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1
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Wilder JM. Race-neutral measures as an equitable path forward. Liver Transpl 2025; 31:131-133. [PMID: 39466194 DOI: 10.1097/lvt.0000000000000526] [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: 10/22/2024] [Accepted: 10/22/2024] [Indexed: 10/29/2024]
Affiliation(s)
- Julius M Wilder
- Division of Gastroenterology, Duke University, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
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2
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Falade-Nwulia O, Kelly SM, Amanor-Boadu S, Nnodum BN, Lim JK, Sulkowski M. Hepatitis C in Black Individuals in the US: A Review. JAMA 2023; 330:2200-2208. [PMID: 37943553 DOI: 10.1001/jama.2023.21981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Abstract
IMPORTANCE In the US, the prevalence of hepatitis C virus (HCV) is 1.8% among people who are Black and 0.8% among people who are not Black. Mortality rates due to HCV are 5.01/100 000 among people who are Black and 2.98/100 000 among people who are White. OBSERVATIONS While people of all races and ethnicities experienced increased rates of incident HCV between 2015 and 2021, Black individuals experienced the largest percentage increase of 0.3 to 1.4/100 000 (367%) compared with 1.8 to 2.7/100 000 among American Indian/Alaska Native (50%), 0.3 to 0.9/100 000 among Hispanic (200%), and 0.9 to 1.6/100 000 among White (78%) populations. Among 47 687 persons diagnosed with HCV in 2019-2020, including 37 877 (79%) covered by Medicaid (7666 Black and 24 374 White individuals), 23.5% of Black people and 23.7% of White people with Medicaid insurance initiated HCV treatment. Strategies to increase HCV screening include electronic health record prompts for universal HCV screening, which increased screening tests from 2052/month to 4169/month in an outpatient setting. Awareness of HCV status can be increased through point-of-care testing in community-based settings, which was associated with increased likelihood of receiving HCV test results compared with referral for testing off-site (69% on-site vs 19% off-site, P < .001). Access to HCV care can be facilitated by patient navigation, in which an individual is assigned to work with a patient to help them access care and treatments; this was associated with greater likelihood of HCV care access (odds ratio, 3.7 [95% CI, 2.9-4.8]) and treatment initiation within 6 months (odds ratio, 3.2 [95% CI, 2.3-4.2]) in a public health system providing health care to individuals regardless of their insurance status or ability to pay compared with usual care. Eliminating Medicaid's HCV treatment restrictions, including removal of a requirement for advanced fibrosis or a specialist prescriber, was associated with increased treatment rates from 2.4 persons per month to 72.3 persons per month in a retrospective study of 10 336 adults with HCV with no significant difference by race (526/1388 [37.8%] for Black vs 2706/8277 [32.6%] for White patients; adjusted odds ratio, 1.02 [95% CI, 0.8-1.3]). CONCLUSIONS AND RELEVANCE In the US, the prevalence of HCV is higher in people who are Black than in people who are not Black. Point-of-care HCV tests, patient navigation, electronic health record prompts, and unrestricted access to HCV treatment in community-based settings have potential to increase diagnosis and treatment of HCV and improve outcomes in people who are Black.
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Affiliation(s)
- Oluwaseun Falade-Nwulia
- Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Sharon M Kelly
- Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | | | | | | | - Mark Sulkowski
- Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, Maryland
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3
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Sims OT, Truong DN, Wang K, Melton PA, Atim K. Time to HCV Treatment Disfavors Patients Living with HIV/HCV Co-infection: Findings from a Large Urban Tertiary Center. J Racial Ethn Health Disparities 2022; 9:1662-1669. [PMID: 34254269 PMCID: PMC8752646 DOI: 10.1007/s40615-021-01105-5] [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: 02/18/2021] [Revised: 05/20/2021] [Accepted: 06/24/2021] [Indexed: 12/09/2022]
Abstract
This study aimed to assess time to hepatitis C (HCV) treatment (i.e., the time between the initial clinic visit for HCV evaluation and the HCV treatment start date), to compare clinical characteristics between patients who received HCV treatment ≥ and < 6 months, and to identify predictors of longer time to HCV treatment in patients living with HCV. This study conducted a retrospective secondary analysis of patients living with HCV mono-infection and HIV/HCV co-infection who received HCV treatment with DAAs (n=214) at a HIV Clinic. Binomial logistic regression was used to identify predictors of longer time to treatment (i.e., ≥ 6 months). The median time to HCV treatment was 211 days. Compared to patients who were treated < 6 months, a higher proportion of patients who were treated ≥ 6 months had HIV/HCV co-infection (31% vs. 49%, p=0.01) and chronic kidney disease (8% vs. 18%, p=0.03). In multivariate analysis, HIV/HCV co-infection was positively associated with a longer time to HCV treatment (adjusted odds ratio, aOR=2.0, p=0.03). Time to HCV treatment disparities between African American and White American did not emerge from the analysis, but time to HCV treatment disfavored patients living with HIV/HCV co-infection. Studies are needed to identify and eliminate factors that disfavor patients living with HIV/HCV co-infection.
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Affiliation(s)
- Omar T Sims
- Department of Social Work, College of Arts and Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
- Department of Health Behavior, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
- Center for AIDS Research, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
- Integrative Center for Aging Research, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
- African American Studies, College of Arts and Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
- Department of Medicine, Division of Prevention Science, Center for AIDS Prevention Studies, University of California San Francisco, 3137 University Hall, 1720 2nd Avenue South, Birmingham, AL, 35294-1260, USA.
| | - Duong N Truong
- Department of Health Care Organization and Policy, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
- Collat School of Business, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Kaiying Wang
- Department of Mathematics and Statistics, College of Arts & Sciences, Georgia State University, Atlanta, GA, USA
| | - Pamela A Melton
- School of Social Work, Tulane University, New Orleans, LA, USA
| | - Kasey Atim
- School of Social Work, University of Alabama, Tuscaloosa, AL, USA
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4
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Meshram RJ, Kathwate GH, Gacche RN. Progress, evolving therapeutic/diagnostic approaches, and challenges in the management of hepatitis C virus infections. Arch Virol 2022; 167:717-736. [PMID: 35089390 PMCID: PMC8795940 DOI: 10.1007/s00705-022-05375-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Accepted: 12/02/2021] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) infections are emerging as one of the foremost challenges in healthcare owing to its chronicity and the virus's quasispecies nature. Worldwide, over 170 million people are chronically infected with HCV, with an annual mortality of over 500,000 people across the world. The emerging pathophysiological evidence links HCV infections to a risk of developing liver diseases such as cirrhosis and hepatocellular carcinoma. Despite the great strides that have been made towards understanding the pathophysiology of disease progression, the tailored treatments of HCV infection remain to be established. The present review provides an update of the literature pertaining to evolving therapeutic approaches and prophylactic measures for the effective management of HCV infections. An extensive discussion of established and experimental immune prophylactic measures also sheds light on current developments in the design of vaccination strategies against HCV infection. We have also attempted to address the application of nanotechnology in formulating effective therapeutic interventions against HCV. Pointing out the limitations of the existing diagnostic methods and therapeutic approaches against HCV might inspire the design and development of novel, efficient, reliable, and cost-effective diagnostic technologies as well as novel therapeutic and immune prophylactic interventions for the effective management of HCV.
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Affiliation(s)
| | | | - Rajesh Nivarti Gacche
- Department of Biotechnology, Savitribai Phule Pune University, Pune, MS, 411007, India.
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Razafindrazoto CI, Rasolonjatovo AS, Rabenjanahary TH, Randriamifidy NH, Rakotozafindrabe ALR, Razafimahefa SH, Ramanampamonjy RM. Treatment of viral hepatitis C genotypes 1 and 2 by sofosbuvir and ledipasvir with or without ribavirin combination: A possible alternative to pangenotypic treatment in a low-income country? Int J Infect Dis 2021; 107:166-169. [PMID: 33895411 DOI: 10.1016/j.ijid.2021.04.061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 04/16/2021] [Accepted: 04/17/2021] [Indexed: 10/21/2022] Open
Abstract
OBJECTIVES The aim of this study was to evaluate the efficacy and safety of sofosbuvir/ledipasvir ± ribavirin in Malagasy patients with hepatitis C virus genotypes 1 and 2, in real conditions. PATIENTS AND METHODS This was a retrospective monocentric clinical study, carried out over a period of 3 years from March 1, 2017 to February 28, 2020, in a hospital hepato-gastroenterology department. RESULTS In total, 26 patients (M/F: 11/15) with hepatitis C virus genotype 1 (n = 13) or genotype 2 (n = 13), were treated with sofosbuvir/ledipasvir without (n = 21) or with (n = 5) ribavirin for 12 weeks. The mean age was 61.38 ± 7.09 years. Seventeen patients (65.4%) had cirrhosis. The overall sustained virological response was 96.2% (95% CI = 80.4-99.9%). There was no significant difference between the sustained virological responses of genotypes 1 and 2 (92.3% vs 100%; p = 0.31) or those of cirrhotic or non-cirrhotic patients (94.1% vs 100%; p = 0.46). A relapse was observed in one patient (5.9%) - cirrhotic and genotype 1b - under sofosbuvir/ledipasvir with ribavirin. Seven patients (26.9%) experienced mild adverse reactions, including asthenia (57.1%) and insomnia (42.9%). CONCLUSION Treatment with sofosbuvir/ledipasvir ± ribavirin for infection with hepatitis C virus genotype 1 has been shown to be safe and effective, even in the presence of cirrhosis. The sofosbuvir/ledipasvir combination is a good option for genotype 2 non-cirrhotic patients.
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Affiliation(s)
- Chantelli Iamblaudiot Razafindrazoto
- University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar; Faculty of Medicine, University of Antananarivo, Antananarivo, Madagascar.
| | - Anjaramalala Sitraka Rasolonjatovo
- University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar; Faculty of Medicine, University of Antananarivo, Antananarivo, Madagascar
| | - Tovo Harimanana Rabenjanahary
- University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar; Faculty of Medicine, University of Antananarivo, Antananarivo, Madagascar
| | | | - Andry Lalaina Rinà Rakotozafindrabe
- University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar; Faculty of Medicine, University of Antananarivo, Antananarivo, Madagascar
| | - Soloniaina Hélio Razafimahefa
- University Hospital Andrainjato, Fianarantsoa, Madagascar; Faculty of Medicine, University of Fianarantsoa, Fianarantsoa, Madagascar
| | - Rado Manitrala Ramanampamonjy
- University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar; Faculty of Medicine, University of Antananarivo, Antananarivo, Madagascar
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Shousha HI, Saad Y, Saleh DA, Dabes H, Alserafy M, ElShazly Y, Said M. Simple predictors of nonresponse to direct-acting antivirals in chronic hepatitis C patients. Eur J Gastroenterol Hepatol 2020; 32:1017-1022. [PMID: 31789947 DOI: 10.1097/meg.0000000000001612] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The introduction of direct acting antivirals (DAAs) has resulted in very high sustained virological response rates (SVR) in patients with chronic hepatitis-C (CHC). There are still a minority who fails to achieve SVR. This study aims to identify simple factors associated with nonresponse to DAAs using routine pretreatment workup. METHODS A retrospective study included 10 655 CHC patients who were candidates for anti-viral therapy. Pretreatment demographics, laboratory results, ultrasonography and FIB-4were obtained. RESULTS At post-treatment week 4, 10 495 patients (98.5%) were responders and 160 (1.5%) were non-responders. About 50.6% of non-responders were males and 61.3% were cirrhotic. Non-responders had significantly higher baseline BMI, liver enzymes, AFP and a significantly lower albumin, platelet count by univariate analysis ((P < 0.001). Sex, previous treatment, BMI, liver cirrhosis, AST, Albumin and platelet counts were the independent predictors of non-response. At post-treatment week 12, HCV-PCR results were available only for 7259 patients and 210 (2.9%) were non-responders. 54.8% of non-responders were cirrhotic and 51.4% were males. Non-responders had significantly higher AST, AFP and INR and a significantly lower albumin level, platelet count by univariate analysis (P < 0.05). Sex, previous treatment, AST, Albumin, WBC and platelet counts were the independent predictors of non-response. SVR-4 among treatment naive patients was 98.6% while among treatment experienced was 96.8%. SVR-12 among treatment naive patients was 97.9% while among treatment experienced was 87.9%.Cirrhotics had SVR-4 rate 97.7% and SVR-12 rate 96.21%. CONCLUSION Routine pre-treatment work up for HCV G4 patients receiving DAAs can help in prediction of non-response.
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Affiliation(s)
| | - Yasmin Saad
- Department of Endemic Medicine and Hepato-gastroenterology
| | - Doa'a A Saleh
- Department of Public Health and Community Medicine, Faculty of Medicine, Cairo University, Cairo
| | - Hosam Dabes
- National Medical Institute of Damnhour, Damnhour
| | - Magdy Alserafy
- Department of Endemic Medicine and Hepato-gastroenterology
| | - Yehia ElShazly
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Said
- Department of Endemic Medicine and Hepato-gastroenterology
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7
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Segal JB. Formulary restrictions may impact enrollment in pragmatic trials and limit generalizability of findings to vulnerable populations. Clin Trials 2020; 17:729-731. [PMID: 32650667 DOI: 10.1177/1740774520941257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Jodi B Segal
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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8
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Vega AD, Hynicka LM, Claeys K, Chua JV, Heil EL. Effectiveness of 8 weeks of ledipasvir/sofosbuvir for hepatitis C in HCV-HIV-coinfected patients. Antivir Ther 2020; 24:11-17. [PMID: 30192231 DOI: 10.3851/imp3263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/27/2018] [Indexed: 10/28/2022]
Abstract
BACKGROUND Data is limited on the use of 8 weeks of therapy with ledipasvir/sofosbuvir (LDV/SOF) for special populations such as HCV-HIV-coinfected patients. The primary objective of this analysis was to compare sustained virological response at 12 weeks after end of therapy (SVR12) rates among HCV-monoinfected and HCV-HIV-coinfected patients in a real-world clinical setting. Additionally, we compared SVR12 rates among patients receiving 8 versus 12 weeks of therapy. METHODS This was a single-centre, retrospective study of HCV-infected patients prescribed LDV/SOF at ambulatory clinics associated with the University of Maryland Medical Center (UMMC) from May 2015 to May 2016. Data were obtained from UMMC electronic medical records and outpatient pharmacy claims database. Comparisons between groups were made using χ2 or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon rank-sum for continuous variables. All analyses were per-protocol; patients missing SVR12 data (25.2%) could not be evaluated for our stated objectives. RESULTS A total of 274 patients were included. Median age was 58 years; 62.8% were male; 82.5% were Black. SVR12 data was available for 65 HCV-HIV-coinfected patients, of which 62 (95.4%) achieved SVR12. There was no difference in SVR12 rate between HCV-HIV-coinfected patients and HCV-monoinfected patients (86/90; 95.6%; P=0.959). Additionally, there was no difference in SVR12 attainment between HIV-HCV-coinfected patients who received 8 versus 12 weeks of therapy (P=0.101). CONCLUSIONS 8 weeks of LDV/SOF was effective for treatment-naive, non-cirrhotic, HCV genotype-1 patients in this real-world setting, regardless of HIV status. Increased uptake of the 8-week regimen can decrease costs for patients and payers without compromising outcomes.
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Affiliation(s)
- Ana D Vega
- University of Maryland School of Pharmacy, Baltimore, MD, USA
| | | | - Kimberly Claeys
- University of Maryland School of Pharmacy, Baltimore, MD, USA
| | - Joel V Chua
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Emily L Heil
- University of Maryland School of Pharmacy, Baltimore, MD, USA
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9
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Mohamed AA, El-Toukhy NETR, Said EM, Gabal HMR, AbdelAziz H, Doss W, El-Hanafi H, El Deeb HH, Mahmoud S, Elkadeem M, Shalby HS, Abd-Elsalam S. Hepatitis C Virus: Efficacy of New DAAs Regimens. Infect Disord Drug Targets 2020; 20:143-149. [PMID: 30663575 DOI: 10.2174/1871526519666190121114003] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Revised: 01/11/2019] [Accepted: 01/14/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND HCV treatment showed dramatical change due to the introduction of potent, strong, direct antiviral drugs. Before the appearance of Direct-acting antivirals, multiple therapeutic interventions were used for hepatitis C, but none of these interventions were effective on patient-centered outcomes. Direct-acting antivirals cause disruption of viral replication because they target specific nonstructural viral proteins. AIM To review the advantages of efficient HCV therapy and its long term drawbacks. METHODS A search of the literature published in indexed databases (PubMed, Medline In-Process, and Embase) within the last 5 years was conducted. Any duplicated citations were excluded before first-pass screening. Citations (titles and abstracts) were screened for eligibility by a single reviewer. Full texts (including congress abstracts, posters and other congress communications) of citations deemed relevant during title and abstract screening were retrieved for second-pass review. RESULTS Studies on the clinical effects of DAAs for hepatitis C show better tolerance, improved survival and fewer complications when compared to previous interferon therapy. CONCLUSION HCV treatment has improved dramatically. Since that time, there are multiple approved oral therapies all with high efficacy. The most important factor which should be considered during choosing appropriate therapy is to ensure that it covers the viral genotype of the infected patients.
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Affiliation(s)
- Amal Ahmed Mohamed
- Biochemistry and Molecular Biology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | | | - Ebada Mohamed Said
- Hepatology, Gastroenterology and Infectious Diseases Department, Benha Faculty of Medicine, Benha University, Banha, Egypt
| | - Hoda Mohamed Rabie Gabal
- Hepatology, Gastroenterology and Infectious Diseases Department, Benha Faculty of Medicine, Benha University, Banha, Egypt
| | - Hossameldin AbdelAziz
- Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Wahid Doss
- Department of Tropical Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hadeel El-Hanafi
- Clinical and Chemical Pathology, Kasr El-Einy Hospitals, Cairo University, Cairo, Egypt
| | - Hala H El Deeb
- Clnical Pathology department, El Sahel Teaching Hospital, Cairo, Egypt
| | - Seham Mahmoud
- Tropical Medicine Department, El Sahel Teaching Hospital, Cairo, Egypt
| | | | - Hassan Salama Shalby
- Internal Medicine Department, Faculty of Medicine, Misr Science and Technology University, Giza, Egypt
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Zoratti MJ, Siddiqua A, Morassut RE, Zeraatkar D, Chou R, van Holten J, Xie F, Druyts E. Pangenotypic direct acting antivirals for the treatment of chronic hepatitis C virus infection: A systematic literature review and meta-analysis. EClinicalMedicine 2020; 18:100237. [PMID: 31922124 PMCID: PMC6948236 DOI: 10.1016/j.eclinm.2019.12.007] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 12/02/2019] [Accepted: 12/05/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recent approval and adoption of pangenotypic direct acting antivirals (DAAs) necessitated a revision of the 2015 World Health Organization guidelines for the management of persons with hepatitis C virus (HCV) infection. METHODS We searched MEDLINE, EMBASE, CENTRAL, and relevant conference proceedings to identify randomized and non-randomized trials, as well as prospective observational studies of DAAs. The proportions of persons with events were pooled for sustained virological response at 12 weeks post-treatment (SVR12), discontinuations due to adverse events (DAEs), serious adverse events (SAEs), and all-cause mortality. Analyses were stratified by HCV genotype and antiviral treatment experience, with subgroup analyses based on presence of cirrhosis and HIV-HCV coinfection. FINDINGS The evidence base consisted of 238 publications describing 142 studies. In the overall analysis, which included all persons irrespective of treatment experience or comorbidities, the pooled proportion achieving SVR12 exceeded 0.94 for all pangenotypic regimens across genotypes 1, 2, and 4. Some heterogeneity may have led to lower SVR rates in persons with genotype 3 infection. High SVR12 (>0.90) was observed in persons with genotype 1 infection with cirrhosis, though evidence varied and was limited for genotypes 2-4. Evidence was sparse for persons with HIV-HCV coinfection. All regimens were associated with small proportions of persons with DAEs, SAEs, or all-cause mortality. INTERPRETATION Based on this and other supporting evidence, the WHO issued updated guidelines with a conditional recommendation, based on moderate quality evidence, for the use of pangenotypic DAA regimens for persons with chronic HCV infection aged 18 years and older (July 2018). FUNDING This study was funded by the World Health Organization.
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Affiliation(s)
- Michael J. Zoratti
- Zoratti HEOR Consulting Inc., Oakville, Ontario, Canada
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Ayesha Siddiqua
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
| | - Rita E. Morassut
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Dena Zeraatkar
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Roger Chou
- Department of Medical Informatics and Clinical Epidemiology, Division of General Internal Medicine and Geriatrics, Oregon Health and Science University, Portland, Oregon, USA
| | - Judith van Holten
- Department of HIV and Global Hepatitis Programme, World Health Organization, Geneva, Switzerland
| | - Feng Xie
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Eric Druyts
- Pharmalytics Group, Vancouver, British Columbia, Canada
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11
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Cabalak M, Bal T, Onlen Y, Demir M. Incidence and predictors of direct-acting antiviral treatment failure in Turkish patients with chronic hepatitis C genotype 1b infection. Trop Doct 2019; 50:141-146. [PMID: 31810415 DOI: 10.1177/0049475519892082] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Evaluation of the incidence and predictors of failure of direct-acting antiviral treatment for hepatitis C virus genotype 1b patients is important. Our retrospective cohort study assessed 172 Turkish patients who had received a full course of such treatment and could be checked for sustained virologic response. The overall treatment failure rate was 2.9% (5/172), all of whom relapsed. In three of these cases with sequencing data available, all had NS5A resistance-associated substitution. Multivariate analysis revealed that a 1 mg/dL increase in pre-treatment total bilirubin level was associated with a sevenfold increased likelihood of treatment failure. The baseline level of total bilirubin was the only significant independent predictor of direct-acting antiviral treatment failure.
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Affiliation(s)
- Mehmet Cabalak
- Assistant professor, Department of Infection Disease and Clinical Microbiology, Mustafa Kemal University School of Medicine, Hatay, Turkey
| | - Tayibe Bal
- Assistant professor, Department of Infection Disease and Clinical Microbiology, Mustafa Kemal University School of Medicine, Hatay, Turkey
| | - Yusuf Onlen
- Professor, Department of Infection Disease and Clinical Microbiology, Mustafa Kemal University School of Medicine, Hatay, Turkey
| | - Mehmet Demir
- Professor, Department of Gastroenterology, Mustafa Kemal University School of Medicine, Hatay, Turkey
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12
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Struble K, Chan-Tack K, Qi K, Valappil T, Connelly S, Mishra P, Price D, Murray J, Birnkrant D. Sustained virological response rates with direct-acting antivirals in black subjects with HCV genotype 1 infection: systematic analysis of clinical trials. J Virus Erad 2019; 5:138-144. [PMID: 31700657 PMCID: PMC6816118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVES Under representation of black subjects in trials of hepatitis C virus (HCV) direct-acting antivirals (DAAs) complicates assessment of differential outcomes for black individuals vs non-black individuals. HCV trials submitted to the Food and Drug Administration (2013-2017) to support approval or to expand an indication of 12-week interferon-free DAA regimens with or without ribavirin to treat HCV genotype 1 (GT1) infection were pooled to explore efficacy comparisons by ethnicity. METHODS Twenty-six trials were pooled and included 2869 individuals with HCV GT1 alone and 742 individuals with both HCV GT1 and HIV. RESULTS Of the 2869 HCV GT1-mono-infected subjects, 408 (14.2%) were black. Sustained virological response assessed 12 weeks following cessation of treatment (SVR12) was 92%-100% in black individuals and 87.5%-100.0% in non-black individuals. In pooled analyses, SVR12 was numerically similar between black and non-black subjects (97.1% vs 97.3%). Baseline characteristics did not affect SVR12 for the two groups. Of the 742 subjects with both HCV GT1 and HIV, 243 (32.7%) were black: SVR12 was 89.5%-100% in black individuals and 94.4%-100% in non-black individuals. In pooled analyses for HCV GT1/HIV co-infection, black individuals had a 4% (95% confidence interval -7.7% to 0.3%) lower SVR12 than non-black individuals (93.4% vs 97.0%). This difference was driven by ION-4 in which study SVR12 was approximately 10% lower for black than for non-black individuals (89.5% vs 99.1%). Baseline characteristics did not affect SVR12 for the two groups. CONCLUSION No notable SVR12 differences were seen in between black and non-black individuals with HCV GT1 alone. Although a numerical difference was observed between black and non-black individuals with both HCV GT1 and HIV, this finding was driven by results from a single trial and may be due to reasons other than ethnicity: 19 subgroup analyses showed baseline characteristics did not affect SVR12 for black and non-black individuals with both HCV GT1 and HIV.
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Affiliation(s)
- Kimberly Struble
- Division of Antiviral Products,
Office of Antimicrobial Products,
Center for Drug Evaluation and Research, Food and Drug Administration,
Silver Spring,
MD,
USA
| | - Kirk Chan-Tack
- Division of Antiviral Products,
Office of Antimicrobial Products,
Center for Drug Evaluation and Research, Food and Drug Administration,
Silver Spring,
MD,
USA
| | - Karen Qi
- Office of Biostatistics,
Center for Drug Evaluation and Research, Food and Drug Administration,
Silver Spring,
MD,
USA
| | - Thamban Valappil
- Office of Biostatistics,
Center for Drug Evaluation and Research, Food and Drug Administration,
Silver Spring,
MD,
USA
| | - Sarah Connelly
- Division of Antiviral Products,
Office of Antimicrobial Products,
Center for Drug Evaluation and Research, Food and Drug Administration,
Silver Spring,
MD,
USA
| | - Poonam Mishra
- Division of Antiviral Products,
Office of Antimicrobial Products,
Center for Drug Evaluation and Research, Food and Drug Administration,
Silver Spring,
MD,
USA
| | - Dionne Price
- Office of Biostatistics,
Center for Drug Evaluation and Research, Food and Drug Administration,
Silver Spring,
MD,
USA
| | - Jeffrey Murray
- Division of Antiviral Products,
Office of Antimicrobial Products,
Center for Drug Evaluation and Research, Food and Drug Administration,
Silver Spring,
MD,
USA
| | - Debra Birnkrant
- Division of Antiviral Products,
Office of Antimicrobial Products,
Center for Drug Evaluation and Research, Food and Drug Administration,
Silver Spring,
MD,
USA
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13
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Sustained virological response rates with direct-acting antivirals in black subjects with HCV genotype 1 infection: systematic analysis of clinical trials. J Virus Erad 2019. [DOI: 10.1016/s2055-6640(20)30043-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
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14
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Cachay ER, Mena A, Morano L, Benitez L, Maida I, Ballard C, Hill L, Torriani F, Castro A, Dore E, Castro S, de Mendoza Fernández C, Soriano V, Mathews WC. Predictors of Hepatitis C Treatment Failure After Using Direct-Acting Antivirals in People Living With Human Immunodeficiency Virus. Open Forum Infect Dis 2019; 6:ofz070. [PMID: 30949524 PMCID: PMC6440685 DOI: 10.1093/ofid/ofz070] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Accepted: 02/10/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Little is known about the influence of ongoing barriers to care in the persistence of hepatitis C virus (HCV) viremia after treatment with direct-acting antivirals (DAAs) among people living with human immunodeficiency virus (PLWH). METHODS We conducted a retrospective cohort analysis of PLWH treated through the standard of care in 3 Western countries, to investigate the predictors of HCV treatment failure (clinical or virologic), defined as having a detectable serum HCV ribonucleic acid within 12 weeks after DAA discontinuation. In addition to HCV and liver-related predictors, we collected data on ongoing illicit drug use, alcohol abuse, mental illness, and unstable housing. Logistic regression analyses were used to identify predictors of HCV treatment failure. RESULTS Between January 2014 and December 2017, 784 PLWH were treated with DAA, 7% (n = 55) of whom failed HCV therapy: 50.9% (n = 28) had a clinical failure (discontinued DAA therapy prematurely, died, or were lost to follow-up), 47.3% (n = 26) had an HCV virologic failure, and 1 (1.8%) was reinfected with HCV. Ongoing drug use (odds ratio [OR] = 2.60) and mental illness (OR = 2.85) were independent predictors of any HCV treatment failure. Having both present explained 20% of the risk of any HCV treatment failure due to their interaction (OR = 7.47; P < .0001). Predictors of HCV virologic failure were ongoing illicit drug use (OR = 2.75) and advanced liver fibrosis (OR = 2.29). CONCLUSIONS People living with human immunodeficiency virus with ongoing illicit drug use, mental illness, and advanced liver fibrosis might benefit from enhanced DAA treatment strategies to reduce the risk of HCV treatment failure.
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Affiliation(s)
- Edward R Cachay
- Department of Medicine, Division of Infectious Diseases, Owen Clinic, UC San Diego, California
| | - Alvaro Mena
- Unidad de Enfermedades Infecciosas, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain
| | - Luis Morano
- Unidad de Patología Infecciosa, Hospital Universitario Álvaro Cunqueiro, Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain
| | - Laura Benitez
- Servicio de Medicina Interna, Puerta de Hierro Research Institute and University Hospital, Madrid, Spain
| | | | - Craig Ballard
- Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, California
| | - Lucas Hill
- Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, California
| | - Francesca Torriani
- Department of Medicine, Division of Infectious Diseases, Owen Clinic, UC San Diego, California
| | - Angeles Castro
- Unidad de Enfermedades Infecciosas, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain
| | | | - Sheila Castro
- Unidad de Patología Infecciosa, Hospital Universitario Álvaro Cunqueiro, Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain
| | | | - Vicente Soriano
- UNIR Health Sciences School and La Paz University Hospital, Madrid, Spain
| | - Wm C Mathews
- Department of Medicine, Division of Infectious Diseases, Owen Clinic, UC San Diego, California
| | - HCV-TREN Cohort
- Department of Medicine, Division of Infectious Diseases, Owen Clinic, UC San Diego, California
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15
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Ojha RP, MacDonald BR, Chu TC, Marcus JL. Potential Overestimation of Racial Disparities in Response to the 8-Week Ledipasvir/Sofosbuvir Regimen for Hepatitis C Virus Genotype 1 Infection. Gastroenterology 2018; 155:1646-1647.e2. [PMID: 30118741 PMCID: PMC6443239 DOI: 10.1053/j.gastro.2018.07.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 07/11/2018] [Accepted: 07/30/2018] [Indexed: 12/02/2022]
Affiliation(s)
- Rohit P. Ojha
- Center for Outcomes Research, JPS Health Network, Fort Worth, TX, USA,Department of Biostatistics and Epidemiology, UNT Health Science Center, Fort Worth, TX, USA
| | | | - Tzu-Chun Chu
- Center for Outcomes Research, JPS Health Network, Fort Worth, TX, USA
| | - Julia L. Marcus
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
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16
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Sofosbuvir based regimens in the treatment of chronic hepatitis C genotype 1 infection in African-American patients: a community-based retrospective cohort study. Eur J Gastroenterol Hepatol 2018; 30:1200-1207. [PMID: 30096090 PMCID: PMC6133221 DOI: 10.1097/meg.0000000000001233] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Direct-acting antiviral (DAA) drugs have been highly effective in the treatment of chronic hepatitis C (HCV) infection. Limited data exist comparing the safety, tolerability, and efficacy of DAAs in African-American (AA) patients with chronic hepatitis C genotype 1 (HCV GT-1) in the community practice setting. We aim to evaluate treatment response of DAAs in these patients. PATIENTS AND METHODS All the HCV GT-1 patients treated with DAAs between January 2014 and January 2018 in a community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with a sustained virologic response at 12 weeks post-treatment (SVR12), and adverse reactions were assessed. RESULTS Two-hundred seventy-eight patients of AA descent were included in the study. One-hundred sixty-two patients were treated with ledipasvir/sofosbuvir (SOF)±ribavirin, 38 were treated with simeprevir/SOF±ribavirin, and 38 patients were treated with SOF/velpatasvir. Overall, SVR at 12 weeks was achieved in 94.6% in patients who received one of the three DAA regimens (93.8% in ledipasvir/SOF group, 92.1% in simeprevir/SOF group, and 97.4% in SOF/velpatasvir group). Previous treatment experience, HCV RNA levels and HIV status had no statistical significance on overall SVR achievement (P=0.905, 0.680, and 0.425, respectively). Compensated cirrhosis in each of the treatment groups did not influence overall SVR of 12. The most common adverse effect was fatigue (27%). None of the patients discontinued the treatment because of adverse events. CONCLUSION In the real-world setting, DAAs are safe, effective, and well tolerated in African-American patients with chronic HCV GT-1 infection with a high overall SVR rate of 94.6%. Treatment rates did not differ on the basis of previous treatment and compensated cirrhosis status.
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17
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Andres J, Lott S, Qureshi K. Eight-Week Outcomes of Ledipasvir/Sofosbuvir in Noncirrhotic Treatment-Naive Patients with Hepatitis C: Analysis of Pharmacy-Based Data. J Manag Care Spec Pharm 2018; 24:23-28. [PMID: 29290174 PMCID: PMC10397704 DOI: 10.18553/jmcp.2018.24.1.23] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Clinical trials have demonstrated that 8 weeks of ledipasvir and sofosbuvir (LDV/SOF) achieved high rates of sustained virologic response at 12 weeks (SVR12) in patients with hepatitis C viral (HCV) genotype 1 infection. The effectiveness of this combination was noted to be robust in treatment-naive noncirrhotic patients and in patients with an HCV viral load of < 6 million IU/mL before treatment. Generalizability of these results to community clinical practice, however, was advised with caution due to the variability of staging methods, fluctuating nature of viral loads, lack of prospective trials, and real-life confirmation. OBJECTIVE To evaluate the efficacy, defined as SVR12, of LDV/SOF in a real-world setting. METHODS Patients met inclusion criteria if given 8 weeks of LDV/SOF by a specialty pharmacy from October 2014 to October 2015 and if SVR12 was assessed after therapy completion. Clinical outcomes data were obtained from the pharmacy database. RESULTS Of the 6,391 prescriptions of LDV/SOF received by the pharmacy, 3,648 (57%) were covered by insurance, and among them, only 511 (14%) were for an 8-week regimen. SVR12 data were available for 380 (74%) patients who completed an 8-week regimen. 230 different prescribers wrote prescriptions, and 57 different insurance plans approved the 8-week regimen. The majority (74%) of patients were followed by gastroenterology clinics. The 380 patients included in the analysis were all treatment-naive HCV genotype 1 patients. Overall, SVR12 was achieved in 97% of patients, while 10 patients relapsed. The SVR12 rates were lower (93%) in patients with stage 3 fibrosis, particularly in African Americans (29 of 35: 83%). CONCLUSIONS Outcomes were favorable for the 8-week use of LDV/SOF in a noncontrolled real-world setting in treatment-naive noncirrhotic patients with a baseline viral load < 6 million IU/mL. Use of this approach in African Americans with evidence of advanced fibrosis should be avoided. DISCLOSURES No outside funding supported this study. Lott is an employee of Diplomat Pharmacy. Andres and Qureshi have nothing to disclose. Study concept and design were contributed by Lott and Qureshi, who also collected the data. All authors contributed equally to data interpretation and manuscript preparation. Andres revised the manuscript, along with Lott and Qureshi. This work was presented in part as a poster at the 2016 International Liver Conference; Barcelona, Spain; April 13-17, 2016.
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Affiliation(s)
- Jennifer Andres
- 1 Department of Pharmacy Practice, Temple University School of Pharmacy
| | | | - Kamran Qureshi
- 2 Section of Gastroenterology and Hepatology, Department of Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania
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18
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Ojha RP, MacDonald BR, Chu TC, Fasanmi EO, Moore JD, Stewart RA. Comparative effectiveness of 8- and 12-week ledipasvir/sofosbuvir regimens for HCV infection. Antivir Ther 2018; 23:585-592. [PMID: 29969099 DOI: 10.3851/imp3249] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2018] [Indexed: 10/28/2022]
Abstract
BACKGROUND Real-world studies have aimed to compare the effects of 8- and 12-week ledipasvir/sofosbuvir regimens on sustained virological response (SVR) among HCV infection genotype-1 (HCV-1) treatment-naive patients. Nevertheless, real-world comparative effectiveness studies pose unique challenges, such as confounding by indication, that were not adequately addressed in prior studies. We thus aimed to address limitations in prior studies and compare overall- and subgroup-specific effectiveness of 8- and 12-week ledipasvir/sofosbuvir regimens among HCV-1 treatment-naive patients. METHODS Patients eligible for our study were aged ≥18 years and initiated 8- or 12-week ledipasvir/sofosbuvir regimens for treatment-naive HCV-1 at an urban public hospital network. We excluded patients with HIV or cirrhosis. We used marginal structural models to estimate overall and subgroup-specific risk ratios (RRs) and 95% confidence limits (CL) comparing the effect of 8- and 12-week ledipasvir/sofosbuvir regimens on 12-week SVR. RESULTS Our study population comprised 191 patients. Among both regimens, the majority were aged >50 years, non-Hispanic White and uninsured. The overall risk of SVR was comparable between the 8- and 12-week regimens (RR=1.01, 95% CL: 0.92, 1.11). The risk of SVR did not vary by race/ethnicity (non-Hispanic Black: RR=1.01, 95% CL: 0.84, 1.21; non-Hispanic White: RR=1.01, 95% CL: 0.89, 1.04). CONCLUSIONS Our real-world results suggest that 8- and 12-week ledipasvir/sofosbuvir have comparable effects on SVR among HCV-1 patients without cirrhosis or HIV. In addition, the comparable effectiveness of 8- and 12-week regimens among non-Hispanic Black individuals adds to the growing body of evidence that supports the removal of race-based treatment guidelines.
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Affiliation(s)
- Rohit P Ojha
- Center for Outcomes Research, JPS Health Network, Fort Worth, TX, USA.,Department of Biostatistics and Epidemiology, UNT Health Science Center School of Public Health, Fort Worth, TX, USA
| | | | - Tzu-Chun Chu
- Center for Outcomes Research, JPS Health Network, Fort Worth, TX, USA
| | - Esther O Fasanmi
- Pharmacy Services Administration, JPS Health Network, Fort Worth, TX, USA
| | - Jonathan D Moore
- Department of Biostatistics and Epidemiology, UNT Health Science Center School of Public Health, Fort Worth, TX, USA
| | - Rachel A Stewart
- Acclaim Gastroenterology, JPS Health Network, Fort Worth, TX, USA
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19
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Elbasvir/grazoprevir in black adults with hepatitis C virus infection: a pooled analysis of phase 2/3 clinical trials. Am J Gastroenterol 2018; 113:863-871. [PMID: 29695828 DOI: 10.1038/s41395-018-0053-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 02/20/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Although direct-acting antiviral regimens have dramatically improved the treatment of hepatitis C virus (HCV) infection, there is some evidence that black race may be an independent predictor of treatment failure. We report a retrospective analysis of black participants receiving elbasvir/grazoprevir (EBR/GZR) in nine phase 2/3 clinical trials. METHODS Black participants with chronic HCV genotype 1 or 4 (GT1 or GT4) infection who received EBR 50 mg/GZR 100 mg once daily for 12 weeks, or in combination with ribavirin for 16 weeks, were included. The primary end point was sustained virologic response 12 weeks after completion of therapy (SVR12, HCV RNA < 15 IU/mL). RESULTS Compared with nonblack participants (n = 1310), black participants (n = 332) were more likely to have chronic kidney disease stage 4/5 (9.2% vs. 31.0%, respectively), while other comorbidities were similar between the groups. In black and nonblack participants receiving EBR/GZR for 12 weeks, SVR12 rates were 93.7% (282/301) and 94.2% (1072/1138) in those with GT1 infection, and 93.8% (15/16) and 94.6% (88/93) in those with GT4 infection. SVR12 was 100.0% (15/15) in black participants and 97.5% (77/79) in nonblack participants with GT1 infection receiving EBR/GZR plus ribavirin for 16 weeks. Rates of drug-related adverse events (AEs) were 30% vs. 36.6%, and serious AEs were 7.6% vs. 3.4% in black and nonblack participants, respectively. CONCLUSION EBR/GZR showed high efficacy in black participants with HCV GT1 or GT4 infection and was generally well tolerated, with a safety profile similar to that reported overall in phase 2/3 clinical trials.
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20
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Marcus JL, Hurley LB, Chamberland S, Champsi JH, Gittleman LC, Korn DG, Lai JB, Lam JO, Pauly MP, Quesenberry CP, Ready J, Saxena V, Seo SI, Witt DJ, Silverberg MJ. No Difference in Effectiveness of 8 vs 12 Weeks of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C in Black Patients. Clin Gastroenterol Hepatol 2018; 16:927-935. [PMID: 29535057 PMCID: PMC5962408 DOI: 10.1016/j.cgh.2018.03.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Revised: 02/16/2018] [Accepted: 03/02/2018] [Indexed: 01/26/2023]
Abstract
BACKGROUND & AIMS Treatment with the combination of ledipasvir and sofosbuvir for 12 weeks has been approved by the Food and Drug Administration for patients with genotype 1 hepatitis C virus (HCV) infection; some patients can be treated with an 8-week course. Guidelines recommend a 12-week treatment course for black patients, but studies have not compared the effectiveness of 8 vs 12 weeks in black patients who are otherwise eligible for an 8-week treatment regimen. METHODS We conducted an observational study of Kaiser Permanente Northern California members with HCV genotype 1 infection who were eligible for 8 weeks of treatment with ledipasvir and sofosbuvir (treatment-naïve, no cirrhosis, no HIV infection, level of HCV RNA <6 million IU/mL) and were treated for 8 or 12 weeks from October 2014 through December 2016. We used χ2 analyses to compare sustained virologic response 12 weeks after the end of treatment (SVR12) among patients treated for 8 vs 12 weeks, and adjusted Poisson models to identify factors associated with receipt of 12 weeks of therapy among patients eligible for 8 weeks. RESULTS Of 2653 patients eligible for 8 weeks of treatment with ledipasvir and sofosbuvir, 1958 (73.8%) received 8 weeks of treatment and 695 (26.2%) received 12 weeks; the proportions of patients with SVR12 were 96.3% and 96.3%, respectively (P = .94). Among 435 black patients eligible for the 8-week treatment regimen, there was no difference in the proportions who achieved an SVR12 following 8 vs 12 weeks' treatment (95.6% vs 95.8%; P = .90). Male sex, higher transient elastography or FIB-4 scores, higher INR and level of bilirubin, lower level of albumin, obesity, diabetes, and ≥15 alcohol drinks consumed/week were independently associated with receiving 12 weeks of treatment among patients eligible for the 8-week treatment regimen, but were not associated with reduced SVR12 after 8 weeks of treatment. CONCLUSION In an observational study of patients who received ledipasvir and sofosbuvir treatment for HCV genotype 1 infection, we found that contrary to guidelines, 8-week and 12-week treatment regimens do not result in statistically significant differences in SVR12 in black patients. Patient characteristics were associated with receipt of 12-week regimens among patients eligible for 8 weeks, but were not associated with reduced SVR12 after 8 weeks. Shorter treatment courses might therefore be more widely used without compromising treatment effectiveness.
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Affiliation(s)
- Julia L Marcus
- Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts.
| | - Leo B Hurley
- Kaiser Permanente Division of Research, Oakland, California
| | - Scott Chamberland
- Kaiser Permanente Northern California, Regional Pharmacy, Oakland, California
| | - Jamila H Champsi
- Kaiser Permanente South San Francisco Medical Center, South San Francisco, California
| | - Laura C Gittleman
- Kaiser Permanente Northern California, Medical Group Support Services, Oakland, California
| | - Daniel G Korn
- Kaiser Permanente Oakland Medical Center, Oakland, California
| | - Jennifer B Lai
- Kaiser Permanente San Rafael Medical Center, San Rafael, California
| | - Jennifer O Lam
- Kaiser Permanente Division of Research, Oakland, California
| | | | | | - Joanna Ready
- Kaiser Permanente Santa Clara Medical Center, Santa Clara, California
| | - Varun Saxena
- Kaiser Permanente South San Francisco Medical Center, South San Francisco, California
| | - Suk I Seo
- Kaiser Permanente Antioch Medical Center, Antioch, California; Kaiser Permanente Walnut Creek Medical Center, Walnut Creek, California
| | - David J Witt
- Kaiser Permanente San Rafael Medical Center, San Rafael, California
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21
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Marcus JL, Hurley LB, Chamberland S, Champsi JH, Gittleman LC, Korn DG, Lai JB, Lam JO, Pauly MP, Quesenberry CP, Ready J, Saxena V, Seo SI, Witt DJ, Silverberg MJ. Disparities in Initiation of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection in an Insured Population. Public Health Rep 2018; 133:452-460. [PMID: 29750893 PMCID: PMC6055302 DOI: 10.1177/0033354918772059] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES The cost of direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection may contribute to treatment disparities. However, few data exist on factors associated with DAA initiation. METHODS We conducted a retrospective cohort study of HCV-infected Kaiser Permanente Northern California members aged ≥18 during October 2014 to December 2016, using Poisson regression models to evaluate demographic, behavioral, and clinical factors associated with DAA initiation. RESULTS Of 14 790 HCV-infected patients aged ≥18 (median age, 60; interquartile range, 53-64), 6148 (42%) initiated DAAs. DAA initiation was less likely among patients who were non-Hispanic black (adjusted rate ratio [aRR] = 0.7; 95% confidence interval [CI], 0.7-0.8), Hispanic (aRR = 0.8; 95% CI, 0.7-0.9), and of other minority races/ethnicities (aRR = 0.9; 95% CI, 0.8-1.0) than among non-Hispanic white people and among those with lowest compared with highest neighborhood deprivation index (ie, a marker of socioeconomic status) (aRR = 0.8; 95% CI, 0.7-0.8). Having maximum annual out-of-pocket health care costs >$3000 compared with ≤$3000 (aRR = 0.9; 95% CI, 0.8-0.9) and having Medicare (aRR = 0.8; 95% CI, 0.8-0.9) or Medicaid (aRR = 0.7; 95% CI, 0.6-0.8) compared with private health insurance were associated with a lower likelihood of DAA initiation. Behavioral factors (eg, drug abuse diagnoses, alcohol use, and smoking) were also significantly associated with a lower likelihood of DAA initiation (all P < .001). Clinical factors associated with a higher likelihood of DAA initiation were advanced liver fibrosis, HCV genotype 1, previous HCV treatment (all P < .001), and HIV infection ( P = .007). CONCLUSIONS Racial/ethnic and socioeconomic disparities exist in DAA initiation. Substance use may also influence patient or provider decision making about DAA initiation. Strategies are needed to ensure equitable access to DAAs, even in insured populations.
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Affiliation(s)
- Julia L. Marcus
- Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Leo B. Hurley
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Scott Chamberland
- Regional Pharmacy, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Jamila H. Champsi
- Kaiser Permanente South San Francisco Medical Center, South San Francisco, CA, USA
| | - Laura C. Gittleman
- Medical Group Support Services, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Daniel G. Korn
- Kaiser Permanente Oakland Medical Center, Oakland, CA, USA
| | - Jennifer B. Lai
- Kaiser Permanente San Rafael Medical Center, San Rafael, CA, USA
| | - Jennifer O. Lam
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Mary Pat Pauly
- Kaiser Permanente Sacramento Medical Center, Sacramento, CA, USA
| | | | - Joanna Ready
- Kaiser Permanente Santa Clara Medical Center, Santa Clara, CA, USA
| | - Varun Saxena
- Kaiser Permanente South San Francisco Medical Center, South San Francisco, CA, USA
| | - Suk I. Seo
- Kaiser Permanente Antioch Medical Center, Antioch, CA, USA
- Kaiser Permanente Walnut Creek Medical Center, Walnut Creek, CA, USA
| | - David J. Witt
- Kaiser Permanente San Rafael Medical Center, San Rafael, CA, USA
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22
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Benhammou JN, Dong TS, May FP, Kawamoto J, Dixit R, Jackson S, Dixit V, Bhattacharya D, Han SB, Pisegna JR. Race affects SVR12 in a large and ethnically diverse hepatitis C-infected patient population following treatment with direct-acting antivirals: Analysis of a single-center Department of Veterans Affairs cohort. Pharmacol Res Perspect 2018; 6:e00379. [PMID: 29484189 PMCID: PMC5821896 DOI: 10.1002/prp2.379] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 11/16/2017] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. HCV cure has been linked to improved patient outcomes. In the era of direct-acting antivirals (DAAs), HCV cure has become the goal, as defined by sustained virological response 12 weeks (SVR12) after completion of therapy. Historically, African-Americans have had lower SVR12 rates compared to White people in the interferon era, which had been attributed to the high prevalence of non-CC interleukin 28B (IL28B) type. Less is known about the association between race/ethnicity and SVR12 in DAA-treated era. The aim of the study is to evaluate the predictors of SVR12 in a diverse, single-center Veterans Affairs population. We conducted a retrospective study of patients undergoing HCV therapy with DAAs from 2014 to 2016 at the VA Greater Los Angeles Healthcare System. We performed a multivariable logistic regression analysis to determine predictors of SVR12, adjusting for age, HCV genotype, DAA regimen and duration, human immunodeficiency virus (HIV) status, fibrosis, nonalcoholic fatty liver disease (NAFLD) fibrosis score, homelessness, mental health, and adherence. Our cohort included 1068 patients, out of which 401 (37.5%) were White people and 400 (37.5%) were African-American. Genotype 1 was the most common genotype (83.9%, N = 896). In the adjusted models, race/ethnicity and the presence of fibrosis were statistically significant predictors of non-SVR. African-Americans had 57% lower odds for reaching SVR12 (adj.OR = 0.43, 95% CI = 1.5-4.1) compared to White people. Advanced fibrosis (adj.OR = 0.40, 95% CI = 0.26-0.68) was also a significant predictor of non-SVR. In a single-center VA population on DAAs, African-Americans were less likely than White people to reach SVR12 when adjusting for covariates.
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Affiliation(s)
- Jihane N. Benhammou
- Division of Gastroenterology, Hepatology and Parenteral NutritionDepartment of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA
- Vatche & Tamar Manoukian Division of Digestive DiseasesLos AngelesCAUSA
| | - Tien S. Dong
- Division of Gastroenterology, Hepatology and Parenteral NutritionDepartment of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA
- Vatche & Tamar Manoukian Division of Digestive DiseasesLos AngelesCAUSA
| | - Folasade P. May
- Division of Gastroenterology, Hepatology and Parenteral NutritionDepartment of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA
- Vatche & Tamar Manoukian Division of Digestive DiseasesLos AngelesCAUSA
| | - Jenna Kawamoto
- Division of Gastroenterology, Hepatology and Parenteral NutritionDepartment of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA
- Division of Infectious Diseases VA Greater Los Angeles Healthcare System Department of MedicineDavid Geffen School of Medicine at UCLALos AngelesCAUSA
| | - Ram Dixit
- Division of Gastroenterology, Hepatology and Parenteral NutritionDepartment of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA
| | - Samuel Jackson
- Division of Gastroenterology, Hepatology and Parenteral NutritionDepartment of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA
| | - Vivek Dixit
- Division of Gastroenterology, Hepatology and Parenteral NutritionDepartment of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA
- Vatche & Tamar Manoukian Division of Digestive DiseasesLos AngelesCAUSA
| | - Debika Bhattacharya
- Division of Infectious Diseases VA Greater Los Angeles Healthcare System Department of MedicineDavid Geffen School of Medicine at UCLALos AngelesCAUSA
| | - Steven B. Han
- Division of Gastroenterology, Hepatology and Parenteral NutritionDepartment of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA
- Vatche & Tamar Manoukian Division of Digestive DiseasesLos AngelesCAUSA
| | - Joseph R. Pisegna
- Division of Gastroenterology, Hepatology and Parenteral NutritionDepartment of Medicine David Geffen School of Medicine at UCLALos AngelesCAUSA
- Vatche & Tamar Manoukian Division of Digestive DiseasesLos AngelesCAUSA
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Real-world effectiveness of 8-week treatment with ledipasvir/sofosbuvir in chronic hepatitis C. J Hepatol 2018; 68:663-671. [PMID: 29133244 DOI: 10.1016/j.jhep.2017.11.009] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Revised: 11/02/2017] [Accepted: 11/03/2017] [Indexed: 01/15/2023]
Abstract
BACKGROUND & AIMS Ledipasvir/sofosbuvir (LDV/SOF) for 8 to 24 weeks is approved for the treatment of chronic hepatitis C virus infection (HCV). In the ION-3 study, 8 weeks of LDV/SOF was non-inferior to 12 weeks in previously untreated genotype 1 (GT1) patients without cirrhosis. According to the Summary of Product Characteristics (SmPC), 8-week treatment may be considered in naïve non-cirrhotic GT1-patients. However, there are only limited data on the effectiveness of an 8-week regimen of LDV/SOF under real-world conditions. The aim of the present study was to characterise patients receiving 8 weeks of LDV/SOF compared to those receiving 12 weeks of LDV/SOF, and to describe therapeutic outcomes in routine clinical practice. METHODS The German Hepatitis C-Registry is a large national real-world cohort that analyses effectiveness and safety of antiviral therapies in chronic HCV. This data set is based on 2,404 patients. Treatment with SOF/LDV (without RBV) for 8 or 12 weeks was initiated on or before September 30, 2015. RESULTS Overall, 84.6% (2,034/2,404) of the safety population (intention-to-treat-1 [ITT1]) and 98.2% (2,029/2,066) of the per protocol (PP) population achieved sustained virological response at week 12 (SVR12). In the 8-week group, 85.1% (824/968) of ITT1 and 98.3% (821/835) of PP patients achieved SVR12, while in the 12-week group, 85.5% (1,210/1,415) of ITT1, and 98.1% (1,208/1,231) of PP patients achieved SVR12. When treated according to the SmPC, 98.7% (739/749) of the patients achieved SVR12 (PP). Relapse was observed in 9.5% (2/21) of cirrhotic patients treated for 8 weeks (PP). CONCLUSIONS Under real-world conditions a high proportion of eligible patients receiving 8-week LDV/SOF treatment achieved SVR12. Relapse occurred more frequently in patients who did not meet the selection criteria according to the SmPC. LAY SUMMARY In a large real-world cohort of patients mainly treated by physicians in private practice in Germany, shorter HCV treatment (8-week) resulted in equivalent cure rates to 12-week treatment in genotype 1 HCV-infected patients. Thus, shorter treatment can be recommended in these patients which would substantially reduce costs of therapy. Clinical Trial number: DRKS00009717 (German Clinical Trials Register, DRKS).
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Wilder JM, Muir A. Direct acting antivirals for the treatment of hepatitis C in ethnic minority populations. Expert Opin Pharmacother 2018; 19:451-456. [PMID: 29488438 DOI: 10.1080/14656566.2018.1446945] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
INTRODUCTION Direct acting antivirals (DAA's) have revolutionized the treatment of hepatitis C (HCV). However, questions persist concerning their efficacy in minority populations. AREAS COVERED In this review, the authors review outcomes for treatment of HCV by race and ethnicity among the clinical trials that have led to the current recommended treatments for HCV. The authors highlight the efficacy and safety differences by race and ethnicity. They also highlight deficiencies within the literature including small populations of racial/ethnic minorities within HCV clinical trials. DAA's can achieve cure rates for HCV over 95% with the use of once daily medications that have minimal side effects and few significant drug-drug interactions. Regimens with high pan-genotypic efficacy have further simplified treatment paradigms. The purpose of this review is to describe the data on DAA's in treating HCV in racial/ethnic populations. EXPERT OPINION While the overall data in racial/ethnic minority populations is sparse, DAA's appear to have high efficacy in curing HCV in diverse racial/ethnic populations. Although achieving high sustained virologic response (SVR) rates, there are also data that suggests that some disparities in SVR persist, especially when considering shorter regimens for HCV treatment in racial/ethnic populations.
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Affiliation(s)
- Julius M Wilder
- a Duke School of Medicine , Duke University , Durham , NC , USA.,b Duke Clinical Research Institute, Duke University , Durham , NC , USA
| | - Andrew Muir
- a Duke School of Medicine , Duke University , Durham , NC , USA.,b Duke Clinical Research Institute, Duke University , Durham , NC , USA
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Ahmed OA, Kaisar HH, Badawi R, Hawash N, Samir H, Shabana SST, Fouad MHA, Rizk FH, Khodeir SA, Abd-Elsalam S. Efficacy and safety of sofosbuvir-ledipasvir for treatment of a cohort of Egyptian patients with chronic hepatitis C genotype 4 infection. Infect Drug Resist 2018; 11:295-298. [PMID: 29535545 PMCID: PMC5840188 DOI: 10.2147/idr.s153060] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND AND AIMS Treatment of hepatitis C virus (HCV) infection has significantly changed during the last few years. The combination of ledipasvir and sofosbuvir has been shown to treat high proportions of patients with HCV genotype 1 with remarkable tolerability. The aim of the work was to assess the efficacy and safety of sofosbuvir plus ledipasvir in treating treatment-naïve Egyptian patients with genotype 4 HCV infection. PATIENTS AND METHODS In this open-label randomized study, 200 treatment-naive patients who were HCV antibody positive and HCV RNA positive by polymerase chain reaction, aged >18 years, were enrolled. The patients were classified into two groups: group I included 100 patients who received single therapy with sofosbuvir plus ledipasvir for 12 weeks and group II included 100 patients who received sofosbuvir plus oral weight-based ribavirin for 24 weeks. The primary end point was a sustained virological response at 12 weeks (SVR12) after the end of treatment, determined by quantitative polymerase chain reaction for HCV RNA. RESULTS Group I patients showed statistically significant (p<0.05) higher SVR12 compared with group II patients (99% vs. 80%). There was no statistical difference (p>0.05%) between the studied groups regarding the frequencies of the side effects (26% vs. 29%). The most common adverse effects were headache, fatigue, myalgia, and cough. CONCLUSION Sofosbuvir and ledipasvir treatment for 12 weeks was well tolerated by patients with HCV genotype 4 and resulted in 99% SVR for all patients who received 12 weeks of the study drugs. ClinicalTrials.gov Identifier: NCT02992457.
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Affiliation(s)
- Ossama A Ahmed
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hany H Kaisar
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Rehab Badawi
- Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Nehad Hawash
- Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Hossam Samir
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sherif ST Shabana
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Hassan A Fouad
- Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Fatma H Rizk
- Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Samy A Khodeir
- Department of Internal Medicine, Tanta University, Tanta, Egypt
| | - Sherief Abd-Elsalam
- Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
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Bhattacharya D, Belperio PS, Shahoumian TA, Loomis TP, Goetz MB, Mole LA, Backus LI. Effectiveness of All-Oral Antiviral Regimens in 996 Human Immunodeficiency Virus/Hepatitis C Virus Genotype 1-Coinfected Patients Treated in Routine Practice. Clin Infect Dis 2018; 64:1711-1720. [PMID: 28199525 DOI: 10.1093/cid/cix111] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 02/01/2017] [Indexed: 12/19/2022] Open
Abstract
Background. Large cohorts are needed to assess human immunodeficiency virus (HIV)/hepatitis C virus (HCV) real-world treatment outcomes. We examined the effectiveness of ledipasvir/sofosbuvir with or without ribavirin (LDV/SOF ± RBV) and ombitasvir/ paritaprevir/ritonavir plus dasabuvir (OPrD) ± RBV in HIV/HCV genotype 1 (GT1)-coinfected patients initiating HCV therapy in clinical practice. Methods. Observational intent-to-treat cohort analysis using the Veterans Affairs Clinical Case Registry to identify HIV/HCV GT1-coinfected veterans initiating 12 weeks of LDV/SOF ± RBV or OPrD ± RBV. Multivariate models of sustained virologic response (SVR) included age, race, cirrhosis, proton pump inhibitor (PPI) prescription, prior HCV treatment, body mass index, genotype subtype, and HCV treatment regimen. Results. Nine hundred ninety-six HIV/HCV GT1-coinfected veterans initiated therapy: 757 LDV/SOF, 138 LDV/SOF + RBV, 28 OPrD, and 73 OPrD + RBV. Overall SVR was 90.9% (823/905); LDV/SOF 92.1% (631/685), LDV/SOF + RBV 86.3% (113/131), OPrD 88.9% (24/27), and OPrD + RBV 88.7% (55/62). SVR was 85.9% (176/205) and 92.4% (647/700) in those with and without cirrhosis (P = .006). SVR was similar between African Americans (90.5% [546/603]) and all others (91.7% [277/302]). PPI use with LDV/SOF ± RBV did not affect SVR (89.7% [131/146] with PPI and 91.5% [613/670] without PPI). Cirrhosis was predictive of reduced SVR (0.51 [95% confidence interval {CI}, .31-.87]; P = .01). Median creatinine change did not differ among patients receiving LDV/SOF and tenofovir disoproxil fumarate (TDF) without a protease inhibitor (PI) (0.18 [interquartile range {IQR}, 0.08-0.30]; n = 372), LDV/SOF and TDF/PI (0.17 [IQR, 0.04-0.30]; n = 100), and LDV/SOF without TDF (0.15 [IQR, 0.00-0.30]; n = 423). Conclusions. SVR rates in HIV/HCV GT1-coinfected patients were high. African American race or PPI use with LDV/SOF ± RBV was not associated with lower SVR rates, but cirrhosis was. Renal function did not worsen on LDV/SOF regimens with TDF.
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Affiliation(s)
- Debika Bhattacharya
- 1 Department of Medicine, Veterans Affairs Greater Los Angeles Health Care System.,2 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, and
| | - Pamela S Belperio
- 3Population Health Services, Department of Veterans Affairs, Palo Alto Health Care System, California
| | - Troy A Shahoumian
- 3Population Health Services, Department of Veterans Affairs, Palo Alto Health Care System, California
| | - Timothy P Loomis
- 3Population Health Services, Department of Veterans Affairs, Palo Alto Health Care System, California
| | - Matthew B Goetz
- 1 Department of Medicine, Veterans Affairs Greater Los Angeles Health Care System.,2 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, and
| | - Larry A Mole
- 3Population Health Services, Department of Veterans Affairs, Palo Alto Health Care System, California
| | - Lisa I Backus
- 3Population Health Services, Department of Veterans Affairs, Palo Alto Health Care System, California
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Tang L, Parker A, Flores Y, Dellario M, Dickson C, Amoroso A, Kottilil S, Wilson E. Treatment of hepatitis C with 8 weeks of ledipasvir/sofosbuvir: Highly effective in a predominantly black male patient population. J Viral Hepat 2018; 25:205-208. [PMID: 28984059 DOI: 10.1111/jvh.12796] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 07/28/2017] [Indexed: 01/25/2023]
Affiliation(s)
- L Tang
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - A Parker
- Department of Pharmacy, VA Maryland Health Care System, Baltimore, MD, USA
| | - Y Flores
- Department of Nursing, VA Maryland Health Care System, Baltimore, MD, USA
| | - M Dellario
- Department of Nursing, VA Maryland Health Care System, Baltimore, MD, USA
| | - C Dickson
- Department of Pharmacy, VA Maryland Health Care System, Baltimore, MD, USA
| | - A Amoroso
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.,Division of Infectious Diseases, Department of Medicine, VA Maryland Health Care System, Baltimore, MD, USA
| | - S Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - E Wilson
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.,Division of Infectious Diseases, Department of Medicine, VA Maryland Health Care System, Baltimore, MD, USA
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Beck KR, Kim NJ, Khalili M. Direct Acting Antivirals Improve HCV Treatment Initiation and Adherence Among Underserved African Americans. Ann Hepatol 2018; 17:413-418. [PMID: 29735789 PMCID: PMC7058131 DOI: 10.5604/01.3001.0011.7385] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Adherence to hepatitis C (HCV) care was suboptimal in the interferon era among underserved African Americans (AA), but adherence data in the era of direct acting antivirals (DAA) is lacking in this population. We aimed to evaluate the impact of DAA on HCV care in underserved AA. MATERIAL AND METHODS Clinical records of AAs undergoing HCV evaluation attending a safety net health system liver clinic were reviewed from 2006 to 2011 (pre-DAA), and January 1, 2014 to December 31, 2016 (post-DAA). RESULTS 291 patients were identified (129 pre-DAA, and 162 post-DAA). Median age was 58, 66% were male, 91% had HCV genotype 1, and 70% had fibrosis ≥ stage 2. Post-DAA patients were older (60 vs. 53 years; p < 0.001), had higher rates of insurance (98 vs. 88%; p < 0.001), liver fibrosis ≥ stage 2 (77 vs. 61%; p = 0.048), ≥ 2 medical comorbidities (19 vs. 0.8%; p < 0.001), and median baseline log10 HCV RNA (6.07 vs. 5.81 IU/mL; p < 0.001), but lower median ALT (46 vs. 62 U/L; p < 0.001). Post-DAA, fewer patients were treatment ineligible (5.6 vs. 39%; p < 0.001) and more initiated therapy (71 vs. 8.5%; < 0.001), were adherent to HCV care (82 vs. 38%; p < 0.001), and achieved cure (95.7 vs. 63.6%, p < 0.001). Availability of DAA was independently associated with improved adherence to HCV care (OR 10.3, 95% CI 4.84-22.0). CONCLUSION Availability of DAA is associated with increased treatment eligibility, initiation, adherence to HCV care, and cure in HCV-infected underserved AAs; highlighting the critical role of access to DAA in this population.
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Affiliation(s)
- Kendall R. Beck
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Nicole J. Kim
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Mandana Khalili
- Department of Medicine, University of California San Francisco, San Francisco, CA, USA.,Liver Center, University of California San Francisco, San Francisco, CA, USA
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30
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Morgan JR, Kim AY, Naggie S, Linas BP. The Effect of Shorter Treatment Regimens for Hepatitis C on Population Health and Under Fixed Budgets. Open Forum Infect Dis 2017; 5:ofx267. [PMID: 29354660 PMCID: PMC5767946 DOI: 10.1093/ofid/ofx267] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 12/06/2017] [Indexed: 12/19/2022] Open
Abstract
Background Direct acting antiviral hepatitis C virus (HCV) therapies are highly effective but costly. Wider adoption of an 8-week ledipasvir/sofosbuvir treatment regimen could result in significant savings, but may be less efficacious compared with a 12-week regimen. We evaluated outcomes under a constrained budget and cost-effectiveness of 8 vs 12 weeks of therapy in treatment-naïve, noncirrhotic, genotype 1 HCV-infected black and nonblack individuals and considered scenarios of IL28B and NS5A resistance testing to determine treatment duration in sensitivity analyses. Methods We developed a decision tree to use in conjunction with Monte Carlo simulation to investigate the cost-effectiveness of recommended treatment durations and the population health effect of these strategies given a constrained budget. Outcomes included the total number of individuals treated and attaining sustained virologic response (SVR) given a constrained budget and incremental cost-effectiveness ratios. Results We found that treating eligible (treatment-naïve, noncirrhotic, HCV-RNA <6 million copies) individuals with 8 weeks rather than 12 weeks of therapy was cost-effective and allowed for 50% more individuals to attain SVR given a constrained budget among both black and nonblack individuals, and our results suggested that NS5A resistance testing is cost-effective. Conclusions Eight-week therapy provides good value, and wider adoption of shorter treatment could allow more individuals to attain SVR on the population level given a constrained budget. This analysis provides an evidence base to justify movement of the 8-week regimen to the preferred regimen list for appropriate patients in the HCV treatment guidelines and suggests expanding that recommendation to black patients in settings where cost and relapse trade-offs are considered.
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Affiliation(s)
- Jake R Morgan
- Section of Infectious Diseases, Department of Medicine, Boston Medical Center, Boston, Massachusetts
| | - Arthur Y Kim
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Susanna Naggie
- School of Medicine, Duke University, Durham, North Caorlina.,Duke Clinical Research Institute, Durham, North Carolina
| | - Benjamin P Linas
- Section of Infectious Diseases, Department of Medicine, Boston Medical Center, Boston, Massachusetts.,Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts
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Sims OT, Guo Y, Shoreibah MG, Venkata K, Fitzmorris P, Kommineni V, Romano J, Massoud OI. Short article: Alcohol and substance use, race, and insurance status predict nontreatment for hepatitis C virus in the era of direct acting antivirals: a retrospective study in a large urban tertiary center. Eur J Gastroenterol Hepatol 2017; 29:1219-1222. [PMID: 28857899 DOI: 10.1097/meg.0000000000000961] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVE Direct acting antivirals (DAAs) have overcome many long-standing medical barriers to hepatitis C virus (HCV) treatment (i.e. host characteristics and medical contraindications) and treatment outcome disparities that were associated with interferon regimens. The public health and clinical benefit of current and forthcoming DAA discoveries will be limited if efforts are not made to examine racial, psychological, and socioeconomic factors associated with being treated with DAAs. This study examined racial, psychological, and socioeconomic factors that facilitate and inhibit patients receiving DAAs for HCV. PATIENTS AND METHODS This was a single-center retrospective cohort study at a large urban tertiary center of patients (n=747) who were referred for evaluation and treatment of HCV. RESULTS Sixty-eight percent of patients were non-Hispanic White, 31% were African American, and 1% were of other ethnicities. The majority of patients received treatment, but 29% (218/747) did not. Patients who were older [odds ratio (OR)=1.02, 95% confidence interval (CI): 1.01-1.04] and insured (OR=2.73, 95% CI: 1.12-6.97) were more likely to receive HCV treatment. Patients who were African American (OR=0.46, 95% CI: 0.46-1.06), used drugs (OR=0.09, 95% CI: 0.04-0.17), smoked (OR=0.55, 95% CI: 0.37-0.81), and used alcohol (OR=0.11, 95% CI: 0.06-0.20) were less likely to receive HCV treatment. CONCLUSION Though DAAs have eliminated many historically, long-standing medical barriers to HCV treatment, several racial, psychological and socioeconomic barriers, and disparities remain. Consequently, patients who are African American, uninsured, and actively use drugs and alcohol will suffer from increased HCV-related morbidity and mortality in the coming years if deliberate public health and clinical efforts are not made to facilitate access to DAAs.
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Affiliation(s)
- Omar T Sims
- aDepartment of Social Work, College of Arts and Sciences bDepartment of Health Behavior, School of Public Health, Center for AIDS Research cDivision of Gastroenterology & Hepatology dDepartment of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham eSchool of Social Work, University of Alabama, Tuscaloosa, Alabama, USA
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He X, Hopkins L, Everett G, Carter WM, SchroppDyce C, Abusaada K, Hsu V. Safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in hepatitis C virus/human immunodeficiency virus co-infected patients. World J Hepatol 2017; 9:1190-1196. [PMID: 29109851 PMCID: PMC5666305 DOI: 10.4254/wjh.v9.i30.1190] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 07/14/2017] [Accepted: 09/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection in an urban HIV clinic.
METHODS A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016. All patients included were receiving antiretroviral therapy (ART) with HIV RNA values of 100 copies/mL or fewer regardless of baseline HCV RNA level. The primary end point was a sustained virologic response of HCV at 12 wk (SVR12) after the end of therapy.
RESULTS Of the 40 patients enrolled, 55% were black, 22.5% had been previously treated for HCV, and 25% had cirrhosis. The patients were on a wide range of ART. Overall, 39 patients (97.5%) had a SVR 12 after the end of therapy, including rates of 97.1% in patients with HCV genotype 1a and 100% in those with HCV genotype 1b. One patient with HCV genotype 3a was included and achieved SVR12. Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis. Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn’t reveal any resistance associated mutation in the NS5A or NS5B region. Interestingly, 7 (17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen. Two (5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy, which resolved after resuming the same ART regimen. No severe adverse events were observed and no patient discontinued treatment because of adverse events. The most common adverse events included headache (12.5%), fatigue (10%), and diarrhea (2.5%).
CONCLUSION This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV, regardless of HCV baseline levels, HCV treatment history or cirrhosis condition. The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV ART. Occasional HIV virologic rebound occurred but later resolved without the need to change ART.
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Affiliation(s)
- Xiaoping He
- the Internal Medicine Residency Program of Florida Hospital, Orlando, FL 32804, United States
| | - Lynne Hopkins
- Sunshine Care Center, Florida Department of Health in Orange County, Orlando, FL 32804, United States
| | - George Everett
- the Internal Medicine Residency Program of Florida Hospital, Orlando, FL 32804, United States
| | - Willie M Carter
- Sunshine Care Center, Florida Department of Health in Orange County, Orlando, FL 32804, United States
| | - Cynthia SchroppDyce
- Sunshine Care Center, Florida Department of Health in Orange County, Orlando, FL 32804, United States
| | - Khalid Abusaada
- the Internal Medicine Residency Program of Florida Hospital, Orlando, FL 32804, United States
| | - Vincent Hsu
- the Internal Medicine Residency Program of Florida Hospital, Orlando, FL 32804, United States
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Curry MP, Tapper EB, Bacon B, Dieterich D, Flamm SL, Guest L, Kowdley KV, Lee Y, Milligan S, Tsai N, Younossi Z, Afdhal NH. Effectiveness of 8- or 12-weeks of ledipasvir and sofosbuvir in real-world treatment-naïve, genotype 1 hepatitis C infected patients. Aliment Pharmacol Ther 2017; 46:540-548. [PMID: 28691377 DOI: 10.1111/apt.14204] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Revised: 11/18/2016] [Accepted: 06/04/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naïve to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks. AIM To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting. METHODS We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naïve genotype 1 HCV patients. RESULTS A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables. CONCLUSIONS In treatment-naïve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen.
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Affiliation(s)
- M P Curry
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - E B Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - B Bacon
- Division of Gastroenterology/ Hepatology, Saint Louis University School of Medicine, Saint Louis, MO, USA
| | - D Dieterich
- Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA
| | - S L Flamm
- Division of Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - L Guest
- Trio Health Analytics, La Jolla, CA, USA
| | - K V Kowdley
- Liver Care Network, Swedish Medical Center, Seattle, WA, USA
| | - Y Lee
- Trio Health Analytics, La Jolla, CA, USA
| | - S Milligan
- Trio Health Analytics, La Jolla, CA, USA
| | - N Tsai
- The Liver Center, Queen's Medical Center, Honolulu, HI, USA
| | - Z Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA
| | - N H Afdhal
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Latt NL, Yanny BT, Gharibian D, Gevorkyan R, Sahota AK. Eight-week ledipasvir/sofosbuvir in non-cirrhotic, treatment-naïve hepatitis C genotype-1 patients with hepatitis C virus-RNA < 6 million: Single center, real world effectiveness and safety. World J Gastroenterol 2017; 23:4759-4766. [PMID: 28765697 PMCID: PMC5514641 DOI: 10.3748/wjg.v23.i26.4759] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Revised: 03/08/2017] [Accepted: 06/09/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate sustained viral response (SVR) of 8-wk ledipasvir/sofosbuvir therapy among non-cirrhotic, genotype-1 hepatitis C virus (HCV) patients with RNA < 6 million IU/mL. METHODS We performed a retrospective cohort study to examine SVR rates, predictors of treatment failure and safety analysis of 8-wk ledipasvir/sofosbuvir (LDV/SOF) therapy among non-cirrhotic, genotype 1 HCV patients with viral load < 6 million IU/mL. Primary outcome was an achievement of SVR at 12 wk after treatment. Secondary outcomes were identifying predictors of treatment failure and adverse events during treatment. RESULTS Total 736 patients: 55% males, 51% Caucasians and 65% were genotype 1a. Non-cirrhotic state of 53% was determined by clinical judgment (imaging, AST, platelet count) and 47% had documented liver fibrosis testing (biopsy, vibration-controlled transient elastography, serum biomarkers). Overall SVR12 was 96%. No difference in SVR12 was seen between patients whose non-cirrhotic state was determined by clinical judgment and patients who had fibrosis testing. Age groups, gender, ethnicity and genotype 1 subtype did not predict SVR. Non-cirrhotic state determined by clinical judgment based on simple, non-invasive tests were not associated with lower SVR [OR = 1.02, 95%CI: 0.48-2.17, P = 0.962]. The AUROC for hepatitis C RNA viral load was 0.734 (P < 0.001, 95%CI: 0.66-0.82). HCV RNA 2.2 million IU/mL was identified as the cutoff value with sensitivity 73% and specificity 64%. HCV RNA < 2.2 million IU/mL was associated with significantly higher SVR 98% with OR = 0.22 (95%CI: 0.1-0.49, P < 0.001) compared to SVR 92% in HCV RNA ≥ 2.2 million IU/mL. No death or morbidities were reported. CONCLUSION Our outcomes validate safety and effectiveness of 8-wk LDV/SOF therapy in non-cirrhotic, untreated HCV genotype 1 patients with HCV RNA < 6 million IU/mL.
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Beste LA, Green PK, Berry K, Kogut MJ, Allison SK, Ioannou GN. Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma. J Hepatol 2017; 67:32-39. [PMID: 28267622 PMCID: PMC6590903 DOI: 10.1016/j.jhep.2017.02.027] [Citation(s) in RCA: 112] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 01/20/2017] [Accepted: 02/18/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) treatment for patients with hepatocellular carcinoma (HCC) was uncommon before direct-acting antiviral (DAA) medications. Real-world effectiveness of DAAs for HCV in patients with HCC is unclear. We describe rates of sustained virologic response (SVR) with DAA regimens by HCV genotype in patients with a history of HCC. METHODS We identified patients who initiated antiviral treatment between January 1, 2014 and June 30, 2015 in the national Veterans Affairs health care system. Regimens included sofosobuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin. HCC patients were divided into those who were treated with liver transplantation after HCC diagnosis ("HCC/LT" group) and those treated with other modalities prior to antiviral therapy ("HCC" group). RESULTS Of 17,487 HCV treatment recipients, 624 (3.6%) had prior HCC, including 142 with HCC/LT and 482 with HCC. Overall SVR was 91.1% in non-HCC, 74.4% in HCC, and 94.0% in HCC/LT. Among HCC patients, genotype 1 had the highest SVR overall (79.1% in HCC and 96.4% in HCC/LT), and genotype 3 the lowest (47.0% in HCC and 88.9% in HCC/LT). After adjustment for confounders, the presence of HCC was associated with lower likelihood of SVR overall (AOR 0.38 [95% CI 0.29, 0.48], p<0.001). CONCLUSION HCV can be cured with DAAs in the majority of patients with prior HCC, and in virtually all HCC patients post-liver transplant. Deferral of HCV treatment until the post-transplant setting may be considered among HCC patients listed for transplantation. LAY SUMMARY Over three-quarters of patients with hepatocellular carcinoma who have hepatitis C can achieve viral cure with direct-acting antiviral drugs. Among patients with hepatocellular carcinoma who subsequently received liver transplantation, over 90% of patients can achieve viral cure.
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Affiliation(s)
- Lauren A. Beste
- General Medicine Service, Veterans Affairs Puget Sound Health Care System, United States,Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, United States,Division of General internal Medicine, University of Washington, United States, Corresponding author. Address: Veterans Affairs Puget Sound Health Care System, 1660 S. Columbian Way (S-111-Gastro), Seattle, WA 98108, United States. Tel.: +1 206 277 4511; fax: +1 206 764 2232. , (L.A. Beste).
| | - Pamela K. Green
- Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, United States
| | - Kristin Berry
- Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, United States
| | - Matthew J. Kogut
- Diagnostic Imaging Service, Veterans Affairs Puget Sound Health Care System, United States,Division of interventional Radiology, University of Washington, United States
| | - Stephen K. Allison
- Diagnostic Imaging Service, Veterans Affairs Puget Sound Health Care System, United States,Division of interventional Radiology, University of Washington, United States
| | - George N. Ioannou
- Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, United States,Gastroenterology Service, Veterans Affairs Puget Sound Health Care System, United States,Division of Gastroenterology, University of Washington, United States
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Forde KA, Bhattacharya D. Treatment of Hepatitis C Virus (HCV) Genotype 1 Disease. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2017; 9:262-276. [PMID: 29805320 PMCID: PMC5966038 DOI: 10.1007/s40506-017-0124-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The landscape of therapeutic options for HCV infection has dramatically changed with the approval of all-oral direct-acting antiviral (DAA) regimens. DAAs target important steps in the HCV viral life cycle, resulting in higher response rates and fewer adverse events than were afforded with interferon and ribavirin, the prior standard of care. The achievement of sustained virologic response (SVR) rates in excess of 90% with use of DAA regimens has not only translated into HCV eradication for the hundreds of thousands treated but is also anticipated to decrease the incidence of major complications associated with chronic HCV infection. Additionally, the favorable side effect profile of DAAs has made HCV therapy feasible in difficult-to-treat populations, including those with previous exposure to interferon and ribavirin, cirrhosis, decompensated liver disease, HIV and HCV co-infection, and severe renal dysfunction/end stage renal disease. Given this tremendous progress, all patients infected with HCV infection should be treated.
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Lai JB, Witt MA, Pauly MP, Ready J, Allerton M, Seo S, Witt DJ. Eight- or 12-Week Treatment of Hepatitis C with Ledipasvir/Sofosbuvir: Real-World Experience in a Large Integrated Health System. Drugs 2017; 77:313-318. [PMID: 28078644 DOI: 10.1007/s40265-016-0684-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Second-generation direct-acting antiviral agents are integral to treatment of hepatitis C (HCV) infection. Eight-week courses of ledipasvir/sofosbuvir (LDV/SOF) have been supported in some studies, but data are limited on efficacy in real-world use. Controversy exists regarding applicability of clinical trials to real-world effectiveness. We report virologic responses of patients with HCV genotype 1 infection receiving LDV/SOF for 8 or 12 weeks in a large integrated healthcare system. METHODS All patients receiving LDV/SOF, without ribavirin, were identified from pharmacy records, and outcomes are reported. Only treatment-naïve patients without evidence of cirrhosis and hepatitis C viral load less than 6 million IU/ml were candidates for 8-week therapy. Treatment was at clinician discretion, but delivered by a multidisciplinary team and reviewed for appropriateness and adherence to these criteria by one of the authors, all experienced in hepatitis C treatment. Sustained viral response at 12 weeks (SVR 12) was contrasted between those receiving 8 and those receiving 12 weeks of treatment. RESULTS Completed prescriptions for LDV/SOF, without ribavirin, as of 30 September 2015 were identified in 1021 patients. Five patients discontinued therapy due to medical reasons and 35 had incomplete follow-up viral load data, thus there were 981 evaluable patients: 377 treated for 8 weeks and 604 treated for 12 weeks. SVR 12 was virtually identical at 93.6 and 93.5%, respectively. Baseline characteristics differed between the two groups, as only treatment-naïve, non-cirrhotic, non-HIV-infected patients were eligible for an 8-week course of therapy. CONCLUSIONS Eight-week courses of LDV/SOF are comparable to 12-week courses in real-world use among selected patients supported by a multidisciplinary team.
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Affiliation(s)
- Jennifer B Lai
- Division of Infectious Diseases, Kaiser Permanente, 99 Montecillo Rd, Northern California Region, San Rafael, CA, 94903, USA
- Division of Gastroenterology, Kaiser Permanente, Northern California Region, San Rafael, CA, USA
| | - Maxwell A Witt
- Division of Infectious Diseases, Kaiser Permanente, 99 Montecillo Rd, Northern California Region, San Rafael, CA, 94903, USA
| | - Mary Patricia Pauly
- Division of Gastroenterology, Kaiser Permanente, Northern California Region, San Rafael, CA, USA
| | - Joanna Ready
- Division of Gastroenterology, Kaiser Permanente, Northern California Region, San Rafael, CA, USA
| | - Michael Allerton
- Division of Infectious Diseases, Kaiser Permanente, 99 Montecillo Rd, Northern California Region, San Rafael, CA, 94903, USA
| | - Suk Seo
- Division of Gastroenterology, Kaiser Permanente, Northern California Region, San Rafael, CA, USA
| | - David J Witt
- Division of Infectious Diseases, Kaiser Permanente, 99 Montecillo Rd, Northern California Region, San Rafael, CA, 94903, USA.
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Lai JB, Witt MA, Pauly MP, Ready J, Allerton M, Seo S, Witt DJ. Eight- or 12-Week Treatment of Hepatitis C with Ledipasvir/Sofosbuvir: Real-World Experience in a Large Integrated Health System. Drugs 2017. [PMID: 28078644 DOI: 10.1007/s40265-016-0684-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Second-generation direct-acting antiviral agents are integral to treatment of hepatitis C (HCV) infection. Eight-week courses of ledipasvir/sofosbuvir (LDV/SOF) have been supported in some studies, but data are limited on efficacy in real-world use. Controversy exists regarding applicability of clinical trials to real-world effectiveness. We report virologic responses of patients with HCV genotype 1 infection receiving LDV/SOF for 8 or 12 weeks in a large integrated healthcare system. METHODS All patients receiving LDV/SOF, without ribavirin, were identified from pharmacy records, and outcomes are reported. Only treatment-naïve patients without evidence of cirrhosis and hepatitis C viral load less than 6 million IU/ml were candidates for 8-week therapy. Treatment was at clinician discretion, but delivered by a multidisciplinary team and reviewed for appropriateness and adherence to these criteria by one of the authors, all experienced in hepatitis C treatment. Sustained viral response at 12 weeks (SVR 12) was contrasted between those receiving 8 and those receiving 12 weeks of treatment. RESULTS Completed prescriptions for LDV/SOF, without ribavirin, as of 30 September 2015 were identified in 1021 patients. Five patients discontinued therapy due to medical reasons and 35 had incomplete follow-up viral load data, thus there were 981 evaluable patients: 377 treated for 8 weeks and 604 treated for 12 weeks. SVR 12 was virtually identical at 93.6 and 93.5%, respectively. Baseline characteristics differed between the two groups, as only treatment-naïve, non-cirrhotic, non-HIV-infected patients were eligible for an 8-week course of therapy. CONCLUSIONS Eight-week courses of LDV/SOF are comparable to 12-week courses in real-world use among selected patients supported by a multidisciplinary team.
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Affiliation(s)
- Jennifer B Lai
- Division of Infectious Diseases, Kaiser Permanente, 99 Montecillo Rd, Northern California Region, San Rafael, CA, 94903, USA
- Division of Gastroenterology, Kaiser Permanente, Northern California Region, San Rafael, CA, USA
| | - Maxwell A Witt
- Division of Infectious Diseases, Kaiser Permanente, 99 Montecillo Rd, Northern California Region, San Rafael, CA, 94903, USA
| | - Mary Patricia Pauly
- Division of Gastroenterology, Kaiser Permanente, Northern California Region, San Rafael, CA, USA
| | - Joanna Ready
- Division of Gastroenterology, Kaiser Permanente, Northern California Region, San Rafael, CA, USA
| | - Michael Allerton
- Division of Infectious Diseases, Kaiser Permanente, 99 Montecillo Rd, Northern California Region, San Rafael, CA, 94903, USA
| | - Suk Seo
- Division of Gastroenterology, Kaiser Permanente, Northern California Region, San Rafael, CA, USA
| | - David J Witt
- Division of Infectious Diseases, Kaiser Permanente, 99 Montecillo Rd, Northern California Region, San Rafael, CA, 94903, USA.
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Kowdley KV, Sundaram V, Jeon CY, Qureshi K, Latt NL, Sahota A, Lott S, Curry MP, Tsai N, Chaiyakunapruk N, Lee Y, Petersen J, Buggisch P. Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection. Hepatology 2017; 65:1094-1103. [PMID: 28027579 DOI: 10.1002/hep.29005] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 11/28/2016] [Accepted: 12/15/2016] [Indexed: 12/22/2022]
Abstract
UNLABELLED Eight weeks duration of ledipasvir/sofosbuvir (LDV/SOF) can be considered in genotype 1 hepatitis C virus-infected patients who are treatment-naive, do not have cirrhosis, and have a pretreatment viral load <6,000,000 IU/mL. The effectiveness of this regimen, however, has not been fully confirmed by real-world experience. Using data from real-world cohorts, we aimed to determine the effectiveness of 8 weeks of LDV/SOF treatment, examine variables associated with relapse after treatment with this regimen, and compare the effectiveness of 8 weeks and 12 weeks of LDV/SOF treatment. To evaluate the effectiveness of 8 weeks of therapy and characteristics associated with relapse, we used individual patient data from the IFI (Institut für Interdisziplinäre Medizin), Burman's Pharmacy, and Kaiser Permanente Southern California. All patients had fibrosis staging assessed with biopsy, transient elastography, or serum biomarkers. We also performed a systematic review and meta-analysis of six additional real-world cohorts, to compare effectiveness of 8 weeks to 12 weeks duration. In our pooled data analysis, 634 patients were treated for 8 weeks with LDV/SOF, of whom all had outcomes of cure or relapse without loss to follow-up. Per protocol rates of sustained virologic response at 12 weeks were 98.1% (622/634) in the full cohort and 97.9% (571/583) among treatment-eligible patients. Exact logistic regression revealed no specific patient characteristics associated with relapse. Our meta-analysis of six additional real-world cohorts, comprised of 5,637 patients, demonstrated similar risk for relapse between 8 weeks and 12 weeks of LDV/SOF (relative risk = 0.99, 95% confidence interval 0.98-1.00). CONCLUSION An 8-week duration of treatment with LDV/SOF is highly effective in properly selected patients; greater use of this regimen is recommended. (Hepatology 2017;65:1094-1103).
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Affiliation(s)
| | - Vinay Sundaram
- Department of Medicine and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Christie Y Jeon
- Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Kamran Qureshi
- Department of Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA
| | - Nyan L Latt
- Department of Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA
| | - Amandeep Sahota
- Department of Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA
| | | | - Michael P Curry
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
| | - Naoky Tsai
- Department of Medicine, University of Hawaii, Honolulu, HI
| | - Nathorn Chaiyakunapruk
- School of Pharmacy, Monash University Malaysia, Malaysia.,Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.,School of Population Health, University of Queensland, Brisbane, Australia.,School of Pharmacy, University of Wisconsin-Madison, Madison, WI
| | | | - Jorg Petersen
- IFI Institut für Interdisziplinäre Medizin, Asklepios Klinik St. Georg, Hamburg, Germany
| | - Peter Buggisch
- IFI Institut für Interdisziplinäre Medizin, Asklepios Klinik St. Georg, Hamburg, Germany
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Naylor PH, Mutchnick M. Decreasing racial disparity with the combination of ledipasvir-sofosbuvir for the treatment of chronic hepatitis C. Hepat Med 2017; 9:13-16. [PMID: 28356778 PMCID: PMC5360405 DOI: 10.2147/hmer.s118063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
African Americans (AA) in the US are twice as likely to be infected with hepatitis C virus (HCV) compared to the non-Hispanic-white US population (Cau). They are also more likely to be infected with HCV genotype 1, more likely to develop hepatocellular carcinoma, and, in addition, have a lower response rate to interferon-based therapies. With the increase in response rates reported for combinations of direct-acting antivirals, the possibility that racial disparity would be eliminated by agents that directly inhibit virus replication has become a reality. The objective of this review is to evaluate the literature from clinical studies and retrospective analysis with respect to the response of AA to the most prescribed antiviral combination sofosbuvir plus ledipasvir. While few studies have focused on AA patients, sufficient information is availed from the literature and studies in our predominately AA clinic population to confirm that ledipasvir–sofosbuvir has a similar effectiveness in AA as compared to Cau.
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Affiliation(s)
- Paul H Naylor
- Department of Internal Medicine/Gastroenterology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Milton Mutchnick
- Department of Internal Medicine/Gastroenterology, Wayne State University School of Medicine, Detroit, MI, USA
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Current therapy for chronic hepatitis C: The role of direct-acting antivirals. Antiviral Res 2017; 142:83-122. [PMID: 28238877 PMCID: PMC7172984 DOI: 10.1016/j.antiviral.2017.02.014] [Citation(s) in RCA: 126] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 02/07/2017] [Accepted: 02/22/2017] [Indexed: 12/12/2022]
Abstract
One of the most exciting developments in antiviral research has been the discovery of the direct-acting antivirals (DAAs) that effectively cure chronic hepatitis C virus (HCV) infections. Based on more than 100 clinical trials and real-world studies, we provide a comprehensive overview of FDA-approved therapies and newly discovered anti-HCV agents with a special focus on drug efficacy, mechanisms of action, and safety. We show that HCV drug development has advanced in multiple aspects: (i) interferon-based regimens were replaced by interferon-free regimens; (ii) genotype-specific drugs evolved to drugs for all HCV genotypes; (iii) therapies based upon multiple pills per day were simplified to a single pill per day; (iv) drug potency increased from moderate (∼60%) to high (>90%) levels of sustained virologic responses; (v) treatment durations were shortened from 48 to 12 or 8 weeks; and (vi) therapies could be administered orally regardless of prior treatment history and cirrhotic status. However, despite these remarkable achievements made in HCV drug discovery, challenges remain in the management of difficult-to-treat patients.
HCV genotype-specific drugs evolve to pan-genotypic drugs. Drug potency increases from moderate (∼60%) to high (>90%) levels of sustained virologic response. Treatment durations are shortened from a 48-week to 12-week or 8-week period. HCV therapies based upon multiple pills per day are simplified to a single pill per day. HCV therapies are administered orally regardless of prior treatment history and cirrhotic status.
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Wansom T, Falade-Nwulia O, Sutcliffe CG, Mehta SH, Moore RD, Thomas DL, Sulkowski MS. Barriers to Hepatitis C Virus (HCV) Treatment Initiation in Patients With Human Immunodeficiency Virus/HCV Coinfection: Lessons From the Interferon Era. Open Forum Infect Dis 2017; 4:ofx024. [PMID: 28480293 DOI: 10.1093/ofid/ofx024] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 02/06/2017] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Hepatitis C is a major cause of mortality among human immunodeficiency virus (HIV)-infected patients, yet hepatitis C virus (HCV) treatment uptake has historically been low. Although the removal of interferon removes a major barrier to HCV treatment uptake, oral therapies alone may not fully eliminate barriers in this population. METHODS Within the Johns Hopkins Hospital HIV cohort, a nested case-control study was conducted to identify cases, defined as patients initiating HCV treatment between January 1996 and 2013, and controls, which were selected using incidence density sampling (3:1 ratio). Controls were matched to cases on date of enrollment. Conditional logistic regression was used to evaluate factors associated with HCV treatment initiation. RESULTS Among 208 treated cases and 624 untreated controls, the presence of advanced fibrosis (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.26-3.95), recent active drug use (OR, 0.36; 95% CI, 0.19-0.69), and non-black race (OR, 2.01; 95% CI, 1.26-3.20) were independently associated with initiation of HCV therapy. An increasing proportion of missed visits was also independently associated with lower odds of HCV treatment (25%-49% missed visits [OR, 0.49; 95% CI, 0.27-0.91] and ≥50% missed visits [OR, 0.24; 95% CI, 0.12-0.48]). CONCLUSIONS Interferon-free treatments may not be sufficient to fully overcome barriers to HCV care in HIV-infected patients. Interventions to increase engagement in care for HIV and substance use are needed to expand HCV treatment uptake.
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Affiliation(s)
- Tanyaporn Wansom
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Oluwaseun Falade-Nwulia
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Catherine G Sutcliffe
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shruti H Mehta
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Richard D Moore
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - David L Thomas
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mark S Sulkowski
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Use of Sofosbuvir-Based Treatment of Chronic Hepatitis C in Liver Transplant Recipients on Hemodialysis. J Clin Gastroenterol 2017; 51:167-173. [PMID: 27548734 DOI: 10.1097/mcg.0000000000000640] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The use of direct acting agents has changed the management paradigm of hepatitis C (HCV) in liver transplant (LT) recipients. However, the appropriate antiviral regimen in LT recipients on hemodialysis (HD) remains unclear. METHODS We retrospectively evaluated the safety and efficacy of sofosbuvir-based LT recipients on HD followed at the University of California Los Angeles. RESULTS Twelve LT recipients on HD were treated for recurrent HCV with sofosbuvir-based therapy. Indications for antiviral therapy included fibrosing cholestatic hepatitis, symptomatic cryoglobulinemia, and recurrent HCV. The causes of renal failure included hepatorenal syndrome, acute tubular necrosis and cryoglobulinemia. Of those who were not on dialysis at the time of transplantation, the mean creatinine (±SD) was 1.7 (±0.8) mg/dL. The mean age (±SD) of the cohort was 62.2 (±6.0) years. Most recipients were male (67%) and infected with genotype 1 (83%). Baseline alanine aminotransferase, total bilirubin, hemoglobin and HCV RNA values (±SD) were 53.2 (±59.4) IU/L, 3.2 (±5.5) mg/dL, 10.5 (±1.8) g/dL, and 30,499,500 (±29,655,754) IU/mL. HCV RNA levels were undetectable in all recipients at the end of therapy. The trough mean (±SD) hemoglobin of patients on treatment and on HD was 8.4 (±2.3). The sustained viral response was 58% (7/12), and the overall patient survival was 42%. All the deaths occurred a mean (±SD) after 5.4 (±3.6) months after treatment was completed. CONCLUSIONS All patients achieved viral suppression from therapy, and over half the recipients achieved a sustained virological response. A high mortality underscores the necessity of starting antiviral treatment sooner in LT recipients and the need for larger cohort studies.
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Su F, Green PK, Berry K, Ioannou GN. The association between race/ethnicity and the effectiveness of direct antiviral agents for hepatitis C virus infection. Hepatology 2017; 65:426-438. [PMID: 27775854 PMCID: PMC6535089 DOI: 10.1002/hep.28901] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 09/28/2016] [Accepted: 10/12/2016] [Indexed: 12/14/2022]
Abstract
Black race and Hispanic ethnicity were associated with lower rates of sustained virologic response (SVR) to interferon-based treatments for chronic hepatitis C virus infection, whereas Asian race was associated with higher SVR rates compared to white patients. We aimed to describe the association between race/ethnicity and effectiveness of new direct-acting antiviral regimens in the Veterans Affairs health care system nationally. We identified 21,095 hepatitis C virus-infected patients (11,029 [52%] white, 6,171 [29%] black, 1,187 [6%] Hispanic, 348 [2%] Asian/Pacific Islander/American Indian/Alaska Native, and 2,360 [11%] declined/missing race or ethnicity) who initiated antiviral treatment with regimens containing sofosbuvir, simeprevir + sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ombitasvir/ritonavir/dasabuvir during the 18-month period from January 1, 2014, to June 30, 2015. Overall SVR rates were 89.8% (95% confidence interval [CI] 89.2-90.4) in white, 89.8% (95% CI 89.0-90.6) in black, 86.0% (95% CI 83.7-88.0) in Hispanic, and 90.7% (95% CI 87.0-93.5) in Asian/Pacific Islander/American Indian/Alaska Native patients. However, after adjustment for baseline characteristics, black (adjusted odds ratio = 0.77, P < 0.001) and Hispanic (adjusted odds ratio = 0.76, P = 0.007) patients were less likely to achieve SVR than white patients, a difference that was not explained by early treatment discontinuations. Among genotype 1-infected patients treated with ledipasvir/sofosbuvir monotherapy, black patients had significantly lower SVR than white patients when treated for 8 weeks but not when treated for 12 weeks. CONCLUSION Direct-acting antivirals produce high SVR rates in white, black, Hispanic, and Asian/Pacific Islander/American Indian/Alaska Native patients; but after adjusting for baseline characteristics, black race and Hispanic ethnicity remain independent predictors of treatment failure. Short 8-week ledipasvir/sofosbuvir monotherapy regimens should perhaps be avoided in black patients with genotype 1 hepatitis C virus. (Hepatology 2017;65:426-438).
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Affiliation(s)
- Feng Su
- Division of Gastroenterology/Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, WA
| | - Pamela K Green
- Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA
| | - Kristin Berry
- Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA
| | - George N Ioannou
- Division of Gastroenterology/Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, WA
- Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, WA
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Yang Y, Dang SS. Safety of direct antiviral agents for treatment of hepatitis C virus infection. Shijie Huaren Xiaohua Zazhi 2017; 25:659. [DOI: 10.11569/wcjd.v25.i8.659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Nirei K, Nakamura H, Matsuoka S, Yamana Y, Yoda S, Hirayama A, Moriyama M. Ventricular Tachycardia as a Complication of Ledipasvir and Sofosbuvir Treatment for HCV Infection. Intern Med 2017; 56:787-790. [PMID: 28381744 PMCID: PMC5457921 DOI: 10.2169/internalmedicine.56.7948] [Citation(s) in RCA: 12] [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] [Indexed: 01/15/2023] Open
Abstract
We experienced two patients with serious arrhythmias associated with the administration of ledipasvir (LDV) and sofosbuvir (SOF). Neither patient took amiodarone, an agent for which concomitant use is prohibited. One patient was 82 years old and hypertensive; the other was 72 years old and had no cardiovascular risk factors such as hypertension or diabetes mellitus. The arrhythmias were both serious ventricular tachycardia (VT) that converted spontaneously to sinus rhythm, without treatment, and both patients had good outcomes. These cases suggest that LDV/SOF may be associated with an increased risk of heart-related events.
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Affiliation(s)
- Kazushige Nirei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Japan
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Horsley-Silva JL, Vargas HE. New Therapies for Hepatitis C Virus Infection. Gastroenterol Hepatol (N Y) 2017; 13:22-31. [PMID: 28420944 PMCID: PMC5390323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Approximately 350 million people worldwide are infected with hepatitis C virus (HCV), which is associated with morbidity and mortality related to cirrhosis, hepatocellular carcinoma, or liver failure. Recently, vast improvements have been made with the development of direct-acting antiviral (DAA) agents, which are all-oral, are better tolerated than interferon-based treatment, and provide a sustained virologic response in more than 90% of treated patients. This article reviews the new therapies available for HCV infection, with a focus on patients who have chronic HCV with and without compensated cirrhosis. As DAA development continues, more attention will need to be given to special patient populations, specifically to patients who fail treatment due to emerging resistant strains. Considerable challenges yet to be overcome are incremental diagnosis of unidentified patients and linkage to care that is affordable and available to all patients.
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Affiliation(s)
- Jennifer L Horsley-Silva
- Dr Horsley-Silva is a senior gastroenterology fellow and Dr Vargas is a professor of medicine in the Division of Gastroenterology and Hepatology at the Mayo Clinic in Phoenix, Arizona
| | - Hugo E Vargas
- Dr Horsley-Silva is a senior gastroenterology fellow and Dr Vargas is a professor of medicine in the Division of Gastroenterology and Hepatology at the Mayo Clinic in Phoenix, Arizona
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Abstract
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections affect millions of persons around the globe and cause profound morbidity and mortality. A major intersection exists between these two epidemics, with HCV infection being more common in persons with HIV than in the general population, largely due to shared routes of transmission. HCV co-infection increases risk for liver- and non-liver-related morbidity and mortality, making HCV treatment a priority in HIV co-infected persons, but the treatment of HCV in co-infected patients has been daunting for multiple reasons. Until recently, HCV treatment has frequently been deferred due to the low rates of cure, significant adverse effects, burdensome duration of therapy and drug-drug interactions with HIV antiretroviral medications. Untreated HCV has resulted in significant health consequences for the millions of those infected and has led to multiple downstream impacts on our healthcare systems around the world. The development of a remarkable number of new HCV direct-acting agents (DAAs) that are significantly more efficacious and tolerable than the previous interferon-based regimens has transformed this important field of medicine, with the potential to dramatically reduce the burden of infection and improve health outcomes in this population. This review will summarize the epidemiology and clinical impact of HIV/HCV co-infection and current approaches to the treatment of HCV in HIV/HCV co-infected patients.
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Affiliation(s)
- Jake A. Scott
- Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Kara W. Chew
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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Werner CR, Schwarz JM, Egetemeyr DP, Beck R, Malek NP, Lauer UM, Berg CP. Second-generation direct-acting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVR12. World J Gastroenterol 2016; 22:8050-8059. [PMID: 27672299 PMCID: PMC5028818 DOI: 10.3748/wjg.v22.i35.8050] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2016] [Revised: 07/21/2016] [Accepted: 08/10/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To gather data on the antiviral efficacy and safety of second generation direct acting antiviral (DAA) treatment with respect to sustained virological response (SVR) 12 wk after conclusion of treatment, and to determine predictors of SVR12 in this setting.
METHODS Two hundred and sixty patients treated with SOF combination partners PR (n = 51), R (n = 10), SMV (n = 30), DCV (n = 81), LDV (n = 73), or 3D (n = 15). 144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets < 100/nL, 25/260 had a MELD score ≥ 10 and 17/260 were post-liver transplantation patients. 194/260 had HCV GT1, 44/260 HCV GT3.
RESULTS Two hundred and forty/256 (93.7%) patients achieved SVR12 (mITT); 4/260 were lost to follow-up. SVR12 rates for subgroups were: 92% for SOF/DCV, 93% for each SOF/SMV, SOF/PR, 94% for SOF/LDV, 100% for 3D, 94% for pretreated, 87% for liver cirrhosis, 82% for patients with platelets < 100/nL, 88% post-liver transplantation, 95% for GT1a, 93% for GT1b, 90% for GT3, 100% for GT2, 4, and 6. 12 patients suffered from relapse, 6 prematurely discontinued treatment, of which 4 died. Negative predictors of SVR12 were a platelet count < 100/nL, MELD score ≥ 10 (P < 0.0001), liver cirrhosis (P = 0.005) at baseline. In Interferon-free treatment GT3 had significantly lower SVR rates than GT1 (P = 0.016). Side effects were mild.
CONCLUSION Excellent SVR12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into “real-world”. Patients with advanced liver disease, signs of portal hypertension, especially with platelets < 100/nL and patients with GT3 are in special need for further research efforts to overcome comparatively higher rates of virological failure.
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Ingiliz P, Christensen S, Kimhofer T, Hueppe D, Lutz T, Schewe K, Busch H, Schmutz G, Wehmeyer MH, Boesecke C, Simon KG, Berger F, Rockstroh JK, Schulze zur Wiesch J, Baumgarten A, Mauss S. Sofosbuvir and Ledipasvir for 8 Weeks for the Treatment of Chronic Hepatitis C Virus (HCV) Infection in HCV-Monoinfected and HIV-HCV-Coinfected Individuals: Results From the German Hepatitis C Cohort (GECCO-01). Clin Infect Dis 2016; 63:1320-1324. [PMID: 27535952 DOI: 10.1093/cid/ciw567] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Accepted: 08/04/2016] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Shortening the duration of treatment with HCV direct-acting antivirals (DAAs) leads to substantial cost reductions. According to the label, sofosbuvir and ledipasvir can be prescribed for 8 weeks (SL8) in noncirrhotic women or men with HCV genotype 1 and low viral loads. However, real-world data about the efficacy and safety of SL8 are largely missing. METHODS Interim results from an ongoing prospective, multicenter cohort of 9 treatment centers in Germany (GECCO). All patients started on treatment with HCV DAAs since January 2014 were included. This report describes safety and efficacy outcomes in 210 patients with HCV monoinfection and 35 with human immunodeficiency virus (HIV)-HCV coinfection given SL8 in a real-world setting. RESULTS Of 1353 patients included into the GECCO cohort until December 2015, a total of 1287 had complete data sets for this analysis; 337 (26.2%) fulfilled the criteria for SL8 according to the package insert, but only 193 (57.2%) were eventually treated for 8 weeks. Another 52 patients did not fulfill the criteria but were treated for 8 weeks. SL8 was generally well tolerated. The overall sustained virologic response rate 12 weeks after the end of treatment was 93.5% (186 of 199). The on-treatment response rate was 99.4% (159 of 160) in HCV-monoinfected and 96.4% (27 of 28) in HIV-HCV-coinfected patients. Ten patients were lost to follow-up. CONCLUSIONS SL8 seems highly effective and safe in well-selected HCV-monoinfected and HIV-HCV-coinfected patients in a real-world setting.
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Affiliation(s)
| | | | - Torben Kimhofer
- Faculty of Medicine, Department of Surgery and Cancer, Imperial College London, United Kingdom
| | | | | | | | | | | | - Malte H Wehmeyer
- Ambulanzzentrum Virushepatologie, University Medical Center Hamburg-Eppendorf and DZIF Partner Site, Hamburg
| | - Christoph Boesecke
- Medical Department I, University Hospital, Bonn.,Klinische Arbeitsgemeinschaft AIDS, Bonn
| | | | | | | | - Julian Schulze zur Wiesch
- Ambulanzzentrum Virushepatologie, University Medical Center Hamburg-Eppendorf and DZIF Partner Site, Hamburg
| | | | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Duesseldorf
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