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Nadeem R, Maghraby AS, Abd-Elshafy DN, Barakat AB, Bahgat MM. Individual expression and processing of hepatitis C virus E1/E2 epitopes-based DNA vaccine candidate in healthy humans' peripheral blood mononuclear cells. Clin Exp Vaccine Res 2023; 12:47-59. [PMID: 36844691 PMCID: PMC9950224 DOI: 10.7774/cevr.2023.12.1.47] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 05/26/2022] [Accepted: 12/23/2022] [Indexed: 02/19/2023] Open
Abstract
Purpose The development and study of hepatitis C virus (HCV) vaccine candidates' individualized responses are of great importance. Here we report on an HCV DNA vaccine candidate based on selected envelope (E1/E2) epitopes. Besides, we assessed its expression and processing in human peripheral blood mononuclear cells (PBMCs) and in vivo cellular response in mice. Materials and Methods HCV E1/E2 DNA construct (EC) was designed. The antigen expression of EC was assayed in PBMCs of five HCV-uninfected donors via a real-time quantitative polymerase chain reaction. Serum samples from 20 HCV antibody-positive patients were used to detect each individual PBMCs expressed antigens via enzyme-linked immunosorbent assay. Two groups, five Swiss albino mice each, were immunized with the EC or a control construct. The absolute count of lymph nodes' CD4+ and CD8+ T-lymphocytes was assessed. Results Donors' PBMCs showed different levels of EC expression, ranging between 0.83-2.61-fold in four donors, while donor-3 showed 34.53-fold expression. The antigens expressed in PBMCs were significantly reactive to the 20 HCV antibody repertoire (all p=0.0001). All showed comparable reactivity except for donor-3 showing the lowest reactivity level. The absolute count % of the CD4+ T-cell significantly increased in four of the five EC-immunized mice compared to the control group (p=0.03). No significant difference in CD8+ T-cells % was observed (p=0.89). Conclusion The inter-individual variation in antigen expression and processing dominance was evident, showing independence in individuals' antigen expression and reactivity levels to antibodies. The described vaccine candidate might result in a promising natural immune response with a possibility of CD4+ T-cell early priming.
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Affiliation(s)
- Rola Nadeem
- Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Center, Cairo, Egypt.,Immune- and Bio-markers for Infection Research Group, Center of Excellence for Advanced Sciences, National Research Center, Cairo, Egypt
| | - Amany Sayed Maghraby
- Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Center, Cairo, Egypt.,Immune- and Bio-markers for Infection Research Group, Center of Excellence for Advanced Sciences, National Research Center, Cairo, Egypt
| | - Dina Nadeem Abd-Elshafy
- Immune- and Bio-markers for Infection Research Group, Center of Excellence for Advanced Sciences, National Research Center, Cairo, Egypt.,Department of Water Pollution Research, Environmental Research Institute, National Research Center, Dokki, Cairo, Egypt
| | | | - Mahmoud Mohamed Bahgat
- Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Center, Cairo, Egypt.,Immune- and Bio-markers for Infection Research Group, Center of Excellence for Advanced Sciences, National Research Center, Cairo, Egypt
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Tasavon Gholamhoseini M, Sharafi H, Hl Borba H, Alavian SM, Sabermahani A, Hajarizadeh B. Economic evaluation of pan-genotypic generic direct-acting antiviral regimens for treatment of chronic hepatitis C in Iran: a cost-effectiveness study. BMJ Open 2022; 12:e058757. [PMID: 35676019 PMCID: PMC9185662 DOI: 10.1136/bmjopen-2021-058757] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Low-cost generic direct-acting antiviral (DAA) regimens for treatment of hepatitis C virus (HCV) are available in several low-income/middle-income countries, important for treatment scale-up. This study evaluated the cost-effectiveness of genotype-dependent and pan-genotypic DAA regimens in Iran as an example of a resource-limited setting. METHODS A Markov model was developed to simulate HCV natural history. A decision tree was developed for HCV treatment, assuming four scenarios, including scenario 1: genotyping, sofosbuvir/ledipasvir (SOF/LDV) for genotype 1, and sofosbuvir/daclatasvir (SOF/DCV) for genotype 3; scenario 2: genotyping, SOF/LDV for genotype 1, and sofosbuvir/velpatasvir (SOF/VEL) for genotype 3; scenario 3: no genotyping and SOF/DCV for all; and scenario 4: no genotyping and SOF/VEL for all. A 1-year cycle length was used to calculate the cumulative cost and effectiveness over a lifetime time horizon. We calculated quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) using a health system perspective. Costs were converted to US dollars using purchasing power parity exchange rate ($PPP). All costs and outcomes were discounted at an annual rate of 3%. RESULTS Among people with no cirrhosis, scenario 3 had the minimum cost, compared with which scenario 4 was cost-effective with an ICER of 4583 $PPP per QALY (willingness-to-pay threshold: 9,311 $PPP per QALY). Among both people with compensated or decompensated cirrhosis, scenario 4 was cost saving. In sensitivity analysis, scenario 4 would be also cost-saving among people with no cirrhosis provided a 39% reduction in the cost of 12 weeks SOF/VEL. CONCLUSION Initiating all patients on pan-genotypic generic DAA regimens with no pretreatment genotyping was cost-effective compared with scenarios requiring pretreatment HCV genotype tests. Among generic pan-genotypic DAA regimens, SOF/VEL was cost-effective, for people with no cirrhosis and cost-saving for those with cirrhosis.
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Affiliation(s)
- Mohammad Tasavon Gholamhoseini
- Health Services Management Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Helena Hl Borba
- Department of Pharmacy, Federal University of Parana, Curitiba, Parana, Brazil
| | | | - Asma Sabermahani
- Department of Management, Health Policy and Health Economics, Kerman University of Medical Sciences, Kerman, Iran
| | - Behzad Hajarizadeh
- The Kirby Institute, University of New South Wales (UNSW Sydney), Sydney, New South Wales, Australia
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Liu J, Guo M, Ke L, You R. Cost-Effectiveness of Elbasvir/Grazoprevir for the Treatment of Chronic Hepatitis C: A Systematic Review. Front Public Health 2022; 10:836986. [PMID: 35646774 PMCID: PMC9136222 DOI: 10.3389/fpubh.2022.836986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 04/04/2022] [Indexed: 11/13/2022] Open
Abstract
Objective This study aims to systematically review recent economic evaluations of elbasvir/grazoprevir (EBR/GZR) for chronic hepatitis C (CHC), to critically appraise the reporting quality and to summarize the results. Methods A literature search was undertaken using Medline, Embase, the Cochrane Library, EconLit, China National Knowledge Infrastructure, Wanfang Data, and Chongqing VIP to identify original articles containing economic evaluations of EBR/GZR for CHC published between 1 January 2000 and 31 December 2020. The Consolidated Health Economic Evaluation Reporting Standards statement was used to assess the quality of reporting of the articles. Results Of 93 articles identified, 13 studies fulfilled the inclusion criteria. These studies were conducted in 4 countries, and 8 active interventions were assessed. The target population was patients infected with CHC genotype 1 infection in all studies. Eight out of 13 studies that compared EBR/GZR vs. other direct antiviral agents suggested that EBR/GZR was generally more cost-effective or dominant than daclatasvir/asunaprevir (DCV/ASV), sofosbuvir/velpatasvir (SOF/VEL), ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir (3D) but not more cost-effective than glecaprevir/pibrentasvir (GLE/PIB). Two studies from China and one study from the USA that compared EBR/GZR vs. pegylated interferon and ribavirin (PegIFN/RBV) consistently indicated that EBR/GZR was generally more cost-effective than PegIFN/RBV. One study from Italy compared EBR/GZR with SOF + PegIFN/RBV and suggested that EBR/GZR had a lower cost and higher effectiveness. One study from France and one study from the USA confirmed that compared with non-therapy for patients with chronic kidney disease, EBR/GZR was cost-effective at commonly accepted current standards. All included studies were of good quality of reporting, with an average score of 21.9 (range 19–23). Conclusion EBR/GZR for CHC genotype 1 might be cost-effective or dominant compared with PegIFN/RBV and other direct antiviral agents (SOF/VEL, 3D, DCV/ASV, LDF/SOF) or non-therapy. However, under certain assumptions, EBR/GZR was not a cost-effective alternative for CHC patients vs. GLE/PIB.
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Affiliation(s)
- Jinyu Liu
- Department of Pharmacy, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Min Guo
- Department of Pharmacy, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Ke
- Department of Pharmacy, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
- Lei Ke
| | - Ruxu You
- Department of Pharmacy, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Ruxu You
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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Zhou HJ, Cao J, Shi H, Naidoo N, Semba S, Wang P, Fan YF, Zhu SC. Cost-Effectiveness Analysis of Pan-Genotypic Sofosbuvir-Based Regimens for Treatment of Chronic Hepatitis C Genotype 1 Infection in China. Front Public Health 2021; 9:779215. [PMID: 34957030 PMCID: PMC8695807 DOI: 10.3389/fpubh.2021.779215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 11/18/2021] [Indexed: 11/21/2022] Open
Abstract
Background: Hepatitis C virus (HCV) genotype 1 is the most prevalent HCV infection in China. Sofosbuvir-based direct antiviral agent (DAA) regimens are the current mainstays of treatment. Sofosbuvir/velpatasvir (SOF/VEL) and sofosbuvir/ledipasvir (SOF/LDV) regimens became reimbursable in China in 2020. Thus, this study aimed to identify the optimal SOF-based regimen and to inform efficient use of healthcare resources by optimizing DAA use in treating HCV genotype 1. Methods and Models: A modeling-based cost-utility analysis was conducted from the payer's perspective targeting adult Chinese patients with chronic HCV genotype 1 infection. Direct medical costs and health utilities were inputted into a Markov model to simulate lifetime experiences of chronically infected HCV patients after receiving SOF/LDV, SOF/VEL or the traditional strategy of pegylated interferon (pegIFN) + ribavirin (RBV). Discounted lifetime cost and quality adjusted life years (QALYs) were computed and compared to generate the incremental cost utility ratio (ICUR). An ICUR below the threshold of 31,500 $/QALY suggests cost-effectiveness. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of model findings. Results: Both SOF/LDV and SOF/VEL regimens were dominant to the pegIFN + RBV regimen by creating more QALYs and incurring less cost. SOF/LDV produced 0.542 more QALYs but cost $10,390 less than pegIFN + RBV. Relative to SOF/LDV, SOF/VEL had an ICUR of 168,239 $/QALY which did not meet the cost-effectiveness standard. Therefore SOF/LDV was the optimal strategy. These findings were robust to linear and random variations of model parameters. However, reducing the SOF/VEL price by 40% would make this regimen the most cost-effective option. Conclusions: SOF/LDV was found to be the most cost-effective treatment, and SOF/VEL was also economically dominant to pegIFN + RBV. These findings indicated that replacing pegIFN + RBV with DAA regimens could be a promising strategy.
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Affiliation(s)
- Hui Jun Zhou
- Department of Public Administration, Business School, University of Shanghai for Science and Technology, Shanghai, China
| | - Jing Cao
- Department of Public Administration, Business School, University of Shanghai for Science and Technology, Shanghai, China
| | - Hui Shi
- Department of Public Administration, Business School, University of Shanghai for Science and Technology, Shanghai, China
| | - Nasheen Naidoo
- Department of Pathology, Stellenbosch University, Cape Town, South Africa
| | - Sherehe Semba
- Department of Public Administration, Business School, University of Shanghai for Science and Technology, Shanghai, China
- Faculty of Science, Dar es Salaam University College of Education, University of Dar es Salaam, Dar es Salaam, Tanzania
| | - Pei Wang
- School of Public Health, Fudan University, Shanghai, China
- Key Lab of Health Technology Assessment, National Health Commission of China (Fudan University), Shanghai, China
| | - Yi Fan Fan
- Department of Public Administration, Business School, University of Shanghai for Science and Technology, Shanghai, China
| | - Shui Cheng Zhu
- Department of Public Administration, Business School, University of Shanghai for Science and Technology, Shanghai, China
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Cost-utility Analysis of Second-generation Direct-acting Antivirals for Hepatitis C. HEPATITIS MONTHLY 2021. [DOI: 10.5812/hepatmon118646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Hepatitis C virus (HCV) can lead to increased mortality, disability, and liver transplantation if left untreated, and it is associated with a possible increase in disease burden in the future, all of which would surely have a significant impact on the health system. New antiviral regimens are effective in the treatment of the disease yet expensive. Objectives: The purpose of the present study was to assess the cost-effectiveness of three medication regimens, namely, ledipasvir/sofosbuvir (LDV/SOF), velpatasvir/sofosbuvir, and daclatasvir/sofosbuvir (DCV/SOF) for HCV patients with genotype 1 in Iran. Methods: A Markov model with a lifetime horizon was developed to predict the costs and outcomes of the three mentioned medication therapy strategies. The final outcome of the study was quality-adjusted life-years (QALYs), which was obtained using the previously published studies. The study was conducted from the perspective of the Health Ministry; therefore, only direct medical costs were estimated. The results were provided as the incremental cost-effectiveness ratio (ICER) per QALY. Ultimately, the one-way and probabilistic sensitivity analyses were used to measure the strength of study results. Results: The results showed that the QALYs for LDV/SOF, DCV/SOF, and VEL/SOF were 13.25, 13.94, and 14.61, and the costs were 4,807, 7,716, and 4,546$, respectively. The VEL/SOF regimen had lower costs and higher effectiveness than the LDV/SOF and DCV/SOF regimens, making it a dominant strategy. The tornado diagram results showed that the study results had the highest sensitivity to chronic hepatitis C (CHC) and compensated cirrhosis (CC) state costs. Moreover, the scatter plots showed that the VEL/SOF was the dominant therapeutic strategy in 73% of the simulations compared to LDV/SOF and 66% of the simulations compared to DCV/SOF; moreover, it was in the acceptable region in 92% of the simulations and below the threshold. Therefore, it was considered the most cost-effective strategy. Moreover, the results showed that DCV/SOF was in the acceptable region below the threshold in 69% of the simulations compared to LDV/SOF. Therefore, the DCV/SOF regimen was more cost-effective than LDV/SOF. Conclusions: According to the present study results, it is suggested that the VEL/SOF regimen be used as the first line of therapy in patients with HCV genotype 1. Moreover, DCV/SOF can be the second-line medication regimen.
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Liu J, Zhang Y, Wu B, Wang S, Bin-Chia Wu D, You R. Cost-Effectiveness of Testing for NS5A Resistance to Optimize Treatment of Elbasvir/Grazoprevir for Chronic Hepatitis C in China. Front Pharmacol 2021; 12:717504. [PMID: 34721016 PMCID: PMC8554024 DOI: 10.3389/fphar.2021.717504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 09/13/2021] [Indexed: 12/05/2022] Open
Abstract
Objectives: Baseline presence of nonstructural protein 5A (NS5A) resistance-associated variants can attenuate the efficacy of new direct-acting antivirals. A potential method to attain the higher efficacy would be to screen for NS5A polymorphisms prior to the initiation of therapy and to adjust the treatment length based on the test results. However, baseline testing adds additional costs and it is unclear whether this would represent a high value strategy for chronic hepatitis C in China. Methods: A hybrid model compared 1) standard 12-weeks treatment (no testing), 2) shortened 8-weeks treatment (no testing), and 3) baseline testing with 12-/8-weeks treatment for those with/without NS5A polymorphisms from a lifetime Chinese health care payer perspective. All model inputs were retrieved from clinical trials and publically available literature. And sensitivity analyses were also conducted to assess the impact of uncertainty. Results: Baseline testing was associated with overall increase in total health care cost of USD 13.50 and in QALYs of 0.002 compared with standard 12-weeks treatment (no testing), yielded in an ICER of USD 6750/QALY gained. Scenario analyses suggested that shortened 8-weeks treatment (no testing) was found to be lower costs and great QALYs compared with other two strategies when the sustained virologic response (SVR) rate increased to 95%. Sensitivity analyses indicated that the results were robust. Conclusions: Our results suggest prior assessment of NS5A sensitivity followed by optimizing treatment duration was an economic strategy. In addition, shortened 8-weeks treatment (no testing) was shown to be dominant with the SVR rate increased to 95%.
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Affiliation(s)
- Jinyu Liu
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Zhang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin Wu
- Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Sen Wang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - David Bin-Chia Wu
- School of Pharmacy, Monash University Malaysia, Kuala Lumpur, Malaysia.,Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - Ruxu You
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Wei X, Zhao J, Yang L. Cost-effectiveness of new antiviral treatments for non-genotype 1 hepatitis C virus infection in China: a societal perspective. BMJ Glob Health 2021; 5:bmjgh-2020-003194. [PMID: 33246983 PMCID: PMC7703443 DOI: 10.1136/bmjgh-2020-003194] [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: 06/29/2020] [Revised: 10/29/2020] [Accepted: 11/04/2020] [Indexed: 12/14/2022] Open
Abstract
Objective This study aimed to estimate the cost-effectiveness of direct-acting antivirals (DAAs) among patients with non-genotype 1 for the eradication of hepatitis C virus (HCV) infection in China. Methods A decision-analytic Markov model was developed to estimate the lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) for DAAs and pegylated interferon plus ribavirin (PEG-RBV) from a societal perspective. The model inputs were derived from the literature, a patient survey, HCV expert opinions and a specialised drug price database available in China. Sensitivity analysis was conducted to evaluate the model robustness and calculate reasonable prices of DAAs. Results For patients infected with HCV genotype 2, the pan-genotypic regimen sofosbuvir/velpatasvir (SOF/VEL) was the most cost-effective strategy compared with PEG-RBV, with an ICER of US$5653/QALY. For genotype 3, the combination of sofosbuvir plus daclatasvir (SOF-DCV) was the most cost-effective approach, with an ICER of US$3314/QALY. All DAA regimens for genotype 6 were cost-saving, and sofosbuvir plus ribavirin (SOF-RBV) was the optimal regimen. One-way sensitivity analysis demonstrated that the ICERs were most sensitive to the utility values, discount rate and drug costs. Probabilistic sensitivity analysis indicated that using a threshold equal to one time the gross domestic product (GDP) per capita in China (US$9769/QALY, 2018), the probability of SOF/VEL, SOF-DCV and SOF-RBV being cost-effective was 58%, 83% and 71% for genotype 2, 3 and 6, respectively. Threshold analysis showed that the price of DAAs should be reduced by some degree to achieve better affordability. Conclusions DAAs were cost-effective compared with traditional treatments. A reasonable reduction in the price of DAAs will increase drug affordability and is of great significance as a global strategy to eradicate viral hepatitis.
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Affiliation(s)
- Xia Wei
- Department of Health policy and management, School of Public Health, Peking University, Beijing, China
| | - Jingyu Zhao
- Department of Health policy and management, School of Public Health, Peking University, Beijing, China
| | - Li Yang
- Department of Health policy and management, School of Public Health, Peking University, Beijing, China
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