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Brzdęk M, Zarębska-Michaluk D, Invernizzi F, Cilla M, Dobrowolska K, Flisiak R. Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C. World J Gastroenterol 2023; 29:949-966. [PMID: 36844142 PMCID: PMC9950869 DOI: 10.3748/wjg.v29.i6.949] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/22/2022] [Accepted: 01/09/2023] [Indexed: 02/10/2023] Open
Abstract
Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.
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Affiliation(s)
- Michał Brzdęk
- Collegium Medicum, Jan Kochanowski University, Kielce 25-516, Poland
| | | | - Federica Invernizzi
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | - Marta Cilla
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, Milan 20-132, Italy
| | | | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland
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Lee J, Ahn SB, Yim SY, An J, Jun DW, Ko MJ, Park DA, Yoo JJ. Efficacy and safety of direct-acting antiviral therapy for hepatitis C virus in elderly patients (≥65 years old): A systematic review and meta-analysis. J Viral Hepat 2022; 29:496-517. [PMID: 35357774 DOI: 10.1111/jvh.13679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 02/07/2022] [Accepted: 03/11/2022] [Indexed: 12/09/2022]
Abstract
Direct-acting agents (DAAs) have launched a new era of hepatitis C virus (HCV) treatment. As aged individuals comprise a large percentage of HCV-infected patients, the effectiveness and safety of DAAs in the elderly have come under scrutiny. This meta-analysis aimed to evaluate the efficacy and safety of DAAs in elderly patients. After a systematic search in PubMed (MEDLINE), Embase, OVID MEDLINE, the Cochrane Library and other databases, two investigators reviewed relevant abstracts and selected manuscripts for examination. The sustained virologic response (SVR) and adverse event (AE) rates were calculated with a random-effects model. Ninety studies evaluating SVR rates of elderly patients (≥65 years old) receiving DAAs were selected. DAAs in elderly patients exhibited a notable SVR rate of 96% (95% confidence interval [CI]: 95%-97%), accompanied by comparable rates in subgroup analyses. The comparison of SVR rates in elderly and non-elderly patients indicated no significant discrepancy (odds ratio [OR] 1.01, 95% CI: 1.00-1.01). The overall event rate of AEs was 45% (95% CI: 31%-60%), though AE rates varied by subgroups. Furthermore, AEs were comparatively more frequent (OR 1.15, 95% CI: 1.04-1.28) in the elderly than non-elderly, especially in subgroups such as SAE (OR 1.89, 95% CI: 1.52-2.36) and dose reduction in ribavirin (OR 1.90, 95% CI: 1.53-2.36). However, in the ribavirin (RBV)-free regimen, there was no significant difference in the incidence of AEs between the elderly and non-elderly groups. DAAs have high efficacy in elderly patients. Considering the possibility of AE, the RBV-free regimen should be given prior consideration for the treatment of elderly patients with HCV.
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Affiliation(s)
- Jieun Lee
- College of Medicine, Soonchunhyang University, Cheonan, Korea
| | - Sang Bong Ahn
- Nowon Eulji Medical Center, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University Hospital, Seoul, Korea
| | - Jihyun An
- Gastroenterology and Hepatology, Hanyang University College of Medicine, Guri, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Min Jung Ko
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Dong Ah Park
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
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Effectiveness and Safety of Sofosbuvir/Velpatasvir/Voxilaprevir as a Hepatitis C Virus Infection Salvage Therapy in the Real World: A Systematic Review and Meta-analysis. Infect Dis Ther 2022; 11:1661-1682. [PMID: 35749010 PMCID: PMC9334482 DOI: 10.1007/s40121-022-00666-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 06/08/2022] [Indexed: 11/28/2022] Open
Abstract
Introduction Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) is the first direct-acting antiviral (DAA) therapy approved for patients who have previously failed a DAA-containing regimen including NS5A inhibitors. In clinical trials, SOF/VEL/VOX was associated with high rates of sustained virologic response at post-treatment week 12 (SVR12) and was well tolerated. However, the effectiveness and safety of SOF/VEL/VOX in the real world remained uncertain. We aimed to perform a systematic review and meta-analysis to assess the real world effectiveness and safety of SOF/VEL/VOX. Methods We systematically searched the PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases for relevant real world studies published before January 28, 2022. Patients with previous treatment failure who received SOF/VEL/VOX were included. The primary outcome was the percentage of patients achieving SVR12. Secondary outcome included adverse events (AEs) during treatment. Results Fifteen studies with a total of 1796 HCV-infected patients with previous treatment failure were included. SVR12 rates were 93% (95% CI 91–95) in the ITT populations (n = 1517, 11 cohorts) and 96% (95% CI 95–97) in the PP populations (n = 1187, 10 cohorts). SVR12 rates were significantly higher in non-GT3-infected patients (OR = 2.29, 95% CI 1.23–4.27, P = 0.009) and non-cirrhotic patients (OR = 2.22, 95% CI 1.07–4.60, P = 0.03) than in GT3-infected patients and cirrhotic patients. Furthermore, the SVR12 rates of previous treatment of SOF/VEL were significantly lower than those of other regimens in both ITT and PP populations (P ≤ 0.001). Adverse events (AEs) were reported in 30% (228/760) of patients. Serious AEs (SAEs) were reported in 3.82% (29/760) of patients. The most frequently reported AEs were headache, asthenia, nausea, fatigue, and diarrhea, which were mostly mild in severity. AE-related treatment discontinuations were reported in 0.66% (5/760) of patients. Conclusions Consistent with clinical trials, the real world evidence indicates that SOF/VEL/VOX is a well-tolerated and highly effective salvage therapy for HCV-infected patients with previous treatment failure. However, there may still be a risk of treatment failure for patients with GT3 infection, cirrhosis, or SOF/VEL treatment failure. The protocol of this study was registered at PROSPERO, registration no. CRD 42022306828.
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Evolution of Hepatitis C Virus Treatment During the Era of Sofosbuvir-Based Therapies: A Real-World Experience in France. Dig Dis Sci 2021; 66:881-898. [PMID: 32303953 DOI: 10.1007/s10620-020-06234-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 03/24/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Treatment of hepatitis C virus (HCV) has been dramatically improved with the introduction of direct-acting antiviral agents (DAAs). Universal access to pangenotypic DAAs was provided in France from 2017, expanding the type of patients treated. Real-world studies are important to confirm effectiveness and safety in clinical practice, particularly in vulnerable populations. AIMS To assess real-world effectiveness and safety of sofosbuvir-based therapy in adults with chronic HCV infection before and after universal access to DAAs in France. METHODS This multicenter, non-interventional, prospective study assessed the effectiveness, safety, patient-reported outcomes and adherence with sofosbuvir-based regimens from October 2015 to July 2016 (Period 1: sofosbuvir-based therapy excluding sofosbuvir/velpatasvir) and from October 2017 to July 2018 (Period 2: pangenotypic sofosbuvir/velpatasvir-based therapy). RESULTS Baseline data were documented for 1029 patients. Overall, 797 (77%) had sustained virologic response data available ≥ 9 weeks after treatment completion. Per protocol response was high (97%) irrespective of age, alcohol consumption, recreational drug use, or HIV/HCV coinfection. Adverse events occurred in approximately 25% of patients with the majority experiencing Grade 1 or 2 events. Sofosbuvir-based regimens improved health-related quality of life from baseline to end of treatment in patients with data at all timepoints. Overall, 99% of patients reported total or almost total adherence to therapy. CONCLUSIONS Sofosbuvir-based therapy, including pangenotypic sofosbuvir/velpatasvir, is effective for the treatment of HCV in real-world clinical practice. This is an important step towards HCV elimination.
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Mizokami M, Liu LJ, Fujiyama N, Littman M, Yuan J, Sekiya T, Hedskog C, Ng LJ. Real-world safety and effectiveness of ledipasvir/sofosbuvir for the treatment of chronic hepatitis C virus genotype 1 in Japan. J Viral Hepat 2021; 28:129-141. [PMID: 32869924 DOI: 10.1111/jvh.13395] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 08/15/2020] [Accepted: 08/17/2020] [Indexed: 01/06/2023]
Abstract
As patients with chronic hepatitis C virus (HCV) tend to be older and/or have advanced liver disease in Japan, real-world data are needed to evaluate safe and effective treatment options. The study aim was to assess safety and effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in a real-world cohort of Japanese patients with HCV genotype (GT) 1 infection overall and by patient subgroups: elderly, compensated cirrhotic, advanced fibrotic and those with hepatocellular carcinoma (HCC). A large prospective observational study was conducted, enrolling adult patients treated for HCV GT1 infection with LDV/SOF at clinical sites across Japan. Patients were observed for safety outcomes during and 4 weeks after treatment, and for sustained virologic response at 12-weeks post-treatment (SVR12). Incidence rates (IRs) of adverse drug reactions (ADRs) and serious ADRs (SADRs) and SVR12 rates were assessed overall and by subgroups. ADR and SADR IRs were low (2.26 and 0.17 per 100 person-months, respectively) and did not significantly differ in elderly patients or those with presence of compensated cirrhosis, worsening fibrosis or HCC. SVR12 rates were high overall (98.5%) and across subgroups investigated (≥94%), including patients who were elderly (98.2%), treatment-experienced (97.6%), advanced fibrotic (≥95.8%), had existing NS5A resistance-associated substitutions reported pre-treatment (95.0%), compensated cirrhosis (95.7%), HCC (94.0%) and other chronic liver diseases (96.1%). In this large, real-world observational study of Japanese patients with HCV GT1 infection, LDV/SOF treatment resulted in low incidence of adverse events, with high real-world effectiveness, even among patients with potentially higher risks of adverse safety outcomes and treatment failure.
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Affiliation(s)
| | | | | | | | - Jason Yuan
- Gilead Sciences Inc., Foster City, CA, USA
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Noninvasive biomarkers predict improvement in liver fibrosis after successful generic DAAs based therapy of chronic hepatitis C in Egypt. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2020. [DOI: 10.1016/j.cegh.2020.04.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Mushtaq S, Mansoor A, Umar M, Khan A, Siddiqi S, Manzoor S. Direct-acting antiviral agents in the treatment of chronic hepatitis C-Real-life experience from clinical practices in Pakistan. J Med Virol 2020; 92:3475-3487. [PMID: 32129507 DOI: 10.1002/jmv.25745] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 03/01/2020] [Indexed: 02/05/2023]
Abstract
This study aims to evaluate the clinical effectiveness in terms of sustained virological response (SVR), predictors of SVR and safety of available second-generation generic direct-acting antivirals in Pakistani chronic hepatitis C patients. This is a retrospective study conducted in multiple centers of Pakistan from January 2015 to January 2019. The samples include patients infected with chronic hepatitis C virus, regardless of virus genotype, cirrhosis, or prior treatment. A total of 993 patients were included in the present study, with the majority receiving sofosbuvir with daclatasvir (95%), sofosbuvir with daclatasvir and ribavirin (4%), and sofosbuvir with ribavirin (1%). There were 96% cases of chronic hepatitis, 3% cases compensated cirrhosis, and 1% cases of decompensated cirrhosis. Genotype 3 (99.6%) was the most common genotype. Overall SVR after 12 weeks was 98% for all treatment regimens. High SVR12 was observed with sofosbuvir in combination with daclatasvir (98.5%), then sofosbuvir in combination with daclatasvir and ribavirin (90.2%) and sofosbuvir in combination with ribavirin (75%). SVR rates were high in chronic hepatitis C patients (98.2%) as compared with cirrhotic patients (92.1%) and it was high in treatment-naive (98.8%) then interferon experienced patients (90.1%). In multivariate binary logistic regression analysis, patients' education status, treatment strategy, viral load, and alanine aminotransferase had a statistically significant association with SVR at 12 weeks. No major adverse events occurred which required treatment discontinuation. Generic oral direct acting antiviralss (sofosbuvir with daclatasvir) achieved higher SVR12 rates and were well tolerated in this large real-world cohort of genotype 3 infected patients.
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Affiliation(s)
- Saima Mushtaq
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | - Atika Mansoor
- Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan
| | - Muhammad Umar
- Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi Medical College and Allied Hospitals, Rawalpindi, Pakistan
| | - Amjad Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | - Saima Siddiqi
- Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan
| | - Sobia Manzoor
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
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Mushtaq S, Akhter TS, Khan A, Sohail A, Khan A, Manzoor S. Efficacy and Safety of Generic Sofosbuvir Plus Daclatasvir and Sofosbuvir/Velpatasvir in HCV Genotype 3-Infected Patients: Real-World Outcomes From Pakistan. Front Pharmacol 2020; 11:550205. [PMID: 32982753 PMCID: PMC7493013 DOI: 10.3389/fphar.2020.550205] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 08/17/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Direct-acting antivirals (DAAs) therapeutic regimens are highly effective against chronic hepatitis C virus (HCV) infection. However, HCV patients with genotype 3 (GT3) respond in a suboptimal way. This study aims to identify which of the DAAs-based therapeutic regimens are the best option for GT3. METHODS Multiple governments and private tertiary care hospitals were involved in this real-life study of HCV-GT3 patients treated with DAAs. The efficacy and safety of generic sofosbuvir+daclatasvir±ribavirin (SOF+DCV±RBV) and sofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) were assessed under the National Hepatitis C Program of Pakistan. RESULTS Out of 1,388 participants, 70% of patients received SOF+DCV in government tertiary care hospitals and 30% received SOF/VEL in private tertiary care hospitals. The overall sustained virological responses (SVR) was 95.5%. The SVR rates at 12 weeks were comparable between SOF+DCV (94.4%) and SOF/VEL (94.7%) in chronic HCV patients. However, The SVR rates at 24 weeks were high in cirrhotic patients treated with SOF/VEL+RBV (88%) then SOF+DCV+RBV (83%). Non-responders were high in SOF-DCV than SOF-VEL (4.1 vs 3.8%, P = 0.05) regimen. In multivariate models, the significant predictors of non-SVR were age >60 years (odds ratio [OR] 4.46; 95% CI, 2.35-8.46, P = <0.001) and cirrhosis (OR 53.91; 95% CI, 26.49-109.6, P = <0.001). Skin rash (51 vs 44%) and oral ulcers (45 vs 40%) were high in patients receiving SOF-DCV then SOF-VEL. CONCLUSIONS Overall, the generic SOF+DCV ±RBV and SOF/VEL ± RBV achieved equally high SVR12 rates. However, SOF/VEL+RBV achieved a high SVR rate in cirrhotic patients then SOF+DCV+RBV. Old age and cirrhosis were significant predictors of reduced odds of SVR regardless of the regimen. Furthermore, the regimens were well tolerated in chronic HCV patients.
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Affiliation(s)
- Saima Mushtaq
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | - Tayyab Saeed Akhter
- Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi Medical College and Allied Hospitals, Rawalpindi, Pakistan
| | - Amjad Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | - Aamir Sohail
- Department of Medicine, Karachi Institute of Medical Sciences, Combined Military Hospital, Karachi, Pakistan
| | - Arshad Khan
- Department of Neurosurgery, Medical Teaching Institution, Lady Reading Hospital, Peshawar, Pakistan
| | - Sobia Manzoor
- Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
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Butt AA, Yan P, Shaikh OS, Lo Re V, Abou-Samra AB, Sherman KE. Treatment of HCV reduces viral hepatitis-associated liver-related mortality in patients: An ERCHIVES study. J Hepatol 2020; 73:277-284. [PMID: 32145260 DOI: 10.1016/j.jhep.2020.02.022] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 02/06/2020] [Accepted: 02/18/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown. METHODS We identified HCV-positive individuals treated for HCV, and propensity score-matched them to HCV-positive/untreated and HCV-uninfected individuals in ERCHIVES between 2002-2016. We extracted cause of death data from the National Center for Health Statistics' National Death Index. Viral hepatitis-associated liver-related mortality rates among treated and untreated HCV-infected persons were calculated by treatment and attainment of sustained virologic response (SVR). RESULTS Among 50,674 HCV-positive/treated (Group A), 31,749 HCV-positive/untreated (Group B) and 73,526 HCV-uninfected persons (Group C), 8.6% in Group A, 35.0% in Group B, and 14.3% in Group C died. Among those who died, viral hepatitis-associated liver-related mortality rates per 100 patient-years (95% CI) were: 0.28 (0.27-0.30) for Group A; 1.44 (1.38-1.49) for Group B; and 0.06 (0.05-0.06) for Group C; (p <0.0001 for both comparisons). Among HCV-positive/treated persons, rates were 0.06 (0.05-0.06) for those with SVR vs. 0.78 (0.74-0.83) for those without SVR. In competing risks Cox proportional hazards analysis, treatment with all-oral DAA regimens (adjusted hazard ratio 0.11; 95% CI 0.09-0.14) and SVR (adjusted hazard ratio 0.10; 95% CI 0.08-0.11) were associated with reduced hazards of liver-related mortality. CONCLUSIONS Treatment for HCV is associated with a significant reduction in viral hepatitis-associated liver-related mortality, which is particularly pronounced in those treated with DAA regimens and those who attain SVR. This may account for a significant proportion of the reduction in all-cause mortality reported in previous studies. LAY SUMMARY Treating hepatitis C virus (HCV) infection is known to reduce overall mortality. However, whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications was previously unknown. Herein, we show that while treating HCV with direct-acting antiviral regimens has numerous extrahepatic benefits, a significant benefit can be attributed specifically to the reduction in liver-related mortality.
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Affiliation(s)
- Adeel Ajwad Butt
- VA Pittsburgh Healthcare System, Pittsburgh, PA; Weill Cornell Medical College, New York, NY and Doha, Qatar; Hamad Medical Corporation, Doha, Qatar.
| | - Peng Yan
- VA Pittsburgh Healthcare System, Pittsburgh, PA
| | | | - Vincent Lo Re
- University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
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Lampertico P, Carrión JA, Curry M, Turnes J, Cornberg M, Negro F, Brown A, Persico M, Wick N, Porcalla A, Pangerl A, Crown E, Larsen L, Yu Y, Wedemeyer H. Real-world effectiveness and safety of glecaprevir/pibrentasvir for the treatment of patients with chronic HCV infection: A meta-analysis. J Hepatol 2020; 72:1112-1121. [PMID: 32061651 DOI: 10.1016/j.jhep.2020.01.025] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 12/19/2019] [Accepted: 01/15/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Glecaprevir/pibrentasvir is approved for treating adults infected with HCV genotypes 1-6. In clinical trials, glecaprevir/pibrentasvir was associated with high rates of sustained virologic response at post-treatment week 12 (SVR12) and was well tolerated. A systematic review and meta-analysis of the real-world effectiveness and safety of glecaprevir/pibrentasvir were undertaken. METHODS Real-world studies reporting SVR12 in adults with HCV infection (n ≥20) treated with glecaprevir/pibrentasvir were identified in journal publications from January 1, 2017, to February 25, 2019, and congress presentations through April 14, 2019. Random-effects meta-analysis was used to determine SVR12 rates using data from ≥2 cohorts; intention-to-treat (ITT) analyses included patients treated with glecaprevir/pibrentasvir who had SVR12 data available, discontinued early, or were lost to follow-up; modified ITT (mITT) analyses excluded those with non-virologic failure. Naïve pooling was used to calculate adverse event (AE) rates. RESULTS Overall, 12,531 adults were treated with glecaprevir/pibrentasvir (18 cohorts). Of patients with post-treatment week 12 data, SVR12 rates were 96.7% (95% CI 95.4-98.1) in the ITT population (n = 8,583, 15 cohorts) and 98.1% (95% CI 97.1-99.2) in the mITT population (n = 7,001, 14 cohorts). SVR12 rates were ≥95% across subgroups (HCV genotype, cirrhosis status, treatment history, treatment duration, on-label treatment, and subgroups of interest). AEs were reported in 17.7% (1,271/7,199) of patients (8 cohorts). Serious AEs were reported in 1.0% (55/5,522) of patients (6 cohorts). The most frequent AEs were pruritus, fatigue, and headache. AE-related treatment discontinuations were reported in 0.6% (33/5,595) of patients (6 cohorts). CONCLUSIONS Consistent with clinical trials, real-world evidence indicates that glecaprevir/pibrentasvir is a well-tolerated and highly effective pangenotypic treatment for a broad range of HCV-infected patients. LAY SUMMARY It is important to assess treatments for hepatitis C virus (HCV) in the real world, as patient populations tend to be more diverse and potentially less adherent to treatment compared to those in clinical trials. Results from 18 studies performed in real-world clinics were pooled and analyzed to investigate the effectiveness and safety of a direct-acting antiviral combination (glecaprevir/pibrentasvir) in routine clinical practice. This analysis showed that glecaprevir/pibrentasvir is highly effective and well tolerated across all HCV genotypes and patient groups studied. It also showed that results seen in the real world are similar to the results seen in clinical trials, even in patients historically considered more challenging to treat.
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Affiliation(s)
- Pietro Lampertico
- CRC "A. M. and A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
| | - Jose A Carrión
- Liver Section, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), HepaC cohort, UAB (Universitat Autonoma de Barcelona), Barcelona, Spain
| | - Michael Curry
- Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Juan Turnes
- Department of Gastroenterology and Hepatology, C.H.U. Pontevedra & IIS Galicia Sur, HepaC cohort, Spain
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Francesco Negro
- Divisions of Gastroenterology and Hepatology and of Clinical Pathology, University Hospital, Geneva, Switzerland
| | - Ashley Brown
- Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | | | | | | | | | | | - Yao Yu
- AbbVie Inc., North Chicago, IL, USA
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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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12
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Wilton J, Wong S, Yu A, Ramji A, Cook D, Butt ZA, Alvarez M, Binka M, Darvishian M, Jeong D, Bartlett SR, Pearce ME, Adu PA, Yoshida EM, Krajden M, Janjua NZ. Real-world Effectiveness of Sofosbuvir/Velpatasvir for Treatment of Chronic Hepatitis C in British Columbia, Canada: A Population-Based Cohort Study. Open Forum Infect Dis 2020; 7:ofaa055. [PMID: 32154326 PMCID: PMC7052750 DOI: 10.1093/ofid/ofaa055] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/12/2020] [Indexed: 12/12/2022] Open
Abstract
Background Clinical trials show high efficacy of sofosbuvir/velpatasvir (SOF/VEL), but there are limited data from “real-world” settings. We aimed to evaluate SOF/VEL effectiveness for all hepatitis C virus (HCV) genotypes (GTs) in British Columbia (BC), Canada. Methods We used the BC Hepatitis Testers Cohort, which includes all HCV cases in the province (1990–2015) linked to administrative databases, including prescriptions to end of 2018. We measured sustained virologic response (SVR; negative RNA ≥10 weeks after treatment end) and identified characteristics associated with non-SVR. Conservatively, we excluded individuals with no assessment for SVR if their last RNA test after treatment initiation was negative (but included if positive). Results Of 2821 eligible participants, most were infected with GT1 (1076, 38.1%) or GT3 (1072, 38.0%), and a minority (278, 9.9%) were treated with RBV. SVR was 94.6% (2670/2821) overall and 94.5% (1017/1076) for GT1, 96.4% (512/531) for GT2, and 93.7% (1004/1072) for GT3. When disaggregated by GT, treatment regimen, and cirrhosis/treatment experience, SVR was lowest (30/40, 75.0%) among treatment-experienced GT3 individuals treated with RBV. Characteristics associated with non-SVR in multivariable analysis included younger age, RBV addition, and being a person with HIV (PWH) or who injects/injected drugs (PWID). When treatment regimen (±RBV) was removed from multivariable model, treatment experience was associated with non-SVR for GT3. Of 151 non-SVR individuals, 56.3% were nonvirological failures (treatment incomplete/no assessment for SVR) and 43.7% were virological failures (nonresponse/relapse). A disproportionately high percentage of non-SVR among PWID was due to nonvirological failure. Conclusions SOF/VEL was highly effective in this “real-world” population-based cohort. Additional support is required for PWID/PWH to reach SVR.
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Affiliation(s)
- James Wilton
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Stanley Wong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Alnoor Ramji
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Darrel Cook
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Zahid A Butt
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Public Health and Health Systems, University of Waterloo, Waterloo, Ontario, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Mawuena Binka
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Maryam Darvishian
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Cancer Control Research, BC Cancer Research Center, Vancouver, British Columbia, Canada.,Population Oncology, BC Cancer Research Center, Vancouver, British Columbia, Canada
| | - Dahn Jeong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Sofia R Bartlett
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.,Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
| | - Margo E Pearce
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Prince A Adu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Eric M Yoshida
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
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13
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Daniel KE, Saeian K, Rizvi S. Real-world experiences with direct-acting antiviral agents for chronic hepatitis C treatment. J Viral Hepat 2020; 27:195-204. [PMID: 31602715 DOI: 10.1111/jvh.13218] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 08/12/2019] [Accepted: 09/03/2019] [Indexed: 12/16/2022]
Abstract
As direct-acting antiviral (DAA) agents become more readily available for the treatment of chronic hepatitis C, it is important to understand real-world treatment experiences. In order to assess the effectiveness of DAA regimens and factors that influence sustained virologic response (SVR) rates in the Veterans Affairs healthcare system, we retrospectively identified veterans with chronic hepatitis C who were treated with DAAs from January 2014 to June 2015. We determined SVR rates and collected data on demographics, genotype (GT), previous interferon-based treatment, antiviral regimens, and co-morbidities (HIV, prior solid organ transplant, haemodialysis) for analysis. Of 15 720 veterans, the majority were infected with genotype 1a (GT1a, 60.5%). Excluding the special populations, the overall cohort SVR rate was 92%. Compared to treatment-experienced patients, treatment-naïve patients had significantly higher SVR rates (90% vs 92%, P = .006). Subgroups associated with lower likelihood of achieving SVR-included African Americans (OR 0.79, 95% CI 0.69-0.91), GT3 (OR 0.65, CI 0.50-0.86), and cirrhosis (OR 0.91, CI 0.84-0.99) or decompensated cirrhosis (ascites: OR 0.78, CI 0.67-0.91, variceal bleed: OR 0.75, CI 0.57-0.99). The only treatment regimen independently associated with lower SVR rates was SOF+RBV+IFN (OR 0.65, CI 0.50-0.84). Special populations achieved high SVR rates: HIV 92%, haemodialysis 93%, liver transplant 96% and renal transplant 94%. In conclusion, overall SVR rates were comparable to those reported in clinical trials and carried over to historically more difficult-to-treat patients. Several patient- and treatment-related factors were identified as independent predictors of treatment failure and suggest subgroups to target for efforts to improve therapeutic strategies.
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Affiliation(s)
- Kimberly E Daniel
- Division of Gastroenterology & Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA.,Division of Gastroenterology and Hepatology, University of Wisconsin, Madison, WI, USA
| | - Kia Saeian
- Division of Gastroenterology & Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Syed Rizvi
- Division of Gastroenterology & Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
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14
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Butt AA, Yan P, Aslam S, Sherman KE, Siraj D, Safdar N, Hameed B. Hepatitis C virologic response in hepatitis B and C coinfected persons treated with directly acting antiviral agents: Results from ERCHIVES. Int J Infect Dis 2020; 92:184-188. [PMID: 31978574 DOI: 10.1016/j.ijid.2020.01.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 12/29/2019] [Accepted: 01/14/2020] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND There are scant data regarding hepatitis C (HCV) virologic response to directly acting antiviral agents (DAAs) in chronic hepatitis B (HBV) and HCV coinfected persons. HCV treatment response in those with spontaneously cleared HBV infection is unknown. METHODS All HCV infected persons treated with a DAA regimen in ERCHIVES were identified and categorized into HBV/HCV-coinfected (HBsAg, HBV DNA or both positive), HCV-monoinfected, and resolved HBV (isolated HBcAb+). SVR rates were determined and compared for all groups. Logistic regression model was used to determine factors associated with SVR. RESULTS Among 115 HCV/HBV-coinfected, 38,570 HCV-monoinfected persons, and 13,096 persons with resolved HBV, 31.6% of HCV/HBV-coinfected, 24.6% of HCV-monoinfected and 26.4% with resolved HBV had cirrhosis at baseline. SVR was achieved in 90.4% of HCV/HBV-coinfected, 83.4% of HCV-monoinfected and 84.5% of those with resolved HBV infection (P = 0.04 HCV/HBV vs. HCV monoinfected). In a logistic regression model, those with HCV/HBV were more likely to achieve SVR compared with HCV monoinfected (OR 2.25, 95% CI 1.17, 4.31). For HCV/HBV coinfected, the SVR rates dropped numerically with increasing severity of liver fibrosis (P-value non-significant). Factors associated with a lower likelihood of attaining SVR included cirrhosis at baseline (OR 0.85, 95% CI 0.80, 0.92), diabetes (OR 0.93, 95% CI 0.87, 0.99) and higher pre-treatment HCV RNA (OR 0.86, 95% CI 0.84, 0.87). CONCLUSION HBV/HCV-coinfected persons have higher overall SVR rates with newer DAA regimens. Though not statistically significant, the virologic response is graded, with decreasing SVR rates with increasing degree of liver fibrosis as determined by the FIB-4 scores.
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Affiliation(s)
- Adeel A Butt
- VA Pittsburgh Healthcare System, Pittsburgh, PA, United States; Weill Cornell Medical College, New York, NY, United States; Weill Cornell Medical College, Doha, Qatar; Hamad Medical Corporation, Doha, Qatar.
| | - Peng Yan
- VA Pittsburgh Healthcare System, Pittsburgh, PA, United States
| | - Samia Aslam
- VA Pittsburgh Healthcare System, Pittsburgh, PA, United States
| | - Kenneth E Sherman
- University of Cincinnati School of Medicine, Cincinnati, OH, United States
| | - Dawd Siraj
- University of Wisconsin School of Medicine, Madison, WI, United States
| | - Nasia Safdar
- University of Wisconsin School of Medicine, Madison, WI, United States
| | - Bilal Hameed
- University of California at San Francisco, San Francisco, CA, United States
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15
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Tsai WL, Wang CF, Cheng JS, Chen WC, Bair MJ, Lo CC. Sofosbuvir-based regimen for genotype 2 HCV infected patients in Taiwan: A real world experience. PLoS One 2020; 15:e0227424. [PMID: 31923251 PMCID: PMC6953822 DOI: 10.1371/journal.pone.0227424] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 12/18/2019] [Indexed: 12/18/2022] Open
Abstract
Background Sofosbuvir (SOF)-based regimens achieve excellent efficacy and safety in the treatment of chronic hepatitis C (CHC) with various genotypes. There are few real-world instances of the use of SOF-based regimens to treat genotype 2 CHC. This study determines the effectiveness and safety of SOF/Ribavirn (RBV), SOF/Daclatasvir (DCV) and SOF/DCV/RBV in the treatment of genotype 2 CHC patients in Taiwan. Material and methods Patients with genotype 2 CHC were treated for 12 weeks with SOF/RBV, SOF/DCV or SOF/DCV/RBV under the National Health Insurance reimbursement program in three hospitals in Taiwan. The sustained virological response at 12 weeks (SVR12) was determined. Adverse events were recorded for a safety analysis. Results A total of 467 genotype 2 CHC patients were enrolled from January to October 2018. One hundred and eleven patients (24%) had cirrhosis, including 10 patients (2.1%) with hepatic decompensation. Fifty-five patients (12%) had already experienced interferon-alpha/RBV treatment. Forty-two patients (9%) had a history of hepatocellular carcinoma (HCC) in the baseline. Three hundred and fifty-five patients received SOF/RBV, forty-seven patients received SOF/DCV and sixty-two patients received SOF/DCV/RBV. The SOF/DCV group featured a greater HCV viral load than the SOF/RBV or SOF/DCV/RBV groups. SVR12 was achieved in 94.6% of the SOF/RBV group, 95.7% of the SOF/DCV group and 96.8% of then SOF/DCV/RBV group (P = NS). Thirteen out of 352 patients (3.7%) in the SOF/RBV group, 1 out of 62 patients (1.6%) in the SOF/DCV/RBV group and 1 out of 47 patients (2.1%) in the SOF/DCV group developed virological failure. There are no differences in virological failure between the three groups (P = NS). Multi-variate analysis shows that history of HCC is an independent factor that is associated with the failure of treatment in the SOF/RBV group (odds ratio:4.905, 95% confidence interval (CI): 1.321–18.205, P = 0.017). Hemoglobin levels at 12 weeks are significantly lower in the SOF/RBV and the SOF/RBV/DCV group than in the SOF/DCV group (P<0.05). Serious adverse events (SAE) occurred in six patients (1.6%) in the SOF/RBV group and in one patient (1.6%) in the SOF/RBV/DCV group. No patients in the SOF/DCV group experienced SAE. Conclusions SOF/RBV, SOF/DCV or SOF/DCV/RBV for 12 weeks all achieve very high SVR rates and are equally effective in the treatment of genotype 2 CHC patients in the real world in Taiwan. Patients in the SOF/RBV group who have a history of HCC exhibit a lower SVR rate.
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Affiliation(s)
- Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chih-Feng Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
- * E-mail: (CCL); (MJB)
| | - Ching-Chu Lo
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
- Chung-Jen junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan
- * E-mail: (CCL); (MJB)
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16
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Niccum BA, Stine JG, Wynter JA, Kelly V, Caldwell SH, Shah NL. Success of Direct-Acting, Antiviral-Based Therapy for Chronic Hepatitis C Is Not Affected by Type 2 Diabetes. Clin Diabetes 2020; 38:40-46. [PMID: 31975750 PMCID: PMC6969670 DOI: 10.2337/cd18-0112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Chronic hepatitis C virus (HCV) is a risk factor for type 2 diabetes. In the era of interferon-based HCV therapy, type 2 diabetes was associated with decreased likelihood of sustained virologic response (SVR). Preliminary studies suggest that type 2 diabetes may not reduce the efficacy of regimens involving direct-acting antiviral (DAA) medications. We aimed to determine whether preexisting type 2 diabetes is associated with a reduced rate of SVR achieved 12 weeks after treatment of HCV with DAA-based regimens.
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Affiliation(s)
- Blake A. Niccum
- Department of Internal Medicine, Massachusetts General Hospital, Boston, MA
| | - Jonathan G. Stine
- Division of Gastroenterology and Hepatology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Javelle A. Wynter
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA
| | - Virginia Kelly
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA
| | - Stephen H. Caldwell
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA
| | - Neeral L. Shah
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA
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17
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Rolt A, Le D, Hu Z, Wang AQ, Shah P, Singleton M, Hughes E, Dulcey AE, He S, Imamura M, Uchida T, Chayama K, Xu X, Marugan JJ, Liang TJ. Preclinical Pharmacological Development of Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection. J Infect Dis 2019; 217:1761-1769. [PMID: 29373739 DOI: 10.1093/infdis/jiy039] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 01/17/2018] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C virus (HCV) is a small, single-stranded, positive-sense RNA virus that infects more than an estimated 70 million people worldwide. Untreated, persistent HCV infection often results in chronic hepatitis, cirrhosis, or liver failure, with progression to hepatocellular carcinoma. Current anti-HCV regimens comprising direct acting antivirals (DAAs) can provide curative treatment; however, due to high costs there remains a need for effective, shorter-duration, and affordable treatments. Recently, we disclosed anti-HCV activity of the cheap antihistamine chlorcyclizine, targeting viral entry. Following our hit-to-lead optimization campaign, we report evaluation of preclinical in vitro absorption, distribution, metabolism, and excretion properties, and in vivo pharmacokinetic profiles of lead compounds. This led to selection of a new lead compound and evaluation of efficacy in chimeric mice engrafted with primary human hepatocytes infected with HCV. Further development and incorporation of this compound into DAA regimens has the potential to improve treatment efficacy, affordability, and accessibility.
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Affiliation(s)
- Adam Rolt
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Derek Le
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Zongyi Hu
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Amy Q Wang
- Division of Pre-Clinical Innovations, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland
| | - Pranav Shah
- Division of Pre-Clinical Innovations, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland
| | - Marc Singleton
- Division of Pre-Clinical Innovations, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland
| | - Emma Hughes
- Division of Pre-Clinical Innovations, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland
| | - Andrés E Dulcey
- Division of Pre-Clinical Innovations, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland
| | - Shanshan He
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - Michio Imamura
- Department of Medicine and Molecular Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Japan
| | - Takuro Uchida
- Department of Medicine and Molecular Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Japan
| | - Kazuaki Chayama
- Department of Medicine and Molecular Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Japan
| | - Xin Xu
- Division of Pre-Clinical Innovations, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland
| | - Juan J Marugan
- Division of Pre-Clinical Innovations, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland
| | - T Jake Liang
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
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18
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Wu SH, Chu CJ, Su CW, Lin CC, Lee SD, Wang YJ, Lee FY, Huang YH, Hou MC. Daclatasvir plus sofosbuvir, with or without ribavirin, is highly effective for all kinds of genotype-2 chronic hepatitis-C infection in Taiwan. J Chin Med Assoc 2019; 82:693-698. [PMID: 31356562 DOI: 10.1097/jcma.0000000000000148] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Based on the previously published results, 12 weeks of sofosbuvir (SOF) 400 mg/day plus ribavirin (RBV), the current direct antiviral agent regimen reimbursed by Bureau-of National-Health-Insurance (BNHI) of Taiwan for genotype-2 chronic hepatitis C (CHC), is suboptimal in efficacy, especially for difficult-to-treat subpopulations such as liver cirrhosis, previous interferon (IFN) treatment failure, and high viral-load. This study aimed to evaluate the efficacy and safety of SOF plus daclatasvir (DCV) for Taiwanese genotype-2 CHC patients. METHODS Between March 2017 and December 2018, a total of 50 consecutive genotype-2 CHC patients who completed 12 weeks combination of SOF (400 mg/day) plus DCV (60 mg/day) with or without RBV by investigators were enrolled for analyses. When RBV was added, weight-based (800-1200 mg/day) approach was applied. Sustained virological response (SVR12) was defined by undetectable HCV RNA (<15 IU/mL) at the end and 12 weeks after completion of therapy. RESULTS The mean age was 62.0 ± 11.4 years, 16 (32.0%) of them were males and 20 (40.0%) of them failed to previous IFN. Severity of liver diseases was as follows: ≤F2 fibrosis: 24.0%; F3 fibrosis: 40.0%, Child-Pugh A cirrhosis: 30.0%; and Child-Pugh B-C cirrhosis: 6.0%. The mean baseline HCV RNA level was 6.19 ± 0.91 log10 IU/mL and 30 (60.0%) had baseline HCV RNA ≥ 2 million IU/mL. The rates of undetectable HCV RNA (<15 IU/mL) at weeks 2, 4, and end-of-treatment were 40%, 94%, and 100%, respectively. Majority (66.7%) of patients with detectable HCV RNA at week 2 belonged to low-level viremia (<50 IU/mL). Subjective adverse events (AEs) and laboratory abnormalities were more common for patients combining RBV. Grades of AEs were generally mild and all patients finished therapy without interruption. After post-treatment follow-up, all 50 patients (100%) achieved SVR12. CONCLUSION Our real-world cohort of Taiwan showed that a 12-week SOF/DCV-based treatment was well-tolerated and highly effective for genotype-2 CHC patients with or without liver cirrhosis.
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Affiliation(s)
- Sih-Hsien Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chi-Jen Chu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chung-Chi Lin
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shou-Dong Lee
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Yuan-Jen Wang
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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19
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Bach TA, Zaiken K. Outcomes of treatment with direct-acting antivirals for infection with hepatitis C virus genotypes 1-4 in an ambulatory care setting. Am J Health Syst Pharm 2019; 74:S1-S9. [PMID: 28213381 DOI: 10.2146/ajhp160567] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Outcomes with direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) genotypes 1-4 were determined. METHODS A total of 360 patients at 36 clinical sites in Massachusetts with HCV genotypes 1-4 and a prescription for at least one DAA medication between May 2011 and October 2015 were included. The primary investigator completed a retrospective and concurrent chart review, and data were collected through April 2016. RESULTS A total of 446 patients were assessed for eligibility into the study, with 86 patients excluded. The majority of patients were white males with genotype 1 infection. About half of the patients were treatment naive (TN), and 40% of patients had documented cirrhosis. TN patients without cirrhosis had the highest overall sustained virologic response (SVR) rate at 107 of 109 (98.2%), followed by treatment-experienced (TE) patients without cirrhosis at 59 of 63 (93.7%), TN patients with cirrhosis at 40 of 46 (87.0%), and TE patients with cirrhosis at 64 of 79 (81.0%) when boceprevir- and telaprevir-containing regimens were excluded. A total of 7 of 360 (1.9%) patients reported missing at least one dose of medication. Adverse drug reactions reported in the electronic medical record (EMR) were collected for analysis and included patients who received at least one dose of medication and had adequate EMR documentation. CONCLUSION In patients treated with DAAs for infection with HCV genotypes 1-4, variables favoring achievement of SVR included an age of <45 years, a body mass index of <25 kg/m2, absence of cirrhosis, a fibrosis score of 0-2, and being TN.
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Real-world safety and efficacy of paritaprevir/ritonavir/ombitasvir plus dasabuvir ± ribavirin in patients with hepatitis C virus genotype 1 and advanced hepatic fibrosis or compensated cirrhosis: a multicenter pooled analysis. Sci Rep 2019; 9:7086. [PMID: 31068655 PMCID: PMC6506536 DOI: 10.1038/s41598-019-43554-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 04/27/2019] [Indexed: 02/08/2023] Open
Abstract
Paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with or without ribavirin shows favorable results in hepatitis C virus genotype 1 (HCV-1) patients in terms of safety and efficacy, but real-world data remain limited for those with advanced hepatic fibrosis (fibrosis 3, F3) or compensated cirrhosis (F4). A total of 941 patients treated in four hospitals (the Keelung, the Linkuo, the Chiayi and the Kaohsiung Chang Gung Memorial Hospital) through a nationwide government-funded program in Taiwan were enrolled. Patients with HCV and advanced hepatic fibrosis or compensated cirrhosis received 12 weeks of PrOD in HCV-1b and 12 or 24 weeks of PrOD plus ribavirin therapy in HCV-1a without or with cirrhosis. Advanced hepatic fibrosis or compensated cirrhosis was confirmed by either ultrasonography, fibrosis index based on 4 factors (FIB-4) test, or transient elastography/acoustic radiation force impulse (ARFI). The safety and efficacy (sustained virologic response 12 weeks off therapy, SVR12) were evaluated. An SVR12 was achieved in 887 of 898 (98.8%) patients based on the per-protocol analysis (subjects receiving ≥1 dose of any study medication and HCV RNA data available at post-treatment week 12). Child-Pugh A6 (odds ratio: 0.168; 95% confidence interval (CI): 0.043–0.659, p = 0.011) was the only significant factor of poor SVR12. Fifty-four (5.7%) patients were withdrawn early from the treatment because of hepatic decompensation (n = 18, 1.9%) and other adverse reactions. Multivariate analyses identified old age (odds ratio: 1.062; 95% CI: 1.008–1.119, p = 0.024) and Child-Pugh A6 (odds ratio: 4.957; 95% CI: 1.691–14.528, p = 0.004) were significantly associated with hepatic decompensation. In conclusion, this large real-world cohort proved PrOD with or without ribavirin to be highly effective in chronic hepatitis C patients with advanced hepatic fibrosis or compensated cirrhosis. However, Child-Pugh A6 should be an exclusion criterion for first-line treatment in these patients.
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Laurain A, Metivier S, Haour G, Larrey D, Dorival C, Hezode C, Zoulim F, Marcellin P, Bourliere M, Zarski JP, Thabut D, Alric L, Ganne-Carrie N, Cales P, Bronowicki JP, Riachi G, Geist C, Causse X, Abergel A, Chazouilleres O, Mathurin P, Guyader D, Samuel D, Tran A, Loustaud-Ratti V, Petrov-Sanchez V, Diallo A, Luzivika-Nzinga C, Fontaine H, Carrat F, Pol S. Safety and efficacy of the combination simeprevir-sofosbuvir in HCV genotype 1- and 4-mono-infected patients from the French ANRS CO22 hepather cohort. BMC Infect Dis 2019; 19:300. [PMID: 30940090 PMCID: PMC6446259 DOI: 10.1186/s12879-019-3923-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 03/19/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Although real-life results of sofosbuvir/simeprevir have been extensively reported from the United States, data from other geographical areas are limited. In the French observational cohort, ANRS CO22 HEPATHER, 9432 patients were given the new oral antivirals from December 2013 to June 30, 2018. We report the results of sofosbuvir/simeprevir in genotypes 1- and 4-infected patients. METHODS Demographics and history of liver disease were collected at entry in the cohort. Clinical, adverse events, and virological data were collected throughout treatment and post-treatment follow-up. The choice of treatment duration or addition of ribavirin was left up to the physician. RESULTS Five hundred ninety-nine HCV (467 genotype 1 and 132 genotype 4) mono-infected, naïve for all oral-DAAs regimen patients were given sofosbuvir/simeprevir with (n = 63) or without ribavirin (n = 536) for 12 or 24 weeks; 56% had cirrhosis (4% decompensated) and 71% had prior treatment failure to interferon-based regimen. 7 patients (1.16%) were lost to follow-up. The overall SVR12 rate was 92.6%. The SVR12 was 90% in GT1a, 94.2% in GT1b and 91.6% in GT4 with no significant difference for genotype, treatment duration or ribavirin addition. Severity of liver disease was not associated with a lower SVR12 rate on multivariate analysis but was associated with a higher rate of severe side effects. Early treatment discontinuations were rare; no new safety signals were reported. CONCLUSION In this real life, observational, prospective cohort study, the 12-week sofosbuvir/simeprevir+/-ribavirin combination appears to be efficient and safe. TRIAL REGISTRATION Trial registration with ClinicalTrials.gov NCT01953458 .
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Affiliation(s)
- Anne Laurain
- Université Paris Descartes ; APHP, Unité d'Hépatologie, Hôpital Cochin ; INSERM U-818 et USM20, Institut Pasteur, Paris, France.
| | - Sophie Metivier
- Department of Hepatology and Gastroenterology, CHU Purpan, Toulouse, France
| | - Georges Haour
- Sorbonne Université, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, F75012, Paris, France
| | - Dominique Larrey
- Liver unit-IRB-INSERM1040, Hôpital Saint Eloi, Montpellier, France
| | - Céline Dorival
- Sorbonne Université, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, F75012, Paris, France
| | - Christophe Hezode
- Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France
| | - Fabien Zoulim
- Department of Hepatology, Hospices Civils de Lyon, INSERM U1052, Université de Lyon, Lyon, France
| | - Patrick Marcellin
- Department of Hepatology, Hôpital Beaujon, AP-HP, Université Paris-Diderot, INSERM CRB3, Clichy, France
| | - Marc Bourliere
- Department of Hepatology and Gastroenterology, Hôpital Saint Joseph, Marseille, France
| | - Jean-Pierre Zarski
- Department of Hepatology and Gastroenterology, Centre Hospitalo-Universitaire, INSERM U823, Grenoble, France
| | - Dominique Thabut
- Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM UMR-S938, Paris, France
| | - Laurent Alric
- Internal Medicine-Digestive Department CHU Purpan, UMR152, IRD, Toulouse 3 University, Toulouse, France
| | - Nathalie Ganne-Carrie
- Functional Genomics of Solid Tumors, Hepatology Unit, Hôpital Jean Verdier, Bondy, AP-HP, University Paris 13, Sorbonne Paris Cité, Bobigny; Inserm UMR-1162, F-93000, Paris, France
| | - Paul Cales
- Liver-Gastroenterology Department, CHU Angers, Angers, France
| | - Jean-Pierre Bronowicki
- Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, INSERM U954, Vandoeuvre-les-Nancy, France
| | - Ghassan Riachi
- Department of Hepatology and Gastroenterology, CHU Charles Nicolle, Rouen, France
| | - Claire Geist
- Department of Hepatology and Gastroenterology, Centre Hospitalier Régional, Metz, France
| | - Xavier Causse
- Department of Hepatology and Gastroenterology, CHR d'Orléans, Orléans, France
| | - Armand Abergel
- Department of Digestive and Hepatobiliary Diseases, Estaing University Hospital, Clermont-Ferrand, France.,UMR Auvergne University/CNRS 6284 ISIT (Image Sciences for Innovations Techniques), Clermont-Ferrand, France
| | - Olivier Chazouilleres
- Department of Hepatology, Hôpital Saint-Antoine, AP-HP, Université Pierre et Marie Curie Paris 6, Paris, France
| | - Philippe Mathurin
- Department of Hepatology and Gastroenterology, Centre Hospitalier Régional et Universitaire Claude Huriez, Lille, France
| | - Dominique Guyader
- Liver disease unit, CHU Rennes, Université de Rennes 1, INSERM U991, Rennes, France
| | - Didier Samuel
- Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, UMR-S785, Université Paris-Sud, INSERM U785, Villejuif, France
| | - Albert Tran
- Digestive Center, Centre Hospitalier Universitaire de Nice, INSERM U1065-8, Nice, France
| | - Véronique Loustaud-Ratti
- Department of Hepatology and Gastroenterology, CHU Limoges, U850 INSERM, Univ. Limoges, F-87000, Limoges, France
| | - Ventzislava Petrov-Sanchez
- ANRS (France Recherche Nord&sud Sida-hiv Hépatites), Unit for Basic and Clinical Research on Viral Hepatitis, Paris, France
| | - Alpha Diallo
- ANRS (France Recherche Nord&sud Sida-hiv Hépatites), Clinical Trial Safety and Public Health, Paris, France
| | - Clovis Luzivika-Nzinga
- Sorbonne Université, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, F75012, Paris, France
| | - Hélène Fontaine
- Université Paris Descartes ; APHP, Unité d'Hépatologie, Hôpital Cochin ; INSERM U-818 et USM20, Institut Pasteur, Paris, France
| | - Fabrice Carrat
- Sorbonne Université, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, F75012, Paris, France.,Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Unité de Santé Publique, F-75012, Paris, France
| | - Stanislas Pol
- Université Paris Descartes ; APHP, Unité d'Hépatologie, Hôpital Cochin ; INSERM U-818 et USM20, Institut Pasteur, Paris, France.
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Janjua NZ, Darvishian M, Wong S, Yu A, Rossi C, Ramji A, Yoshida EM, Butt ZA, Samji H, Chong M, Chapinal N, Cook D, Alvarez M, Tyndall M, Krajden M. Effectiveness of Ledipasvir/Sofosbuvir and Sofosbuvir/Velpatasvir in People Who Inject Drugs and/or Those in Opioid Agonist Therapy. Hepatol Commun 2019; 3:478-492. [PMID: 30976739 PMCID: PMC6442698 DOI: 10.1002/hep4.1307] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 12/14/2018] [Indexed: 12/12/2022] Open
Abstract
We evaluated the effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treating hepatitis C virus (HCV) genotype 1 and SOF/velpatasvir (SOF/VEL) for all genotypes among people who inject drugs (PWID) and those not injecting drugs and who were on or off opioid agonist therapy (OAT). Study participants comprised a population-based cohort in British Columbia, Canada. The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV from 1990 to 2016 that are integrated with medical visits, hospitalization, and prescription drug data. We classified study participants as off OAT/recent injection drug use (off-OAT/RIDU), off OAT/past IDU (off-OAT/PIDU), off OAT/no IDU (off-OAT/NIDU), on OAT/IDU (on-OAT/IDU), and on OAT/no IDU (on-OAT/NIDU). We assessed sustained virologic response (SVR) 10 weeks after HCV treatment among study groups treated with LDV/SOF or SOF/VEL until January 13, 2018. Analysis included 5,283 eligible participants: 390 off-OAT/RIDU, 598 off-OAT/PIDU, 3,515 off-OAT/NIDU, 609 on-OAT/IDU, and 171 on-OAT/NIDU. The majority were male patients (64%-74%) and aged ≥50 years (58%-85%). The SVRs for off-OAT/RIDU, off-OAT/PIDU, off-OAT/NIDU, on-OAT/IDU, and on-OAT/NIDU were 91% (355/390), 95% (570/598), 96% (3,360/3,515), 93% (567/609), and 95% (163/171), respectively. Among those with no SVR, 14 individuals died while on treatment or before SVR assessment, including 4 from illicit drug overdose. In the overall multivariable model, off-OAT/RIDU, on-OAT/IDU, male sex, cirrhosis, treatment duration <8 weeks, treatment duration 8 weeks, and treatment with SOF/VEL were associated with not achieving SVR. Conclusion: In this large real-world cohort, PWID and/or those on OAT achieved high SVRs, although slightly lower than people not injecting drugs. This finding also highlights the need for additional measures to prevent loss to follow-up and overdose-related deaths among PWID.
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Affiliation(s)
- Naveed Z. Janjua
- British Columbia Centre for Disease ControlVancouverCanada
- School of Population and Public HealthUniversity of British ColumbiaVancouverCanada
| | - Maryam Darvishian
- British Columbia Centre for Disease ControlVancouverCanada
- School of Population and Public HealthUniversity of British ColumbiaVancouverCanada
| | - Stanley Wong
- British Columbia Centre for Disease ControlVancouverCanada
| | - Amanda Yu
- British Columbia Centre for Disease ControlVancouverCanada
| | - Carmine Rossi
- British Columbia Centre for Disease ControlVancouverCanada
- School of Population and Public HealthUniversity of British ColumbiaVancouverCanada
| | - Alnoor Ramji
- Division of Gastroenterology of the Department of MedicineUniversity of British ColumbiaVancouverCanada
| | - Eric M. Yoshida
- Division of Gastroenterology of the Department of MedicineUniversity of British ColumbiaVancouverCanada
| | - Zahid A. Butt
- British Columbia Centre for Disease ControlVancouverCanada
- School of Population and Public HealthUniversity of British ColumbiaVancouverCanada
| | - Hasina Samji
- British Columbia Centre for Disease ControlVancouverCanada
- Faculty of Health SciencesSimon Fraser UniversityBurnabyCanada
| | - Mei Chong
- British Columbia Centre for Disease ControlVancouverCanada
| | - Nuria Chapinal
- British Columbia Centre for Disease ControlVancouverCanada
| | - Darrel Cook
- British Columbia Centre for Disease ControlVancouverCanada
| | - Maria Alvarez
- British Columbia Centre for Disease ControlVancouverCanada
| | - Mark Tyndall
- British Columbia Centre for Disease ControlVancouverCanada
- School of Population and Public HealthUniversity of British ColumbiaVancouverCanada
| | - Mel Krajden
- British Columbia Centre for Disease ControlVancouverCanada
- Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada
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23
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Pott-Junior H, Bricks G, Grandi G, Figueiredo Senise J, Castelo Filho A. Sofosbuvir in combination with daclatasvir or simeprevir for 12 weeks in noncirrhotic subjects chronically infected with hepatitis C virus genotype 1: a randomized clinical trial. Clin Microbiol Infect 2019; 25:365-371. [PMID: 29906601 DOI: 10.1016/j.cmi.2018.06.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 05/31/2018] [Accepted: 06/02/2018] [Indexed: 01/27/2023]
Abstract
OBJECTIVE To investigate the efficacy and safety of sofosbuvir (SOF) plus daclatasvir (DCV) or simeprevir (SMV) in a randomized, open-label, noninferiority trial of patients infected with hepatitis C virus genotype 1, who were previously unresponsive to pegylated interferon and ribavirin or were treatment naive. METHODS Patients were randomly assigned to receive SOF (400 mg once daily) plus DCV (60 mg once daily) or SMV (150 mg once daily) for 12 weeks. The analysis included all participants who received at least one dose of the study drugs. The primary endpoint was sustained virologic response 12 weeks after ending treatment (SVR12; hepatitis C virus RNA measured using COBAS TaqMan RT-PCR (lower limit of detection and quantification of 12 UI/mL)). This study was registered at ClinicalTrials.gov (NCT02624063). RESULTS A total of 125 of 127 enrolled and randomized patients started treatment (n = 65 SOF + DCV; n = 60 SOF + SMV). SVR12 was attained in 121 patients (96.8%): 65 (100%) receiving SOF + DCV (95% confidence interval (CI), 94.5 to 100) and 56 (93.3%) receiving SOF + SMV (95% CI, 83.8 to 98.2; absolute difference, 6.6%; 95% CI, -15.0 to 0). The most common adverse events were fatigue (n = 32, 25.6%), headache (n = 27, 21.6%), and mood swings (n = 24, 19.2%). No patients discontinued therapy. CONCLUSIONS The overall SVR rate was 96.9%; SOF + DCV (100%) was higher than that of SOF + SMV (93.3%). Despite no statistically significant intergroup difference in SVR12 rates, the noninferiority of SOF + SMV to SOF + DCV could not be established because the difference in efficacy was clinically relevant.
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Affiliation(s)
- H Pott-Junior
- Division of Infectious Diseases, Federal University of São Paulo, São Paulo, Brazil.
| | - G Bricks
- Division of Infectious Diseases, Federal University of São Paulo, São Paulo, Brazil
| | - G Grandi
- Division of Infectious Diseases, Federal University of São Paulo, São Paulo, Brazil
| | - J Figueiredo Senise
- Division of Infectious Diseases, Federal University of São Paulo, São Paulo, Brazil
| | - A Castelo Filho
- Division of Infectious Diseases, Federal University of São Paulo, São Paulo, Brazil
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24
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Bayatpoor ME, Khosravi MH, Sharafi H, Rezaee-Zavareh MS, Behnava B, Alavian SM. Sofosbuvir and Ribavirin with or Without Pegylated-Interferon in Hepatitis C Virus Genotype-2 or -3 Infections: A Systematic Review and Meta-Analysis. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2019; In Press. [DOI: 10.5812/archcid.79465] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
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Yin S, Barker L, White JZ, Jiles RB. Sofosbuvir-Based Regimens for Chronic Hepatitis C in a Well-Insured U.S. Population: Patient Characteristics, Treatment Adherence, Effectiveness, and Health Care Costs, 2013-2015. J Manag Care Spec Pharm 2019; 25:195-210. [PMID: 30698086 PMCID: PMC6753523 DOI: 10.18553/jmcp.2019.25.2.195] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Chronic hepatitis C (CHC) is a leading cause of morbidity and mortality and has imposed a high health care burden in the United States. Direct-acting antiviral (DAA) regimens are well tolerated and highly effective for CHC therapy but were initially marketed at a high price. Studies of their real-world use with a nationwide population are limited. OBJECTIVE To examine patient characteristics, treatment adherence, effectiveness, and health care costs in a large U.S. population with commercial and Medicare supplemental insurance plans who received simeprevir (SIM), sofosbuvir (SOF), or ledipasvir/sofosbuvir (LED/SOF) during the years 2013-2015. METHODS Patients with at least 1 diagnosis code for CHC and at least 1 claim for SIM, SOF, or LED/SOF prescriptions were selected. The date of the first claim for SIM, SOF, or LED/SOF was defined as the index date. Analyses were stratified by 4 regimens: SOF + SIM ± ribavirin (RBV), SOF + peginterferon alpha-2a or 2b (PEG) + RBV, SOF + RBV, and LED/SOF ± RBV. Adherence was defined by the proportion of days covered (PDC) ≥ 80%. Sustained virologic response (SVR12) was defined as a hepatitis C virus (HCV) RNA load of ≤ 25 IU/mL measured at ≥ 12 weeks following the end of the days supply of the last DAA refill. Health care costs such as DAA drug costs and medical costs (inpatient costs plus outpatient costs) were described. RESULTS Of 10,808 CHC patients, approximately two thirds were male, and mean age was 55 years. The proportion of patients with compensated cirrhosis among each regimen ranged from 7.4% in LED/SOF ± RBV to 13.8% in SOF + SIM ± RBV, and the proportion of patients with decompensated cirrhosis ranged from 3.9% in LED/SOF ± RBV to 10.7% in SOF + SIM ± RBV. The majority of patients (89.0%) used the newer regimen LED/SOF ± RBV in 2015. Adherence rates were estimated at 80.5%, 81.5%, 85.7%, and 91.4% for SOF + SIM ± RBV (n = 1,761); SOF + PEG + RBV (n = 1,314); SOF + RBV (n = 1,994); and LED/SOF ± RBV (n = 5,739), respectively. Regimen-specific adherence predictors included sex, age group, payer type, health plan, and treatment option with RBV. Being born during 1945-1965, liver disease severity, and Charlson Comorbidity Index levels did not predict adherence in any regimen. Overall SVR12 was 92.6% in 203 patients with available HCV RNA results: 100% (41/41) in SOF + SIM ± RBV; 83.3% (25/30) in SOF + PEG + RBV; 90.6% (29/32) in SOF + RBV; and 93% (93/100) in LED/SOF ± RBV. While the drug costs for these DAA regimens were initially high, they had decreased 18.9% (P < 0.001) during 2013-2015. Medical costs decreased 9.2% (P < 0.001) 1 year after the index dates. CONCLUSIONS These results indicate that DAA drug costs decreased steadily during 2013-2015 and that 89% of patients on SOF-based DAA regimens took newer, lower-cost regimens with adherence rates above 80%. Available data show that SVR12 rates were close to those obtained in clinical studies. Medical costs also significantly decreased 1 year after the index dates. DISCLOSURES No outside funding supported this study. All authors are U.S. federal employees of the Centers for Disease Control and Prevention. The authors declare that they have no competing interests. The findings and conclusions in this research are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
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Affiliation(s)
- Shaoman Yin
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Laurie Barker
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Jianglan Z. White
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Ruth B. Jiles
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
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Backus LI, Belperio PS, Shahoumian TA, Mole LA. Direct-acting antiviral sustained virologic response: Impact on mortality in patients without advanced liver disease. Hepatology 2018; 68:827-838. [PMID: 29377196 DOI: 10.1002/hep.29811] [Citation(s) in RCA: 126] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 01/11/2018] [Accepted: 01/22/2018] [Indexed: 12/12/2022]
Abstract
UNLABELLED The impact of sustained virologic response (SVR) on mortality after direct-acting antiviral (DAA) treatment is not well documented in patients without advanced liver disease and affects access to treatment. This study evaluated the impact of SVR achieved with interferon-free DAA treatment on all-cause mortality in hepatitis C virus-infected patients without advanced liver disease. This observational cohort analysis was comprised of 103,346 genotype 1, 2, and 3, hepatitis C virus-monoinfected patients without advanced liver disease, defined by FIB-4 ≤3.25 and no diagnosis of cirrhosis, hepatic decompensation, or hepatocellular carcinoma or history of liver transplantation, identified from the Veterans Affairs Hepatitis C Clinical Case Registry. Among 40,664 patients treated with interferon-free DAA regimens, 39,374 (96.8%) achieved SVR and 1,290 (3.2%) patients were No SVR; 62,682 patients constituted the untreated cohort. The mortality rate for SVR patients of 1.18 deaths/100 patient-years was significantly lower than the rates for both No SVR patients (2.84 deaths/100 patient-years; P < 0.001) and untreated patients (3.84 deaths/100 patient-years; P < 0.001). SVR patients with FIB-4 <1.45 and 1.45-3.25 had a 46.0% (P = 0.036) and 63.2% (P < 0.001) reduction in mortality rates, respectively, compared to No SVR patients and 66.7% (P < 0.001) and 70.6% (P < 0.001) reduction in mortality rates, respectively, compared to untreated patients. In multivariate Cox proportional hazard models controlling for baseline demographics, clinical characteristics, and comorbidities, SVR was independently associated with reduced risk of death compared to No SVR (hazard ratio, 0.44; 95% confidence interval, 0.32-0.59; P < 0.001) and compared to untreated patients (hazard ratio, 0.32; 95% confidence interval, 0.29-0.36; P < 0.001). CONCLUSION Successfully treating hepatitis C virus with DAAs in patients without clinically apparent advanced liver disease translates into a significant mortality benefit. (Hepatology 2018).
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Affiliation(s)
- Lisa I Backus
- Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA
| | - Pamela S Belperio
- Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA
| | - Troy A Shahoumian
- Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA
| | - Larry A Mole
- Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA
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Chronic Hepatitis C in Elderly Patients: Current Evidence with Direct-Acting Antivirals. Drugs Aging 2018; 35:117-122. [PMID: 29417462 DOI: 10.1007/s40266-017-0515-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Since the introduction of direct-acting antivirals (DAAs), the outcomes of hepatitis C (HCV) treatment have shown an improvement in cure rates with minimal side effects. However, to date, the safety and efficacy of DAAs have not been specifically examined in elderly patients. The treatment of HCV in the era of pegylated interferon and ribavirin was more challenging among elderly patients due to the increased prevalence of multiple comorbid conditions associated with an increased risk of side effects, including anemia, and high rates of discontinuation, likely as a result of poor tolerability, resulting in lower rates of sustained virologic response (SVR). The advent of highly efficacious all-oral DAA agents with minimal adverse events has provided more data on the outcomes of treatment in the elderly population. The current evidence shows that DAA agents have been effective and safe in the elderly population, with comparable rates of SVR. The aim of this article was to review the safety and efficacy of commonly prescribed DAA agents in the management of chronic HCV in the elderly population.
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Wei B, Ji F, Yeo YH, Ogawa E, Zou B, Stave CD, Dang S, Li Z, Furusyo N, Cheung RC, Nguyen MH. Real-world effectiveness of sofosbuvir plus ribavirin for chronic hepatitis C genotype 2 in Asia: a systematic review and meta-analysis. BMJ Open Gastroenterol 2018; 5:e000207. [PMID: 30002863 PMCID: PMC6038840 DOI: 10.1136/bmjgast-2018-000207] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 06/02/2018] [Accepted: 06/08/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Sofosbuvir plus ribavirin (SOF+RBV) for 12 weeks is the standard treatment for chronic hepatitis C (CHC) genotype 2 (GT2) in most of Asia despite availability of new CHC medications. SOF-RBV real-world effectiveness has only been reported in small and/or single-centre studies. Our goal was to determine the real-world effectiveness of 12-week SOF+RBV therapy for CHC GT2 in Asia. METHODS A systematic search on PubMed and Embase was conducted through 30 June 2017. We identified full articles and conference proceedings of at least 10 adult patients with CHC GT2 treated with SOF+RBV for 12 weeks under real-world setting in Asia. RESULTS A total of 2208 patients from 13 studies were included. The pooled sustained virological response 12 weeks after the end of treatment (SVR12) was 95.8% (95% CI 94.6% to 96.9%) with non-significant heterogeneity (I2=34.4%). Anaemia (27.9%) was the most common adverse event (AE), with serious AEs in 2.0% and only 0.7% discontinued therapy prematurely. In subgroup analyses, patients with cirrhosis had 8.7% lower SVR12 than non-cirrhotic patients (P<0.0001), and treatment-experienced patients had 7.2% lower SVR12 than treatment-naïve patients (P=0.0002). Cirrhotic treatment-experienced patients had the lowest SVR12 at 84.5%. There were no significant differences in pooled SVR12 among patient subgroups: RBV dose reduction versus no dose reduction (P=0.30); hepatocellular carcinoma (HCC) versus no HCC (P=0.10); GT 2a versus 2b (P=0.86); and <65 vs ≥65 years of age (P=0.20). CONCLUSIONS SOF+RBV for 12 weeks was safe and effective for patients with CHC GT2 in Asia, although those with cirrhosis and prior treatment failure had a lower pooled SVR12 rate. TRIAL REGISTRATION NUMBER CRD42017067928.
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Affiliation(s)
- Bin Wei
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Fanpu Ji
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Eiichi Ogawa
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Biyao Zou
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Christopher D Stave
- Lane Medical Library, Stanford University School of Medicine, Palo Alto, California, USA
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zongfang Li
- Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
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Modi AA, Nazario HE, Gonzales GR, Gonzalez SA. Safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in hepatitis C genotype 1 patients including those with decompensated cirrhosis who failed prior treatment with simeprevir/sofosbuvir. Aliment Pharmacol Ther 2018; 47:1409-1415. [PMID: 29569736 DOI: 10.1111/apt.14604] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 04/18/2017] [Accepted: 02/16/2018] [Indexed: 12/24/2022]
Abstract
BACKGROUND Combination therapy of simeprevir (SIM)/sofosbuvir (SOF) is an approved treatment for hepatitis C genotype (gen) 1 with overall SVR12 rate of 85%-95%. The single tablet fixed-dose combination of ledipasvir (LDV)/SOF is also approved for gen 1 with sustained virologic response at 12 weeks (SVR12) rates ≥95%. No data are available on the efficacy of retreatment with LDV/SOF in patients who failed initial treatment with SIM/SOF. AIM To evaluate the efficacy of retreatment with LDV/SOF ± ribavirin (RBV) in gen 1 patients who had previously failed treatment with SIM/SOF. METHODS Data from a combined treatment cohort of 2 hepatology centres, which included patients previously treated with SIM/SOF ± RBV for 12 weeks but failed to achieve SVR and then underwent retreatment with LDV/SOF ± RBV, were analysed (n = 30). LDV/SOF ± RBV was administered for 12-24 weeks based on the discretion of the treating hepatologist. RESULTS Of the 30 patients, 23 (77%) were male, 77% were Caucasian and 26 (87%) were gen 1a. 26 (86%) had cirrhosis, of which 16 (62%) had decompensated, Child's class B or C cirrhosis. Three patients were liver transplant recipients with recurrent hepatitis C. Overall, 27/30 (90%) achieved SVR. Treatment was well tolerated with 37% reporting no adverse events. The most common adverse events were fatigue, headache, insomnia and nausea. Two patients with Child's B cirrhosis required hospitalization during treatment for variceal haemorrhage and abdominal pain respectively. However, no treatment discontinuations or deaths occurred. CONCLUSION Single tablet fixed-dose combination LDV/SOF ± RBV is efficacious and well tolerated in patients who previously failed treatment with SIM/SOF, including those with decompensated cirrhosis and recurrent hepatitis C following liver transplantation.
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Affiliation(s)
- A A Modi
- Liver Consultants of Texas, Baylor All Saints Medical Center, Fort Worth, TX, USA
| | - H E Nazario
- The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA
| | - G R Gonzales
- University of North Texas Health Science Center, Fort Worth, TX, USA
| | - S A Gonzalez
- Liver Consultants of Texas, Baylor All Saints Medical Center, Fort Worth, TX, USA
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Bagwell A, Kelley T, Carver A, Lee JB, Newman B. Advancing Patient Care Through Specialty Pharmacy Services in an Academic Health System. J Manag Care Spec Pharm 2018; 23:815-820. [PMID: 28737983 PMCID: PMC10398086 DOI: 10.18553/jmcp.2017.23.8.815] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND With the rapid growth of specialty pharmacies, including those within academic health systems, pharmacists have the opportunity to improve patient care through the management of specialty medications. Specialty pharmacists within academic health systems are uniquely positioned to overcome restrictions to medication access, financial constraints, and provider burdens that often lead to obstacles for patients to start and maintain necessary treatments. The Vanderbilt Specialty Pharmacy (VSP) model at Vanderbilt University Medical Center (VUMC) provides an example of a patient-centered, collaborative care prototype that places pharmacists directly into specialty clinics to assist with comprehensive management of patients on specialty medications. PROGRAM DESCRIPTION VSP integrates specialty pharmacy services within existing specialty clinics based on the needs of each individual clinic. Each clinic is staffed with at least 1 clinical pharmacist and 1 pharmacy technician. The pharmacist is integrally involved in medication selection, initiation, and monitoring. The specialty pharmacy team ensures appropriate medication access and cost, provides extensive medication education, ensures patients are adherent to treatment, and coordinates care between patients and providers using the electronic medical record. OBSERVATIONS Integration of pharmacists within specialty clinics at VUMC benefits providers, the health system, and patient care. This model has demonstrated decreased provider and clinic burden, decreased time to medication approval and initiation, excellent patient and provider satisfaction, substantial patient cost savings, optimal medication adherence, and overall improved continuity of care for patients on specialty medications. Since its inception in 2011, VSP has integrated 24 clinical pharmacists and 17 pharmacy technicians into 20 specialty clinics, with continued quarterly growth. IMPLICATIONS The VSP model advances the role of pharmacists in managing patients on specialty medications in collaboration with providers. The integrated collaborative approach as presented by VSP represents a best practices model for those establishing and advancing specialty pharmacy services within academic health systems. DISCLOSURES No outside funding supported this study. The authors have nothing to disclose. Study concept and design were principally contributed by Bagwell and Newman, along with the other authors. Lee took the lead in data collection, along with Carver, Bagwell, Kelley, and Newman. Data interpretation was performed by Carver, Kelley, Lee, and Bagwell, with assistance from Newman. The manuscript was written by Bagwell, Carver, Kelley, and Lee and revised primarily by Bagwell, along with the other authors.
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Affiliation(s)
| | - Tara Kelley
- 1 Vanderbilt Specialty Pharmacy, Nashville, Tennessee
| | - Alicia Carver
- 1 Vanderbilt Specialty Pharmacy, Nashville, Tennessee
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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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Zhu J, Hazen RJ, Joyce C, Delpino A, Kirkham HS, Strickland CD, Markes-Wilson S, Kim T, Kang M, Rubin RA, Stein LL. Local specialty pharmacy and specialty clinic collaboration assists access to hepatitis C direct-acting antivirals. J Am Pharm Assoc (2003) 2018; 58:89-93.e2. [DOI: 10.1016/j.japh.2017.10.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 10/17/2017] [Accepted: 10/19/2017] [Indexed: 01/06/2023]
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Perazzo H, Jorge MJ, Silva JC, Avellar AM, Silva PS, Romero C, Veloso VG, Mujica-Mota R, Anderson R, Hyde C, Castro R. Micro-costing analysis of guideline-based treatment by direct-acting agents: the real-life case of hepatitis C management in Brazil. BMC Gastroenterol 2017; 17:119. [PMID: 29169329 PMCID: PMC5701370 DOI: 10.1186/s12876-017-0676-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Accepted: 11/15/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Eradication of hepatitis C virus (HCV) using direct-acting agents (DAA) has been associated with a financial burden to health authorities worldwide. We aimed to evaluate the guideline-based treatment costs by DAAs from the perspective of the Brazilian Ministry of Health (BMoH). METHODS The activity based costing method was used to estimate the cost for monitoring/treatment of genotype-1 (GT1) HCV patients by the following strategies: peg-interferon (PEG-IFN)/ribavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or telaprevir (TEL) for 48 weeks, and sofosbuvir (SOF) plus daclastavir (DCV) or simeprevir (SIM) for 12 weeks. Costs were reported in United States Dollars without (US$) and with adjustment for purchasing power parity (PPP$). Drug costs were collected at the National Database of Health Prices and an overview of the literature was performed to assess effectiveness of SOF/DCV and SOF/SIM regimens in real-world cohorts. RESULTS Treatment costs of GT1-HCV patients were PPP$ 43,176.28 (US$ 24,020.16) for PEG-IFN/RBV, PPP$ 71,196.03 (US$ 39,578.23) for PEG-IFN/RBV/BOC and PPP$ 86,250.33 (US$ 47,946.92) for PEG-IFN/RBV/TEL. Treatment by all-oral interferon-free regimens were the less expensive approach: PPP$ 19,761.72 (US$ 10,985.90) for SOF/DCV and PPP$ 21,590.91 (US$ 12,002.75) for SOF/SIM. The overview reported HCV eradication in up to 98% for SOF/DCV and 96% for SOF/SIM. CONCLUSION Strategies with all oral interferon-free might lead to lower costs for management of GT1-HCV patients compared to IFN-based regimens in Brazil. This occurred mainly because of high discounts over international DAA prices due to negotiation between BMoH and pharmaceutical industries.
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Affiliation(s)
- Hugo Perazzo
- Fundação Oswaldo Cruz, FIOCRUZ, Instituto Nacional de Infectologia Evandro Chagas, INI, Laboratório de Pesquisa Clínica em DST e AIDS, LAPCLIN-AIDS, Rio de Janeiro, Brazil.
| | - Marcelino Jose Jorge
- Fundação Oswaldo Cruz, FIOCRUZ, Instituto Nacional de Infectologia Evandro Chagas, INI, Laboratório de Pesquisa em Economia das Organizações de Saúde, LAPECOS, Rio de Janeiro, Brazil
| | - Julio Castro Silva
- Fundação Oswaldo Cruz, FIOCRUZ, Instituto Nacional de Infectologia Evandro Chagas, INI, Plataforma de Pesquisa Clínica, Rio de Janeiro, Brazil
| | - Alexandre Monken Avellar
- Fundação Oswaldo Cruz, FIOCRUZ, Instituto Nacional de Infectologia Evandro Chagas, INI, Laboratório de Pesquisa em Economia das Organizações de Saúde, LAPECOS, Rio de Janeiro, Brazil
| | - Patrícia Santos Silva
- Fundação Oswaldo Cruz, FIOCRUZ, Instituto Nacional de Infectologia Evandro Chagas, INI, Laboratório de Pesquisa em Economia das Organizações de Saúde, LAPECOS, Rio de Janeiro, Brazil
| | - Carmen Romero
- Fundação Oswaldo Cruz, FIOCRUZ, Centro de Desenvolvimento Tecnológico em Saúde, CDTS, Rio de Janeiro, Brazil
| | - Valdilea Gonçalves Veloso
- Fundação Oswaldo Cruz, FIOCRUZ, Instituto Nacional de Infectologia Evandro Chagas, INI, Laboratório de Pesquisa Clínica em DST e AIDS, LAPCLIN-AIDS, Rio de Janeiro, Brazil
| | - Ruben Mujica-Mota
- University of Exeter Medical School, UEMS, Evidence Synthesis & Modelling for Health Improvement, ESMI, Exeter, UK
| | - Rob Anderson
- University of Exeter Medical School, UEMS, Evidence Synthesis & Modelling for Health Improvement, ESMI, Exeter, UK
| | - Chris Hyde
- University of Exeter Medical School, UEMS, Evidence Synthesis & Modelling for Health Improvement, ESMI, Exeter, UK
| | - Rodolfo Castro
- Fundação Oswaldo Cruz, FIOCRUZ, Instituto Nacional de Infectologia Evandro Chagas, INI, Laboratório de Pesquisa Clínica em DST e AIDS, LAPCLIN-AIDS, Rio de Janeiro, Brazil.,Universidade Federal do Estado do Rio de Janeiro, UNIRIO, Instituto de Saúde Coletiva, ISC, Rio de Janeiro, Brazil
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Nagaty A, Abd El-Wahab EW. Real-life results of sofosbuvir based therapy in chronic hepatitis C -naïve and -experienced patients in Egypt. PLoS One 2017; 12:e0184654. [PMID: 28981513 PMCID: PMC5628811 DOI: 10.1371/journal.pone.0184654] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 08/28/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND More than ten million Egyptians are infected with HCV. Every one of them is going to infect about three to four persons every year. Treating those patients is a matter of national security. A dramatic improvement in hepatitis C virus (HCV) infection treatment was achieved in the last five years. A new era of direct-acting antivirals is now dawning in Egypt. OBJECTIVE(S) We share in this report our clinical experience in treating chronic HCV Egyptian patients with Sofosbuvir based regimens to evaluate its safety and efficacy on real life practical ground. METHODS A total of 205 chronic HCV patients (195 naive and 15 experienced) were enrolled in the study. Patient were treated with Sofosbuvir+Ribavirin 24 weeks as standard of care. Two interferon eligible patients were treated with PEG-INF+ Sofosbuvir+Ribavirin for 12 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response at 24 weeks after cessation of therapy. RESULTS The overall response rate was 97.1%. Sustained virological response rate did not differ among treatment-naive patients and patients with previous history of IFN-based therapy. Portal hypertension, prediabetes, and lack of early virologic response were predictors of non response. No clinically significant treatment-emergent adverse effects were noted. No treatment discontinuation was encountered. CONCLUSION In the real-life setting, Sofosbuvir based regimens for 24 weeks has established an efficacious and well tolerated treatment in naïve and experienced patients with chronic HCV genotype 4 infection; although shorter treatment durations may be possible. However, patient follow up should extent to at least 6 months post-treatment and verifying viral load on yearly basis is warranted to track any late relapse.
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Affiliation(s)
- Ahmed Nagaty
- Consultant of Hepatology and Infectious Diseases, Ministry of Health, Alexandria, Egypt
| | - Ekram W. Abd El-Wahab
- Tropical Health Department, High Institute of Public Health, Alexandria University, Alexandria, Egypt
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Welzel TM, Nelson DR, Morelli G, Di Bisceglie A, Reddy RK, Kuo A, Lim JK, Darling J, Pockros P, Galati JS, Frazier LM, Alqahtani S, Sulkowski MS, Vainorius M, Akushevich L, Fried MW, Zeuzem S. Effectiveness and safety of sofosbuvir plus ribavirin for the treatment of HCV genotype 2 infection: results of the real-world, clinical practice HCV-TARGET study. Gut 2017; 66:1844-1852. [PMID: 27418632 PMCID: PMC5595101 DOI: 10.1136/gutjnl-2016-311609] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Revised: 06/01/2016] [Accepted: 06/04/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Due to a high efficacy in clinical trials, sofosbuvir (SOF) and ribavirin (RBV) for 12 or 16 weeks is recommended for treatment of patients with HCV genotype (GT) 2 infection. We investigated safety and effectiveness of these regimens for GT2 in HCV-TARGET participants. DESIGN HCV-TARGET, an international, prospective observational study evaluates clinical practice data on novel antiviral therapies at 44 academic and 17 community medical centres in North America and Europe. Clinical data were centrally abstracted from medical records. Selection of treatment regimen and duration was the investigator's choice. The primary efficacy outcome was sustained virological response 12 weeks after therapy (SVR12). RESULTS Between December 2013 and April 2015, 321 patients completed 12 weeks (n=283) or 16 weeks (n=38) of treatment with SOF and RBV. Prior treatment experience and cirrhosis was more frequent among patients in the 16-week regimen compared with 12 weeks (52.6% vs 27.6% and 63.2% vs 21.9%, respectively). Overall, SVR12 was 88.2%. The SVR12 in patients without cirrhosis was 91.0% and 92.9% for 12 or 16 weeks of therapy, respectively. In patients with cirrhosis treated for 12 or 16 weeks, SVR12 was 79.0% and 83%. In the multivariate analysis, liver cirrhosis, lower serum albumin and RBV dose at baseline were significantly associated with SVR12. Common adverse events (AEs) included fatigue, anaemia, nausea, headache, insomnia, rash and flu-like symptoms. Discontinuation due to AEs occurred in 2.8%. CONCLUSIONS In this clinical practice setting, SOF and RBV was safe and effective for treatment of patients with HCV GT2 infection. TRIAL REGISTRATION NUMBER NCT01474811.
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Affiliation(s)
- Tania M Welzel
- JW Goethe University Hospital, Frankfurt am Main, Germany
| | | | | | | | | | - Alexander Kuo
- University of California, San Diego, San Diego, California, USA
| | - Joseph K Lim
- Yale University of School of Medicine, New Haven, Connecticut, USA
| | - Jama Darling
- University of North Carolina, Chapel Hill, North Carolina, USA
| | | | | | | | | | | | | | - Lucy Akushevich
- University of North Carolina, Chapel Hill, North Carolina, USA
| | - Michael W Fried
- University of North Carolina, Chapel Hill, North Carolina, USA
| | - Stefan Zeuzem
- JW Goethe University Hospital, Frankfurt am Main, Germany
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Shin HP, Burman B, Kozarek RA, Zeigler A, Wang C, Lee H, Zehr T, Edwards AM, Siddique A. Real-World Single-Center Experience with Sofosbuvir-Based Regimens for the Treatment of Chronic Hepatitis C Genotype 1 Patients. Gut Liver 2017; 11:711-720. [PMID: 28651301 PMCID: PMC5593334 DOI: 10.5009/gnl16447] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Revised: 01/06/2017] [Accepted: 01/11/2017] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND/AIMS The approval of sofosbuvir (SOF), a direct-acting antiviral, has revolutionized the treatment of chronic hepatitis C virus (HCV). METHODS We assessed the sustained virological response (SVR) of SOF-based regimens in a real-world single-center setting for the treatment of chronic HCV genotype 1 (G1) patients. This was a retrospective review of chronic HCV G1 adult patients treated with a SOF-based regimen at Virginia Mason Medical Center between December 2013 and August 2015. RESULTS The cohort comprised 343 patients. Patients received SOF+ledipasvir (LDV) (n=155), SOF+simeprevir (SIM) (n=154), or SOF+peginterferon (PEG)+ribavirin (RBV) (n=34). Of the patients, 50.1% (n=172) had cirrhosis. The SVR rate was 92.2% for SOF/LDV, 87.0% for SOF/SIM, and 82.4% for SOF/PEG/RBV. Compared with the cirrhotic patients, the patients without cirrhosis had a higher SVR (96.8% vs 85.5%, p=0.01, SOF/LDV; 98.2% vs 80.6%, p=0.002, SOF/SIM; 86.4% vs 75.0%, p=0.41, SOF/PEG/RBV). In this study, prior treatment experience adversely affected the response rate in subjects treated with SOF/PEG/RBV. CONCLUSIONS In this single-center, real-world setting, the treatment of chronic HCV G1 resulted in a high rate of SVR, especially in patients without cirrhosis.
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Affiliation(s)
- Hyun Phil Shin
- Hepatology Division, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul,
Korea
| | - Blaire Burman
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA,
USA
| | - Richard A. Kozarek
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA,
USA
| | - Amy Zeigler
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA,
USA
| | - Chia Wang
- Department of Infectious Disease, Virginia Mason Medical Center, Seattle, WA,
USA
| | - Houghton Lee
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA,
USA
| | - Troy Zehr
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA,
USA
| | - Alicia M. Edwards
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA,
USA
| | - Asma Siddique
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA,
USA
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Kan H, Imamura M, Kawakami Y, Daijo K, Teraoka Y, Honda F, Nakamura Y, Morio K, Kobayashi T, Nakahara T, Nagaoki Y, Kawaoka T, Tsuge M, Aikata H, Hayes CN, Miki D, Ochi H, Honda Y, Mori N, Takaki S, Tsuji K, Chayama K. Emergence of drug resistance-associated variants and changes in serum lipid profiles in sofosbuvir plus ledipasvir-treated chronic hepatitis C patients. J Med Virol 2017; 89:1963-1972. [PMID: 28657143 DOI: 10.1002/jmv.24885] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 06/08/2017] [Indexed: 12/22/2022]
Abstract
Combination of sofosbuvir plus ledipasvir therapy has been expected to enhance sustained virological response (SVR) rates in hepatitis C virus (HCV) genotype 1 chronic infected patients. We analyzed the emergence of drug resistance-associated variants (RAVs) in treatment failure and changes in lipid profiles in sofosbuvir/ledipasvir-treated patients. A total of 176 patients with chronic HCV genotype 1 infection without decompensated liver cirrhosis were treated with sofosbuvir/ledipasvir for 12 weeks. NS5A and NS5B RAVs were determined by either Invader assay or direct sequencing. Serum lipid-related markers were measured at the start of treatment and at week 4 in patients who received sofosbuvir/ledipasvir and ombitasvir/paritaprevir/ritonavir therapies. SVR was achieved in 94.9% (167 out of 176) of patients. SVR12 rate was 97.1% for patietns with low frequncy (<25%) of baseline NS5A RAVs, but 82.8% for patients with high frequency (>75%) of NS5A RAVs. In multivariate regression analysis, higher albumin (odds ratio [OR] = 0.020 for presence; P = 0.007), and NS5A-L31/Y93 RAVs with a population frequency <75% (OR = 29.860 for presence; P = 0.023) were identified as significant independent predictors for SVR12. NS5A-Y93H substitutions were detected in all nine treatment failures at HCV relapse, and three out of six patients with NS5A inhibitor-naïve patients achieved additional NS5A RAVs. Serum low-density lipoprotein cholesterol and apolipoprotein B levels were significantly elevated at week 4 in sofosbuvir/ledipasvir-treated patients. These elevations were greater than in ombitasvir/paritaprevir/ritonavir-treated patients. In conclusion, NS5A multi-RAVs are likely to develop in patients who fail to respond to sofosbuvir/ledipasvir therapy. Inhibition of HCV replication with sofosbuvir might affect lipid metabolism.
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Affiliation(s)
- Hiromi Kan
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kana Daijo
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuji Teraoka
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Fumi Honda
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuki Nakamura
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomoki Kobayashi
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuko Nagaoki
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Clair Nelson Hayes
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Daiki Miki
- Laboratory for Digestive Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan
| | - Hidenori Ochi
- Laboratory for Digestive Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan
| | - Yoji Honda
- Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan
| | - Nami Mori
- Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan
| | - Shintaro Takaki
- Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan
| | - Keiji Tsuji
- Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.,Laboratory for Digestive Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan
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Leventer-Roberts M, Hammerman A, Brufman I, Hoshen M, Braun M, Ashur Y, Lieberman N, Balicer R. Effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir for hepatitis C virus in clinical practice: A population-based observational study. PLoS One 2017; 12:e0176858. [PMID: 28686590 PMCID: PMC5501432 DOI: 10.1371/journal.pone.0176858] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Accepted: 04/18/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Direct acting antivirals for hepatitis C virus have shown dramatic results in clinical trials. However, their effectiveness has yet to be demonstrated within observational cohorts which lack exclusion criteria found in randomized control trials. AIM To determine the effectiveness of dasabuvir/ombitasvir/paritaprevir/ritonavir in achieving sustained virological response. METHODS Retrospective observational cohort study of all Clalit Health Services members with hepatitis C virus genotype 1 who were dispensed dasabuvir/ombitasvir/paritaprevir/ritonavir from January 1, 2015 to-November 31, 2015. RESULTS There were 564 participants during the study period. The average age was 61.9 years, 52.0% were male, and 61.5% were born Eastern/Central Europe or Central Asia. The prevalence of diabetes was 31.7% and 70.3% were overweight/obese. Cirrhosis was present in 41.0% of participants, of whom 52.8% had stage 4 fibrosis. Of the cohort, 416 (74.8%) had follow-up viral load testing at 10 or more weeks after the end of treatment. We report a sustained virological response of 98.8% among those tested. CONCLUSIONS Treatment with dasabuvir/ombitasvir/paritaprevir/ritonavir demonstrated a near universal effectiveness in achieving a sustained virological response among HCV patients in a large cohort.
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Affiliation(s)
- Maya Leventer-Roberts
- Clalit Research Institute, Tel Aviv, Israel
- Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Ariel Hammerman
- Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel
| | | | | | - Marius Braun
- Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel
- Liver Unit, Beilinson Hospital, Petach Tikva, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yaffa Ashur
- Hepatology, Clalit Health Services, Tel Aviv, Israel
| | - Nicky Lieberman
- Community Medicine Division, Clalit Health Services, Tel Aviv, Israel
| | - Ran Balicer
- Clalit Research Institute, Tel Aviv, Israel
- Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel
- Department of Epidemiology, Faculty of Health Sciences, Ben Gurion University, Be'er Sheva, Israel
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Morio K, Imamura M, Kawakami Y, Nakahara T, Nagaoki Y, Kawaoka T, Tsuge M, Hiramatsu A, Aikata H, Hayes CN, Makokha GN, Ochi H, Amano H, Arataki K, Moriya T, Ito H, Tsuji K, Kohno H, Waki K, Tamura T, Nakamura T, Chayama K. ITPA polymorphism effects on decrease of hemoglobin during sofosbuvir and ribavirin combination treatment for chronic hepatitis C. J Gastroenterol 2017; 52:746-753. [PMID: 27822709 DOI: 10.1007/s00535-016-1279-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Accepted: 10/19/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Polymorphisms in the inosine triphosphatase (ITPA) gene is associated with anemia induced by peg-interferon (PEG-IFN) plus ribavirin (RBV) treatment for patients with chronic hepatitis C virus (HCV) infection. However, the effect of ITPA polymorphism on sofosbuvir plus RBV treatment is unknown. METHODS Two hundred and forty-four patients with chronic HCV genotype 2 infection without decompensated liver cirrhosis were treated with sofosbuvir plus RBV for 12 weeks. The effects of ITPA polymorphism on hemoglobin levels and RBV dose reduction and treatment response were analyzed. ITPA (rs1127354) was genotyped using the Invader assay. Multivariate regression analysis was performed to identify factors associated with sustained virological response (SVR). RESULTS Overall, SVR12 was achieved in 231 (94.7%) patients, based on intention to treat analysis. During the therapy, reduction of hemoglobin levels was significantly greater in ITPA genotype CC patients than CA/AA patients. Therefore, the cumulative proportion of patients with RBV dose reduction was significantly higher and total dose of RBV was significantly lower in patients with CC genotype compared to CA/AA genotypes. SVR12 rates were similar between ITPA genotypes CC and CA/AA (94.7 and 94.4%, respectively, P = 0.933). Multivariate logistic regression analysis identified FIB4 index <3.25 (odds ratio [OR], 9.388 for ≥3.25; P = 0.005) and low body weight (OR, 1.059, for high body weight; P = 0.017) as independent predictors for SVR12. CONCLUSIONS ITPA polymorphism influences hemoglobin levels and incidence of RBV dose reduction during sofosbuvir plus RBV therapy. However, ITPA genotype CC patients can expect a curative effect equivalent to CA/AA patients for chronic HCV genotype 2 infection.
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Affiliation(s)
- Kei Morio
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yuko Nagaoki
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Clair Nelson Hayes
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Grace Naswa Makokha
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hidenori Ochi
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
- Laboratory for Digestive Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan
| | | | | | | | | | - Keiji Tsuji
- Hiroshima Red Cross Hospital, Hiroshima, Japan
| | | | - Koji Waki
- Hiroshima City Asa Hospital, Hiroshima, Japan
| | | | | | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
- Laboratory for Digestive Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
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40
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Calleja JL, Crespo J, Rincón D, Ruiz-Antorán B, Fernandez I, Perelló C, Gea F, Lens S, García-Samaniego J, Sacristán B, García-Eliz M, Llerena S, Pascasio JM, Turnes J, Torras X, Morillas RM, Llaneras J, Serra MA, Diago M, Rodriguez CF, Ampuero J, Jorquera F, Simon MA, Arenas J, Navascues CA, Bañares R, Muñoz R, Albillos A, Mariño Z. Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: Results from a Spanish real-world cohort. J Hepatol 2017; 66:1138-1148. [PMID: 28189751 DOI: 10.1016/j.jhep.2017.01.028] [Citation(s) in RCA: 142] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 01/25/2017] [Accepted: 01/29/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Clinical trials evaluating second-generation direct-acting antiviral agents (DAAs) have shown excellent rates of sustained virologic response (SVR) and good safety profiles in patients with chronic hepatitis C virus (HCV) genotype 1 infection. We aimed to investigate the effectiveness and safety of two oral DAA combination regimens, ombitasvir/paritaprevir/ritonavir plus dasabuvir (OMV/PTV/r+DSV) and ledipasvir/sofosbuvir (LDV/SOF), in a real-world clinical practice. METHODS Data from HCV genotype 1 patients treated with either OMV/PTV/r+DSV±ribavirin (RBV) (n=1567) or LDV/SOF±RBV (n=1758) in 35 centers across Spain between April 1, 2015 and February 28, 2016 were recorded in a large national database. Demographic, clinical and virological data were analyzed. Details of serious adverse events (SAEs) were recorded. RESULTS The two cohorts were not matched with respect to baseline characteristics and could not be compared directly. The SVR12 rate was 96.8% with OMV/PTVr/DSV±RBV and 95.8% with LDV/SOF±RBV. No significant differences were observed in SVR according to HCV subgenotype (p=0.321 [OMV/PTV/r+DSV±RBV] and p=0.174 [LDV/SOF]) or degree of fibrosis (c0.548 [OMV/PTV/r/DSV±RBV] and p=0.085 [LDV/SOF]). Only baseline albumin level was significantly associated with failure to achieve SVR (p<0.05) on multivariate analysis. Rates of SAEs and SAE-associated treatment discontinuation were 5.4% and 1.7%, in the OMV/PTV/r+DSV subcohort and 5.5% and 1.5% in the LDV/SOF subcohort, respectively. Hepatocellular carcinoma (HCC) recurred in 30% of patients with a complete response to therapy for previous HCC. Incident HCC was reported in 0.93%. CONCLUSIONS In this large cohort of patients managed in the real-world setting in Spain, OMV/PTV/r+DSV and LDV/SOF achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with similarly good safety profiles. LAY SUMMARY In clinical trials, second-generation direct-acting antiviral agents (DAAs) have been shown to cure over 90% of patients chronically infected with the genotype 1 hepatitis C virus and have been better tolerated than previous treatment regimens. However, patients enrolled in clinical trials do not reflect the real patient population encountered in routine practice. The current study, which includes almost 4,000 patients, demonstrates comparable rates of cure with two increasingly used DAA combinations as those observed in the clinical trial environment, confirming that clinical trial findings with DAAs translate into the real-world setting, where patient populations are more diverse and complex.
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Affiliation(s)
- Jose Luis Calleja
- Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid and CIBERehd, Madrid, Spain.
| | - Javier Crespo
- Hospital Universitario Marques de Valdecilla, IDIVAL, Santander and Facultad de Medicina, Universidad de Cantabria, Spain
| | - Diego Rincón
- Hospital General Universitario Gregorio Marañón, Facultad de Medicina de la Universidad Complutense and CIBERehd, Madrid, Spain
| | | | | | | | | | - Sabela Lens
- Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | | | | | | | - Susana Llerena
- Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Cantabria, Spain
| | | | - Juan Turnes
- Complejo Hospitalario Universitario de Pontevedra and IISGS, Spain
| | - Xavier Torras
- Hospital Santa Creu i Sant Pau and CIBERehd, Barcelona, Spain
| | | | | | | | - Moises Diago
- Hospital Universitario General de Valencia, Valencia, Spain
| | | | - Javier Ampuero
- Hospital Universitario Virgen del Rocío, IBIS and CIBERehd, Spain
| | - Francisco Jorquera
- Complejo Asistencial Universitario León, León, IBIOMED and CIBERehd, Spain
| | - Miguel A Simon
- Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - Juan Arenas
- Hospital Universitario Donostia, San Sebastian, Spain
| | | | - Rafael Bañares
- Hospital General Universitario Gregorio Marañón, Facultad de Medicina de la Universidad Complutense and CIBERehd, Madrid, Spain
| | - Raquel Muñoz
- Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | - Zoe Mariño
- Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
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Abstract
The development of oral hepatitis C virus (HCV) direct-acting antivirals (DAAs) has revolutionized the therapeutic field. Nowadays, multiple safe and highly effective antiviral regimens are commercially available to treat adults with hepatitis C infection. These new regimens for the first time genuinely raise the prospects of eradicating HCV. Many challenges, however, remain from identifying infected individuals to optimizing treatment and ensuring global access to antiviral therapy to all population groups, including children. Recently, in April 2017, the association of sofosbuvir with ribavirin and the fixed-dose combination sofosbuvir/ledipasvir have been approved by the Food and Drug Administration for treatment of children with chronic HCV infection 12 years of age and older. The only drugs currently approved for children younger than 12 years are pegylated interferon and ribavirin. There are 6 registered ongoing pediatric trials assessing safety and efficacy of DAAs, but their current completion timelines are years away. Herein, we summarize the state of the art of DAAs' development for adult and children and highlight the crucial importance of overcoming barriers to treating children with HCV.
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42
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Ramos H, Linares P, Badia E, Martín I, Gómez J, Almohalla C, Jorquera F, Calvo S, García I, Conde P, Álvarez B, Karpman G, Lorenzo S, Gozalo V, Vásquez M, Joao D, de Benito M, Ruiz L, Jiménez F, Sáez-Royuela F, Asociación Castellano y Leonesa de Hepatología (ACyLHE). Interferon-free treatments in patients with hepatitis C genotype 1-4 infections in a real-world setting. World J Gastrointest Pharmacol Ther 2017; 8:137-146. [PMID: 28533924 PMCID: PMC5421113 DOI: 10.4292/wjgpt.v8.i2.137] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Revised: 01/14/2017] [Accepted: 02/13/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigated the real-world effectiveness and safety of various regimens of interferon-free treatments in patients infected with hepatitis C virus (HCV).
METHODS We performed an observational study to analyze different antiviral treatments administered to 462 HCV-infected patients, of which 56.7% had liver cirrhosis. HCV RNA after 4 wk of treatment and at 12 wk after treatment sustained virologic response (SVR) as well as serious adverse events (SAEs) was analyzed first for the whole cohort and then separately in patients who met or did not meet the inclusion criteria of a clinical trial (CT-met and CT-unmet, respectively).
RESULTS The most frequently prescribed treatment was simeprevir/sofosbuvir (36.4%), followed by sofosbuvir/ledipasvir (24.9%) and ombitasvir/paritaprevir/ritonavir (r)/dasabuvir (19.9%). Ribavirin (RBV) was administered in 198 patients (42.9%). SVRs occurred in 437/462 patients (94.6%). The SVRs ranged between 93.3% and 100% for genotypes 1-4. SVRs were achieved in 96.2% patients in the CT-met group vs 91.9% patients in the CT-unmet group (P = 0.049). Undetectable HCV RNA at week 4 occurred in 72.9% of the patients. In the univariate analysis, the factors associated with SVRs were lower liver stiffness, absence of cirrhosis, higher platelet count, higher albumin levels, no RBV dose reduction, undetectable HCV RNA at week 4 and CT-met group. In the multivariate analysis, only albumin was an independent predictor of treatment failure (P = 0.04). Eleven patients (2.4%) developed SAEs; 5.2% and 0.7% of the patients in the CT-unmet and CT-met groups, respectively (P = 0.003).
CONCLUSION A high proportion of patients with HCV infection achieved SVRs. For patients who did not meet the CT criteria, treatment regimens must be optimized.
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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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Desbois AC, Cacoub P. Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review. World J Gastroenterol 2017; 23:1697-1711. [PMID: 28321170 PMCID: PMC5340821 DOI: 10.3748/wjg.v23.i9.1697] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 11/10/2016] [Accepted: 02/08/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk.
METHODS We conducted a PubMed search and selected all studies found with the key words "HCV" or "hepatitis C virus" and "diabetes" or "insulin resistance". We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [i.e., severe liver fibrosis, response to antivirals, and the occurrence of hepatocellular carcinoma (HCC)].
RESULTS HCV infection is significantly associated with DM/IR compared with healthy volunteers and patients with hepatitis B virus infection. Glucose abnormalities were associated with advanced liver fibrosis, lack of sustained virologic response to interferon alfa-based treatment and with a higher risk of HCC development. As new antiviral therapies may offer a cure for HCV infection, such data should be taken into account, from a therapeutic and preventive point of view, for liver and non-liver consequences of HCV disease. The efficacy of antidiabetic treatment in improving the response to antiviral treatment and in decreasing the risk of HCC has been reported by some studies but not by others. Thus, the effects of glucose abnormalities correction in reducing liver events need further studies.
CONCLUSION Glucose abnormalities are strongly associated with HCV infection and show a negative impact on the main liver related outcomes.
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Ogawa E, Furusyo N, Yamashita N, Kawano A, Takahashi K, Dohmen K, Nakamuta M, Satoh T, Nomura H, Azuma K, Koyanagi T, Kotoh K, Shimoda S, Kajiwara E, Hayashi J. Effectiveness and safety of daclatasvir plus asunaprevir for patients with hepatitis C virus genotype 1b aged 75 years and over with or without cirrhosis. Hepatol Res 2017; 47:E120-E131. [PMID: 27142311 DOI: 10.1111/hepr.12738] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Revised: 04/03/2016] [Accepted: 04/22/2016] [Indexed: 02/08/2023]
Abstract
AIM The aim of this study was to evaluate the efficacy and safety of 24-week daclatasvir (NS5A inhibitor) plus asunaprevir (NS3/4 A protease inhibitor) treatment for elderly patients with hepatitis C virus (HCV) genotype 1b infection. METHODS This prospective, multicenter study consisted of 321 Japanese HCV genotype 1b patients who were interferon-ineligible/intolerant or non-responders to interferon-based regimens, including 103 (32.1%) aged ≥75 years and 127 (39.6%) with cirrhosis. Sustained virological response (SVR) at 24 weeks after the end of treatment and adverse effects were analyzed according to age. RESULTS The overall SVR rate was 90.3%. In terms of by age, 94.5% (69/73), 88.3% (128/145), and 90.3% (93/103) of the patients aged <65, 65-74, and ≥75 years, respectively, achieved SVR. For the entire cohort, pre-existent NS5A resistance-associated variants and prior simeprevir failure were independently associated with treatment failure. According to the analysis of patients without these unfavorable pretreatment factors, 90.8% (89/98) aged ≥75 years achieved SVR, although this was significantly lower than for those aged <65 years (98.5%, 66/67) (P < 0.05). The frequency of adverse effects was comparable for the <75 and ≥75 age groups, the most common being an elevated alanine aminotransferase level (>150 U/L, 8.7%), however, no decompensating events were seen. CONCLUSIONS Daclatasvir plus asunaprevir for HCV genotype 1b was well tolerated and effective for patients without pre-existent NS5A resistance-associated variants or simeprevir failure, irrespective of fibrosis status. However, it was less effective for very old patients aged ≥75 years compared to those aged <65.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Naoki Yamashita
- Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan
| | - Akira Kawano
- Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
| | | | - Kazufumi Dohmen
- Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan
| | - Makoto Nakamuta
- Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan
| | - Takeaki Satoh
- Center for Liver Disease, Kokura Medical Center, National Hospital Organization, Kitakyushu, Japan
| | - Hideyuki Nomura
- The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan
| | - Koichi Azuma
- Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan
| | | | - Kazuhiro Kotoh
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Shimoda
- Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | | | - Jun Hayashi
- Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan
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46
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Abstract
With the arrival of all-oral directly acting antiviral (DAA) therapy with high cure rates, the promise of hepatitis C virus (HCV) eradication is within closer reach. The availability of generic DAAs has improved access to countries with constrained resources. However, therapy is only one component of the HCV care continuum, which is the framework for HCV management from identifying patients to cure. The large number of undiagnosed HCV cases is the biggest concern, and strategies to address this are needed, as risk factor screening is suboptimal, detecting <20% of known cases. Improvements in HCV confirmation through either reflex HCV RNA screening or ideally a sensitive point of care test are needed. HCV notification (e.g., Australia) may improve diagnosis (proportion of HCV diagnosed is 75%) and may lead to benefits by increasing linkage to care, therapy and cure. Evaluations for cirrhosis using non-invasive markers are best done with a biological panel, but they are only moderately accurate. In resource-constrained settings, only generic HCV medications are available, and a combination of sofosbuvir, ribavirin, ledipasvir or daclatasvir provides sufficient efficacy for all genotypes, but this is likely to be replaced with pangenetypic regimens such as sofosbuvir/velpatasvir and glecaprevir/pibrentaasvir. In conclusion, HCV management in resource-constrained settings is challenging on multiple fronts because of the lack of infrastructure, facilities, trained manpower and equipment. However, it is still possible to make a significant impact towards HCV eradication through a concerted effort by individuals and national organisations with domain expertise in this area.
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Affiliation(s)
- Seng Gee Lim
- Division of Gastroenterology and Hepatology, National University Hospital, 1E Kent Ridge Road, Singapore, 119228, Singapore.
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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47
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Tacke F, Günther R, Buggisch P, Klinker H, Schober A, John C, Lutz T, Pfeiffer-Vornkahl H, Niederau C, Cornberg M, Sarrazin C, Mauss S. Treatment of HCV genotype 2 with sofosbuvir and ribavirin results in lower sustained virological response rates in real life than expected from clinical trials. Liver Int 2017; 37:205-211. [PMID: 27428297 DOI: 10.1111/liv.13206] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 07/11/2016] [Indexed: 01/07/2023]
Abstract
BACKGROUND AND AIMS Hepatitis C virus (HCV) infections with genotype 2 (GT2) are generally considered as easy to treat. The current standard therapy is 12 weeks of sofosbuvir and ribavirin. However, sustained virological response (SVR) rates varied substantially in distinct subgroups. Therefore, re-assessing the efficacy of interferon-free therapy in cohorts with larger patient numbers is warranted. METHODS The German Hepatitis C registry is a national multicenter cohort. Patients are treated at the discretion of the physician. Data are collected by a web-based data system and confirmed by plausibility checks and on-site monitoring. RESULTS A total of 265 (4.3%) of 6034 patients enrolled in the registry were infected with GT2, and 236 had initiated treatment (60% males, 98% Caucasian, median age 54 years). Treatment with sofosbuvir and ribavirin for 12 weeks achieved SVR at week 12 post-treatment (SVR12) in 136/164 (83%) patients. SVR12 rates for this regimen were 80% (35/44) in treatment-experienced patients, 74% (20/27) in cirrhotics and 75% (21/28) in patients with HCV-RNA ≥6 million IU/mL. The overall SVR rate in patients treated with sofosbuvir/ribavirin 12 weeks per protocol (PP), excluding therapy discontinuation or lost to follow-up, was 135/151 (89%). PP SVR12 rates were 91% for treatment naïve, 83% for cirrhotic and 80% for treatment-experienced patients respectively. CONCLUSIONS In this large GT2 cohort, sofosbuvir and ribavirin for 12 weeks achieved lower SVR rates compared to treatment outcomes expected from phase 3 trials. These findings highlight the need for establishing alternative treatment strategies for GT2 patients, especially in patients with unfavourable outcome factors.
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Affiliation(s)
- Frank Tacke
- Department of Medicine III, University Hospital Aachen, Aachen, Germany
| | - Rainer Günther
- Universitätsklinikum Schleswig-Holstein (UKSH), Kiel, Germany
| | - Peter Buggisch
- IFI-Institute for Interdisciplinary Medicine, Hamburg, Germany
| | | | | | | | | | | | - Claus Niederau
- St. Josef-Hospital, Katholisches Klinikum Oberhausen, Oberhausen, Germany
| | | | | | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Duesseldorf, Germany
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48
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Ho SB, Monto A, Peyton A, Kaplan DE, Byrne S, Moon S, Copans A, Rossaro L, Roy A, Le H, Dvory-Sobol H, Zhu Y, Brainard DM, Guyer W, Shaikh O, Fuchs M, Morgan TR. Efficacy of Sofosbuvir Plus Ribavirin in Veterans With Hepatitis C Virus Genotype 2 Infection, Compensated Cirrhosis, and Multiple Comorbidities. Clin Gastroenterol Hepatol 2017; 15:282-288. [PMID: 27237429 DOI: 10.1016/j.cgh.2016.05.024] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 05/10/2016] [Accepted: 05/13/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We conducted a phase 4, open-label study with limited exclusion criteria to evaluate the safety and efficacy of sofosbuvir and ribavirin in veterans with hepatitis C virus genotype 2 infection, and compensated cirrhosis. This population is often excluded from clinical studies. METHODS We performed a prospective study of treatment-naive (n = 47) and treatment-experienced (n = 19) patients with chronic hepatitis C virus genotype 2 infection and compensated cirrhosis at 15 Department of Veterans Affairs sites. All subjects were given sofosbuvir (400 mg, once daily) plus ribavirin (1000-1200 mg/day) in divided doses for 12 weeks. Patients with major psychiatric diseases or alcohol or substance use disorders were not excluded. The primary endpoint was sustained virologic response 12 weeks after therapy. RESULTS Fifty-two patients achieved a sustained virologic response 12 weeks after therapy (79%; 95% confidence interval, 67%-88%); 16 of these patients were treatment experienced (84%; 95% confidence interval, 60%-97%) and 36 were treatment naive (77%; 95% confidence interval, 62%-88%). All patients had at least 1 comorbidity. Thirty-five percent had depression, 24% had posttraumatic stress disorder, and 30% had anxiety disorder. In addition, 29% had current substance use. Of the 7 patients (11%) who discontinued the study treatment prematurely, 3 did so because of adverse events. The most common adverse events were fatigue, anemia, nausea, and headache. Serious adverse events occurred in 8 patients. Only 2 of the serious adverse events (anemia and nausea) were considered to be related to study treatment. CONCLUSIONS In a phase 4 study, 12 weeks treatment with sofosbuvir and ribavirin led to a sustained virologic response 12 weeks after therapy in almost 80% of veterans with hepatitis C virus genotype 2 infection, compensated cirrhosis, and multiple comorbidities, regardless of their treatment history. ClinicalTrials.gov, Number: NCT02128542.
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Affiliation(s)
- Samuel B Ho
- Veterans Affairs San Diego Healthcare System, San Diego, California.
| | - Alexander Monto
- San Francisco Veterans Affairs Healthcare System, San Francisco, California
| | - Adam Peyton
- Miami Veterans Affairs Healthcare System, Miami, Florida
| | - David E Kaplan
- Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania
| | - Sean Byrne
- Gilead Sciences, Foster City, California
| | - Scott Moon
- Gilead Sciences, Foster City, California
| | | | | | - Anupma Roy
- Gilead Sciences, Foster City, California
| | - Hadley Le
- Gilead Sciences, Foster City, California
| | | | - Yanni Zhu
- Gilead Sciences, Foster City, California
| | | | | | - Obaid Shaikh
- Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
| | - Michael Fuchs
- Richmond Veterans Affairs Medical Center, Richmond, Virginia
| | - Timothy R Morgan
- Veterans Affairs Long Beach Healthcare System, Long Beach, California
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49
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Tapper EB, Bacon BR, Curry MP, Dieterich DT, Flamm SL, Guest LE, Kowdley KV, Lee Y, Tsai NC, Younossi ZM, Afdhal NH. Real-world effectiveness for 12 weeks of ledipasvir-sofosbuvir for genotype 1 hepatitis C: the Trio Health study. J Viral Hepat 2017; 24:22-27. [PMID: 27730717 DOI: 10.1111/jvh.12611] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 07/13/2016] [Indexed: 12/12/2022]
Abstract
Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir-sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted.
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Affiliation(s)
- E B Tapper
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - B R Bacon
- Division of Gastroenterology/Hepatology, Saint Louis University School of Medicine, Saint Louis, MO, USA
| | - M P Curry
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - D T 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 E 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
| | - N C Tsai
- The Liver Center, Queen's Medical Center, Honolulu, HI, USA
| | - Z M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA
| | - N H Afdhal
- Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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50
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Wilson EM, Rosenthal ES, Kattakuzhy S, Tang L, Kottilil S. Clinical Laboratory Testing in the Era of Directly Acting Antiviral Therapies for Hepatitis C. Clin Microbiol Rev 2017; 30:23-42. [PMID: 27795306 PMCID: PMC5217793 DOI: 10.1128/cmr.00037-16] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Directly acting antiviral (DAA) combination therapies for chronic hepatitis C virus (HCV) infection are highly effective, but treatment decisions remain complex. Laboratory testing is important to evaluate a range of viral, host, and pharmacological factors when considering HCV treatment, and patients must be monitored during and after therapy for safety and to assess the viral response. In this review, we discuss the laboratory tests relevant for the treatment of HCV infection in the era of DAA therapy, grouped according to viral and host factors.
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Affiliation(s)
- Eleanor M Wilson
- Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland, USA
- Critical Care Medicine Department of the NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
| | - Elana S Rosenthal
- Critical Care Medicine Department of the NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
| | - Sarah Kattakuzhy
- Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland, USA
- Critical Care Medicine Department of the NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
| | - Lydia Tang
- Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland, USA
| | - Shyam Kottilil
- Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland, USA
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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