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hepatitis C antiviral

E D Manea, I Stefan, C Olariu, O C Calina, R E Jipa, A Hristea
BACKGROUND: In our country, the national program for hepatitis C virus treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir was approved for patients with stage four of liver fibrosis and stage three associated with specific comorbidities. Our aim was to analyze the characteristics associated with the presence of adverse events in patients receiving this antiviral regimen, with ribavirin in cirrhotic patients. METHODS: We prospectively studied a cohort of adults with hepatitis C virus infection with Child A cirrhosis, treated for 12 weeks with ombitasvir/paritaprevir/ritonavir/dasabuvir and ribavirin, which have been followed in an infectious diseases tertiary-care hospital...
January 2018: Acta Gastro-enterologica Belgica
Muhammad Tahir, Levea Charles
No abstract text is available yet for this article.
March 15, 2018: American Journal of Therapeutics
Moisés Uriarte-Pinto, Herminia Navarro-Aznarez, Natalia De La Llama-Celis, Piedad Arazo-Garcés, Ana María Martínez-Sapiña, María Reyes Abad-Sazatornil
Background HIV-HCV coinfection produces high morbi-mortality. Direct-acting antivirals (DAAs) have shown high efficacy, although special attention should be paid to the risk of drug interactions. However, due to the lack of representativeness of coinfected patients in clinical trials, it is important to know real-world results. Objective To evaluate DAA treatment effectiveness in coinfected patients. We also analyse safety profile of DAA treatment and drug interactions between HCV and HIV therapy. Setting Descriptive study carried in a tertiary hospital of Spain Method HIV-HCV coinfected patients treated with DAAs between November 2014 and June 2016 were included...
March 20, 2018: International Journal of Clinical Pharmacy
Nagraj Mani, Andrew G Cole, Janet R Phelps, Andrzej Ardzinski, Kyle D Cobarrubias, Andrea Cuconati, Bruce D Dorsey, Ellen Evangelista, Kristi Fan, Fang Guo, Haitao Guo, Ju-Tao Guo, Troy O Harasym, Salam Kadhim, Steven G Kultgen, Amy C H Lee, Alice H L Li, Quanxin Long, Sara A Majeski, Richeng Mao, Kevin D McClintock, Stephen P Reid, Rene Rijnbrand, Nicholas M Snead, Holly M Micolochick Steuer, Kim Stever, Sunny Tang, Xiaohe Wang, Qiong Zhao, Michael J Sofia
AB-423 is a sulfamoylbenzamide (SBA) class of HBV capsid inhibitor in Phase 1 clinical trials. In cell culture models AB-423 showed potent inhibition of HBV replication (EC50 /EC90 = 0.08-0.27 μM/0.33-1.32 μM) with no significant cytotoxicity (CC50 >10 μM). Addition of 40% human serum resulted in a 5-fold increase in the EC50 values. AB-423 inhibited HBV genotypes A through D and nucleos/tide-resistant variants in vitro Treatment of HepDES19 cells with AB-423 resulted in capsid particles devoid of encapsidated pgRNA and rcDNA indicating it is a class II capsid inhibitor...
March 19, 2018: Antimicrobial Agents and Chemotherapy
Alajos Pár, Gabriella Pár
More than 25 years after the discovery of hepatitis C virus, the development of the direct acting antivirals can lead to the regional or long-term global elimination of the virus with over 90% efficacy. This is the success of basic and clinical translational research. Yet, some unsolved challanges remain, such as the great number of unidentified patients who are not aware of their condition, the limited access to the therapy due to the high prices of the drugs, and the treatment of resistance-associated variants...
March 2018: Orvosi Hetilap
Hung-Chih Yang, Hsiao-Hui Tsou, Sung-Nan Pei, Cheng-Shyong Chang, Jia-Hong Chen, Ming Yao, Shyh-Jer Lin, Johnson Lin, Quan Yuan, Ningshao Xia, Tsang-Wu Liu, Pei-Jer Chen, Ann-Lii Cheng, Chiun Hsu
BACKGROUND AND AIMS: Absence or low anti-hepatitis B (HBV) surface antibody (anti-HBs) is associated with increased risk of HBV reactivation in lymphoma patients with resolved HBV infection receiving rituximab-containing chemotherapy. Quantification of anti-HBV core antibody (anti-HBc) is a new marker associated with the natural history and treatment response of chronic HBV infection. This study investigated whether baseline anti-HBc and anti-HBs levels may better predict HBV reactivation...
March 15, 2018: Journal of Hepatology
Yao-Chun Hsu, Terry Cheuk-Fung Yip, Hsiu J Ho, Vincent Wai-Sun Wong, Yen-Tsung Huang, Hashem B El-Serag, Teng-Yu Lee, Ming-Shiang Wu, Jaw-Town Lin, Grace Lai-Hung Wong, Chun-Ying Wu
BACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) during antiviral therapy in patients with chronic hepatitis B (CHB) is inadequately predicted by the scores built from untreated patients. We aimed to develop and validate a risk score to predict HCC in CHB patients on entecavir or tenofovir treatment. METHODS: This study analyzed population-wide data from the healthcare databases in Taiwan and Hong Kong to identify CHB patients continuously receiving entecavir or tenofovir...
March 15, 2018: Journal of Hepatology
Antonietta Romano, Paolo Angeli, Sara Piovesan, Franco Noventa, Georgios Anastassopoulos, Liliana Chemello, Luisa Cavalletto, Martina Gambato, Francesco Paolo Russo, Patrizia Burra, Valter Vincenzi, Pier Giorgio Scotton, Sandro Panese, Diego Tempesta, Tosca Bertin, Maurizio Carrara, Antonio Carlotto, Franco Capra, Giada Carolo, Giovanna Scroccaro, Alfredo Alberti
BACKGROUND & AIMS: Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of Hepatocellular carcinoma (HCC) during/after therapy with DAAs. Aim of this study was to evaluate incidence of newly diagnosed hepatocellular carcinoma and associated risk factors in patients with advanced hepatitis C treated with DAAs. METHODS: The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in Veneto region (Italy)...
March 15, 2018: Journal of Hepatology
Massimo Puoti, Graham R Foster, Stanley Wang, David Mutimer, Edward Gane, Christophe Moreno, Ting Tsung Chang, Samuel S Lee, Rui Marinho, Jean-Francois DuFour, Stanislas Pol, Christophe Hezode, Stuart C Gordon, Simone I Strasser, Paul J Thuluvath, Zhenzhen Zhang, Sandra Lovell, Tami Pilot-Matias, Federico J Mensa
BACKGROUND AND AIMS: Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase 2 or 3 clinical trials, G/P achieved sustained virologic response 12 weeks post-treatment (SVR12) rates of 93-100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P in non-cirrhotic patients with HCV GT1-6 infection was performed. METHODS: Data were pooled from nine phase 2 and 3 trials and included patients with chronic HCV GT 1, 2, 3, 4, 5 or 6 infection without cirrhosis who received G/P (300mg/120mg) for either 8 or 12 weeks...
March 15, 2018: Journal of Hepatology
Victor Virlogeux, Pascale Berthillon, Isabelle Bordes, Sylvie Larrat, Stéphanie Crouy, Caroline Scholtès, Pierre Pradat, Marianne Maynard, Fabien Zoulim, Vincent Leroy, Isabelle Chemin, Christian Trépo, Marie-Anne Petit
INTRODUCTION: Presence of anti-E1E2 antibodies was previously associated with spontaneous cure of hepatitis C virus (HCV) and predictive before treatment of a sustained virological response (SVR) to bi- or tri-therapy in naïve or experienced patients, regardless of HCV genotype. We investigated the impact of anti-E1E2 seroprevalence at baseline on treatment response in patients receiving direct-acting antiviral (DAA) therapy. MATERIAL AND METHODS: We screened anti-E1E2 antibodies by ELISA in serum samples collected at treatment initiation for two groups of patients: 59 with SVR at the end of DAA treatment and 44 relapsers after DAA treatment...
March 15, 2018: Clinics and Research in Hepatology and Gastroenterology
Sarene Koh, Janine Kah, Christine Y L Tham, Ninghan Yang, Erica Ceccarello, Adeline Chia, Margaret Chen, Atefeh Khakpoor, Andrea Pavesi, Anthony T Tan, Maura Dandri, Antonio Bertoletti
BACKGROUND & AIMS: Strategies to develop virus-specific T cells against hepatic viral infections have been hindered by safety concerns. We engineered non-lytic human T cells to suppress replication of hepatitis B virus (HBV) and hepatitis C virus (HCV) without overt hepatotoxicity, and investigated their antiviral activity. METHODS: We electroporated resting T cells or T cells activated by anti-CD3 with mRNAs encoding HBV or HCV-specific T-cell receptors (TCRs) to create 2 populations of TCR-reprogrammed T cells...
March 14, 2018: Gastroenterology
Yibeltal Assefa, Peter S Hill, Owain D Williams
At September's 2017 United Nations General Assembly, a state-of-the-art HIV medicine was announced to be made available at just $75 per person per year. There have been a number of strategies that the global AIDS community and countries have utilized to reduce prices and make antiretrovirals (ARVs) accessible for people living with HIV/AIDS. There appears to be an opportunity for the treatment of hepatitis C virus infection using direct-acting antivirals (DAAs) to benefit from the often painful and laboured history of driving down the prices of ARVs...
March 14, 2018: International Journal of Infectious Diseases: IJID
Vladimir Reinharz, Harel Dahari, Danny Barash
Age-structured PDE models have been developed to study viral infection and treatment. However, they are notoriously difficult to solve. Here, we investigate the numerical solutions of an age-based multiscale model of hepatitis C virus (HCV) dynamics during antiviral therapy and compare them with an analytical approximation, namely its long-term approximation. First, starting from a simple yet flexible numerical solution that also considers an integral approximated over previous iterations, we show that the long-term approximation is an underestimate of the PDE model solution as expected since some infection events are being ignored...
March 14, 2018: Mathematical Biosciences
Adel Abdel-Moneim, Alaa Aboud, Mohamed Abdel-Gabbar, Mohamed Zanaty, Mohamed Ramadan
BACKGROUND: The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). However, rare clinical trials have been reported on the combination regimen of sofosbuvir (SOF) with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) plus ribavirin (RBV) for treated patients with HCV genotype 4 (GT4) infection. AIMS: To clarify the retreatment efficacy and safety of the recent regimen, SOF with OBV/PTV/r + RBV, for chronic HCV GT4-experienced patients who failed treatment with DAA-based regimens...
March 15, 2018: Digestive Diseases and Sciences
Young-A Heo, Emma D Deeks
A fixed-dose combination of the hepatitis C virus (HCV) NS5B polymerase inhibitor sofosbuvir, the HCV NS5A inhibitor velpatasvir and the HCV NS3/4A protease inhibitor voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir; Vosevi® ) is approved in the EU for the treatment of chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in adults. In the phase III POLARIS trials, in patients who had HCV genotype 1-6 infection with or without compensated cirrhosis, overall rates of sustained virological response at 12 weeks post-treatment (SVR12 ) with sofosbuvir/velpatasvir/voxilaprevir were high after 8 weeks of treatment in direct-acting antiviral (DAA)-naïve patients and 12 weeks of treatment in DAA-experienced patients...
March 15, 2018: Drugs
Andrea Galli, Helene Mens, Judith M Gottwein, Jan Gerstoft, Jens Bukh
Ribavirin (RBV) is a broad-spectrum antiviral active against a wide range of RNA viruses. Despite having been used for decades in the treatment of chronic hepatitis C virus (HCV) infection, the precise mechanism of action of RBV is unknown. In other viruses, it inhibits propagation by increasing the rate of G-to-A and C-to-U transitions. Here, we utilized the J6/JFH1 HCV cell-culture system to investigate whether RBV inhibits HCV through the same mechanism. Infected Huh7.5 cells were treated with increasing concentrations of RBV or its phosphorylated forms...
March 15, 2018: Scientific Reports
Alexandre Karras
Cryoglobulins are immunoglobulins that undergo reversible precipitation at low temperatures. They can induce systemic vasculitis, characterized by purpuric cutaneous lesions, arthritis, peripheral neuropathy, hypocomplementemia and glomerular disease. Renal pathology reveals membranoproliferative glomerulonephritis, with particularly intense mesangial cell proliferation and infiltration by macrophages, associated with intracapillary thrombi. This renal disease presents as a nephritic syndrome, with heavy proteinuria, haematuria severe hypertension and rapidly progressive kidney failure that can lead to end-stage renal disease...
March 12, 2018: Néphrologie & Thérapeutique
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
Lin Cao, Jizheng Chen, Yaxin Wang, Yuting Yang, Jie Qing, Zihe Rao, Xinwen Chen, Zhiyong Lou
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. Although several HCV protease/polymerase inhibitors were recently approved by U.S. FDA, the combination of antivirals targeting multiple processes of HCV lifecycle would optimize anti-HCV therapy and against potential drug-resistance. Viral entry is an essential target step for antiviral development, but FDA-approved HCV entry inhibitor remains exclusive. Here we identify serotonin 2A receptor (5-HT2A R) is a HCV entry factor amendable to therapeutic intervention by a chemical biology strategy...
March 14, 2018: Protein & Cell
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