital, Mumbai, India
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15
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Nakitanda AO, Duffell E. Hospital discharges of hepatocellular carcinoma and non-alcohol related cirrhosis in the EU/EEA and United Kingdom: a descriptive analysis of 2004-2015 data. Infect Dis (Lond) 2020; 52:816-827. [PMID: 32838640 DOI: 10.1080/23744235.2020.1799068] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Viral hepatitis is a leading cause of mortality globally, comparable to that of HIV and TB. Most hepatitis deaths are related to liver cirrhosis and hepatocellular carcinoma (HCC) associated with chronic hepatitis B and C infections. To examine the progress towards the elimination goals set in the global health sector strategy for viral hepatitis, we aimed to assess the impact of mortality-indicative morbidity. METHODS We retrieved inpatients and day cases hospital discharges data from the Eurostat hospital activities database, and analysed ICD-10 and ICD-9 specific codes related to primary HCC and non-alcohol related cirrhosis registered by European Union/European Economic Area (EU/EEA) countries and United Kingdom (UK) for 2004 to 2015. RESULTS In 2015, 20 countries (45.7% of total EU/EEA/UK population) reported 13,236 (Range 0-6294) day cases and 36,012 (4-9097) inpatients discharges of HCC. Romania, Croatia, Luxembourg and UK reported increasing day cases discharge rates between 2004 and 2015; while HCC inpatients discharge rates increased overall during this period. There were 13,865 (0-5918) day cases and 56,176 (3-29,118) inpatients discharges reported for cirrhosis across the 20 countries in 2015. Over the 12 years, day cases discharge rates for cirrhosis increased in Romania, Croatia and UK. Though higher than for day cases, cirrhosis inpatients discharge rates remained stable. CONCLUSIONS The hospital burden of HCC and cirrhosis is high, with considerable inpatient load including sustained increasing trends in HCC discharge rates. Further interpretation in light of local health system contexts, and more robust harmonised data are needed to better understand the impact of the viral hepatitis epidemic in the region.
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Affiliation(s)
- Aya Olivia Nakitanda
- Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,European Centre for Disease Prevention and Control, Stockholm, Sweden
| | - Erika Duffell
- European Centre for Disease Prevention and Control, Stockholm, Sweden
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16
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Martinello M, Orkin C, Cooke G, Bhagani S, Gane E, Kulasegaram R, Shaw D, Tu E, Petoumenos K, Marks P, Grebely J, Dore GJ, Nelson M, Matthews GV. Short-Duration Pan-Genotypic Therapy With Glecaprevir/Pibrentasvir for 6 Weeks Among People With Recent Hepatitis C Viral Infection. Hepatology 2020; 72:7-18. [PMID: 31652357 DOI: 10.1002/hep.31003] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 10/21/2019] [Indexed: 01/18/2023]
Abstract
BACKGROUND AND AIMS Among treatment-naive individuals with chronic hepatitis C viral (HCV) infection and without cirrhosis, glecaprevir/pibrentasvir for 8 weeks is recommended. The aim of this analysis was to evaluate the efficacy of glecaprevir/pibrentasvir for 6 weeks in people with acute and recent HCV infection. APPROACH AND RESULTS In this open-label, single-arm, multicenter, international pilot study, adults with recent HCV (duration of infection < 12 months) received glecaprevir/pibrentasvir 300/120 mg daily for 6 weeks. Primary infection was defined by first positive anti-HCV antibody and/or HCV RNA within 6 months of enrollment and either acute clinical hepatitis within the past 12 months (symptomatic seroconversion illness or alanine aminotransferase > 10 × upper limit of normal) or anti-HCV antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within 6 months of enrollment and evidence of prior spontaneous or treatment-induced clearance. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Thirty men (median age 43 years, 90% men who have sex with men) received treatment, of whom 77% (n = 23) were human immunodeficiency virus-positive, 47% (n = 14) had ever injected drugs, and 13% (n = 4) had HCV reinfection. The majority had HCV genotype 1 (83%, n = 25), followed by genotype 4 (10%, n = 3) and genotype 3 (7%, n = 2). At baseline, median estimated duration of infection was 29 weeks (range 13, 52) and median HCV RNA was 6.2 log10 IU/mL (range 0.9, 7.7). SVR12 in the intention-to-treat and per-protocol populations was achieved in 90% (27/30) and 96% (27/28), respectively. There was one case of relapse, and there were two cases of nonvirological failure (death, n = 1; loss to follow-up, n = 1). No treatment-related serious adverse events were seen. CONCLUSIONS Glecaprevir/pibrentasvir for 6 weeks was highly effective among people with acute and recent HCV infection, supporting further evaluation of shortened-duration pan-genotypic therapy in this setting.
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Affiliation(s)
- Marianne Martinello
- Kirby Institute, University of New South Wales Sydney, Sydney, Australia.,St. Vincent's Hospital, Sydney, Australia.,Department of Infectious Diseases, Blacktown Mt. Druitt Hospital, Sydney, Australia
| | | | - Graham Cooke
- Department of Infectious Diseases, Imperial College NHS Trust, St. Mary's Hospital, London, UK
| | - Sanjay Bhagani
- Department of Infectious Diseases/HIV Medicine, Royal Free Hospital, London, UK
| | - Edward Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | | | - David Shaw
- Department of Infectious Diseases, Royal Adelaide Hospital, Adelaide, Australia
| | - Elise Tu
- Kirby Institute, University of New South Wales Sydney, Sydney, Australia
| | - Kathy Petoumenos
- Kirby Institute, University of New South Wales Sydney, Sydney, Australia
| | - Philippa Marks
- Kirby Institute, University of New South Wales Sydney, Sydney, Australia
| | - Jason Grebely
- Kirby Institute, University of New South Wales Sydney, Sydney, Australia
| | - Gregory J Dore
- Kirby Institute, University of New South Wales Sydney, Sydney, Australia.,St. Vincent's Hospital, Sydney, Australia
| | - Mark Nelson
- Chelsea and Westminster Hospital, London, UK
| | - Gail V Matthews
- Kirby Institute, University of New South Wales Sydney, Sydney, Australia.,St. Vincent's Hospital, Sydney, Australia
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17
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Nsanzimana S, Penkunas MJ, Liu CY, Sebuhoro D, Ngwije A, Remera E, Umutesi J, Ntirenganya C, Mugeni SD, Serumondo J. Effectiveness of Direct-Acting Antivirals for the treatment of chronic hepatitis C in Rwanda: A retrospective study. Clin Infect Dis 2020; 73:e3300-e3307. [PMID: 32505127 DOI: 10.1093/cid/ciaa701] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 06/01/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Direct-acting antivirals (DAAs) are becoming accessible in sub-Saharan Africa. This study examined the effectiveness of DAAs in patients treated through the Rwandan national health system and identified factors associated with treatment outcomes. METHODS This retrospective study utilized data from the national HCV program for patients who initiated DAAs between November 2015 and March 2017. Sustained virological response at 12 weeks post-treatment (SVR12) was the primary outcome. Logistic regression models were fit to estimate the relationship between patients' clinical and demographic characteristics and treatment outcome. RESULTS 894 patients initiated treatment during the study period; 590 completed treatment and had SVR12 results. Among the 304 patients without SVR12 results, 48 were lost to follow-up and 256 had no SVR12 results but clinical data indicated they likely completed treatment - these patients were classified as non-virological failure since viral clearance could not be determined. In a per-protocol analysis for 590 patients with SVR12 results, 540 (92%) achieved SVR12 and 50 (8%) experienced virological failure. Pre-treatment HCV RNA above the median split was associated with virological failure. Intention-to-treat analyses including all patients indicated 540 (60%) achieved SVR12, 304 (34%) experienced non-virological failure, and 50 (6%) experienced virological failure. Patients in Western Province were more likely to experience non-virological failure than patients in Kigali, likely due to the five- to seven-hour travel required to access testing and treatment. CONCLUSIONS DAAs were effective when implemented through the Rwandan national health system. Decentralization and enhanced financing are underway in Rwanda, which could improve access to treatment and follow-up as the country prepares for HCV elimination.
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Affiliation(s)
| | | | - Carol Y Liu
- Clinton Health Access Initiative, Kigali, Rwanda
| | | | - Alida Ngwije
- Clinton Health Access Initiative, Kigali, Rwanda
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18
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Synthesis and evaluation of 2'-dihalo ribonucleotide prodrugs with activity against hepatitis C virus. Bioorg Med Chem 2020; 28:115208. [PMID: 31740203 DOI: 10.1016/j.bmc.2019.115208] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 10/31/2019] [Accepted: 11/04/2019] [Indexed: 11/21/2022]
Abstract
Hepatitis C virus (HCV) nucleoside inhibitors have been a key focus of nearly 2 decades of HCV drug research due to a high barrier to drug resistance and pan-genotypic activity profile provided by molecules in this drug class. Our investigations focused on several potent 2'-halogenated uridine-based HCV polymerase inhibitors, resulting in the discovery of novel 2'-deoxy-2'-dihalo-uridine analogs that are potent inhibitors in replicon assays for all genotypes. Further studies to improve in vivo performance of these nucleoside inhibitors identified aminoisobutyric acid ethyl ester (AIBEE) phosphoramidate prodrugs 18a and 18c, which provide high levels of the active triphosphate in dog liver. AIBEE prodrug 18c was compared with sofosbuvir (1) by co-dosing both compounds by oral administration in dog (5 mg/kg each) and measuring liver concentrations of the active triphosphate metabolite at both 4 and 24 h post dosing. In this study, 18c provided liver triphosphate concentrations that were 6-fold higher than sofosbuvir (1) at both biopsy time points, suggesting that 18c could be a highly effective agent for treating HCV infected patients in the clinic.
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19
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Zhu X, Wang M, Liu M, Yu X, Huang P. Efficacy and safety of direct-acting antivirals for treatment-naive patients with genotype 1 hepatitis C virus infection. Per Med 2019; 16:421-429. [PMID: 31591934 DOI: 10.2217/pme-2018-0121] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This systematic review was performed on the basis of Preferred Reporting Items for Systematic Reviews and Meta-analyses and Cochrane recommendations to compare sustained virological response (SVR12) and the serious adverse events in patients treated by directing-acting antivirals. We conducted a literature search in PubMed/Medline, EBSCO, Embase and the Cochrane Library until 2018. A consistency model was used to get the relative effect of odds ratio among regimens and the possibility for the efficacy and safety of 13 regimen, and we divided these regimens into DUAL or TRIO regimens to conduct integrated data analysis. The results demonstrated that dual or triple directing-acting antiviral-combined regimens had higher SVR12 rates, Daclatasvir plus Asunaprevir may be a good choice for genotype 1 patients, and regimens without Ribavirin and interferon are safer.
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Affiliation(s)
- Xiaobo Zhu
- Department of Pharmacy, People's Hospital of Danyang, Danyang 212300, China
| | - Mingqi Wang
- Department of Epidemiology, Xu Zhou Medical University, Xuzhou 221000, China
| | - Mei Liu
- Department of Epidemiology, Nanjing Medical University, Nanjing 211166, China
| | - Xinghao Yu
- Department of Epidemiology, Xu Zhou Medical University, Xuzhou 221000, China
| | - Peng Huang
- Department of Epidemiology, Nanjing Medical University, Nanjing 211166, China.,Key Laboratory of Infectious Diseases, Nanjing Medical University, Nanjing 211166, China
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20
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Sadeghimehr M, Bertisch B, Schaetti C, Wandeler G, Richard JL, Scheidegger C, Keiser O, Estill J. Modelling the impact of different testing strategies for HCV infection in Switzerland. J Virus Erad 2019. [DOI: 10.1016/s2055-6640(20)30036-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
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21
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Abstract
Aim of the study According to the World Health Organization (WHO) strategy, elimination of hepatitis C virus (HCV) as a major public health threat by 2030 includes diagnosis and cure of 90% of those infected between 2015 and 2030. The aim of this study is to estimate the realistic possibility to achieve the WHO elimination targets in Poland. Material and methods The Polish population was established according to data from Statistics Poland for the year 2017. Treatment efficacy was estimated based on publications in time-frames depending on the availability of therapeutic options in Poland. The mortality of HCV-infected patients was assumed on the basis of Statistics Poland and the EpiTer-2 database The number of annual antiviral treatments was estimated based on data from the National Health Fund. Two scenarios were considered, without and with intervention dependent on the national screening program. Results The current diagnosis rate in Poland was calculated as 31%. The scenario without intervention resulted in gradual reduction of annual treatments accompanied by a decrease in the number of infected patients in 2030 to 118 000 (0.31% of the current Polish population), which is only 38% compared with 2015 established as a baseline by WHO. Introduction of the HCV screening program, which includes 3 million people annually, would increase treatment uptake to 12 000 per year and reduce the number of HCV-infected persons in Poland by 90%. Conclusions The urgent implementation of the national screening program for HCV in Poland is essential to achieve the WHO goal by 2030. The screening strategy should include up to 3 million persons annually to achieve treatment uptake of 12 thousand patients per year.
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22
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Klimova EA, Burnevich EZ, Chulanov VP, Gusev DA, Znoyko OO, Batskikh SN, Kizlo SN, Mamonova NA, Tarkhova EP, Krasavina EN, Samsonov MY, Yushchuk ND. [Efficacy and safety of narlaprevir/ritonavir and daclatasvir non interferon combination in population of Russian patients with chronic hepatitis C]. TERAPEVT ARKH 2019; 91:67-74. [PMID: 32598756 DOI: 10.26442/00403660.2019.08.000384] [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: 04/16/2020] [Indexed: 11/22/2022]
Abstract
AIM Evaluate efficacy and safety of a combination of direct - acting antivirals narlaprevir/ritonavir with daclatasvir in patients with viral hepatitis C. MATERIALS AND METHODS The study enrolled adult patients with HCV genotype 1b infection without demonstrated NS5A resistance - associated substitutions Y93C/H/N/S and/or L31F/M/V/I. Patients were treated with narlaprevir 200 mg QD, ritonavir 100 mg QD and daclatasvir 60 mg QD. Treatment duration was 12 weeks. Proportion of patients achieving sustained virological response 12 weeks after treatment (SVR12) was the primary efficacy endpoint. RESULTS AND DISCUSSION In total, 105 (75.0%) patients were treatment with the study combination. Patients' age varied from 21 to 69 years, the mean age being 43.2±10.9 years. There were slightly more women (55.2%), and 69 patients (65.7%) had comorbidities. SVR 12 was 89.5% (95% CI 82.0-94.7%). In 10 of 11 patients with treatment failures NS5A resistance - associated substitutions in residues 31 and/or 93 were found, as well as less clinically relevant substitutions L28M, P58S, R30Q, Q62K. Adverse events (AEs) were found in less than one half of patients (45 patients, or 42.9% in the safety population). Almost all recorded AEs were mild to moderate. CONCLUSION Efficacy of treatment with a combination of narlaprevir/ritonavir and daclatasvir in treatment - naïve patients with HCV genotype 1b was close to 90%. This combination was found to be safe and well - tolerated.
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Affiliation(s)
- E A Klimova
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - E Z Burnevich
- Sechenov First Moscow State Medical University (Sechenov University).,City Clinical Hospital №24
| | - V P Chulanov
- Sechenov First Moscow State Medical University (Sechenov University).,Central Research Institute of Epidemiology
| | - D A Gusev
- Centre for the Prevention and Control of AIDS and Infectious Diseases
| | - O O Znoyko
- Yevdokimov Moscow State University of Medicine and Dentistry
| | | | - S N Kizlo
- Centre for the Prevention and Control of AIDS and Infectious Diseases
| | | | | | | | | | - N D Yushchuk
- Yevdokimov Moscow State University of Medicine and Dentistry
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23
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Cost-effectiveness and budgetary impact of HCV treatment with direct-acting antivirals in India including the risk of reinfection. PLoS One 2019; 14:e0217964. [PMID: 31170246 PMCID: PMC6553784 DOI: 10.1371/journal.pone.0217964] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 05/22/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND HCV direct-acting antivirals (DAAs) are produced in India at low cost. However, concerns surrounding reinfection and budgetary impact limit treatment scale-up in India. We evaluate the cost-effectiveness and budgetary impact of HCV treatment in India, including reinfection. METHODS A closed cohort Markov model of HCV disease progression, treatment, and reinfection was parameterized. We compared treatment by fibrosis stage (F2-F4 or F0-F4) to no treatment from a health care payer perspective. Costs (2017 USD$, based on India-specific data) and health utilities (in quality-adjusted life years, QALYs) were attached to each health state. We assumed DAAs with 90% sustained viral response at $900/treatment and 1%/year reinfection, varied in the sensitivity analysis from 0.1-15%. We deemed the intervention cost-effective if the incremental cost-effectiveness ratio (ICER) fell below India's per capita GDP ($1,709). We assessed the budgetary impact of treating all diagnosed individuals. RESULTS HCV treatment for diagnosed F2-F4 individuals was cost-saving (net costs -$2,881 and net QALYs 3.18/person treated; negative ICER) compared to no treatment. HCV treatment remained cost-saving with reinfection rates of 15%/year. Treating all diagnosed individuals was likely cost-effective compared to delay until F2 (mean ICER $1,586/QALY gained, 67% of simulations falling under the $1,709 threshold) with 1%/year reinfection. For all scenarios, annual retesting for reinfection was more cost-effective than the current policy (one-time retest). Treating all diagnosed individuals and reinfections results in net costs of $445-1,334 million over 5 years (<0.25% of total health care expenditure over 5 years), and cost-savings within 14 years. CONCLUSIONS HCV treatment was highly cost-effective in India, despite reinfection. Annual retesting for reinfection was cost-effective, supporting a policy change towards more frequent retesting. A comprehensive HCV treatment scale-up plan is warranted in India.
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Ekpanyapong S, Reddy KR. Hepatitis C virus therapy in advanced liver disease: Outcomes and challenges. United European Gastroenterol J 2019; 7:642-650. [PMID: 31210942 PMCID: PMC6545711 DOI: 10.1177/2050640619840149] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 02/26/2019] [Indexed: 01/06/2023] Open
Abstract
While for many years investigators had worked on highly effective direct-acting antiviral agent (DAA) therapy, we are now encountering challenges on the appropriate timing of DAA therapy in patients with decompensated cirrhosis. Improvement in hepatic function and quality of life can be achieved following successful therapy but not in all patients. Predictors of improvement or failure to improve have been noted but these are currently not robust enough to ubiquitously apply them to clinical practice. The lowest probability of improvement in hepatic function and avoidance of Model for End-stage Liver Disease (MELD) "purgatory" appears to be in those with MELD >20 while the more likely scenario of improvements is in those with MELD <15. Ideally, patients with a MELD score >20 should be transplanted first and treated for hepatitis C virus (HCV) infection after liver transplantation (LT). Those with MELD score <15 should be considered readily for treatment while in those with MELD of 15-20, treatment has to be individualized with full discussion of the pros and cons of treating them pre- or post-LT. However, it is to be appreciated that the majority of patients with decompensated cirrhosis across the world may not be eligible for liver transplant or may not have access to LT; thus, these patients should be considered for HCV therapy with the hope and expectation that they still gain variable degrees of benefit from successful DAA therapy.
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Affiliation(s)
- Sirina Ekpanyapong
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, USA
| | - K Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, USA
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25
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Petruzziello A, Loquercio G, Sabatino R, Balaban DV, Ullah Khan N, Piccirillo M, Rodrigo L, di Capua L, Guzzo A, Labonia F, Botti G. Prevalence of Hepatitis C virus genotypes in nine selected European countries: A systematic review. J Clin Lab Anal 2019; 33:e22876. [PMID: 30843304 PMCID: PMC6595292 DOI: 10.1002/jcla.22876,] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a global health problem especially for its increasing level of mortality. Detailed knowledge of HCV genotypes prevalence has clinical relevance since the efficacy of therapies is impacted by genotypes and subtypes distribution. Moreover, HCV exhibits a great genetic variability regionally. To date, there are no published studies assessing HCV genotypes distribution in specific countries of the Mediterranean basin. The aim of this study was to review data published from 2000 to 2017 with the purpose to estimate genotypes distribution of HCV infection in nine European countries all located in the Mediterranean basin. METHODS A systematic research of peer-reviewed journals indexed in PubMed, Scopus, and EMBASE databases selected if containing data regarding distribution of HCV genotypes in nine selected European countries (Albania, Bosnia, Croatia, France, Greece, Italy, Montenegro, Slovenia, and Spain) was performed. RESULTS Genotype 1 is the most common (61.0%), ranging from 80.0% in Croatia to 46.0% in Greece, followed by genotype 3 (20.0%), varying from 38.0% in Slovenia to 7.0% and 8.0%, respectively, in Italy and in Albania and by genotype 4 (10.0%) that shows an increase of 1.1% with respect to data obtained till 2014 probably due to the increasing migrants arrivals to Southern Europe. G2, the fourth most frequent genotype (8.5%), particularly common in Italy (27.0%) and Albania (18.0%) might be probably introduced in Southern Italy as a result of Albanian campaign during Second World War and more and more increased by the migration flows from Albania to Italy in the 90s. CONCLUSION Epidemiology of HCV infection shows a high variability across the European countries that border the Mediterranean Sea. HCV genotyping is a relevant tool to monitor the dynamic process influenced by both evolving transmission trends and new migration flows on HCV scenario.
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Affiliation(s)
| | - Giovanna Loquercio
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Rocco Sabatino
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Daniel Vasile Balaban
- Carol Davila" University of Medicine and Pharmacy, "Dr. Carol Davila" Central Military Emergency University HospitalBucharestRomania
| | - Najeeb Ullah Khan
- Institute of Biotechnology and Genetic Engineering (Health Davison)The University of AgriculturePeshawarPakistan
| | - Mauro Piccirillo
- Hepatobiliar and Pancreatic Unit, Department of Surgical OncologyIstituto Nazionale Tumori–Fondazione “G. Pascale”IRCCS ItaliaNaplesItaly
| | - Luis Rodrigo
- Gastroenterology ServiceHospital Universitario Central de Asturias, University of OviedoOviedoSpain
| | - Lucia di Capua
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Annunziata Guzzo
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Francesco Labonia
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Gerardo Botti
- Scientific DirectorIRCCS Fondazione PascaleNaplesItaly
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26
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Petruzziello A, Loquercio G, Sabatino R, Balaban DV, Ullah Khan N, Piccirillo M, Rodrigo L, di Capua L, Guzzo A, Labonia F, Botti G. Prevalence of Hepatitis C virus genotypes in nine selected European countries: A systematic review. J Clin Lab Anal 2019; 33:e22876. [PMID: 30843304 PMCID: PMC6595292 DOI: 10.1002/jcla.22876] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 02/08/2019] [Accepted: 02/11/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a global health problem especially for its increasing level of mortality. Detailed knowledge of HCV genotypes prevalence has clinical relevance since the efficacy of therapies is impacted by genotypes and subtypes distribution. Moreover, HCV exhibits a great genetic variability regionally. To date, there are no published studies assessing HCV genotypes distribution in specific countries of the Mediterranean basin. The aim of this study was to review data published from 2000 to 2017 with the purpose to estimate genotypes distribution of HCV infection in nine European countries all located in the Mediterranean basin. METHODS A systematic research of peer-reviewed journals indexed in PubMed, Scopus, and EMBASE databases selected if containing data regarding distribution of HCV genotypes in nine selected European countries (Albania, Bosnia, Croatia, France, Greece, Italy, Montenegro, Slovenia, and Spain) was performed. RESULTS Genotype 1 is the most common (61.0%), ranging from 80.0% in Croatia to 46.0% in Greece, followed by genotype 3 (20.0%), varying from 38.0% in Slovenia to 7.0% and 8.0%, respectively, in Italy and in Albania and by genotype 4 (10.0%) that shows an increase of 1.1% with respect to data obtained till 2014 probably due to the increasing migrants arrivals to Southern Europe. G2, the fourth most frequent genotype (8.5%), particularly common in Italy (27.0%) and Albania (18.0%) might be probably introduced in Southern Italy as a result of Albanian campaign during Second World War and more and more increased by the migration flows from Albania to Italy in the 90s. CONCLUSION Epidemiology of HCV infection shows a high variability across the European countries that border the Mediterranean Sea. HCV genotyping is a relevant tool to monitor the dynamic process influenced by both evolving transmission trends and new migration flows on HCV scenario.
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Affiliation(s)
| | - Giovanna Loquercio
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Rocco Sabatino
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Daniel Vasile Balaban
- Carol Davila" University of Medicine and Pharmacy, "Dr. Carol Davila" Central Military Emergency University HospitalBucharestRomania
| | - Najeeb Ullah Khan
- Institute of Biotechnology and Genetic Engineering (Health Davison)The University of AgriculturePeshawarPakistan
| | - Mauro Piccirillo
- Hepatobiliar and Pancreatic Unit, Department of Surgical OncologyIstituto Nazionale Tumori–Fondazione “G. Pascale”IRCCS ItaliaNaplesItaly
| | - Luis Rodrigo
- Gastroenterology ServiceHospital Universitario Central de Asturias, University of OviedoOviedoSpain
| | - Lucia di Capua
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Annunziata Guzzo
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Francesco Labonia
- SSD Virology and Molecular Biology, Department of Diagnostic AreaIstituto Nazionale Tumori – Fondazione “G. Pascale”, IRCCS ItaliaNaplesItaly
| | - Gerardo Botti
- Scientific DirectorIRCCS Fondazione PascaleNaplesItaly
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Prevalence of hepatitis C virus infection in patients hospitalised for ischemic heart disease versus controls - PRO-CARDIO-C study. Clin Exp Hepatol 2019; 5:118-122. [PMID: 31501787 PMCID: PMC6728861 DOI: 10.5114/ceh.2019.84782] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 11/06/2018] [Indexed: 01/01/2023] Open
Abstract
Aim of the study Ongoing national screening programmes suggest that the prevalence of chronic hepatitis C (CHC) in Poland ranges between 0.5% and 1%. It has been recently noted that patients with confirmed coronary artery disease may be at higher risk for hepatitis C virus (HCV) infection. Material and methods Testing for the presence of anti-HCV antibodies was performed in a group of patients admitted to the Cardiology Department with symptomatic ischemic heart disease (IHD) and in patients hospitalised in the Dermatology Department. Results A total of 1171 patients underwent anti-HCV testing: 672 patients in the Cardiology Department (K group) and 499 patients in the Dermatology Department (D group). Twenty-eight (2.4%) positive anti-HCV results were detected. The prevalence of positive anti-HCV antibodies in groups K and D was 2.23% and 2.61%, respectively (p > 0.05). Presence of HCV RNA was confirmed in 15 cases (1.28%) - 7 patients in group K and 8 patients in group D (1.04% and 1.6%, respectively; p > 0.05). Conclusions Our findings suggest that this patient cohort has increased risk of HCV infection, which may influence screening strategies.
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28
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Heffernan A, Cooke GS, Nayagam S, Thursz M, Hallett TB. Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model. Lancet 2019; 393:1319-1329. [PMID: 30704789 PMCID: PMC6484702 DOI: 10.1016/s0140-6736(18)32277-3] [Citation(s) in RCA: 187] [Impact Index Per Article: 31.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 08/13/2018] [Accepted: 09/12/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met. METHODS We developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions. FINDINGS By 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0-15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000-670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8-16·1) new infections and 1·5 million (1·4-1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78-82) reduction in incidence and a 61% (60-62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan. INTERPRETATION Further improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic. FUNDING Wellcome Trust.
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Affiliation(s)
- Alastair Heffernan
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK
| | - Graham S Cooke
- Division of Infectious Diseases, St Mary's Hospital, Imperial College London, London, UK
| | - Shevanthi Nayagam
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK; Division of Digestive Diseases, St Mary's Hospital, Imperial College London, London, UK
| | - Mark Thursz
- Division of Digestive Diseases, St Mary's Hospital, Imperial College London, London, UK
| | - Timothy B Hallett
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK.
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29
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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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30
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Lim AG, Qureshi H, Mahmood H, Hamid S, Davies CF, Trickey A, Glass N, Saeed Q, Fraser H, Walker JG, Mukandavire C, Hickman M, Martin NK, May MT, Averhoff F, Vickerman P. Curbing the hepatitis C virus epidemic in Pakistan: the impact of scaling up treatment and prevention for achieving elimination. Int J Epidemiol 2019; 47:550-560. [PMID: 29309592 PMCID: PMC5913612 DOI: 10.1093/ije/dyx270] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/13/2017] [Indexed: 02/07/2023] Open
Abstract
Background The World Health Organization (WHO) has developed a global health strategy to eliminate viral hepatitis. We project the treatment and prevention requirements to achieve the WHO HCV elimination target of reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030 in Pakistan, which has the second largest HCV burden worldwide. Methods We developed an HCV transmission model for Pakistan, and calibrated it to epidemiological data from a national survey (2007), surveys among people who inject drugs (PWID), and blood donor data. Current treatment coverage data came from expert opinion and published reports. The model projected the HCV burden, including incidence, prevalence and deaths through 2030, and estimated the impact of varying prevention and direct-acting antiviral (DAA) treatment interventions necessary for achieving the WHO HCV elimination targets. Results With no further treatment (currently ∼150 000 treated annually) during 2016–30, chronic HCV prevalence will increase from 3.9% to 5.1%, estimated annual incident infections will increase from 700 000 to 1 100 000, and 1 400 000 HCV-associated deaths will occur. To reach the WHO HCV elimination targets by 2030, 880 000 annual DAA treatments are required if prevention is not scaled up and no treatment prioritization occurs. By targeting treatment toward persons with cirrhosis (80% treated annually) and PWIDs (double the treatment rate of non-PWIDs), the required annual treatment number decreases to 750 000. If prevention activities also halve transmission risk, this treatment number reduces to 525 000 annually. Conclusions Substantial HCV prevention and treatment interventions are required to reach the WHO HCV elimination targets in Pakistan, without which Pakistan’s HCV burden will increase markedly.
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Affiliation(s)
- Aaron G Lim
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Huma Qureshi
- Pakistan Health Research Council, Islamabad, Pakistan
| | - Hassan Mahmood
- Pakistan Health Research Council, Islamabad, Pakistan.,TEPHINET, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | | | - Charlotte F Davies
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Adam Trickey
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Nancy Glass
- National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Quaid Saeed
- National AIDS Control Programme, Islamabad, Pakistan
| | - Hannah Fraser
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Josephine G Walker
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | | | - Matthew Hickman
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Natasha K Martin
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.,Division of Global Public Health, Department of Medicine, University of California San Diego, CA, USA
| | - Margaret T May
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Francisco Averhoff
- National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Peter Vickerman
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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31
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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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32
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Goutzamanis S, Doyle J, Higgs P, Hellard M. Improving hepatitis C direct-acting antiviral access and uptake: A role for patient-reported outcomes and lived experience. J Viral Hepat 2019; 26:218-223. [PMID: 30315689 DOI: 10.1111/jvh.13020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 09/05/2018] [Accepted: 09/10/2018] [Indexed: 12/12/2022]
Abstract
Hepatitis C virus contributes to substantial and growing mortality and morbidity. Fortunately, the advent of highly effective interferon-free direct-acting antiviral (DAA) medications and new diagnostic tests has the potential to dramatically alter the epidemiologic trajectory of hepatitis C, particularly for "hard-to-reach" populations. Treatment advances and cure will also likely alter the individual experience of living with hepatitis C. However, it is not yet known in what capacity. This paper provides an overview of the population-level impact of DAA treatment, highlighting the need to further our understanding of the impact of treatment on behaviour, health and wellbeing through lived experience and more sensitive patient-reported outcome measures.
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Affiliation(s)
- Stelliana Goutzamanis
- Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia
- School of Population Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Joseph Doyle
- Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia
- Department of Infectious Diseases, Alfred Health, Melbourne, Australia
| | - Peter Higgs
- Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia
- Department of Public Health, La Trobe University, Bundoora, Victoria, Australia
| | - Margaret Hellard
- Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia
- School of Population Health and Preventive Medicine, Monash University, Melbourne, Australia
- Department of Infectious Diseases, Alfred Health, Melbourne, Australia
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Isakov V, Chulanov V, Abdurakhmanov D, Burnevich E, Nurmukhametova E, Kozhevnikova G, Gankina N, Zhuravel S, Romanova S, Hyland RH, Lu S, Svarovskaia ES, McNally J, Brainard DM, Ivashkin V, Morozov V, Bakulin I, Lagging M, Zhdanov K, Weiland O. Sofosbuvir/velpatasvir for the treatment of HCV: excellent results from a phase-3, open-label study in Russia and Sweden. Infect Dis (Lond) 2019; 51:131-139. [PMID: 30499360 DOI: 10.1080/23744235.2018.1535186] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 10/05/2018] [Accepted: 10/08/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND In both Russia and Sweden, the dominant hepatitis C virus (HCV) is genotype 1, but around one-third of patients have genotype 3 infection. For such countries, HCV genotype testing is recommended prior to therapy. An effective pangenotypic therapy may potentially eliminate the need for genotyping. In this study, we evaluated the efficacy and safety of sofosbuvir/velpatasvir for 12 weeks in patients from Russia and Sweden. METHODS In an open-label, single-arm phase-3 study, patients could have HCV genotype 1-6 infection and were treatment-naïve or interferon treatment-experienced. All patients received sofosbuvir/velpatasvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS Of 122 patients screened, 119 were enrolled and treated. Overall, half (50%) were male, 18% had cirrhosis, and 24% had failed prior interferon-based therapy. In total, 66% of patients were infected with HCV genotype 1 (59% 1b and 7% 1a), 6% with genotype 2, and 29% with genotype 3. The overall SVR12 rate was 99% (118/119, 95% confidence interval 95-100%). One treatment-experienced patient infected with HCV genotype 3 experienced virologic relapse after completing treatment. The most common adverse events were headache (16%) and fatigue (7%). Serious adverse events were observed in four patients, but none were related to treatment. No patients discontinued treatment due to adverse events. CONCLUSION Sofosbuvir/velpatasvir as a pangenotypic treatment for 12 weeks was highly effective in patients from Russia and Sweden infected with HCV genotypes 1, 2, or 3. Sofosbuvir/velpatasvir was safe and well-tolerated. Clinical trial number: ClinicalTrials.gov NCT02722837.
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Affiliation(s)
- Vasily Isakov
- a 1 Department of Gastroenterology and Hepatology , Institute of Nutrition , Moscow , Russia
| | - Vladimir Chulanov
- b 2 Central Research Institute of Epidemiology , Moscow , Russia
- c 3 Hepatology Unit, Sechenov First State Medical University , Moscow , Russia
| | | | - Eduard Burnevich
- c 3 Hepatology Unit, Sechenov First State Medical University , Moscow , Russia
- d 4 City Clinical Hospital #24 of Moscow Healthcare Department , Moscow , Russia
| | | | - Galina Kozhevnikova
- f 6 Central Scientific and Research Institute of Epidemiology , Moscow , Russia
| | - Natalya Gankina
- g 7 Krasnoyarsk Regional Center of AIDS Prevention , Krasnoyarsk , Russia
| | - Sergey Zhuravel
- h 8 Sklifosovsky Scientific Research Institution of Emergency Care of Moscow Healthcare Department , Moscow , Russia
| | - Svetlana Romanova
- i 9 Center for Prevention and Control AIDS and Infectious Diseases , Saint Petersburg , Russia
| | | | - Sophia Lu
- j 10 Gilead Sciences , Foster City , CA, USA
| | | | | | | | - Vladimir Ivashkin
- c 3 Hepatology Unit, Sechenov First State Medical University , Moscow , Russia
| | | | - Igor Bakulin
- l 12 Propedeutics of Internal Diseases, Gastroenterology and Dietology, I.I. Mechnikov North-West State Medical University , Saint Petersburg , Russia
| | - Martin Lagging
- m 13 Department of Infectious Diseases/Virology , Institute of Biomedicine Sahlgrenska Academy University of Gothenburg , Gothenburg , Sweden
| | | | - Ola Weiland
- o 15 Department of Internaö Medicine Division of Infectious Diseases , Karolinska Institutet, Karolinska University Hospital Huddinge , Stockholm , Sweden
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Abdel-Lateef MA, Omar MA, Ali R, Derayea SM. Micellar spectrofluorimetric protocol for the innovative determination of HCV antiviral (daclatasvir) with enhanced sensitivity: Application to human plasma and stability study. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2019; 206:57-64. [PMID: 30081268 DOI: 10.1016/j.saa.2018.07.101] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 07/17/2018] [Accepted: 07/31/2018] [Indexed: 06/08/2023]
Abstract
Daclatasvir dihydrochloride (DAC) is a new, direct-acting antiviral drug with powerful inhibitory effect against all hepatitis C virus (HCV) genotypes. A sensitive, simple, fast and specific fluorometric method for estimation of DAC in the presence of sofosbuvir was developed and validated. The method is based on reinforcement the fluorescence intensity of DAC by 170% of its original value in an aqueous solution of hexadecyl trimethyl ammonium bromide (pH 5.5, Teorell and Stenhagen buffer). The fluorescence intensity measurements were accomplished at 387 nm with 328 nm for excitation wavelength. A linear relationship was achieved between the DAC concentration and the fluorescence intensity in a range of 50.0-2000.0 ng ml-1 with 0.9998 and 0.9999 for the determination and correlation coefficients, respectively. The detection and quantitation limits were 13.4, 40.8 ng ml-1, respectively. The excellent sensitivity and specificity of the proposed method allowed the efficient estimation of DAC in real human plasma with adequate recovery (81.78 ± 1.57), and the selective determination for DAC in its commercial dosage form without interference from tablet excipient. Moreover, the proposed method was expanded to examine the stability of DAC by determination the parent drug of DAC in the presence of its oxidative, alkaline, acidic, UV, daylight and sunlight degradations products in agreement with ICH guidelines. Furthermore, the kinetic study of acidic and oxidative degradations of DAC was inspected. In addition, the half-life times of the reaction (t1/2) and the first-order reaction rate constants were estimated. Moreover, a suggestion for the degradation pathway was supposed.
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Affiliation(s)
- Mohamed A Abdel-Lateef
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Mahmoud A Omar
- Department of Analytical Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
| | - Ramadan Ali
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Sayed M Derayea
- Department of Analytical Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
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35
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Shoreibah M, Romano J, Sims OT, Guo Y, Jones D, Venkata K, Kommineni V, Orr J, Fitzmorris P, Massoud OI. Effect of Hepatitis C Treatment on Renal Function in Liver Transplant Patients. J Clin Transl Hepatol 2018; 6:391-395. [PMID: 30637216 PMCID: PMC6328736 DOI: 10.14218/jcth.2018.00026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 06/17/2018] [Accepted: 06/23/2018] [Indexed: 12/13/2022] Open
Abstract
Background and Aims: Hepatitis C Virus (HCV) is uniformly recurrent after liver transplant (LT) and recurrence is associated with an increased risk of mortality. Immunosuppressive medications increase the risk of chronic kidney disease, and the presence of chronic kidney disease presents a challenge for HCV treatment in LT recipients. The aim of this study was to assess changes in glomerular filtration rates (GFRs) of LT recipients receiving HCV treatment. Methods: This is a retrospective study of LT patients who received HCV treatment between 2015 and 2016 (n = 60). The outcomes of interest were differences in serum creatinine levels and in GFR, measured at treatment initiation and at 24 weeks after treatment. The average age of the patients was 59 years-old, and 17% were cirrhotic and 67% were treatment-experienced. All patients received sofosbuvir/ledipasvir without ribavirin. Results: All patients achieved sustained virologic response at 12 weeks after treatment (SVR12). At baseline, 55% of patients had GFR <60 mL/min per 1.73 m2. Among those patients, GFR did not change in 18%, 33% had improved GFR, and 48% had worsened GFR. Up to 45% of the patients had a GFR >60 mL/min per 1.73 m2. Among those patients, GFR did not change in 81%, and 19% had worsened GFR. In the entire cohort, 65% of patients had improved or stable GFR and 35% had worsened GFR. The average change in serum creatinine between baseline and 24 weeks was 0.10 (p = 0.18). Conclusions: This study showed improved or unchanged GFR in 65% and worsened GFR in 35% of LT recipients who achieved SVR12. Worsening of GFR was more frequently encountered in those with impaired renal function at baseline. Caution should be used when treating HCV in LT recipients, especially those with baseline status of renal impairment.
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Affiliation(s)
- Mohamed Shoreibah
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - John Romano
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Omar T. Sims
- Department of Social Work, College of Arts and Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
- Department of Health Behavior, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
- Center for AIDS Research, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Yuqi Guo
- School of Social Work, University of Alabama, Tuscaloosa, AL, USA
| | - DeAnn Jones
- Department of Pharmacology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Krishna Venkata
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Vishnu Kommineni
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jordan Orr
- Division of Gastroenterology and Hepatology, Department of Medicine, Vanderbilt University, Nashville, TN, USA
| | - Paul Fitzmorris
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Omar I. Massoud
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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36
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Goel A, Chen Q, Chhatwal J, Aggarwal R. Cost-effectiveness of generic pan-genotypic sofosbuvir/velpatasvir versus genotype-dependent direct-acting antivirals for hepatitis C treatment. J Gastroenterol Hepatol 2018; 33:2029-2036. [PMID: 29864213 DOI: 10.1111/jgh.14301] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 04/15/2018] [Accepted: 05/25/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Treatment of hepatitis C virus (HCV) infection with low-cost generic direct-acting antivirals (DAAs) available in India and other developing countries needs determination of HCV genotype ("genotype-dependent" regimens). Generic velpatasvir, a DAA that obviates the need for genotype determination ("pan-genotypic" regimen), recently became available but is costlier. The aim of this study was to evaluate the cost-effectiveness of genotype-dependent versus pan-genotypic DAA treatments in India. METHODS A previously validated microsimulation model, adapted to Indian population, was used to compare the costs and long-term outcomes of three scenarios: no treatment, treatment with genotype-dependent regimens, and treatment with pan-genotypic regimen. Input parameters were derived from literature. Using a payer's perspective and lifetime time horizon, quality-adjusted life-years (QALYs), total costs, and incremental cost-effectiveness ratio were calculated. Both deterministic and probabilistic sensitivity analyses were also conducted. RESULTS At the current price ($US223 for 4 weeks), pan-genotypic regimen was cost-saving compared with no treatment. Compared with genotype-dependent regimens, it increased QALYs by 0.92 and increased costs by $US107 but was deemed cost-effective with an incremental cost-effectiveness ratio of $US242 per QALY gained. Probabilistic sensitivity analysis also supported the cost-effectiveness of pan-genotypic regimen. At the reduced price of $US188 for 4 weeks, the pan-genotypic regimen will become cost-neutral to genotype-dependent regimens (current price: $US100 for 4 weeks). CONCLUSIONS At current prices, velpatasvir-based pan-genotypic regimen is cost-effective for HCV treatment in India where generic drugs are available. A reduction in the prices of pan-genotypic regimen has the potential to make its use cost-saving while simplifying treatment in community-level programs aimed at HCV elimination.
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Affiliation(s)
- Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Qiushi Chen
- Harold and Inge Marcus Department of Industrial and Manufacturing Engineering, Penn State University, State College, Pennsylvania, USA
- Massachusetts General Hospital Institute for Technology Assessment, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Jagpreet Chhatwal
- Massachusetts General Hospital Institute for Technology Assessment, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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37
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Flisiak R, Janczewska E, Łucejko M, Karpińska E, Zarębska-Michaluk D, Nazzal K, Bolewska B, Białkowska J, Berak H, Fleischer-Stępniewska K, Tomasiewicz K, Karwowska K, Simon K, Piekarska A, Tronina O, Tuchendler E, Garlicki A. Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness 2 years after treatment with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in the AMBER, real-world experience study. J Viral Hepat 2018; 25:1298-1305. [PMID: 29888828 DOI: 10.1111/jvh.12945] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 05/17/2018] [Indexed: 12/28/2022]
Abstract
We followed for 2 years patients treated with direct-acting agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction in liver stiffness (LS) and risk of hepatocellular carcinoma (HCC). The study included patients from 16 hepatologic centres involved in the AMBER, investigator-initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. A total of 204 patients among 209 from the primary study were enrolled, 200 with available testing at 2-year follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 nonresponders retreated). During 2yFU, 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post-treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses were lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, 2-year follow-up confirmed durability of virologic response after treatment of HCV infection with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics that support the need for longer than 2-year monitoring for possible disease progression.
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Affiliation(s)
- R Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - E Janczewska
- Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, Bytom, Poland
| | - M Łucejko
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - E Karpińska
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland
| | - D Zarębska-Michaluk
- Department of Infectious Diseases, Voivodship Hospital and Jan Kochanowski University, Kielce, Poland
| | - K Nazzal
- Department of Tropical and Infectious Disease and Hepatology, Medical University of Warsaw, Warsaw, Poland
| | - B Bolewska
- Department of Infectious Diseases, Poznań University of Medical Sciences, Poznań, Poland
| | - J Białkowska
- Department of Infectious and Liver Diseases, Medical University of Lódź, Łódź, Poland
| | - H Berak
- Daily Unit, Hospital of Infectious Diseases in Warsaw, Warsaw, Poland
| | - K Fleischer-Stępniewska
- Department of Infectious Diseases, Liver Diseases and Immune Deficiencies, Wroclaw Medical University, Wroclaw, Poland
| | - K Tomasiewicz
- Department of Infectious Diseases and Hepatology, Medical University of Lublin, Lublin, Poland
| | - K Karwowska
- Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - K Simon
- Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Wroclaw, Poland
| | - A Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łodź, Poland
| | - O Tronina
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - E Tuchendler
- 2nd Department of Infectious Diseases, Voivodship Specialistic Hospital, Wroclaw, Poland
| | - A Garlicki
- Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, Krakow, Poland
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38
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Llibre A, Shimakawa Y, Mottez E, Ainsworth S, Buivan TP, Firth R, Harrison E, Rosenberg AR, Meritet JF, Fontanet A, Castan P, Madejón A, Laverick M, Glass A, Viana R, Pol S, McClure CP, Irving WL, Miele G, Albert ML, Duffy D. Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus. Gut 2018; 67:2017-2024. [PMID: 29615488 PMCID: PMC6176522 DOI: 10.1136/gutjnl-2017-315783] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 03/09/2018] [Accepted: 03/14/2018] [Indexed: 12/31/2022]
Abstract
OBJECTIVE Recently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucleic acid testing remains limited. The aim of this study was to develop and validate a point-of-care (PoC) assay for the qualitative detection of HCV RNA. DESIGN We developed a PoC assay for the qualitative detection of HCV RNA on the PCR Genedrive instrument. We validated the Genedrive HCV assay through a case-control study comparing results with those obtained with the Abbott RealTime HCV test. RESULTS The PoC assay identified all major HCV genotypes, with a limit of detection of 2362 IU/mL (95% CI 1966 to 2788). Using 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA, the Genedrive HCV assay showed 98.6% sensitivity (95% CI 96.9% to 99.5%) and 100% specificity (95% CI 99.3% to 100%) to detect HCV. In addition, melting peak ratiometric analysis demonstrated proof-of-principle for semiquantification of HCV. The test was further validated in a real clinical setting in a resource-limited country. CONCLUSION We report a rapid, simple, portable and accurate PoC molecular test for HCV, with sensitivity and specificity that fulfils the recent FIND/WHO Target Product Profile for HCV decentralised testing in low-income and middle-income countries. This Genedrive HCV assay may positively impact the continuum of HCV care from screening to cure by supporting real-time treatment decisions. TRIAL REGISTRATION NUMBER NCT02992184 .
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Affiliation(s)
- Alba Llibre
- Immunobiology of Dendritic Cells, Institut Pasteur, Paris, France
- Inserm U1223, Institut Pasteur, Paris, France
| | - Yusuke Shimakawa
- Unité d’Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France
| | - Estelle Mottez
- Centre for Translational Research, Institut Pasteur, Paris, France
- INSERM UMS20, Institut Pasteur, Paris, France
| | | | - Tan-Phuc Buivan
- Centre for Translational Research, Institut Pasteur, Paris, France
- INSERM UMS20, Institut Pasteur, Paris, France
| | | | | | - Arielle R Rosenberg
- Université Paris Descartes, EA4474 "Hepatitis C Virology", AP-HP, Hôpital Cochin, Service de Virologie, Paris, France
| | - Jean-François Meritet
- Université Paris Descartes, EA4474 "Hepatitis C Virology", AP-HP, Hôpital Cochin, Service de Virologie, Paris, France
| | - Arnaud Fontanet
- Unité d’Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France
- PACRI Unit, Conservatoire National des Arts et Métiers, Paris, France
| | | | - Antonio Madejón
- Liver Unit, Hospital Universitario La Paz, CIBERehd, IdiPAZ, Madrid, Spain
| | | | | | | | - Stanislas Pol
- Immunobiology of Dendritic Cells, Institut Pasteur, Paris, France
- Inserm U1223, Institut Pasteur, Paris, France
- Centre for Translational Research, Institut Pasteur, Paris, France
- Université Paris Descartes, EA4474 "Hepatitis C Virology", AP-HP, Hôpital Cochin, Service de Virologie, Paris, France
| | - C Patrick McClure
- Gastrointestinal and Liver Disorders Theme, NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | - William Lucien Irving
- Gastrointestinal and Liver Disorders Theme, NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, UK
| | | | - Matthew L Albert
- Immunobiology of Dendritic Cells, Institut Pasteur, Paris, France
- Inserm U1223, Institut Pasteur, Paris, France
- Centre for Translational Research, Institut Pasteur, Paris, France
- Department of Cancer Immunology, Genentech Inc, San Francisco, California, USA
| | - Darragh Duffy
- Immunobiology of Dendritic Cells, Institut Pasteur, Paris, France
- Inserm U1223, Institut Pasteur, Paris, France
- Centre for Translational Research, Institut Pasteur, Paris, France
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Brar G, Greten TF, Brown ZJ. Current frontline approaches in the management of hepatocellular carcinoma: the evolving role of immunotherapy. Therap Adv Gastroenterol 2018; 11:1756284818808086. [PMID: 30377451 PMCID: PMC6202741 DOI: 10.1177/1756284818808086] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 09/24/2018] [Indexed: 02/04/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer-associated mortality worldwide and is expected to rise. Patients with early-stage disease may have a good prognosis with a 5-year survival rate of greater than 70%. However, the majority of patients are diagnosed with late-stage disease with a dismal overall survival rate of less than 16%. Therefore, there is a great need for advances in the treatment of advanced HCC, which for approximately the past decade, has been sorafenib. Immunotherapy is an evolving cancer treatment and has shown promise in treating patients with advanced HCC. In this review, we discuss the current standard of care for advanced HCC and then discuss the evolving role of immunotherapies.
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Affiliation(s)
- Gagandeep Brar
- Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Tim F. Greten
- Thoracic and GI Malignancies Branch, Center for Cancer Research, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD 20892, USA
| | - Zachary J. Brown
- Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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40
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Pradat P, Virlogeux V, Trépo E. Epidemiology and Elimination of HCV-Related Liver Disease. Viruses 2018; 10:E545. [PMID: 30301201 PMCID: PMC6213504 DOI: 10.3390/v10100545] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 10/01/2018] [Accepted: 10/03/2018] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) infection, defined by active carriage of HCV RNA, affects nearly 1.0% of the worldwide population. The main risk factors include unsafe injection drug use and iatrogenic infections. Chronic HCV infection can promote liver damage, cirrhosis and hepatocellular carcinoma (HCC) in affected individuals. The advent of new second-generation, direct-acting antiviral (DAA) agents allow a virological cure in more than 90% of treated patients, and therefore prevent HCV-related complications. Recently, concerns have been raised regarding the safety of DAA-regimens in cirrhotic patients with respect to the occurrence and the recurrence of HCC. Here, we review the current available data on HCV epidemiology, the beneficial effects of therapy, and discuss the recent controversy with respect to the potential link with liver cancer. We also highlight the challenges that have to be overcome to achieve the ambitious World Health Organization objective of HCV eradication by 2030.
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Affiliation(s)
- Pierre Pradat
- Centre for Clinical Research, Groupement Hospitalier Nord, Hospices Civils de Lyon, 69004 Lyon, France.
- Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France.
- Lyon University, Lyon, France.
| | - Victor Virlogeux
- Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, 69008 Lyon, France.
- Lyon University, Lyon, France.
- Department of Hepatology, Croix-Rousse Hospital, Hospices Civils de Lyon, 69004 Lyon, France.
| | - Eric Trépo
- Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Bruxelles, Belgium.
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41
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Kranidioti H, Chatzievagelinou C, Protopapas A, Papatheodoridi M, Zisimopoulos K, Evangelidou E, Antonakaki P, Vlachogiannakos J, Triantos C, Elefsiniotis I, Goulis J, Mela M, Anagnostou O, Tsoulas C, Deutsch M, Papatheodoridis G, Manolakopoulos S. Clinical and epidemiological characteristics of hepatitis C virus-infected people who inject drugs: a Greek descriptive analysis. Ann Gastroenterol 2018; 31:598-603. [PMID: 30174397 PMCID: PMC6102460 DOI: 10.20524/aog.2018.0293] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 06/26/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND It is estimated that 17,000 people who inject drugs (PWID) in Greece have hepatitis C virus (HCV) viremia. The aim of our study was to explore the characteristics of the HCV-infected, direct acting antiviral (DAA)-naïve PWID. METHODS This is a retrospective analysis of PWID with HCV infection. We selected data from six liver clinics during the period from 1st May 2014 to 31st May 2017 in order to record the characteristics of infected PWID. RESULTS We included 800 PWID with HCV infection (78.5% male, mean age 42±10 years) who had not received DAAs before 1st June 2017. One third of the patients had comorbidities (diabetes mellitus, arterial hypertension and psychological disorders); 70% were smokers, 27% alcohol users, 67% unemployed, 29% married, and 34% had education >12 years; 65% were attending addiction programs; 57% were receiving methadone and 36% buprenorphine. Sporadic or systemic drug use was reported by 37% while 1.4% and 2.9% had HIV and HBV coinfection, respectively. The genotype distribution was 20.5%, 4.6%, 3.3%, 61% and 10% for genotypes 1a, 1b, 2, 3 and 4, respectively. Mean (±SD) liver stiffness was 9±7 kPa and 21% of the patients had cirrhosis. Half of the patients were in the F0-F1 stage of liver disease, defined as stiffness ≤7 kPa. CONCLUSIONS Our real-life data suggest that HCV genotype 3 remains the predominant genotype among PWID. One third of PWID had comorbidities and one-fifth cirrhosis. Half of PWID had early-stage liver disease and remained without access to DAAs according to the Greek prioritization criteria.
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Affiliation(s)
- Hariklia Kranidioti
- 2 Academic Department of Internal Medicine, Hippokration General Hospital, Athens (Hariklia Kranidioti, Pinelopi Antonakaki, Olga Anagnostou, Melanie Deutsch, Spilios Manolakopoulos), Greece
| | - Christina Chatzievagelinou
- Department of Gastroenterology, Evangelismos–Opthalmiatrion Athinon–Polykliniki Hospitals, Athens (Christina Chatzievagelinou, Maria Mela), Greece
| | - Adonis Protopapas
- 4 Academic Department of Internal Medicine, Hippokration General Hospital, Thessaloniki (Adonis Protopapas, John Goulis), Greece
| | - Margarita Papatheodoridi
- Academic Department of Gastroenterology, Laiko General Hospital, Athens (Margarita Papatheodoridi, John Vlachogiannakos, George Papatheodoridis, Spilios Manolakopoulos), Greece
| | - Konstantinos Zisimopoulos
- Department of Gastroenterology, University of Patras (Konstantinos Zisimopoulos, Christos Triantos), Greece
| | - Eftychia Evangelidou
- “Agioi Anargyroi” General and Oncology Hospital of Kifissia, Athens (Eftychia Evangelidou, Ioannis Elefsiniotis), Greece
| | - Pinelopi Antonakaki
- 2 Academic Department of Internal Medicine, Hippokration General Hospital, Athens (Hariklia Kranidioti, Pinelopi Antonakaki, Olga Anagnostou, Melanie Deutsch, Spilios Manolakopoulos), Greece
| | - John Vlachogiannakos
- Academic Department of Gastroenterology, Laiko General Hospital, Athens (Margarita Papatheodoridi, John Vlachogiannakos, George Papatheodoridis, Spilios Manolakopoulos), Greece
| | - Christos Triantos
- Department of Gastroenterology, University of Patras (Konstantinos Zisimopoulos, Christos Triantos), Greece
| | - Ioannis Elefsiniotis
- “Agioi Anargyroi” General and Oncology Hospital of Kifissia, Athens (Eftychia Evangelidou, Ioannis Elefsiniotis), Greece
| | - John Goulis
- 4 Academic Department of Internal Medicine, Hippokration General Hospital, Thessaloniki (Adonis Protopapas, John Goulis), Greece
| | - Maria Mela
- Department of Gastroenterology, Evangelismos–Opthalmiatrion Athinon–Polykliniki Hospitals, Athens (Christina Chatzievagelinou, Maria Mela), Greece
| | - Olga Anagnostou
- 2 Academic Department of Internal Medicine, Hippokration General Hospital, Athens (Hariklia Kranidioti, Pinelopi Antonakaki, Olga Anagnostou, Melanie Deutsch, Spilios Manolakopoulos), Greece
| | | | - Melanie Deutsch
- 2 Academic Department of Internal Medicine, Hippokration General Hospital, Athens (Hariklia Kranidioti, Pinelopi Antonakaki, Olga Anagnostou, Melanie Deutsch, Spilios Manolakopoulos), Greece
| | - George Papatheodoridis
- Academic Department of Gastroenterology, Laiko General Hospital, Athens (Margarita Papatheodoridi, John Vlachogiannakos, George Papatheodoridis, Spilios Manolakopoulos), Greece
| | - Spilios Manolakopoulos
- 2 Academic Department of Internal Medicine, Hippokration General Hospital, Athens (Hariklia Kranidioti, Pinelopi Antonakaki, Olga Anagnostou, Melanie Deutsch, Spilios Manolakopoulos), Greece
- Academic Department of Gastroenterology, Laiko General Hospital, Athens (Margarita Papatheodoridi, John Vlachogiannakos, George Papatheodoridis, Spilios Manolakopoulos), Greece
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High SVR12 with 8-week and 12-week glecaprevir/pibrentasvir therapy: An integrated analysis of HCV genotype 1-6 patients without cirrhosis. J Hepatol 2018; 69:293-300. [PMID: 29551706 DOI: 10.1016/j.jhep.2018.03.007] [Citation(s) in RCA: 119] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 01/29/2018] [Accepted: 03/05/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase II or III clinical trials, G/P therapy achieved rates of sustained virologic response 12 weeks after treatment (SVR12) of 93-100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P therapy in patients without cirrhosis with HCV GT 1-6 infection was performed. METHODS Data were pooled from nine phase II and III trials including patients with chronic HCV GT 1-6 infection without cirrhosis who received G/P (300 mg/120 mg) for either 8 or 12 weeks. Patients were treatment naïve or treatment experienced with peginterferon, ribavirin, and/or sofosbuvir; all patients infected with HCV GT 3 were treatment naïve. Efficacy was evaluated as the SVR12 rate. RESULTS The analysis included 2,041 patients without cirrhosis. In the intent-to-treat population, 943/965 patients (98%) achieved SVR12 when treated for eight weeks, and 1,060/1,076 patients (99%) achieved SVR12 when treated for 12 weeks; the difference in rates was not significant (p = 0.2). A subgroup analysis demonstrated SVR12 rates > 95% across baseline factors traditionally associated with lower efficacy. G/P was well tolerated, with one DAA-related serious adverse event (<0.1%); grade 3 laboratory abnormalities were rare. CONCLUSIONS G/P therapy for eight weeks in patients with chronic HCV GT 1-6 infection without cirrhosis achieved an overall SVR12 rate of 98% irrespective of baseline patient or viral characteristics; four additional weeks of treatment did not significantly increase the SVR12 rate, demonstrating that the optimal treatment duration in this population is eight weeks. LAY SUMMARY In this integrated analysis of nine clinical trials, patients with chronic HCV genotype 1-6 infection without cirrhosis were treated for either 8 or 12 weeks with the direct-acting antiviral regimen glecaprevir/pibrentasvir (G/P). The cure rate was 98% and 99% following 8 and 12 weeks of treatment, respectively; the difference in rates was not significant (p = 0.2), nor was there a significant difference in the cure rates across the two treatment durations on the basis of baseline patient or viral characteristics. These results, along with a favourable safety profile, indicate that G/P is a highly efficacious and well-tolerated pangenotypic eight-week therapy for most patients with chronic HCV infection.
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Martinello M, Hajarizadeh B, Grebely J, Dore GJ, Matthews GV. Management of acute HCV infection in the era of direct-acting antiviral therapy. Nat Rev Gastroenterol Hepatol 2018; 15:412-424. [PMID: 29773899 DOI: 10.1038/s41575-018-0026-5] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The management of acute HCV infection has not been standardized following the availability of direct-acting antiviral agents (DAAs) for chronic HCV infection, and substantial uncertainty exists regarding the optimal treatment regimen and duration. Despite the lack of direct evidence, the 2016 American Association for the Study of Liver Diseases (AASLD)-Infectious Diseases Society of America (IDSA) guidelines supported "the same regimens for acute HCV as recommended for chronic HCV infection … owing to high efficacy and safety", whereas the 2016 European Association for the Study of the Liver (EASL) guidelines recommended sofosbuvir-ledipasvir, sofosbuvir-velpatasvir or sofosbuvir plus daclatasvir for 8 weeks in acute HCV infection, with a longer duration of 12 weeks recommended for those infected with HIV and/or baseline HCV RNA levels >1,000,000 IU/ml. This Review outlines the epidemiology, natural history and diagnosis of acute HCV infection and provides contemporary information on DAAs for acute and recent HCV infection. The Review also discusses the 2016 AASLD-IDSA and EASL recommendations for acute HCV infection management in light of available evidence and highlights key differences in study populations and design that influence interpretation. We focus on populations at high risk of HCV transmission and acquisition, including people who inject drugs and HIV-positive men who have sex with men, and highlight the potential effects of diagnosis and treatment of acute HCV infection in contributing to HCV elimination.
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Affiliation(s)
- Marianne Martinello
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia.
| | - Behzad Hajarizadeh
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia
| | - Jason Grebely
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia
| | - Gregory J Dore
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia
| | - Gail V Matthews
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia
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Flisiak R, Zarębska-Michaluk D, Janczewska E, Staniaszek A, Gietka A, Mazur W, Tudrujek M, Tomasiewicz K, Belica-Wdowik T, Baka-Ćwierz B, Dybowska D, Halota W, Lorenc B, Sitko M, Garlicki A, Berak H, Horban A, Orłowska I, Simon K, Socha Ł, Wawrzynowicz-Syczewska M, Jaroszewicz J, Deroń Z, Czauż-Andrzejuk A, Citko J, Krygier R, Piekarska A, Laurans Ł, Dobracki W, Białkowska J, Tronina O, Pawłowska M. Treatment of HCV infection in Poland at the beginning of the interferon-free era-the EpiTer-2 study. J Viral Hepat 2018; 25:661-669. [PMID: 29316039 DOI: 10.1111/jvh.12861] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 11/21/2017] [Indexed: 02/06/2023]
Abstract
The aim of the EpiTer-2 study was to analyse patient characteristics and their medication for HCV infection in Poland at the beginning of the interferon-free era. Analysis of data of HCV infected patients treated during the initial period of availability of interferon-free regimens in Poland, who started therapy after 1 July 2015 and had available an efficacy evaluation report before 30 June 2017 was undertaken. A total of 2879 patients with chronic hepatitis C were entered, including 46% with liver cirrhosis. The most common was genotype 1b (86.8%). The study population was gender balanced, the majority of patients were overweight or obese and 69% presented comorbidities, with the highest prevalence that for hypertension. More than half of patients were retreated due to failure of previous therapy with pegylated interferon and ribavirin. Almost two-third of patients received current therapy with ombitasvir/paritaprevir/ritonavir±dasabuvir (OPrD) ±ribavirin. Other patients received mostly sofosbuvir-based regimens including combination with ledipasvir and pegylated interferon and ribavirin for genotype 3-infected patients. Efficacy of treatment in the whole study population measured as intent-to-treat analysis was 95%. The most frequent regimen, administered for patients infected with genotype 1b, was 12 weeks of OPrD, resulting in an SVR rate of 98%. At least one adverse event was reported in 38% of patients, and the death rate was 0.8%. In conclusion, data from the EpiTer-2 study confirmed the excellent efficacy and safety profile of the real-world experience with recently introduced therapeutic options for genotype 1 HCV infection, but demonstrated weakness of the current therapeutic programme regarding genotype 3 infections.
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Affiliation(s)
- R Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - D Zarębska-Michaluk
- Department of Infectious Diseases, Voivodship Hospital and Jan Kochanowski University, Kielce, Poland
| | - E Janczewska
- Hepatology Outpatient Clinic, ID Clinic, Mysłowice, Poland
| | - A Staniaszek
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw, Poland
| | - A Gietka
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw, Poland
| | - W Mazur
- Clinical Department of Infectious Diseases, Specialist Hospital in Chorzów, Medical University of Silesia, Katowice, Poland
| | - M Tudrujek
- Department of Infectious Diseases and Hepatology, Medical University of Lublin, Lublin, Poland
| | - K Tomasiewicz
- Department of Infectious Diseases and Hepatology, Medical University of Lublin, Lublin, Poland
| | - T Belica-Wdowik
- Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology, John Paul II Hospital, Kraków, Poland
| | - B Baka-Ćwierz
- Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology, John Paul II Hospital, Kraków, Poland
| | - D Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, Toruń, Poland
| | - W Halota
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, Toruń, Poland
| | - B Lorenc
- Pomeranian Center of Infectious Diseases, Department of Infectious Diseases, Medical University of Gdańsk, Gdańsk, Poland
| | - M Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University Collegium Medicum, Kraków, Poland
| | - A Garlicki
- Department of Infectious and Tropical Diseases, Jagiellonian University Collegium Medicum, Kraków, Poland
| | - H Berak
- Hospital for Infectious Diseases in Warsaw, Medical University in Warsaw, Warsaw, Poland
| | - A Horban
- Hospital for Infectious Diseases in Warsaw, Medical University in Warsaw, Warsaw, Poland
| | - I Orłowska
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Warsaw, Poland
| | - K Simon
- Department of Infectious Diseases and Hepatology, Wrocław Medical University, Warsaw, Poland
| | - Ł Socha
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland
| | - M Wawrzynowicz-Syczewska
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland
| | - J Jaroszewicz
- Department of Infectious Diseases, Medical University of Silesia in Katowice, Bytom, Poland
| | - Z Deroń
- Ward of Infectious Diseases and Hepatology, Biegański Regional Specialist Hospital, Łódź, Poland
| | - A Czauż-Andrzejuk
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland
| | - J Citko
- Medical Practice of Infections, Regional Hospital, Olsztyn, Poland
| | - R Krygier
- Infectious Diseases and Hepatology Outpatient Clinic NZOZ "Gemini", Żychlin, Poland
| | - A Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź, Poland
| | - Ł Laurans
- Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland.,Multidisciplinary Regional Hospital in Gorzów Wielkopolski, Gorzów Wielkopolski, Poland
| | | | - J Białkowska
- Department of Infectious and Liver Diseases, Medical University of Łódź, Łódź, Poland
| | - O Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - M Pawłowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University Toruń, Toruń, Poland
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Hecht R, Hiebert L, Spearman WC, Sonderup MW, Guthrie T, Hallett TB, Nayagam S, Razavi H, Soe-Lin S, Vilakazi-Nhlapo K, Pillay Y, Resch S. The investment case for hepatitis B and C in South Africa: adaptation and innovation in policy analysis for disease program scale-up. Health Policy Plan 2018; 33:528-538. [PMID: 29529282 PMCID: PMC5894072 DOI: 10.1093/heapol/czy018] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/30/2018] [Indexed: 12/13/2022] Open
Abstract
Even though WHO has approved global goals for hepatitis elimination, most countries have yet to establish programs for hepatitis B and C, which account for 320 million infections and over a million deaths annually. One reason for this slow response is the paucity of robust, compelling analyses showing that national HBV/HCV programs could have a significant impact on these epidemics and save lives in a cost-effective, affordable manner. In this context, our team used an investment case approach to develop a national hepatitis action plan for South Africa, grounded in a process of intensive engagement of local stakeholders. Costs were estimated for each activity using an ingredients-based, bottom-up costing tool designed by the authors. The health impact and cost-effectiveness of the Action Plan were assessed by simulating its four priority interventions (HBV birth dose vaccination, PMTCT, HBV treatment and HCV treatment) using previously developed models calibrated to South Africa's demographic and epidemic profile. The Action Plan is estimated to require ZAR3.8 billion (US$294 million) over 2017-2021, about 0.5% of projected government health spending. Treatment scale-up over the initial 5-year period would avert 13 000 HBV-related and 7000 HCV-related deaths. If scale up continues beyond 2021 in line with WHO goals, more than 670 000 new infections, 200 000 HBV-related deaths, and 30 000 HCV-related deaths could be averted. The incremental cost-effectiveness of the Action Plan is estimated at $3310 per DALY averted, less than the benchmark of half of per capita GDP. Our analysis suggests that the proposed scale-up can be accommodated within South Africa's fiscal space and represents good use of scarce resources. Discussions are ongoing in South Africa on the allocation of budget to hepatitis. Our work illustrates the value and feasibility of using an investment case approach to assess the costs and relative priority of scaling up HBV/HCV services.
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Affiliation(s)
| | | | - Wendy C Spearman
- Division of Hepatology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Mark W Sonderup
- Division of Hepatology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Teresa Guthrie
- Guthrie Health Financing Consultants, Cape Town, South Africa
| | - Timothy B Hallett
- Department of Infectious Disease Epidemiology, Imperial College, London, UK
| | - Shevanthi Nayagam
- Department of Infectious Disease Epidemiology, Imperial College, London, UK
- Division of Digestive Diseases, Imperial College, London, UK
| | | | | | | | - Yogan Pillay
- South Africa National Department of Health, Pretoria, South Africa
| | - Stephen Resch
- Department of Health Policy and Management, Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA
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Wagner R, Randolph JT, Patel SV, Nelson L, Matulenko MA, Keddy R, Pratt JK, Liu D, Krueger AC, Donner PL, Hutchinson DK, Flentge C, Betebenner D, Rockway T, Maring CJ, Ng TI, Krishnan P, Pilot-Matias T, Collins C, Panchal N, Reisch T, Dekhtyar T, Mondal R, Stolarik DF, Gao Y, Gao W, Beno DA, Kati WM. Highlights of the Structure-Activity Relationships of Benzimidazole Linked Pyrrolidines Leading to the Discovery of the Hepatitis C Virus NS5A Inhibitor Pibrentasvir (ABT-530). J Med Chem 2018; 61:4052-4066. [PMID: 29653491 DOI: 10.1021/acs.jmedchem.8b00082] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Curative interferon and ribavirin sparing treatments for hepatitis C virus (HCV)-infected patients require a combination of mechanistically orthogonal direct acting antivirals. A shared component of these treatments is usually an HCV NS5A inhibitor. First generation FDA approved treatments, including the component NS5A inhibitors, do not exhibit equivalent efficacy against HCV virus genotypes 1-6. In particular, these first generation NS5A inhibitors tend to select for viral drug resistance. Ombitasvir is a first generation HCV NS5A inhibitor included as a key component of Viekira Pak for the treatment of patients with HCV genotype 1 infection. Since the launch of next generation HCV treatments, functional cure for genotype 1-6 HCV infections has been achieved, as well as shortened treatment duration across a wider spectrum of genotypes. In this paper, we show how we have modified the anchor, linker, and end-cap architecture of our NS5A inhibitor design template to discover a next generation NS5A inhibitor pibrentasvir (ABT-530), which exhibits potent inhibition of the replication of wild-type genotype 1-6 HCV replicons, as well as improved activity against replicon variants demonstrating resistance against first generation NS5A inhibitors.
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Affiliation(s)
- Rolf Wagner
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - John T Randolph
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Sachin V Patel
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Lissa Nelson
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Mark A Matulenko
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Ryan Keddy
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - John K Pratt
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Dachun Liu
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - A Chris Krueger
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Pamela L Donner
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Douglas K Hutchinson
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Charles Flentge
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - David Betebenner
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Todd Rockway
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Clarence J Maring
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Teresa I Ng
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Preethi Krishnan
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Tami Pilot-Matias
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Christine Collins
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Neeta Panchal
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Thomas Reisch
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Tatyana Dekhtyar
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Rubina Mondal
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - DeAnne F Stolarik
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Yi Gao
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Wenqing Gao
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - David A Beno
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
| | - Warren M Kati
- Global Pharmaceutical Research and Development , AbbVie , 1 North Waukegan Road , North Chicago , Illinois 60064 , United States
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Efficacy of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2, 4, 5, or 6 Infection Without Cirrhosis. Clin Gastroenterol Hepatol 2018; 16:417-426. [PMID: 28951228 DOI: 10.1016/j.cgh.2017.09.027] [Citation(s) in RCA: 170] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Accepted: 09/08/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) has high genotypic diversity and global distribution. Agents that are effective against all major HCV genotypes, with shorter treatment duration, are needed to reduce disease burden. Glecaprevir (an NS3/4A protease inhibitor) and pibrentasvir (an NS5A inhibitor) have a high barrier to resistance and synergistic antiviral activity. We evaluated the safety and efficacy of 8 and 12 weeks' treatment with glecaprevir/pibrentasvir in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis in 3 separate phase 3 trials. METHODS We performed 2 open label, single-arm studies (SURVEYOR-II, Part 4 and ENDURANCE-4) and a randomized, double-blind, placebo-controlled study (ENDURANCE-2). In the ENDURANCE-2 study, adult patients with untreated or previously treated HCV genotype 2 infection without cirrhosis were randomly assigned (2:1) to groups given once-daily oral glecaprevir/pibrentasvir (n = 202; 300 mg/120 mg) or placebo (n = 100) for 12 weeks. In the SURVEYOR-II, Part 4 and ENDURANCE-4 studies, adult patients with untreated or previously treated patients with HCV genotype 2, genotype 4, genotype 5, or genotype 6 infection, without cirrhosis, were given once-daily oral glecaprevir/pibrentasvir (n = 121 in ENDURANCE-4 and n = 145 in SURVEYOR-II) for 12 or 8 weeks, respectively. In all studies the primary endpoint was sustained virologic response at 12 weeks after treatment (SVR12) in the intention-to-treat population. RESULTS Among patients receiving glecaprevir/pibrentasvir for 8 weeks, rates of SVR12 were 98% (95% CI, 94.1-99.3) in those infected with HCV genotype 2 and 93% (95% CI, 83.6-97.3) in those infected with HCV genotypes 4, 5, or 6. Among patients receiving glecaprevir/pibrentasvir for 12 weeks, rates of SVR12 were 99.5% (95% CI, 98.5-100) in those infected with HCV genotype 2 and 99% (95% CI, 97.6-100) in those infected with HCV genotype 4, 5, or 6. No virologic failures occurred in patients with HCV genotype 4, 5, or 6 infections. The frequency and severity of adverse events in patients receiving glecaprevir/pibrentasvir were similar to those of patients who received placebo. CONCLUSION In 3 Phase 3 studies, 8 weeks' treatment with glecaprevir/pibrentasivr produced an SVR12 in at least 93% of patients with chronic HCV genotype 2, 4, 5, or 6 infection without cirrhosis, with virologic failure in less than 1%. The drug combination had a safety profile comparable to 12 week's treatment with glecaprevir/pibrentasvir. ClinicalTrials.gov numbers: NCT02640482 (ENDURANCE-2), NCT02636595 (ENDURANCE-4), and NCT02243293 (SURVEYOR-II).
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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: 74] [Impact Index Per Article: 10.6] [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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Marshall AD, Cunningham EB, Nielsen S, Aghemo A, Alho H, Backmund M, Bruggmann P, Dalgard O, Seguin-Devaux C, Flisiak R, Foster GR, Gheorghe L, Goldberg D, Goulis I, Hickman M, Hoffmann P, Jancorienė L, Jarcuska P, Kåberg M, Kostrikis LG, Makara M, Maimets M, Marinho RT, Matičič M, Norris S, Ólafsson S, Øvrehus A, Pawlotsky JM, Pocock J, Robaeys G, Roncero C, Simonova M, Sperl J, Tait M, Tolmane I, Tomaselli S, van der Valk M, Vince A, Dore GJ, Lazarus JV, Grebely J. Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe. Lancet Gastroenterol Hepatol 2018; 3:125-133. [PMID: 28986139 DOI: 10.1016/s2468-1253(17)30284-4] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 08/18/2017] [Accepted: 08/18/2017] [Indexed: 01/15/2023]
Abstract
All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.
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Affiliation(s)
| | | | | | - Alessio Aghemo
- Department of Biomedical Sciences and Humanitas Clinical and Research Center, Humanitas University, Milan, Italy
| | - Hannu Alho
- Abdominal Center, Helsinki University Hospital, Helsinki University, Helsinki, Finland
| | | | | | - Olav Dalgard
- Department of Infectious Diseases, Akershus University Hospital, University of Oslo, Oslo, Norway
| | - Carole Seguin-Devaux
- Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg City, Luxembourg
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
| | | | - Liana Gheorghe
- Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania
| | | | - Ioannis Goulis
- Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | | | - Ligita Jancorienė
- Centre of Infectious Diseases, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania
| | - Peter Jarcuska
- First Department of Internal Medicine, University Hospital, University of Pavol Jozef Safarik, Kosice, Slovakia
| | - Martin Kåberg
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
| | | | - Mihály Makara
- Hepatology Center, St István and St László Hospital, Budapest, Hungary
| | - Matti Maimets
- Department of Internal Medicine, University of Tartu, Estonia
| | - Rui Tato Marinho
- Department of Gastroenterology and Hepatology, Hospital Santa Maria, Medical School Lisbon, University of Lisbon, Lisbon, Portugal
| | - Mojca Matičič
- Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre, Ljubljana, Slovenia
| | - Suzanne Norris
- National Hepatitis C Treatment Programme, Health Service Executive, Dr Steevens' Hospital, Dublin, Ireland
| | - Sigurður Ólafsson
- Division of Gastroenterology, Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland
| | - Anne Øvrehus
- Department of Infectious Diseases, Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | | | - James Pocock
- Gastroenterology Department, Mater Dei Hospital, Msida, Malta
| | - Geert Robaeys
- Department of Gastroenterology and Hepatology, Ziekenhuis Oost Limburg, Genk, Belgium; Department of Medicine and Life Sciences, University of Hasselt, Hasselt, Belgium; Department of Hepatology, UZ Leuven, Leuven, Belgium
| | - Carlos Roncero
- Addiction and Dual Diagnosis Unit, Psychiatric Department, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - Marieta Simonova
- Department of Gastroenterology, Hepato-Pancreato-Biliary Surgery and Transplantology, Military Medical Academy, Sofia, Bulgaria
| | - Jan Sperl
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Michele Tait
- National Hepatitis C Treatment Programme, Health Service Executive, Dr Steevens' Hospital, Dublin, Ireland
| | - Ieva Tolmane
- Department of Hepatology, Infectology Center of Latvia, Riga East University Hospital, Riga, Latvia; Faculty of Medicine, University of Latvia, Riga, Latvia
| | | | - Marc van der Valk
- Department of Infectious Diseases, Academic Medical Center, Amsterdam, Netherlands
| | - Adriana Vince
- University Hospital for Infectious Diseases, University of Zagreb, Zagreb, Croatia
| | | | - Jeffrey V Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, Univeristy of Barcelona, Barcelona, Spain; CHIP, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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Bennett H, Gordon J, Jones B, Ward T, Webster S, Kalsekar A, Yuan Y, Brenner M, McEwan P. Hepatitis C disease transmission and treatment uptake: impact on the cost-effectiveness of new direct-acting antiviral therapies. THE EUROPEAN JOURNAL OF HEALTH ECONOMICS : HEPAC : HEALTH ECONOMICS IN PREVENTION AND CARE 2017; 18:1001-1011. [PMID: 27803989 DOI: 10.1007/s10198-016-0844-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 10/18/2016] [Indexed: 05/23/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) treatment can reduce the incidence of future infections through removing opportunities for onward transmission. This benefit is not captured in conventional cost-effectiveness evaluations of treatment and is particularly relevant in patient groups with a high risk of transmission, such as those people who inject drugs (PWID), where the treatment rates have been historically low. This study aimed to quantify how reduced HCV transmission changes the cost-effectiveness of new direct-acting antiviral (DAA) regimens as a function of treatment uptake rates. METHODS An established model of HCV disease transmission and progression was used to quantify the impact of treatment uptake (10-100%), within the PWID population, on the cost-effectiveness of a DAA regimen versus pre-DAA standard of care, conducted using daclatasvir plus sofosbuvir in the UK setting as an illustrative example. RESULTS The consequences of reduced disease transmission due to treatment were associated with additional net monetary benefit of £24,304-£90,559 per patient treated at £20,000/QALY, when 10-100% of eligible patients receive treatment with 100% efficacy. Dependent on patient genotype, the cost-effectiveness of HCV treatment using daclatasvir plus sofosbuvir improved by 36-79% versus conventional analysis, at 10-100% treatment uptake in the PWID population. CONCLUSIONS The estimated cost-effectiveness of HCV treatment was shown to improve as more patients are treated, suggesting that the value of DAA regimens to the NHS could be enhanced by improved treatment uptake rates among PWID. However, the challenge for the future will lie in achieving increased rates of treatment uptake, particularly in the PWID population.
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Affiliation(s)
- Hayley Bennett
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK.
| | - Jason Gordon
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK
- Department of Public Health, University of Adelaide, Adelaide, Australia
| | - Beverley Jones
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK
| | - Thomas Ward
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK
| | - Samantha Webster
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK
| | - Anupama Kalsekar
- World Wide Health Economics and Outcomes Research, Bristol-Myers Squibb Pharmaceuticals Ltd, Princeton, USA
| | - Yong Yuan
- World Wide Health Economics and Outcomes Research, Bristol-Myers Squibb Pharmaceuticals Ltd, Princeton, USA
| | - Michael Brenner
- UK HEOR, Bristol-Myers Squibb Pharmaceuticals Ltd, Uxbridge, UK
| | - Phil McEwan
- HEOR, Health Economics and Outcomes Research Ltd, 9 Oak Tree Court, Mulberry Drive, Cardiff Gate Business Park, Cardiff, CF23 8RS, UK
- School of Human and Health Sciences, Swansea University, Swansea, UK
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