Journal ArticleDOI
Grazoprevir–Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial
Stefan Zeuzem,Reem Ghalib,K. Rajender Reddy,Paul J. Pockros,Ziv Ben Ari,Yue Zhao,Deborah D. Brown,Shuyan Wan,Mark J. DiNubile,Bach-Yen Nguyen,Michael N. Robertson,Janice Wahl,Eliav Barr,Joan R. Butterton +13 more
TLDR
Grazoprevir and elbasvir were evaluated in a randomized, blinded, placebo-controlled trial in treatment-naive patients with hepatitis C virus (HCV) infection.Abstract:
BACKGROUND Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection. OBJECTIVE To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients. DESIGN Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467). SETTING 60 centers in the United States, Europe, Australia, Scandinavia, and Asia. PATIENTS Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection. INTERVENTION Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy. MEASUREMENTS Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups. RESULTS Among 421 participants, 194 (46%) were women, 157 (37%) were nonwhite, 382 (91%) had genotype 1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95% [95% CI, 92% to 97%]) achieved SVR12, including 144 of 157 (92% [CI, 86% to 96%]) with genotype 1a, 129 of 131 (99% [CI, 95% to 100%]) with genotype 1b, 18 of 18 (100% [CI, 82% to 100%]) with genotype 4, 8 of 10 (80% [CI, 44% to 98%]) with genotype 6, 68 of 70 (97% [CI, 90% to 100%]) with cirrhosis, and 231 of 246 (94% [CI, 90% to 97%]) without cirrhosis. Virologic failure occurred in 13 patients (4%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI, -5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17%), fatigue (16%), and nausea (9%). LIMITATION The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections. CONCLUSION Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection. PRIMARY FUNDING SOURCE Merck & Co.read more
Citations
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Treatment failure with DAA therapy: Importance of resistance.
TL;DR: In this paper, the importance of viral resistance mainly depends on the DAA regimen and HCV genotype, and resistance testing may help to optimise therapy in certain subgroups of patients.
Journal ArticleDOI
Protease inhibitor therapy for hepatitis C virus-infection.
P de Leuw,Christoph Stephan +1 more
TL;DR: Third-generation pan-genotypic NS3/4A protease inhibitors show high antiviral activity and a genetic resistance barrier with cure rates of over 95% when combined with an NS5A inhibitor, irrespective of baseline resistance associated variants (RASs) being present.
Journal ArticleDOI
Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990–2019
Dan-Yi Zeng,Jing-Mao Li,Su Lin,Xuan Dong,Xuan Dong,Jia You,Qing-Qing Xing,Yan-Dan Ren,Wei-Ming Chen,Yan-Yan Cai,Kuangnan Fang,Mei-Zhu Hong,Yueyong Zhu,Jin-Shui Pan +13 more
TL;DR: In this paper, the authors identified a negative association between socioeconomic development status and the burden of acute viral hepatitis (AVH) in the Global Burden of Disease (GBD) 2019 database.
Journal ArticleDOI
Screening for Hepatitis C Virus Infection in Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
Roger Chou,Tracy Dana,Rongwei Fu,Bernadette Zakher,Jesse Wagner,Shaun Ramirez,Sara Grusing,Janice H. Jou +7 more
TL;DR: Direct evidence on the effects of HCV screening on clinical outcomes remains unavailable, but DAA regimens were associated with SVR rates greater than 5% and few short-term harms relative to older antiviral therapies.
Journal ArticleDOI
Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 4 infection: A pooled analysis.
Tarik Asselah,Hendrik W. Reesink,Jan Gerstoft,Victor de Ledinghen,Paul J. Pockros,Michael N. Robertson,Peggy Hwang,Ernest Asante-Appiah,Janice Wahl,Bach-Yen Nguyen,Eliav Barr,Rohit Talwani,Lawrence Serfaty +12 more
TL;DR: The aim of this integrated analysis was to assess the efficacy of the once‐daily combination of elbasvir 50 mg and grazoprevir 100 mg, with and without ribavirin in HCV genotype 4 (GT4)‐infected participants enrolled in the Phase 2/3 clinical programme withElbasvir/grazoprevIR.
References
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Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis
Kris V. Kowdley,Stuart C. Gordon,K. Rajender Reddy,Lorenzo Rossaro,David E. Bernstein,Eric Lawitz,Mitchell L. Shiffman,Eugene R. Schiff,Reem Ghalib,Michael J. Ryan,Vinod K. Rustgi,Mario Chojkier,Robert Herring,Adrian M. Di Bisceglie,Paul J. Pockros,G. Mani Subramanian,Di An,Evguenia S. Svarovskaia,Robert H. Hyland,Phillip S. Pang,William T. Symonds,John G. McHutchison,Andrew J. Muir,David Pound,Michael W. Fried +24 more
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Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.
Jordan J. Feld,Kris V. Kowdley,Eoin Coakley,Samuel H. Sigal,David R. Nelson,Darrell H. G. Crawford,Ola Weiland,Humberto Aguilar,Junyuan Xiong,Tami Pilot-Matias,Barbara DaSilva-Tillmann,Lois Larsen,Thomas Podsadecki,B. Bernstein +13 more
TL;DR: In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r-ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation.
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