Read by QxMD icon Read


Soon Young Ko, Won Hyeok Choe
The advent of novel, direct-acting antiviral (DAA) regimens for hepatitis C viral (HCV) infection has revolutionized its treatment by producing a sustained virologic response of more than 95% with few side effects and no comorbidities in the general population. Until recently, ideal DAA regimens have not been available to patients with severe renal impairment and end-stage renal disease because there are limited data on the pharmacokinetics, safety, and efficacy of treatment in this unique population. In a hemodialysis context, identifying patients in need of treatment and preventing HCV transmission may also be a matter of concern...
March 16, 2018: Clinical and Molecular Hepatology
Franck Maunoury, Aurore Clément, Chizoba Nwankwo, Laurie Levy-Bachelot, Armand Abergel, Vincent Di Martino, Eric Thervet, Isabelle Durand-Zaleski
OBJECTIVE: To assess the cost-effectiveness of the elbasvir/grazoprevir (EBR/GZR) regimen in patients with genotype 1 chronic hepatitis C virus (HCV) infection with severe and end-stage renal disease compared to no treatment. DESIGN: This study uses a health economic model to estimate the cost-effectiveness of treating previously untreated and treatment experienced chronic hepatitis C patients who have severe and end stage renal disease with the elbasvir-grazoprevir regimen versus no treatment in the French context...
2018: PloS One
Christine M Durand, Mary G Bowring, Diane M Brown, Michael A Chattergoon, Guido Massaccesi, Nichole Bair, Russell Wesson, Ashraf Reyad, Fizza F Naqvi, Darin Ostrander, Jeremy Sugarman, Dorry L Segev, Mark Sulkowski, Niraj M Desai
Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource. Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R- transplantation)...
March 6, 2018: Annals of Internal Medicine
Graham R Foster, Kosh Agarwal, Matthew E Cramp, Sulleman Moreea, Stephen Barclay, Jane Collier, Ashley S Brown, Stephen D Ryder, Andrew Ustianowski, Daniel M Forton, Ray Fox, Fiona Gordon, William M Rosenberg, David J Mutimer, Jiejun Du, Christopher L Gilbert, Ernest Asante-Appiah, Janice Wahl, Michael N Robertson, Eliav Barr, Barbara Haber
Many direct-acting antiviral regimens have reduced activity in people with hepatitis C virus (HCV) genotype (GT)3 infection and cirrhosis. The C-ISLE study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) plus sofosbuvir (SOF) with and without ribavirin (RBV) in compensated cirrhotic participants with GT3 infection. This was a phase 2, randomized, open-label study. Treatment-naive participants received EBR/GZR + SOF + RBV for 8 weeks or EBR/GZR + SOF for 12 weeks and peginterferon/RBV treatment-experienced participants received EBR/GZR + SOF ± RBV for 12 weeks or EBR/GZR + SOF for 16 weeks...
February 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Tarik Asselah, Hendrik Reesink, Jan Gerstoft, Victor de Ledinghen, Paul J Pockros, Michael Robertson, Peggy Hwang, Ernest Asante-Appiah, Janice Wahl, Bach-Yen Nguyen, Eliav Barr, Rohit Talwani, Lawrence Serfaty
BACKGROUND & AIMS: The aim of this integrated analysis was to assess the efficacy of the once-daily combination of elbasvir (EBR) 50 mg and grazoprevir (GZR) 100 mg, with and without ribavirin (RBV) in HCV genotype 4 (GT4)-infected participants enrolled in the Phase 2/3 clinical program with EBR/GZR. METHODS: Treatment-naïve and treatment-experienced participants 18 years of age or older with chronic HCV GT4 infection and baseline HCV RNA ≥10,000 IU/mL were included in the analysis...
February 20, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Kazuo Tarao, Akira Sato
Oral direct-acting antivirals comprise the main therapy for hepatitis C virus (HCV)-associated liver disease in Japan. Daclatasvir/asunaprevir is the primary agent and sofosbuvir/ledipasvir is the secondary agent for HCV genotype 1b. Ombitasvir/paritaprevir/ritonavir was also recommended as a therapy for HCV genotype 1b. More recently, elbasvir (NS5A inhibitor)/grazoprevir (NS3/4A protease inhibitor) was also recommended as a potent therapy for HCV genotype 1b infection. This agent achieved an SVR12 as high as 96...
September 2017: Case Reports in Gastroenterology
Christophe Hézode
Direct-acting antivirals (DAAs) have transformed traditional treatment options for hepatitis C virus (HCV) infection. DAA combinations have been shown to be highly effective in reducing the burden of chronic HCV infection in clinical trials and have been recommended by the European Association for the Study of the Liver (EASL) treatment guidelines. This review examines the results of second-generation DAA combinations in real-life clinical practice in patients with genotypes 1-3 and in those co-infected with HIV (real-world data in genotypes 4-6 are rare)...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Nancy Reau, Michael N Robertson, Hwa-Ping Feng, Luzelena Caro, Wendy W Yeh, Bach-Yen T Nguyen, Janice Wahl, Eliav Barr, Peggy Hwang, Stephanie O Klopfer
Concomitant proton pump inhibitor (PPI) use reduces plasma concentrations of certain nonstructural protein 5A inhibitors, which are key components of modern hepatitis C infection (HCV) treatments. These reduced concentrations may decrease efficacy, leading to challenging treatment failures due to the development of resistance-associated substitutions. This post-hoc analysis assessed 12-week sustained viral response (SVR12) and pharmacokinetics of fixed-dose combination elbasvir/grazoprevir (EBR/GZR) in patients with HCV infection and self-reported PPI use...
October 2017: Hepatology Communications
Petr Husa, Libuše Husová
Hepatitis C virus infection (HCV) is one of the leading causes of chronic liver disease worldwide. The new fixed-dose combination of the highly potent second wave first generation NS5A inhibitor elbasvir (50 mg) and the second generation protease inhibitor grazoprevir (100 mg) is contained in the drug Zepatier. This combination is indicated for the treatment of patients chronically infected with HCV genotypes 1 or 4. Between June and August 2017, the treatment was initiated in 22 patients with chronic viral hepatitis C, with 17 patients being treated in the Department of Infectious Diseases University Hospital Brno and five patients in the Center of Cardiovascular and Transplant Surgery in Brno...
December 2017: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
Stefan Zeuzem, Lawrence Serfaty, John Vierling, Wendy Cheng, Jacob George, Jan Sperl, Simone Strasser, Hiromitsu Kumada, Peggy Hwang, Michael Robertson, Janice Wahl, Eliav Barr, Rohit Talwani, Heather Platt
BACKGROUND: Genotype 1b (GT1b) is the most common subtype of the hepatitis C virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b infection from 30 countries who received elbasvir/grazoprevir for 12 weeks. METHODS: This is a retrospective analysis of data from participants with chronic HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks...
January 17, 2018: Journal of Gastroenterology
Hwa-Ping Feng, Luzelena Caro, Christine M Fandozzi, Zifang Guo, Jennifer Talaty, Dennis Wolford, Deborah Panebianco, Marian Iwamoto, Joan R Butterton, Wendy W Yeh
Elbasvir (EBR)/grazoprevir (GZR) may be coadministered with immunosuppressant drugs in posttransplant people who are infected with hepatitis C virus. The aim of the present study was to assess the safety and pharmacokinetic interactions between EBR and GZR and single doses of cyclosporine, tacrolimus, mycophenolate mofetil (MMF), and prednisone. This was a 4-part, open-label study in 58 healthy volunteers. Participants received single doses of cyclosporine 400 mg, tacrolimus 2 mg, MMF 1 g, or prednisone 40 mg alone or in the presence of once-daily EBR 50 mg/GZR 200 mg...
January 12, 2018: Journal of Clinical Pharmacology
Donald F Chute, Raymond T Chung, Meghan E Sise
Hepatitis C virus infection (HCV) is a common comorbidity in patients who have undergone kidney transplantation and is associated with increased morbidity and mortality compared with recipients who do not have chronic HCV infection. Because interferon-α-based therapies can precipitate acute rejection, they are relatively contraindicated after kidney transplantation. Thus, the majority of kidney transplant recipients with HCV remain untreated. There are now all-oral, interferon-free direct-acting antiviral therapies for HCV infection that are extremely effective and well tolerated in the general population...
January 9, 2018: Kidney International
Hussien Ahmed, Abdelrahman Ibrahim Abushouk, Amr Menshawy, Attia Attia, Arwa Mohamed, Ahmed Negida, Mohamed M Abdel-Daim
BACKGROUND AND AIM: Grazoprevir is an NS3/4A protease inhibitor (PI), while elbasvir is an NS5A inhibitor. We performed this meta-analysis to directly compare grazoprevir plus elbasvir and ribavirin regimen vs. grazoprevir and elbasvir without ribavirin in the treatment of hepatitis C virus genotype 1 infection and to precisely evaluate the efficacy of the latter regimen in cirrhotic, IL28 CC genotype patients and those coinfected with human immunodeficiency virus. MATERIAL AND METHODS: A computer literature search of PubMed, Scopus, EBSCO, Embase, and Cochrane central was conducted...
December 27, 2017: Annals of Hepatology
William L Marshall, Hwa-Ping Feng, Larissa Wenning, Graigory Garrett, Xiaobi Huang, Fang Liu, Deborah Panebianco, Luzelena Caro, Christine Fandozzi, Kenneth C Lasseter, Richard A Preston, Thomas Marbury, Joan R Butterton, Marian Iwamoto, Wendy W Yeh
BACKGROUND: The combination of elbasvir and grazoprevir is approved for the treatment of hepatitis C virus genotype 1 or 4 infection. OBJECTIVE: To evaluate the pharmacokinetics and safety of single-dose elbasvir 50 mg in participants with hepatic impairment. METHODS: Participants with mild, moderate, or severe hepatic impairment and age-, sex-, and weight-matched healthy controls were enrolled in a 3-part, open-label, sequential-panel, single-dose pharmacokinetic study...
December 15, 2017: European Journal of Drug Metabolism and Pharmacokinetics
A Brown, C Hézode, E Zuckerman, G R Foster, A Zekry, S K Roberts, F Lahser, C Durkan, C Badshah, B Zhang, M Robertson, J Wahl, E Barr, B Haber
People with hepatitis C virus (HCV) infection other than genotype 1 represent a heterogeneous group. The aim of the phase 2 C-SCAPE study was to evaluate elbasvir/grazoprevir (EBR/GZR), with or without ribavirin (RBV), in participants with HCV genotype 2, 4, 5 or 6 infection. This was a part randomized, open-label, parallel-group study (NCT01932762; PN047-03) of treatment-naive, non-cirrhotic participants. Participants with HCV genotype 2 infection received GZR 100 mg+RBV±EBR 50 mg for 12 weeks and those with genotype 4, 5 or 6 infection were randomized to receive EBR/GZR±RBV for 12 weeks...
November 20, 2017: Journal of Viral Hepatitis
Hosnieh Fathi, Andrew Clark, Nathan R Hill, Geoffrey Dusheiko
BACKGROUND: Six distinct genetic variants (genotypes 1 - 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions than in others but, globally, genotype 3 (GT3) is the second most common. Patients infected with HCV GT1, 2, 4, 5 or 6 recover to a greater extent, as measured by sustained virological response (SVR), following treatment with regimens based on direct-acting antivirals (DAAs) than after treatment with older regimens based on pegylated interferon (Peg-IFN)...
November 16, 2017: BMC Infectious Diseases
Victor de Lédinghen, Claire Laforest, Christophe Hézode, Stanislas Pol, Alain Renault, Laurent Alric, Dominique Larrey, Sophie Métivier, Albert Tran, Caroline Jézéquel, Didier Samuel, Fabien Zoulim, Christelle Tual, Aurélie Pailhé, Séverine Gibowski, Marc Bourlière, Eric Bellissant, Jean-Michel Pawlotsky
Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral-based regimens is commonly associated with emergence of resistance-associated substitutions (RAS). Re-treatment of patients who failed prior direct-acting antivirals remain challenging. The aim of this prospective and randomized study was to evaluate the efficacy (SVR12 primary endpoint) and safety of sofosbuvir + grazoprevir/elbasvir + ribavirin for 16 or 24 weeks in patients who had failed to achieve SVR on previous NS5A or NS3-based therapy and with evidence of RAS at failure...
October 25, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Feng Xu, Yong-Li Zhong, Hongming Li, Ji Qi, Richard Desmond, Zhiguo J Song, Jeonghan Park, Tao Wang, Matthew Truppo, Guy R Humphrey, Rebecca T Ruck
A practical and asymmetric synthesis of a functionalized trans-cyclopropoxy building block for the preparation of the HCV NS3/4a protease inhibitor grazoprevir is reported. Intramolecular SN2 displacement-ring closure, followed by a Baeyer-Villiger oxidation, yields the desired trans-cyclopropanol with full control of diastereoselectivity. A terminal alkyne is then effectively installed using LiNH(CH2)2NEt2. Starting from (S)-epichlorohydrin, the cyclopropoxy building block is prepared in 51% overall yield with >99...
October 20, 2017: Organic Letters
Yan Huang, Ming-Hui Li, Min Hou, Yao Xie
BACKGROUND: The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE: Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population...
October 15, 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
Shelby Corman, Elamin H Elbasha, Steven N Michalopoulos, Chizoba Nwankwo
OBJECTIVE: To evaluate the cost-utility of treatment with elbasvir/grazoprevir (EBR/GZR) regimens compared with ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± RBV), and sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C genotype (GT) 1 infection. METHODS: A Markov cohort state-transition model was constructed to evaluate the cost-utility of EBR/GZR ± RBV over a lifetime time horizon from the payer perspective...
September 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"