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Wang W, Chen C, Re VL, Chang SH, Wilson DL, Park H. Association between treatment of hepatitis C virus and risk of cardiovascular disease among insured patients with the virus in the United States. Pharmacoepidemiol Drug Saf 2023; 32:1142-1151. [PMID: 37278688 PMCID: PMC10655016 DOI: 10.1002/pds.5651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 05/03/2023] [Accepted: 05/25/2023] [Indexed: 06/07/2023]
Abstract
PURPOSE Hepatitis C virus (HCV) infection has been associated with increased risk of cardiovascular disease (CVD). It is unclear whether HCV treatment affects risk of CVD among patients infected with HCV. We assessed the incidence and risk of CVD among insured patients with HCV infection and evaluated if HCV treatment was associated with reduced CVD risk. METHODS This retrospective cohort study used MarketScan Commercial and Medicare Supplement databases. Patients newly diagnosed with HCV (vs. patients without HCV) between January 2008 and August 2015 were categorized by treatment (none, insufficient, or minimum effective) based on receipt and duration of anti-HCV treatments. After propensity score matching, time-dependent Cox proportional hazards models were used to compare CVD risk between patients with HCV versus without and between patients with HCV by treatment type and duration. RESULTS HCV was associated with 13% increased risk of developing CVD overall (adjusted hazard ratio [aHR] 95% CI 1.26-1.35) and with 13% (aHR 1.07-1,18), 9% (aHR 1.03-1.15), and 32% (aHR 1.24-1.40) significantly increased risks of developing coronary artery disease, cerebrovascular disease, and peripheral vascular disease, respectively. Among patients with HCV, compared with no treatment, receipt of minimum effective treatment was associated with 24% decreased risk of CVD, and receipt of insufficient treatment was associated with 14% decreased risk of CVD. CONCLUSIONS Individuals chronically infected with HCV had a higher incidence of CVD. Among patients with HCV, receipt of antiviral treatment for HCV was associated with decreased risk of CVD.
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Affiliation(s)
- Wei Wang
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida
- Merck & Co., Inc., Rahway, New Jersey, USA
| | - Chao Chen
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida
- Regeneron, NY, USA
| | - Vincent Lo Re
- Division of Infectious Diseases, Department of Medicine; Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania
| | - Shao-Hsuan Chang
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida
| | - Debbie L. Wilson
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida
| | - Haesuk Park
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida
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Brzdęk M, Zarębska-Michaluk D, Invernizzi F, Cilla M, Dobrowolska K, Flisiak R. Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C. World J Gastroenterol 2023; 29:949-966. [PMID: 36844142 PMCID: PMC9950869 DOI: 10.3748/wjg.v29.i6.949] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/22/2022] [Accepted: 01/09/2023] [Indexed: 02/10/2023] Open
Abstract
Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.
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Affiliation(s)
- Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce 25-516, Poland
| | | | - Federica Invernizzi
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | - Marta Cilla
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
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Wong YJ, Thurairajah PH, Kumar R, Fock KM, Law NM, Chong SY, Manejero FG, Ang TL, Teo EK, Tan J. The impact of unrestricted access to direct-acting antiviral among incarcerated hepatitis C virus-infected patients. Clin Mol Hepatol 2021; 27:474-485. [PMID: 33601868 PMCID: PMC8273645 DOI: 10.3350/cmh.2021.0015] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/16/2021] [Accepted: 02/17/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS Despite the disproportionally high prevalence rates of hepatitis C virus (HCV) amongst the incarcerated population, eradication remains challenging due to logistic and financial barriers. Although treatment prioritization based on disease severity is commonly practiced, the efficacy of such approach remained uncertain. We aimed to compare the impact of unrestricted access to direct-acting antiviral (DAA) among incarcerated HCV-infected patients in Singapore. METHODS In this retrospective study, we reviewed all incarcerated HCV-infected patients treated in our hospital during the restricted DAA era (2013-2018) and unrestricted DAA access era (2019). Study outcomes included the rate of sustained virological response (SVR), treatment completion and treatment default. Subgroup analysis was performed based on the presence of liver cirrhosis, HCV genotype and HCV treatment types. RESULTS A total of 1,001 HCV patients was followed-up for 1,489 person-year. They were predominantly male (93%) with genotype-3 HCV infection (71%), and 38% were cirrhotic. The overall SVR during the restricted DAA access era and unrestricted DAA access era were 92.1% and 99.1%, respectively. Unrestricted access to DAA exponentially improved the treatment access among HCV-infected patients by 460%, resulting in a higher SVR rate (99% vs. 92%, P=0.003), higher treatment completion rate (99% vs. 93%, P<0.001) and lower treatment default rate (1% vs. 9%, P<0.001). CONCLUSION In this large cohort of incarcerated HCV-infected patients, we demonstrated that unrestricted access to DAA is an impactful strategy to allow rapid treatment up-scale in HCV micro-elimination.
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Affiliation(s)
- Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Duke-NUS Medical School, Singapore
| | | | - Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Duke-NUS Medical School, Singapore
| | - Kwong Ming Fock
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Duke-NUS Medical School, Singapore
| | - Ngai Moh Law
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Sin-Yoong Chong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | | | - Tiing-Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Duke-NUS Medical School, Singapore
| | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Duke-NUS Medical School, Singapore
| | - Jessica Tan
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
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Montvida O, Dibato JE, Paul S. Evaluating the Representativeness of US Centricity Electronic Medical Records With Reports From the Centers for Disease Control and Prevention: Comparative Study on Office Visits and Cardiometabolic Conditions. JMIR Med Inform 2020; 8:e17174. [PMID: 32490850 PMCID: PMC7301254 DOI: 10.2196/17174] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 02/08/2020] [Accepted: 04/21/2020] [Indexed: 12/25/2022] Open
Abstract
Background Electronic medical record (EMR)–based clinical and epidemiological research has dramatically increased over the last decade, although establishing the generalizability of such big databases for conducting epidemiological studies has been an ongoing challenge. To draw meaningful inferences from such studies, it is essential to fully understand the characteristics of the underlying population and potential biases in EMRs. Objective This study aimed to assess the generalizability and representativity of the widely used US Centricity Electronic Medical Record (CEMR), a primary and ambulatory care EMR for population health research, using data from the National Ambulatory Medical Care Surveys (NAMCS) and the National Health and Nutrition Examination Surveys (NHANES). Methods The number of office visits reported in the NAMCS, designed to meet the need for objective and reliable information about the provision and the use of ambulatory medical care services, was compared with similar data from the CEMR. The distribution of major cardiometabolic diseases in the NHANES, designed to assess the health and nutritional status of adults and children in the United States, was compared with similar data from the CEMR. Results Gender and ethnicity distributions were similar between the NAMCS and the CEMR. Younger patients (aged <15 years) were underrepresented in the CEMR compared with the NAMCS. The number of office visits per 100 persons per year was similar: 277.9 (95% CI 259.3-296.5) in the NAMCS and 284.6 (95% CI 284.4-284.7) in the CEMR. However, the number of visits for males was significantly higher in the CEMR (CEMR: 270.8 and NAMCS: 239.0). West and South regions were underrepresented and overrepresented, respectively, in the CEMR. The overall prevalence of diabetes along with age and gender distribution was similar in the CEMR and the NHANES: overall prevalence, 10.1% and 9.7%; male, 11.5% and 10.8%; female, 9.1% and 8.8%; age 20 to 40 years, 2.5% and 1.8%; and age 40 to 60 years, 9.4% and 11.1%, respectively. The prevalence of obesity was similar: 42.1% and 39.6%, with similar age and female distribution (41.5% and 41.1%) but different male distribution (42.7% and 37.9%). The overall prevalence of high cholesterol along with age and female distribution was similar in the CEMR and the NHANES: overall prevalence, 12.4% and 12.4%; and female, 14.8% and 13.2%, respectively. The overall prevalence of hypertension was significantly higher in the CEMR (33.5%) than in the NHANES (95% CI: 27.0%-31.0%). Conclusions The distribution of major cardiometabolic diseases in the CEMR is comparable with the national survey results. The CEMR represents the general US population well in terms of office visits and major chronic conditions, whereas the potential subgroup differences in terms of age and gender distribution and prevalence may differ and, therefore, should be carefully taken care of in future studies.
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Affiliation(s)
- Olga Montvida
- Melbourne EpiCentre, University of Melbourne, Melbourne, Australia
| | - John Epoh Dibato
- Melbourne EpiCentre, University of Melbourne, Melbourne, Australia
| | - Sanjoy Paul
- Melbourne EpiCentre, University of Melbourne, Melbourne, Australia
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Su TH, Yang HC, Tseng TC, Chou SW, Lin CH, Liu CH, Liu CJ, Chen CL, Kao JH. Antiviral Therapy in Patients With Chronic Hepatitis C Is Associated With a Reduced Risk of Parkinsonism. Mov Disord 2019; 34:1882-1890. [PMID: 31505068 DOI: 10.1002/mds.27848] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 08/06/2019] [Accepted: 08/08/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The risk of parkinsonism after antiviral treatment against chronic hepatitis C (CHC) is unclear. OBJECTIVES To investigate the association between CHC and parkinsonism and the efficacy of antiviral therapy. METHODS Using the National Health Insurance Research Database of Taiwan from 2004 to 2012, patients with and without CHC, patients receiving pegylated interferon-based antiviral therapy, and those without such therapy were matched by age, gender, and comorbidities by propensity scores and followed for new diagnoses of parkinsonism and Parkinson's disease (PD). Multivariable Cox proportional hazards regression analyses were performed. RESULTS Overall, 49,342 patients with CHC were matched with 49,342 non-CHC patients. After adjustment for confounding factors, there was a significantly increased risk (31%) of parkinsonism (hazard ratio [HR] 1.306; 95% confidence interval [CI], 1.208-1.412) in those with CHC and the risk of parkinsonism requiring anti-Parkinson medication (HR 1.323; 95% CI, 1.214-1.441). Furthermore, 23,647 untreated CHC patients were matched with 23,647 patients receiving antiviral therapy. Patients receiving antiviral therapy had a significantly lower risk of developing parkinsonism (38%; HR 0.618; 95% CI, 0.498-0.765) and a reduced risk of parkinsonism requiring anti-Parkinson medication (HR 0.651; 95% CI, 0.515-0.823). In sensitivity analyses, antiviral therapy significantly reduced the risk of parkinsonism and PD after adjustment for detection, selection, disease latency biases, and competing mortality. Our results suggest successful antiviral therapy associates with a reduced risk of hepatitis C virus-related parkinsonism compared with those with treatment failure. CONCLUSIONS CHC infection is associated with an increased risk of parkinsonism or PD. Antiviral therapy against CHC is associated with a reduced risk of parkinsonism or PD. © 2019 International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Wan Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chin-Hsien Lin
- Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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Su TH, Liu CJ, Tseng TC, Chou SW, Liu CH, Yang HC, Wu SJ, Chen PJ, Chen DS, Chen CL, Kao JH. Early antiviral therapy reduces the risk of lymphoma in patients with chronic hepatitis C infection. Aliment Pharmacol Ther 2019; 49:331-339. [PMID: 30592071 DOI: 10.1111/apt.15101] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 01/26/2018] [Accepted: 11/27/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chronic hepatitis C infection is linked to lymphoma development. AIM To investigate whether antiviral therapy prevents the risk of HCV-related lymphoma. METHODS Patients diagnosed with chronic hepatitis C were retrieved from the Taiwan National Health Insurance Research Database during 2004-2012. We included patients who received pegylated interferon and ribavirin (PegIFN/RBV) antiviral therapy for ≥24 weeks (PegIFN/RBV cohort) or hepatoprotectants for ≥90 days without antiviral therapy (HCV-untreated cohort). Both cohorts were matched by age, sex, and comorbidities through propensity scores and followed for newly diagnosed lymphoma or non-Hodgkin's lymphoma (NHL). RESULTS In total, 24 133 patients were included in both the PegIFN/RBV and HCV-untreated cohort. The lymphoma incidence was significantly higher in the untreated than in the treated cohort (66.48 vs 43.34 per 100 000 person-years, P = 0.029). After adjusting for confounders, the patients who received PegIFN/RBV therapy were at a lower risk of developing lymphoma compared with the untreated patients (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.43-0.96, P = 0.030). Moreover, this beneficial effect was mainly observed in patients with chronic hepatitis C <60 years old with a relative risk reduction of 51% for all lymphoma (HR: 0.49, 95% CI: 0.29-0.82, P = 0.007) and 48% for non-Hodgkin's lymphoma (HR: 0.52, 95% CI: 0.30-0.91, P = 0.022). The risk of all lymphoma or non-Hodgkin's lymphoma development after antiviral therapy was lowered to that of subjects without HCV. CONCLUSIONS PegIFN/RBV-based antiviral therapy significantly reduced the risk of lymphoma, especially non-Hodgkin's lymphoma; the reduction was mostly among patients <60 years old. Early antiviral therapy for chronic hepatitis C is suggested.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Wan Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Ju Wu
- Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Ding-Shinn Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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Tasillo A, Eftekhari Yazdi G, Nolen S, Schillie S, Vellozzi C, Epstein R, Randall L, Salomon JA, Linas BP. Short-Term Effects and Long-Term Cost-Effectiveness of Universal Hepatitis C Testing in Prenatal Care. Obstet Gynecol 2019; 133:289-300. [PMID: 30633134 PMCID: PMC6501827 DOI: 10.1097/aog.0000000000003062] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To estimate the clinical effects and cost-effectiveness of universal prenatal hepatitis C screening, and to calculate potential life expectancy, quality of life, and health care costs associated with universal prenatal hepatitis C screening and linkage to treatment. METHODS Using a stochastic individual-level microsimulation model, we simulated the lifetimes of 250 million pregnant women matched at baseline with the U.S. childbearing population on age, injection drug use behaviors, and hepatitis C virus (HCV) infection status. Modeled outcomes included hepatitis C diagnosis, treatment and cure, lifetime health care costs, quality-adjusted life years (QALY) and incremental cost-effectiveness ratios comparing universal prenatal hepatitis C screening to current practice. We modeled whether neonates exposed to maternal HCV at birth were identified as such. RESULTS Pregnant women with hepatitis C infection lived 1.21 years longer and had 16% lower HCV-attributable mortality with universal prenatal hepatitis C screening, which had an incremental cost-effectiveness ratio of $41,000 per QALY gained compared with current practice. Incremental cost-effectiveness ratios remained below $100,000 per QALY gained in most sensitivity analyses; notable exceptions included incremental cost-effectiveness ratios above $100,000 when assuming mean time to cirrhosis of 70 years, a cost greater than $500,000 per false positive diagnosis, or population HCV infection prevalence below 0.16%. Universal prenatal hepatitis C screening increased identification of neonates exposed to HCV at birth from 44% to 92%. CONCLUSIONS In our model, universal prenatal hepatitis C screening improves health outcomes in women with HCV infection, improves identification of HCV exposure in neonates born at risk, and is cost-effective.
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Affiliation(s)
- Abriana Tasillo
- Boston Medical Center, Section of Infectious Diseases, Boston, Massachusetts; the Centers for Disease Control and Prevention, Division of Viral Hepatitis, Atlanta, Georgia; Boston Medical Center, Section of Infectious Diseases, Section of Pediatric Infectious Diseases; and the Bureau of Infectious Disease and Laboratory Sciences, Massachusetts Department of Public Health, Boston, Massachusetts; and Stanford University, Center for Health Policy and Center for Primary Care and Outcomes Research, Stanford, California
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Barnett PG, Joyce VR, Lo J, Gidwani-Marszowski R, Goldhaber-Fiebert JD, Desai M, Asch SM, Holodniy M, Owens DK. Effect of Interferon-Free Regimens on Disparities in Hepatitis C Treatment of US Veterans. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2018; 21:921-930. [PMID: 30098669 DOI: 10.1016/j.jval.2017.12.025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 12/07/2017] [Accepted: 12/11/2017] [Indexed: 06/08/2023]
Abstract
OBJECTIVES To determine whether implementation of interferon-free treatment for hepatitis C virus (HCV) reached groups less likely to benefit from earlier therapies, including patients with genotype 1 virus or contraindications to interferon treatment, and groups that faced treatment disparities: African Americans, patients with HIV co-infection, and those with drug use disorder. METHODS Electronic medical records of the US Veterans Health Administration (VHA) were used to characterize patients with chronic HCV infection and the treatments they received. Initiation of treatment in 206,544 patients with chronic HCV characterized by viral genotype, demographic characteristics, and comorbid medical and mental illness was studied using a competing events Cox regression over 6 years. RESULTS With the advent of interferon-free regimens, the proportion treated increased from 2.4% in 2010 to 18.1% in 2015, an absolute increase of 15.7%. Patients with genotype 1 virus, poor response to previous treatment, and liver disease had the greatest increase. Large absolute increases in the proportion treated were observed in patients with HIV co-infection (18.6%), alcohol use disorder (11.9%), and drug use disorder (12.6%) and in African American (13.7%) and Hispanic (13.5%) patients, groups that were less likely to receive interferon-containing treatment. The VHA spent $962 million on interferon-free treatments in 2015, 1.5% of its operating budget. CONCLUSIONS The proportion of patients with HCV treated in VHA increased sevenfold. The VHA was successful in implementing interferon treatment in previously undertreated populations, and this may become the community standard of care.
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Affiliation(s)
- Paul G Barnett
- Health Economics Resource Center, VA Palo Alto Health Care System, Menlo Park, CA, USA; VA Center for Innovation to Implementation, Menlo Park, CA, USA.
| | - Vilija R Joyce
- Health Economics Resource Center, VA Palo Alto Health Care System, Menlo Park, CA, USA
| | - Jeanie Lo
- Health Economics Resource Center, VA Palo Alto Health Care System, Menlo Park, CA, USA
| | - Risha Gidwani-Marszowski
- Health Economics Resource Center, VA Palo Alto Health Care System, Menlo Park, CA, USA; VA Center for Innovation to Implementation, Menlo Park, CA, USA; Division of Primary Care and Population Health, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Jeremy D Goldhaber-Fiebert
- Stanford Health Policy, Centers for Health Policy and Primary Care and Outcomes Research, Stanford University, Stanford, CA, USA
| | - Manisha Desai
- Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Steven M Asch
- VA Center for Innovation to Implementation, Menlo Park, CA, USA; Division of Primary Care and Population Health, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Mark Holodniy
- Public Health Research Center, VA Palo Alto Health Care System, Palo Alto, CA, USA; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Douglas K Owens
- VA Center for Innovation to Implementation, Menlo Park, CA, USA; Stanford Health Policy, Centers for Health Policy and Primary Care and Outcomes Research, Stanford University, Stanford, CA, USA
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Jang ES, Kim YS, Kim KA, Lee YJ, Chung WJ, Kim IH, Lee BS, Jeong SH. Final Report of Unmet Needs of Interferon-Based Therapy for Chronic Hepatitis C in Korea: Basis for Moving into the Direct-Acting Antiviral Era. Gut Liver 2017; 11:543-550. [PMID: 28506027 PMCID: PMC5491090 DOI: 10.5009/gnl16530] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Revised: 12/19/2016] [Accepted: 12/19/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS To evaluate the era of direct acting antivirals (DAAs), we must understand the treatment patterns and outcomes of interferon-based therapy for hepatitis C virus (HCV) infection. We aimed to elucidate the treatment rate, factors affecting treatment decisions, and efficacy of interferon- based therapy in a real-world setting. METHODS This nationwide cohort study included 1,191 newly diagnosed patients with chronic HCV infection at seven tertiary hospitals in South Korea. Subjects were followed retrospectively until March 2015, which was just before the approval of DAA therapy. RESULTS In total, 48.2% and 49.3% of the patients had HCV genotypes 1 and 2, respectively. Interferon-based therapy was initiated in 541 patients (45.4%). The major reasons for no treatment included ineligibility (18.9%), concern about adverse events (22.3%), cost (21.5%), and an age >75 years (19.5%). Interferon-based therapy was discontinued (18.5%) mainly due to adverse events (n=66). The intent-to-treat analysis found that the sustained virologic response (SVR) rate was 58.3% in genotype 1 patients and 74.7% in nongenotype 1 patients. CONCLUSIONS Approximately one-third of newly diagnosed HCV patients in South Korea received interferon-based therapy and showed a suboptimal SVR rate. Diagnosis of patients at younger ages and with a less advanced liver status and reducing the DAA therapy cost may fulfill unmet needs.
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Affiliation(s)
- Eun Sun Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam,
Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon,
Korea
| | - Kyung-Ah Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang,
Korea
| | - Youn Jae Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan,
Korea
| | - Woo Jin Chung
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu,
Korea
| | - In Hee Kim
- Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju,
Korea
| | - Byung Seok Lee
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon,
Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam,
Korea
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10
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Lapi F, Capogrosso Sansone A, Mantarro S, Simonetti M, Tuccori M, Blandizzi C, Rossi A, Corti G, Bartoloni A, Bellia A, Baiocchi L, Cricelli I, Cricelli C. Hepatitis C virus infection: opportunities for an earlier detection in primary care. Eur J Gastroenterol Hepatol 2017; 29:271-276. [PMID: 27849644 DOI: 10.1097/meg.0000000000000785] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND/AIM In the era of direct-acting antiviral medications, which can cure the hepatitis C virus (HCV) infection, the actual epidemiology of this condition in the general population is still unclear. We therefore aimed to estimate the prevalence rate of HCV and assess the determinants for incident cases of HCV in primary care in Italy. METHODS We identified outpatients aged at least 15 years registered in the Italian Health Search IMS Health Longitudinal Patient Database from 1 January 2002 to 30 June 2013. The annual trend of HCV prevalence was estimated. The candidate determinants for the risk of incident HCV infection included geographical area of residence, sex, age, infections by the HIV, hepatitis B virus (HBV), or other forms of hepatitis, and abuse of illicit substances or drugs. RESULTS The eligible cohort included 826 300 patients (53.5% women, mean age 48.1±19.1 years). The prevalence rate of HCV increased over the 11-year study period, ranging from 0.24 to 0.50%, with a small increase in men versus women. Patients aged more than 24 years had a higher risk than those aged 14-24 years, with up to a five-fold increase among patients aged 65-74 years. Being resident of Southern/Islands Italy, concurrent diagnosis HBV or HIV, and drug or illicit substance abuse were significant determinants for HCV infection. CONCLUSION Our study shows that the prevalence of HCV in Italy has doubled over the last decade. Patients with certain demographics and clinical characteristics are more prone to be infected by HCV. In this scenario, general practitioners may play a crucial role in screening, early identification, and therapy of high-risk patients.
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Affiliation(s)
- Francesco Lapi
- aHealth Search, Italian College of General Practitioners and Primary Care bItalian College of General Practitioners and Primary Care cInfectious Disease Unit, Department of Experimental and Clinical Medicine, University of Florence School of Medicine, Florence dDepartment of Clinical and Experimental Medicine, University of Pisa eUnit of Adverse Drug Reactions Monitoring, University Hospital of Pisa, Pisa fDepartment of Systems Medicine gHepatology Unit, Department of Medicine, University of Rome Tor Vergata, Rome, Italy
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11
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Ushering in an Era Where No Group Who Wants to Be Treated Should Be Excluded. Clin Gastroenterol Hepatol 2017; 15:289-291. [PMID: 27650325 DOI: 10.1016/j.cgh.2016.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 09/11/2016] [Accepted: 09/12/2016] [Indexed: 02/07/2023]
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12
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Zanaga LP, Vigani AG, Angerami RN, Giorgetti A, Escanhoela CAF, Ataíde EC, Boin IFSF, Stucchi RSB. Survival benefits of interferon-based therapy in patients with recurrent hepatitis C after orthotopic liver transplantation. ACTA ACUST UNITED AC 2017; 50:e5540. [PMID: 28076451 PMCID: PMC5264534 DOI: 10.1590/1414-431x20165540] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 11/01/2016] [Indexed: 12/13/2022]
Abstract
Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and
can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment
can be used to prevent these detrimental outcomes. The aim of this study was to
describe rates of hepatitis C recurrence and sustained virological response (SVR) to
interferon-based treatment after OLT and its relationship to survival and progression
of liver disease through retrospective analysis of medical records of 127 patients
who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic
hepatitis C between January 2002 and December 2013. Fifty-six patients were diagnosed
with recurrent disease, 42 started interferon-based therapy and 37 completed
treatment. Demographic, treatment- and outcome-related variables were compared
between SVR and non-responders (non-SVR). There was an overall 54.1% SVR rate with
interferon-based therapies. SVR was associated with longer follow-up after treatment
(median 66.5 vs 37 months for non-SVR, P=0.03) and after OLT (median
105 vs 72 months, P=0.074), and lower rates of disease progression
(15 vs 64.7%, P=0.0028) and death (5 vs 35.3%,
P=0.033). Regardless of the result of therapy (SVR or non-SVR), there was a
significant difference between treated and untreated patients regarding the
occurrence of death (P<0.001) and months of survival (P<0.001). Even with
suboptimal interferon-based therapies (compared to the new direct-acting antivirals)
there is a 54.1% SVR rate to treatment. SVR is associated with improved survival and
reduced risks of clinical decompensation, loss of the liver graft and death.
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Affiliation(s)
- L P Zanaga
- Disciplina de Infectologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - A G Vigani
- Disciplina de Infectologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - R N Angerami
- Disciplina de Infectologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - A Giorgetti
- Disciplina de Infectologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - C A F Escanhoela
- Departamento de Anatomia Patológica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - E C Ataíde
- Unidade de Transplante de Fígado, Departamento de Cirurgia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - I F S F Boin
- Unidade de Transplante de Fígado, Departamento de Cirurgia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - R S B Stucchi
- Disciplina de Infectologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil
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13
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Visual Hallucinations During Hepatitis C Treatment With Sofosbuvir and Simeprevir. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2016. [DOI: 10.1097/ipc.0000000000000425] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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14
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Zanaga LP, Miotto N, Mendes LC, Stucchi RSB, Vigani AG. Treatment of hepatitis C virus genotype 3 infection with direct-acting antiviral agents. ACTA ACUST UNITED AC 2016; 49:e5504. [PMID: 27783808 PMCID: PMC5089232 DOI: 10.1590/1414-431x20165504] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Accepted: 08/31/2016] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) genotype 3 is responsible for 30.1% of chronic hepatitis C infection cases worldwide. In the era of direct-acting antivirals, these patients have become one of the most challenging to treat, due to fewer effective drug options, higher risk of developing cirrhosis and hepatocellular carcinoma and lower sustained virological response (SVR) rates. Currently there are 4 recommended drugs for the treatment of HCV genotype 3: pegylated interferon (PegIFN), sofosbuvir (SOF), daclatasvir (DCV) and ribavirin (RBV). Treatment with PegIFN, SOF and RBV for 12 weeks has an overall SVR rate of 83–100%, without significant differences among cirrhotic and non-cirrhotic patients. However, this therapeutic regimen has several contraindications and can cause significant adverse events, which can reduce adherence and impair SVR rates. SOF plus RBV for 24 weeks is another treatment option, with SVR rates of 82–96% among patients without cirrhosis and 62–92% among those with cirrhosis. Finally, SOF plus DCV provides 94–97% SVR rates in non-cirrhotic patients, but 59–69% in those with cirrhosis. The addition of RBV to the regimen of SOF plus DCV increases the SVR rates in cirrhotic patients above 80%, and extending treatment to 24 weeks raises SVR to 90%. The ideal duration of therapy is still under investigation. For cirrhotic patients, the optimal duration, or even the best regimen, is still uncertain. Further studies are necessary to clarify the best regimen to treat HCV genotype 3 infection.
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Affiliation(s)
- L P Zanaga
- Divisão de Moléstias Infecciosas Departamento de Clínica Médica, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - N Miotto
- Divisão de Moléstias Infecciosas Departamento de Clínica Médica, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - L C Mendes
- Divisão de Moléstias Infecciosas Departamento de Clínica Médica, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - R S B Stucchi
- Divisão de Moléstias Infecciosas Departamento de Clínica Médica, Universidade Estadual de Campinas, Campinas, SP, Brasil
| | - A G Vigani
- Divisão de Moléstias Infecciosas Departamento de Clínica Médica, Universidade Estadual de Campinas, Campinas, SP, Brasil
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15
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Maan R, de Knegt RJ, Veldt BJ. Management of Thrombocytopenia in Chronic Liver Disease: Focus on Pharmacotherapeutic Strategies. Drugs 2016; 75:1981-92. [PMID: 26501978 PMCID: PMC4642582 DOI: 10.1007/s40265-015-0480-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Thrombocytopenia (platelet count <150 × 109/L) often complicates chronic liver disease, impeding optimal management of these patients. The prevalence of this manifestation ranges from 6 % among non-cirrhotic patients with chronic liver disease to 70 % among patients with liver cirrhosis. It has also been shown that the severity of liver disease is associated with both prevalence and level of thrombocytopenia. Its development is often multifactorial, although thrombopoietin is thought to be a major factor. The discovery of and ability to clone thrombopoietin led to new treatment opportunities for this clinical manifestation. This review discusses data on the three most important thrombopoietin receptor agonists: eltrombopag, avatrombopag, and romiplostim. Currently, only eltrombopag is approved for usage among patients with thrombocytopenia and chronic hepatitis C virus infection in order to initiate and maintain interferon-based antiviral treatment. Nevertheless, the optimal management of hematologic abnormalities among patients with chronic liver disease, and its risk for bleeding complications, is still a matter of discussion. Thrombocytopenia definitely contributes to hemostatic defects but is often counterbalanced by the enhanced presence of procoagulant factors. Therefore, a thorough assessment of the patient’s risk for thrombotic events is essential when the use of thrombopoietin receptor agonists is considered among patients with chronic liver disease and thrombocytopenia.
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Affiliation(s)
- Raoel Maan
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, 's Gravendijkwal 230, Room Ha 206, 3015 CE, Rotterdam, The Netherlands.
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, 's Gravendijkwal 230, Room Ha 206, 3015 CE, Rotterdam, The Netherlands.
| | - Bart J Veldt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, 's Gravendijkwal 230, Room Ha 206, 3015 CE, Rotterdam, The Netherlands.
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16
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Selvapatt N, Brown A. A real-world intention-to-treat analysis of a decade's experience of treatment of hepatitis C with interferon-based therapies. F1000Res 2016; 5:2061. [PMID: 27746906 PMCID: PMC5034792 DOI: 10.12688/f1000research.9114.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/22/2016] [Indexed: 12/24/2022] Open
Abstract
Objectives: To assess the uptake of pegylated interferon (PegIFN) plus ribavirin (RBV)-based regimens in patients with hepatitis C virus (HCV) in a large, single-centre, real-world setting over 10 years. Methods: This was a single centre, retrospective analysis of data from patients who attended their first appointment for treatment of HCV genotype 1–3 between 2003 and 2013. Patients were stratified by HCV genotype. The total number of patients who attended their first appointment, incidence of patients who did not proceed to treatment and associated reasons, and incidence of patients treated were analysed. Sustained virological response (SVR) rates were also reported for all patient populations. Results: Overall, 1,132 patients attended their first appointment; 47.8% were included in the genotype 1 group (genotype 1a: 22.2%, genotype 1b: 13.3%, genotype 1 other: 12.3%), 7.7% in the genotype 2 group and 44.5% in the genotype 3 group. A greater proportion of patients received treatment versus those who did not receive treatment (84.4% vs 15.6%, respectively). Reasons for declining treatment included: patient declined treatment with PegIFN plus RBV: 35.0%, medical contraindications: 20.3% and mental health-related contraindications: 13.6%. An SVR was achieved in 52.6% of patients who attended their first appointment and 62.3% of patients who received treatment. Conclusions: Approximately half of the patients included in this study achieved an SVR. A noteworthy proportion of patients did not receive treatment due to a reluctance to receive PegIFN plus RBV or contraindications to therapy. Results suggest an ongoing need for improvement in the treatment uptake and overall outcomes – particularly for genotype 2 and 3 patients for whom availability of interferon-free regimens is limited. The introduction of more tolerable direct-acting antiviral regimes may help overcome barriers to uptake demonstrated within this cohort.
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Affiliation(s)
- Nowlan Selvapatt
- Liver and Antiviral Unit, Imperial College NHS Trust Liver Unit, St Mary's Hospital, London, W2 1NY, UK; Department of Hepatology, Imperial College, St Mary's Hospital, London, W2 1NY, UK
| | - Ashley Brown
- Liver and Antiviral Unit, Imperial College NHS Trust Liver Unit, St Mary's Hospital, London, W2 1NY, UK
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17
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Scheiner B, Schwabl P, Steiner S, Bucsics T, Chromy D, Aichelburg MC, Grabmeier-Pfistershammer K, Trauner M, Peck-Radosavljevic M, Reiberger T, Mandorfer M. Interferon-free regimens improve health-related quality of life and fatigue in HIV/HCV-coinfected patients with advanced liver disease: A retrospective study. Medicine (Baltimore) 2016; 95:e4061. [PMID: 27399090 PMCID: PMC5058819 DOI: 10.1097/md.0000000000004061] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2016] [Revised: 05/27/2016] [Accepted: 06/02/2016] [Indexed: 02/06/2023] Open
Abstract
Health-related quality of life (HRQoL) is impaired in HIV/HCV-coinfected patients (HIV/HCV) and further decreased by interferon (IFN)-based therapies. We aimed to investigate the impact of IFN- and ribavirin (RBV)-free therapies on HRQoL and fatigue.Thirty-three HIV/HCV-coinfected patients who underwent HCV therapy with sofosbuvir in combination with daclatasvir or ledipasvir were retrospectively studied and compared to 17 patients who received boceprevir (BOC)/PEGIFN/RBV. HRQoL (mental [MCS] and physical [PCS] component score) and fatigue were assessed using the SF-36 (Short Form 36 Health Survey) and the FSS (Fatigue Severity Scale), respectively. HRQoL/fatigue was evaluated at baseline (BL), midway, and 12 weeks after the end of treatment (FU).At BL, both domains of HRQoL as well as the severity of fatigue were significantly impaired in HIV/HCV, when compared to a healthy population. Already during treatment, IFN/RBV-free therapy improved physical health (PCS: 41.4 ± 9.7 vs. 47.0 ± 11.2; P < 0.01) and reduced fatigue (37.8 ± 14.0 vs. 31.9 ± 15.2; P = 0.01), whereas we observed a substantial worsening of both factors in patients treated with BOC/PEGIFN/RBV. Since these improvements were maintained, patients treated with IFN/RBV-free therapy reported an improvement in physical health (PCS: 41.4 ± 9.7 vs. 45.8 ± 12.7; P < 0.01) and fatigue (37.8 ± 14.0 vs. 30.9 ± 14.8; P = 0.04) at FU. While AIDS-patients had a higher severity of fatigue at BL and showed a reduction of fatigue (42.5 ± 14.0 vs. 31.6 ± 15.7; P = 0.01), mental health only improved in patients without AIDS (MCS: 35.7 ± 5.3 vs.40.7 ± 6.4; P = 0.04). HIV/HCV with severe fatigue at BL (>median BL-FSS) showed most pronounced improvements in severity of fatigue (49.7 ± 7.0 vs. 32.0 ± 16.7; P < 0.01).In contrast to IFN-based regimens, highly effective and well-tolerated IFN-/RBV-free regimens improve HRQoL (especially physical health) and fatigue already during treatment. All patients with HIV/HCV coinfection should be considered for HCV treatment; however, patients with severe fatigue should be prioritized.
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Affiliation(s)
- Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III
- Vienna HIV & Liver Study Group
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III
- Vienna HIV & Liver Study Group
| | - Sebastian Steiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III
- Vienna HIV & Liver Study Group
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III
| | - David Chromy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III
| | - Maximilian C. Aichelburg
- Vienna HIV & Liver Study Group
- Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Katharina Grabmeier-Pfistershammer
- Vienna HIV & Liver Study Group
- Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III
- Vienna HIV & Liver Study Group
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III
- Vienna HIV & Liver Study Group
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III
- Vienna HIV & Liver Study Group
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18
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King A, Bornschlegel K, Johnson N, Rude E, Laraque F. Barriers to Treatment Among New York City Residents with Chronic Hepatitis C Virus Infection, 2014. Public Health Rep 2016; 131:430-7. [PMID: 27252563 PMCID: PMC4869091 DOI: 10.1177/003335491613100309] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVE New, highly effective hepatitis C virus (HCV) medications recently changed the landscape of HCV treatment. Access to treatment, however, is limited. The New York City Department of Health and Mental Hygiene conducted an enhanced surveillance project to better understand the reasons patients are not treated for HCV. METHODS In June 2014, we randomly selected 300 adults who were reported through routine surveillance as having a positive HCV ribonucleic acid test result and who had seen a medical provider since June 2012. We collected information on demographics, treatment, and barriers to treatment from these 300 patients and their providers by telephone, fax, mail, and medical record review. RESULTS Of 179 providers, 74 (41%) cited co-occurring conditions and 50 (28%) cited patients not keeping follow-up or referral appointments with specialists as common barriers to treatment. Forty providers (22%) reported that they do not prescribe HCV medications and instead refer patients to specialists for treatment. Of 89 patients citing barriers to treatment, 30 (34%) cited co-occurring conditions, 26 (29%) cited concerns about side effects, 21 (24%) indicated not feeling sick, 15 (17%) cited waiting for a better treatment regimen, and 12 (13%) cited medication costs or insurance issues. Only 11 providers and 10 patients denied any barriers to treatment. CONCLUSION Increasing the number of New York City residents with HCV infection who are treated and cured will require programs to increase provider capacity, change provider behavior in treating patients with substance use and medical conditions, improve patient awareness of new medications, provide patient navigation and care coordination support through treatment, and initiate advocacy and policy work.
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Affiliation(s)
- Andrea King
- New York City Department of Health and Mental Hygiene, Queens, NY
| | | | - Nirah Johnson
- New York City Department of Health and Mental Hygiene, Queens, NY
| | - Eric Rude
- New York City Department of Health and Mental Hygiene, Queens, NY
| | - Fabienne Laraque
- New York City Department of Health and Mental Hygiene, Queens, NY
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19
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Leroy V, Angus P, Bronowicki J, Dore GJ, Hezode C, Pianko S, Pol S, Stuart K, Tse E, McPhee F, Bhore R, Jimenez‐Exposito MJ, Thompson AJ. Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+). Hepatology 2016; 63:1430-41. [PMID: 26822022 PMCID: PMC5069621 DOI: 10.1002/hep.28473] [Citation(s) in RCA: 204] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 01/20/2016] [Accepted: 01/24/2016] [Indexed: 12/13/2022]
Abstract
UNLABELLED Patients with hepatitis C virus (HCV) genotype 3 infection, especially those with advanced liver disease, are a challenging population in urgent need of optimally effective therapies. The combination of daclatasvir (DCV; pangenotypic nonstructural protein 5A inhibitor) and sofosbuvir (SOF; nucleotide nonstructural protein 5B inhibitor) for 12 weeks previously showed high efficacy (96%) in noncirrhotic genotype 3 infection. The phase III ALLY-3+ study (N = 50) evaluated DCV-SOF with ribavirin (RBV) in treatment-naïve (n = 13) or treatment-experienced (n = 37) genotype 3-infected patients with advanced fibrosis (n = 14) or compensated cirrhosis (n = 36). Patients were randomized 1:1 to receive open-label DCV-SOF (60 + 400 mg daily) with weight-based RBV for 12 or 16 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12). SVR12 (intention-to-treat) was 90% overall (45 of 50): 88% (21 of 24) in the 12-week (91% observed) and 92% (24 of 26) in the 16-week group. All patients with advanced fibrosis achieved SVR12. SVR12 in patients with cirrhosis was 86% overall (31 of 36): 83% (15 of 18) in the 12-week (88% observed) and 89% (16 of 18) in the 16-week group; for treatment-experienced patients with cirrhosis, these values were 87% (26 of 30), 88% (14 of 16; 93% observed), and 86% (12 of 14), respectively. One patient (12-week group) did not enter post-treatment follow-up (death unrelated to treatment). There were 4 relapses (2 per group) and no virological breakthroughs. The most common adverse events (AEs) were insomnia, fatigue, and headache. There were no discontinuations for AEs and no treatment-related serious AEs. CONCLUSION The all-oral regimen of DCV-SOF-RBV was well tolerated and resulted in high and similar SVR12 after 12 or 16 weeks of treatment among genotype 3-infected patients with advanced liver disease, irrespective of past HCV treatment experience.
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Affiliation(s)
- Vincent Leroy
- Clinique Universitaire d'Hepato‐Gastroentérologie, Pôle DigiduneCHU de Grenoble and Unité INSERM/Université Grenoble Alpes U823, IAPC Institut Albert BonniotGrenobleFrance
| | | | | | - Gregory J. Dore
- St. Vincent's Hospital and Kirby InstituteUNSW AustraliaSydneyAustralia
| | | | | | | | | | | | - Fiona McPhee
- Bristol‐Myers Squibb Research & DevelopmentWallingfordCT
| | - Rafia Bhore
- Bristol‐Myers Squibb Research & DevelopmentPrincetonNJ
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20
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Spera AM, Eldin TK, Tosone G, Orlando R. Antiviral therapy for hepatitis C: Has anything changed for pregnant/lactating women? World J Hepatol 2016; 8:557-565. [PMID: 27134703 PMCID: PMC4840161 DOI: 10.4254/wjh.v8.i12.557] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Revised: 02/09/2016] [Accepted: 03/22/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) affects about 3% of the world's population, with the highest prevalence in individuals under 40. The prevalence in pregnant women varies with geographical distribution (highest in developing countries). Prevalence also increases in sub-populations of women at high risk for blood-transmitted infections. HCV infection in pregnancy represents a non-negligible problem. However, most of the past antiviral regimens cannot be routinely offered to pregnant or breastfeeding women because of their side effects. We briefly reviewed the issue of treatment of HCV infection in pregnant/breastfeeding women focusing on the effects of the new direct-acting antivirals on fertility, pregnancy and lactation in animal studies and on the potential risk for humans based on the pharmacokinetic properties of each drug. Currently, all new therapy regimens are contraindicated in this setting because of lack of sufficient safety information and adequate measures of contraception are still routinely recommended for female patients of childbearing potential.
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Affiliation(s)
- Anna Maria Spera
- Anna Maria Spera, Tarek Kamal Eldin, Grazia Tosone, Raffaele Orlando, Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Napoli, Italy
| | - Tarek Kamal Eldin
- Anna Maria Spera, Tarek Kamal Eldin, Grazia Tosone, Raffaele Orlando, Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Napoli, Italy
| | - Grazia Tosone
- Anna Maria Spera, Tarek Kamal Eldin, Grazia Tosone, Raffaele Orlando, Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Napoli, Italy
| | - Raffaele Orlando
- Anna Maria Spera, Tarek Kamal Eldin, Grazia Tosone, Raffaele Orlando, Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Napoli, Italy
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21
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Innes H, Goldberg D, Dillon J, Hutchinson SJ. Strategies for the treatment of Hepatitis C in an era of interferon-free therapies: what public health outcomes do we value most? Gut 2015; 64:1800-9. [PMID: 25378522 DOI: 10.1136/gutjnl-2014-308166] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Accepted: 09/29/2014] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The expense of new therapies for HCV infection may force health systems to prioritise the treatment of certain patient groups over others. Our objective was to forecast the population impact of possible prioritisation strategies for the resource-rich setting of Scotland. DESIGN We created a dynamic Markov simulation model to reflect the HCV-infected population in Scotland. We determined trends in key outcomes (e.g., incident cases of chronic infection and severe liver morbidity (SLM)) until the year 2030, according to treatment strategies involving prioritising, either: (A) persons with moderate/advanced fibrosis or (B) persons who inject drugs (PWID). RESULTS Continuing to treat the same number of patients with the same characteristics will give rise to a fall in incident infection (from 600 cases in 2015 to 440 in 2030) and a fall in SLM (from 195 cases in 2015 to 145 in 2030). Doubling treatment-uptake and prioritising PWID will reduce incident infection to negligible levels (<50 cases per year) by 2025, while SLM will stabilise (at 70-75 cases per year) in 2028. Alternatively, doubling the number of patients treated, but, instead, prioritising persons with moderate/advanced fibrosis will reduce incident infection less favourably (only to 280 cases in 2030), but SLM will stabilise by 2023 (i.e., earlier than any competing strategy). CONCLUSIONS Prioritising treatment uptake among PWID will substantially impact incident transmission, however, this approach foregoes the optimal impact on SLM. Conversely, targeting those with moderate/advanced fibrosis has the greatest impact on SLM but is suboptimal in terms of averting incident infection.
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Affiliation(s)
- Hamish Innes
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK Health Protection Scotland, Glasgow, UK
| | - David Goldberg
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK Health Protection Scotland, Glasgow, UK
| | - John Dillon
- Ninewells hospital and Medical School, Dundee, UK
| | - Sharon J Hutchinson
- School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK Health Protection Scotland, Glasgow, UK
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Rowan PJ, Bhulani N. Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments. World J Hepatol 2015; 7:2209-2213. [PMID: 26380046 PMCID: PMC4561775 DOI: 10.4254/wjh.v7.i19.2209] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 08/07/2015] [Accepted: 08/31/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) is a global concern. With the 2014 Food and Drug Administration approvals of two direct-acting antiviral (DAA) regimens, ledipasvir/sofosbuvir regimen and the ombitasvir/paritaprevir/ritonavir and dasabuvir regimen, we may now be in the era of all-pill regimens for HCV. Until this development, interferon-alpha along with Ribavirin has remained part of the standard of care for HCV patients. That regimen necessitates psychosocial assessment of factors affecting treatment eligibility, including interferon-alpha-related depressive symptoms, confounding psychiatric conditions, and social aspects such as homelessness affecting treatment eligibility. These factors have delayed as much as 70% of otherwise eligible candidates from interferon-based treatment, and have required treating physicians to monitor psychiatric as well as medical side effects throughout treatment. All-pill DAA regimens with the efficaciousness that would preclude reliance upon interferon-alpha or ribavirin have been anticipated for years. Efficacy studies for these recently approved DAA regimens provide evidence to assess the degree that psychosocial assessment and monitoring will be required. With shorter treatment timelines, greatly reduced side effect profiles, and easier regimens, psychosocial contraindications are greatly reduced. However, current or recent psychiatric comorbidity, and drug-drug interactions with psychiatric drugs, will require some level of clinical attention. Evidence from these efficacy studies tentatively demonstrate that the era of needing significant psychosocial assessment and monitoring may be at an end, as long as a manageable handful of clinical issues are managed.
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Correlates of Initiation of Treatment for Chronic Hepatitis C Infection in United States Veterans, 2004-2009. PLoS One 2015; 10:e0132056. [PMID: 26167690 PMCID: PMC4500464 DOI: 10.1371/journal.pone.0132056] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2015] [Accepted: 06/09/2015] [Indexed: 11/19/2022] Open
Abstract
We describe the rates and predictors of initiation of treatment for chronic hepatitis C (HCV) infection in a large cohort of HCV positive Veterans seen in U.S. Department of Veterans Affairs (VA) facilities between January 1, 2004 and December 31, 2009. In addition, we identify the relationship between homelessness among these Veterans and treatment initiation. Univariate and multivariable Cox Proportional Hazards regression models with time-varying covariates were used to identify predictors of initiation of treatment with pegylated interferon alpha plus ribavirin. Of the 101,444 HCV treatment-naïve Veterans during the study period, rates of initiation of treatment among homeless and non-homeless Veterans with HCV were low and clinically similar (6.2% vs. 7.4%, p<0.0001). For all U.S. Veterans, being diagnosed with genotype 2 or 3, black or other/unknown race, having Medicare or other insurance increased the risk of treatment. Veterans with age ≥50 years, drug abuse, diabetes, and hemoglobin < 10 g/dL showed lower rates of treatment. Initiation of treatment for HCV in homeless Veterans is low; similar factors predicted initiation of treatment. Additionally, exposure to treatment with medications for diabetes predicted lower rates of treatment. As newer therapies become available for HCV, these results may inform further studies and guide strategies to increase treatment rates in all U.S. Veterans and those who experience homelessness.
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Younossi ZM, Jiang Y, Smith NJ, Stepanova M, Beckerman R. Ledipasvir/sofosbuvir regimens for chronic hepatitis C infection: Insights from a work productivity economic model from the United States. Hepatology 2015; 61:1471-8. [PMID: 25706754 DOI: 10.1002/hep.27757] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Accepted: 02/10/2015] [Indexed: 12/20/2022]
Abstract
UNLABELLED Patients with chronic hepatitis C (CHC) exhibit reduced work productivity owing to their disease. Historically, most regimens indicated for CHC genotype 1 (GT1) patients were administered with pegylated interferon (Peg-IFN) and/or ribavirin (RBV), which further compromised work productivity during treatment. The aim of this study was to model the impact of LDV/SOF (ledipasvir/sofosbuvir), the first Peg-IFN- and RBV-free regimen for CHC GT1 patients, on work productivity from an economic perspective, compared to receiving no treatment. The WPAI-SHP (Work Productivity and Activity Index-Specific Health Problem) questionnaire was administered to patients across the ION clinical trials (N = 1,923 U.S. patients). Before initiation of treatment, patients with CHC GT1 in the ION trials exhibited absenteeism and presenteeism impairments of 2.57% and 7.58%, respectively. Patients with cirrhosis exhibited greater work productivity impairment than patients without cirrhosis. In total, 93.21% of U.S. patients in the ION trials achieved SVR; these patients exhibited absenteeism and presenteeism impairments of 2.62% (P = 0.76, when compared to baseline) and 3.53% (P < 0.0001), respectively. Monetizing these data to the entire U.S. population, our model projects an annual societal cost of $7.1 billion owing to productivity loss in untreated GT1 CHC patients. Our model projects that, when compared to no treatment, treating all CHC GT1 patients with a regimen with very high viral eradication rates (LDV/SOF) would translate to annual productivity loss savings of $2.7 billion over a 1-year time horizon. CONCLUSIONS Patients with untreated HCV impose a substantial societal burden owing to reduced work productivity. As a result of improvements in work productivity, treatment of CHC GT1 patients with LDV/SOF-based regimens is likely to result in significant cost savings from a societal perspective, relative to no treatment.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA; Center for Outcomes Research in Liver Diseases, Washington, DC
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Chhatwal J, Kanwal F, Roberts MS, Dunn MA. Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States. Ann Intern Med 2015; 162:397-406. [PMID: 25775312 PMCID: PMC4435698 DOI: 10.7326/m14-1336] [Citation(s) in RCA: 273] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Sofosbuvir and ledipasvir, which have recently been approved for treatment of chronic hepatitis C virus (HCV) infection, are more efficacious and safer than the old standard of care (oSOC) but are substantially more expensive. Whether and in which patients their improved efficacy justifies their increased cost is unclear. OBJECTIVE To evaluate the cost-effectiveness and budget impact of sofosbuvir and ledipasvir. DESIGN Microsimulation model of the natural history of HCV infection. DATA SOURCES Published literature. TARGET POPULATION Treatment-naive and treatment-experienced HCV population defined on the basis of HCV genotype, age, and fibrosis distribution in the United States. TIME HORIZON Lifetime. PERSPECTIVE Third-party payer. INTERVENTION Simulation of sofosbuvir-ledipasvir compared with the oSOC (interferon-based therapies). OUTCOME MEASURES Quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and 5-year spending on antiviral drugs. RESULTS OF BASE-CASE ANALYSIS Sofosbuvir-based therapies added 0.56 QALY relative to the oSOC at an ICER of $55 400 per additional QALY. The ICERs ranged from $9700 to $284 300 per QALY depending on the patient's status with respect to treatment history, HCV genotype, and presence of cirrhosis. At a willingness-to-pay threshold of $100 000 per QALY, sofosbuvir-based therapies were cost-effective in 83% of treatment-naive and 81% of treatment-experienced patients. Compared with the oSOC, treating eligible HCV-infected persons in the United States with the new drugs would cost an additional $65 billion in the next 5 years, whereas the resulting cost offsets would be $16 billion. RESULTS OF SENSITIVITY ANALYSIS Results were sensitive to drug price, drug efficacy, and quality of life after successful treatment. LIMITATION Data on real-world effectiveness of new antivirals are lacking. CONCLUSION Treatment of HCV is cost-effective in most patients, but additional resources and value-based patient prioritization are needed to manage patients with HCV. PRIMARY FUNDING SOURCE National Institutes of Health.
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Affiliation(s)
- Jagpreet Chhatwal
- Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Fasiha Kanwal
- Department of Medicine, Baylor College of Medicine, Houston, TX USA
- Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center
| | - Mark S. Roberts
- Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA
| | - Michael A. Dunn
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA
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Duberg AS, Blach S, Falconer K, Kåberg M, Razavi H, Aleman S. The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment strategies. Scand J Gastroenterol 2015; 50:233-44. [PMID: 25515032 DOI: 10.3109/00365521.2014.990505] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
UNLABELLED OBJECTIVE. Recently, new highly effective direct-acting antivirals (DAAs) against hepatitis C virus (HCV) were introduced. Whether these will alleviate the anticipated increase of liver disease burden in Sweden is unknown, partly because high costs may restrict the use. The objectives were to model the HCV epidemic in Sweden, the burden of disease, and the potential impact of different treatment strategies. MATERIAL AND METHODS HCV disease progression was modeled to 2030. Scenarios were simulated using new DAAs with sustained annual treatment rate (n = 1130), reduced treatment rate (n = 380) to maintain budget, and increased treatment rates (n = 1430 or 2260) to reduce HCV infections. RESULTS With today's triple therapies, the estimated number of serious liver complications and death are expected to peak in 2021. Using new DAAs among F0-F4 patients, an unchanged annual treatment rate can reduce the number of HCV infections by 10% by 2030; however, hepatocellular carcinoma (HCC) and mortality will remain unchanged. By reducing to 380 treatments annually and focusing on patients with advanced fibrosis (F3-F4), serious complications will remain constant but the total number of HCV infections will increase. By doubling the number of DAA treatments, HCC-incidence and liver-related deaths would decrease by 65-70% by 2030. CONCLUSION Mortality and HCC can be reduced with new DAAs and sustained treatment uptake when restricted to F2-F4 patients, or with increased uptake in F0-F4 patients. Treatment restrictions to limit cost may reduce the positive effects and increase the burden of HCV infection. These results may be important for the future strategies of HCV management.
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Affiliation(s)
- Ann-Sofi Duberg
- Department of Infectious Diseases, Örebro University Hospital , Örebro , Sweden
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Multiplex protein analysis to determine fibrosis stage and progression in patients with chronic hepatitis C. Clin Gastroenterol Hepatol 2014; 12:2113-20.e1-3. [PMID: 24815325 PMCID: PMC4225180 DOI: 10.1016/j.cgh.2014.04.037] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 04/09/2014] [Accepted: 04/14/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Noninvasive tests cannot differentiate between adjacent stages of fibrosis, which limits assessment of disease progression and regression during therapy. We investigated whether levels of cytokines and extracellular matrix proteins in serum and biopsy samples can be used to determine actual stage of liver fibrosis in patients with chronic hepatitis C (CHC) and in prognosis. METHODS We collected data from 383 treatment-naive patients with CHC from the Duke Hepatology Clinical Research Database and Biorepository, from 2006 through 2009, for use in the training set. Serum samples were obtained from 100 individuals without CHC (controls). We selected 37 serum biomarkers for customized array analysis by using the SearchLight multiplex sandwich enzyme-linked immunosorbent assay. Data from 434 treatment-naive patients with CHC, which were obtained from the Trent HCV cohort, were used in the validation analysis. Multivariable modeling, marker selection, and validation included randomForest and Obuchowski measures, with independent comparison with FibroSURE. RESULTS Four serum markers (levels of hyaluronic acid, vascular cell adhesion molecule 1, alpha-2 macroglobulin, and retinol-binding protein 4) and age associated with fibrosis stage (F0-1, F2-3, or F4); these had Obuchowski measures of 0.85-0.89, with misclassification rates of 38% and 29% in training and validation sets, compared with 50% for the FibroSURE test. In the training set, area under the curve values for the multiplex markers were similar to those from the FibroSURE test: stages F0 vs F1 (0.51 vs 0.53), F1 vs F2 (0.60 vs 0.59), F2 vs F3 (0.69 vs 0.72), and F3 vs F4 (0.51 vs 0.52). Area under the curve values were similar in the validation cohort. In longitudinal analyses of 133 paired biopsies, 9 markers (level of alanine aminotransferase, γ-glutamyltransferase, hyaluronic acid, intracellular adhesion molecule 1, interleukin 4, CXCL10, CXCL9, and vascular cell adhesion molecule 1) were associated with change in the histologic activity index (P values ranging from .000 to .049), and 4 (granulocyte-macrophage colony-stimulating factor, interleukin 12, interleukin 2, and matrix metalloproteinase 13) were associated with a change in fibrosis stage (P values ranging from .001 to .042). CONCLUSIONS We identified serum biomarkers that can be measured by multiplex enzyme-linked immunosorbent assay to determine levels of fibrosis in patients with CHC, although misclassification is frequent and results are comparable with those from the FibroSURE test. Changes in protein levels in biopsy samples were associated with progression of fibrosis in patients.
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Clark JA, Gifford AL. Resolute efforts to cure hepatitis C: Understanding patients' reasons for completing antiviral treatment. Health (London) 2014; 19:473-89. [PMID: 25377666 DOI: 10.1177/1363459314555237] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Antiviral treatment for hepatitis C is usually difficult, demanding, and debilitating and has long offered modest prospects of successful cure. Most people who may need treatment have faced stigma of an illness associated with drug and alcohol misuse and thus may be deemed poor candidates for treatment, while completing a course of treatment typically calls for resolve and responsibility. Patients' efforts and their reasons for completing treatment have received scant attention in hepatitis C clinical policy discourse that instead focuses on problems of adherence and patients' expected failures. Thus, we conducted qualitative interviews with patients who had recently undertaken treatment to explore their reasons for completing antiviral treatment. Analysis of their narrative accounts identified four principal reasons: cure the infection, avoid a bad end, demonstrate the virtue of perseverance through a personal trial, and achieve personal rehabilitation. Their reasons reflect moral rationales that mark the social discredit ascribed to the infection and may represent efforts to restore creditable social membership. Their reasons may also reflect the selection processes that render some of the infected as good candidates for treatment, while excluding others. Explication of the moral context of treatment may identify opportunities to support patients' efforts in completing treatment, as well as illuminate the choices people with hepatitis C make about engaging in care.
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Affiliation(s)
- Jack A Clark
- Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, USA; Boston University School of Public Health, Boston, MA, USA
| | - Allen L Gifford
- Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, USA; Boston University School of Public Health, Boston, MA, USA
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Papatheodoridis GV, Tsochatzis E, Hardtke S, Wedemeyer H. Barriers to care and treatment for patients with chronic viral hepatitis in Europe: a systematic review. Liver Int 2014; 34:1452-63. [PMID: 24750532 DOI: 10.1111/liv.12565] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Accepted: 04/17/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Despite the availability of effective therapies for hepatitis B (HBV) and C virus (HCV), only a minority of these patients receive treatment. We systematically reviewed published data on barriers to management for chronic HBV/HCV patients in Europe. METHODS Literature search to identify studies including adult patients with chronic HBV/HCV infection from European countries and data on barriers to treatment. RESULTS Twenty-five studies including 6253 chronic HBV and 19,014 HCV patients were identified, of which only two were from Eastern Europe. The mean rate of no treatment in HBV patients was 42% being higher in North-Western European countries than Italy (56% vs. 39%, P < 0.001). Immigrants represented the most common barrier to HBV treatment. The mean rate of no treatment in HCV RNA-positive patients was 57%, being highest in Romania (89%), intermediate in France (79%) and lower though still high in other European countries (52%, P < 0.001). The predominant barriers to HCV treatment were lack of financial resources in Romania and direct/indirect limitations of interferon-alfa and/or parenteral drug and alcohol abuse in other countries. The mean rate of no treatment was highest in HCV RNA-positive parenteral drug users (72%) and intermediate in those with HCV-HIV co-infection (64%). CONCLUSIONS A substantial proportion of diagnosed chronic HBV and the majority of diagnosed HCV patients remain untreated. The rates and most importantly the reasons of barriers to treatment in chronic HBV/HCV patients vary widely among European countries supporting the need for country-specific national strategies, resource allocation and implementation of global management policies.
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Affiliation(s)
- George V Papatheodoridis
- Department of Gastroenterology, Athens University Medical School, Laiko General Hospital of Athens, Athens, Greece
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Tosone G, Maraolo AE, Mascolo S, Palmiero G, Tambaro O, Orlando R. Vertical hepatitis C virus transmission: Main questions and answers. World J Hepatol 2014; 6:538-548. [PMID: 25232447 PMCID: PMC4163737 DOI: 10.4254/wjh.v6.i8.538] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) affects about 3% of the world’s population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low (1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behaviors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV infection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related immune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune restoration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunodeficiency virus coinfection, prolonged rupture of membranes, fetal exposure to maternal infected blood consequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmission. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antiviral therapy to HCV-infected pregnant women because it is based on ribavirin (pregnancy category X) because of its embryocidal and teratogenic effects in animal species. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.
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Randomized, placebo-controlled, single-ascending-dose study of BMS-791325, a hepatitis C virus (HCV) NS5B polymerase inhibitor, in HCV genotype 1 infection. Antimicrob Agents Chemother 2014; 58:3496-503. [PMID: 24733462 DOI: 10.1128/aac.02579-13] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BMS-791325 is a nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B polymerase with low-nanomolar potency against genotypes 1a (50% effective concentration [EC50], 3 nM) and 1b (EC50, 7 nM) in vitro. BMS-791325 safety, pharmacokinetics, and antiviral activity were evaluated in a double-blind, placebo-controlled, single-ascending-dose study in 24 patients (interferon naive and experienced) with chronic HCV genotype 1 infection, randomized (5:1) to receive a single dose of BMS-791325 (100, 300, 600, or 900 mg) or placebo. The prevalence and phenotype of HCV variants at baseline and specific posttreatment time points were assessed. Antiviral activity was observed in all cohorts, with a mean HCV RNA decline of ≈2.5 log10 copies/ml observed 24 h after a single 300-mg dose. Mean plasma half-life among cohorts was 7 to 9 h; individual 24-hour levels exceeded the protein-adjusted EC90 for genotype 1 at all doses. BMS-791325 was generally well tolerated, with no serious adverse events or discontinuations. Enrichment for resistance variants was not observed at 100 to 600 mg. At 900 mg, variants (P495L/S) associated with BMS-791325 resistance in vitro were transiently observed in one patient, concurrent with an observed HCV RNA decline of 3.4 log10 IU/ml, but were replaced with wild type by 48 h. Single doses of BMS-791325 were well tolerated; demonstrated rapid, substantial, and exposure-related antiviral activity; displayed dose-related increases in exposure; and showed viral kinetic and pharmacokinetic profiles supportive of once- or twice-daily dosing. These results support its further development in combination with other direct-acting antivirals for HCV genotype 1 infection. (This trial has been registered at ClinicalTrials.gov under registration no. NCT00664625.).
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Preclinical characterization of BMS-791325, an allosteric inhibitor of hepatitis C Virus NS5B polymerase. Antimicrob Agents Chemother 2014; 58:3485-95. [PMID: 24733465 DOI: 10.1128/aac.02495-13] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
BMS-791325 is an allosteric inhibitor that binds to thumb site 1 of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. BMS-791325 inhibits recombinant NS5B proteins from HCV genotypes 1, 3, 4, and 5 at 50% inhibitory concentrations (IC50) below 28 nM. In cell culture, BMS-791325 inhibited replication of HCV subgenomic replicons representing genotypes 1a and 1b at 50% effective concentrations (EC50s) of 3 nM and 6 nM, respectively, with similar (3 to 18 nM) values for genotypes 3a, 4a, and 5a. Potency against genotype 6a showed more variability (9 to 125 nM), and activity was weaker against genotype 2 (EC50, 87 to 925 nM). Specificity was demonstrated by the absence of activity (EC50s of >4 μM) against a panel of mammalian viruses, and cytotoxic concentrations (50%) were >3,000-fold above the HCV EC50. Resistance substitutions selected by BMS-791325 in genotype 1 replicons mostly mapped to a single site, NS5B amino acid 495 (P495A/S/L/T). Additive or synergistic activity was observed in combination studies using BMS-791325 with alfa interferon plus ribavirin, inhibitors of NS3 protease or NS5A, and other classes of NS5B inhibitor (palm site 2-binding or nucleoside analogs). Plasma and liver exposures in vivo in several animal species indicated that BMS-791325 has a hepatotropic disposition (liver-to-plasma ratios ranging from 1.6- to 60-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥ 10-fold above the inhibitor EC50s observed with HCV genotype 1 replicons. These findings support the evaluation of BMS-791325 in combination regimens for the treatment of HCV. Phase 3 studies are ongoing.
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Anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors with sub-micromolar potency in the cell-based replicon assay. Bioorg Med Chem Lett 2013; 23:6879-85. [DOI: 10.1016/j.bmcl.2013.09.102] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Revised: 09/27/2013] [Accepted: 09/30/2013] [Indexed: 01/09/2023]
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Gordon SC, Hamzeh FM, Pockros PJ, Hoop RS, Buikema AR, Korner EJ, Terrault NA. Hepatitis C virus therapy is associated with lower health care costs not only in noncirrhotic patients but also in patients with end-stage liver disease. Aliment Pharmacol Ther 2013; 38:784-93. [PMID: 23981040 PMCID: PMC4553220 DOI: 10.1111/apt.12454] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Revised: 06/20/2013] [Accepted: 07/27/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND The effect of anti-viral treatment on downstream costs for hepatitis C virus (HCV)-infected patients is unknown. AIM To evaluate follow-up costs in patients with chronic HCV, stratified by liver disease severity. METHODS Using a US private insurance database, mean all-cause per-patient-per-month (PPPM) US (2010) medical costs were calculated for HCV-infected persons who did and did not receive anti-HCV treatment between January 2002 and August 2010. Analysis was stratified by liver disease severity [noncirrhotic disease (NCD), compensated cirrhosis (CC) or end-stage liver disease (ESLD)] defined by ICD-9 and CPT codes. RESULTS A total of 33 309 patients were included (78% NCD, 7% CC and 15% ESLD); 4111 individuals (12%) received anti-HCV treatment during the 2-year baseline period. Mean PPPM follow-up health care costs were significantly lower among treated patients with NCD ($900 vs. $1378 in untreated patients, P < 0.001) and ESLD ($3634 vs. $5071, P < 0.001) groups but not in the CC group ($1404 vs. $1795, P < 0.071; t-test). In a multivariable model adjusted for demographic characteristics, comorbidities, index date and geographical region, incremental cost ratios for total health care costs differed significantly (P < 0.001) between treated and untreated patients in the NCD and ESLD groups but not in the CC group. From this model, mean PPPM total health care costs between treated and untreated patients were $885 and $1370 in the NCD, $1369 and $1802 in the CC, and $3547 and $5137 in the ESLD groups, respectively. CONCLUSIONS Anti-HCV therapy was associated with lower follow-up US health care costs, and these savings were independent of baseline patient comorbidities and stage of disease.
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Affiliation(s)
| | | | | | | | | | | | - N. A. Terrault
- University of California at San Francisco, San Francisco, CA, USA
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Sarkar S, Schaefer M. Antidepressant pretreatment for the prevention of interferon alfa-associated depression: a systematic review and meta-analysis. PSYCHOSOMATICS 2013; 55:221-34. [PMID: 24012293 DOI: 10.1016/j.psym.2013.06.015] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2013] [Revised: 06/17/2013] [Accepted: 06/18/2013] [Indexed: 10/26/2022]
Abstract
BACKGROUND Depression is a major complication during treatment with interferon alfa (IFN-α). AIM The aim of this study was to clarify whether preemptive antidepressant treatment can reduce the incidence and severity of IFN-associated depression. METHOD Based on a systematic review of the literature up to July 2012, a meta-analysis of the data from 8 trials investigating patients with malignant melanoma or hepatitis C was performed. The influence of antidepressants on the incidence of major depression and depression severity was defined as the primary outcome and the influence of somatic disorder, psychiatric comorbidity, type of antidepressants, type of IFN, and possible effects on treatment outcome as secondary outcome criteria. RESULTS Antidepressant pretreatment reduced the overall incidence of major depression during IFN treatment in all patients (odds ratio = 0.42; 95% confidence interval, 0.26-0.68; p < 0.001, n = 589) and was associated with lower mean depression scores after 12 weeks of IFN treatment (g = -0.37; 95% confidence interval -0.59 to -0.18; p < 0.001, n = 375). For patients with hepatitis C virus infection, antidepressants reduced the incidence of major depression (odds ratio = 0.38; 95% confidence interval 0.22-0.66; p < 0.001, n = 549) and the mean depression scores after 24 weeks of IFN treatment (g = -0.50; 95% confidence interval -0.70 to -0.29; p < 0.001, n = 335). The effects of selective serotonin reuptake inhibitors on the incidence and severity of depression were not dependent on pre-existing psychiatric disorders. CONCLUSION Antidepressant pretreatment with selective serotonin reuptake inhibitors lowers the incidence and severity of IFN-associated depression in patients with chronic hepatitis C infection or malignant melanoma.
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Affiliation(s)
- Susanne Sarkar
- Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
| | - Martin Schaefer
- Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany; Department of Psychiatry, Psychotherapy and Addiction Medicine, Kliniken Essen-Mitte, Essen, Germany.
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Talal AH, Lafleur J, Hoop RS, Pandya P, Martin P, Jacobson IM, Han J, Korner EJ. Commentary: absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C--authors' reply. Aliment Pharmacol Ther 2013; 38:554-5. [PMID: 23937463 DOI: 10.1111/apt.12424] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2013] [Accepted: 07/01/2013] [Indexed: 12/08/2022]
Affiliation(s)
- A H Talal
- State University of New York, Buffalo, NY, USA.
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Aghemo A, Lampertico P. Commentary: absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C. Aliment Pharmacol Ther 2013; 38:553-4. [PMID: 23937462 DOI: 10.1111/apt.12406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Accepted: 06/20/2013] [Indexed: 12/13/2022]
Affiliation(s)
- A Aghemo
- 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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