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direct acting antiviral

Emma Hathorn, Ahmed M Elsharkawy
Genotype 4 chronic hepatitis C (G4 HCV) accounts for 13% of worldwide HCV infections; with 10 million people infected with the virus across the world. Up to the end of 2013, the only treatment option for G4 HCV was treatment with pegylated interferon and ribavirin for 24-48 weeks. Since late 2013, treatment of G4 HCV has been transformed by the licensing of many directly acting antiviral agents (DAA). It is an exciting time to be involved in the management of HCV generally and G4 particularly. Interferon-free DAA regimens are now a reality for G4 HCV...
2016: BMJ Open Gastroenterology
Satoru Hagiwara, Naoshi Nishida, Tomohiro Watanabe, Toshiharu Sakurai, Hiroshi Ida, Yasunori Minami, Masahiro Takita, Tomohiro Minami, Mina Iwanishi, Hirokazu Chishina, Kazuomi Ueshima, Yoriaki Komeda, Tadaaki Arizumi, Masatoshi Kudo
OBJECTIVE: Treatment for chronic hepatitis C has recently developed in a very rapid manner. In Japan, in September 2014, IFN-free asunaprevir (ASV) and daclatasvir (DCV) became available for combination therapy. We report the treatment outcomes achieved at our hospital using this combination therapy. METHODS: Sustained virological response (SVR) 24 could be evaluated in 120 of 125 patients with chronic liver disease type C who visited our hospital and were treated with ASV/DCV after September 2014, and these patients were analyzed...
2016: Digestive Diseases
Laurent Alric, Caroline Besson, Nathanael Lapidus, Juliette Jeannel, Jean-Marie Michot, Patrice Cacoub, Danielle Canioni, Stanislas Pol, Frédéric Davi, Pascaline Rabiega, Loic Ysebaert, Delphine Bonnet, Olivier Hermine
: Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. METHODS: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL...
2016: PloS One
Zobair M Younossi, Atsushi Tanaka, Yuichiro Eguchi, Young-Suk Lim, Ming-Lung Yu, Norifumi Kawada, Yock Young Dan, Craig Brooks-Rooney, Francesco Negro, Mario U Mondelli
Between 80 and 115 million people worldwide are chronically infected with hepatitis C virus, with 60-90% of these being undiagnosed. Untreated chronic hepatitis C (CHC) is associated with progressive liver disease, cirrhosis, hepatocellular carcinoma and liver-related mortality. A number of extrahepatic manifestations are also reported in CHC patients, further adding to the burden of the disease. CHC also impacts patients in terms of lower health-related quality of life, higher levels of fatigue and reduced productivity...
October 17, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Nowlan Selvapatt, Ashley Brown
Objectives: To assess the uptake of pegylated interferon (PegIFN) plus ribavirin (RBV)-based regimens in patients with hepatitis C virus (HCV) in a large, single-centre, real-world setting over 10 years. Methods: This was a single centre, retrospective analysis of data from patients who attended their first appointment for treatment of HCV genotype 1-3 between 2003 and 2013. Patients were stratified by HCV genotype. The total number of patients who attended their first appointment, incidence of patients who did not proceed to treatment and associated reasons, and incidence of patients treated were analysed...
2016: F1000Research
Sern Wei Yeoh
Direct acting antiviral (DAA) regimens containing ritonavir have been developed to treat hepatitis C, with fewer side effects than that by interferon-based regimens. However prescribers must be aware of drug-drug interactions. There are multiple reports of iatrogenic Cushing syndrome (CS) caused by ritonavir, when used to treat human immunodeficiency virus, increasing the bioavailability of exogenous steroids by inhibiting cytochrome p450 enzymes in the liver and gut wall and thus reducing steroid metabolism...
September 2016: Journal of Clinical and Experimental Hepatology
L Benítez-Gutiérrez, C de Mendoza, I Baños, A Duca, A Arias, A Treviño, S Requena, M J Citores, V Cuervas-Mons
New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR) rates in patients treated for chronic hepatitis C. Although the safety of these agents has been very good in registration trials, unexpected side effects have been reported after much broader use of DAAs on marketing. We retrospectively examined all liver transplant recipients with chronic hepatitis C that received sofosbuvir-based regimens at our clinic. A total of 24 liver transplant recipients with recurrent chronic hepatitis C had received sofosbuvir up to April 2015...
September 2016: Transplantation Proceedings
Simonetta Bandiera, C Billie Bian, Yujin Hoshida, Thomas F Baumert, Mirjam B Zeisel
Hepatitis C virus (HCV) infection is one of the major causes of advanced liver disease and hepatocellular carcinoma (HCC) worldwide. While the knowledge about the molecular virology of HCV infection has markedly advanced, the molecular mechanisms of disease progression leading to fibrosis, cirrhosis and HCC are still unclear. Accumulating experimental and clinical studies indicate that HCV may drive hepatocarcinogenesis directly via its proteins or transcripts, and/or indirectly through induction of chronic liver inflammation...
October 11, 2016: Current Opinion in Virology
Perica Davitkov, Apoorva Krishna Chandar, Amy Hirsch, Anita Compan, Marina G Silveira, Donald D Anthony, Suzanne Smith, Clare Gideon, Robert A Bonomo, Yngve Falck-Ytter
BACKGROUND: Clinicians often face dilemmas with decisions related to formulary choices when two similar drugs are simultaneously available in the market. We studied the comparative safety, effectiveness, and treatment costs of the two first generation direct-acting antiviral agents (DAA), boceprevir and telaprevir as uncertainty existed regarding the drug of choice between these two seemingly equally Hepatitis-C treatment options. METHODS: We randomly assigned 50 patients in an open-label, pragmatic randomized controlled trial (RCT) at a VA Medical Center to either boceprevir or telaprevir in combination with peginterferon and ribavirin, stratified by the presence of cirrhosis and prior treatment experience...
2016: PloS One
Zobair M Younossi, Haesuk Park, Douglas Dieterich, Sammy Saab, Aijaz Ahmed, Stuart C Gordon
BACKGROUND: New direct-acting antiviral (DAA) therapy has dramatically increased cure rates for patients infected with hepatitis C virus (HCV), but has also substantially raised treatment costs. AIM: The aim of this analysis was to evaluate the therapeutic benefit and net costs (i.e. efficiency frontier) and the quality-adjusted cost of care associated with the evolution of treatment regimens for patients with HCV genotype 1 in the United States. DESIGN: A decision-analytic Markov model...
October 2016: Medicine (Baltimore)
Maribel Rodriguez-Torres, Eric Lawitz, Bienvenido Yangco, Lennox Jeffers, Steven-Huy Han, Paul J Thuluvath, Vinod Rustgi, Stephen Harrison, Reem Ghalib, John M Vierling, Velimir Luketic, Philippe J Zamor, Natarajan Ravendhran, Timothy R Morgan, Brian Pearlman, Christopher O'Brien, Hicham Khallafi, Nikolaos Pyrsopoulos, George Kong, Fiona McPhee, Philip D Yin, Eric Hughes, Michelle Treitel
:  Background. Patient race and ethnicity have historically impacted HCV treatment response. This phase 3 study evaluated daclatasvir with peginterferon-alfa-2a/ribavirin (pegIFN alfa-2a/RBV) in treatment-naive black/African American (AA), Latino, and white non-Latino patients with chronic HCV genotype 1 infection. MATERIAL AND METHODS: In this single-arm, open-label study, 246 patients received daclatasvir plus pegIFN alfa-2a and weight-based RBV. Patients with an extended rapid virologic response (eRVR; undetectable HCV-RNA at treatment weeks 4 and 12) received 24 weeks of treatment; those without eRVR received an additional 24 weeks of treatment with pegIFN alfa-2a/RBV...
November 2016: Annals of Hepatology
Claudia Minosse, Emanuela Giombini, Barbara Bartolini, Maria R Capobianchi, Anna R Garbuglia
Hepatitis C virus (HCV) is classified into seven phylogenetically distinct genotypes, which are further subdivided into related subtypes. Accurate assignment of genotype/subtype is mandatory in the era of directly acting antivirals. Several molecular methods are available for HCV genotyping; however, a relevant number of samples with indeterminate, mixed, or unspecified subtype results, or even with misclassified genotypes, may occur. Using NS5B direct (DS) and ultra-deep pyrosequencing (UDPS), we have tested 43 samples, which resulted in genotype 1 unsubtyped (n = 17), mixed infection (n = 17), or indeterminate (n = 9) with the Abbott RealTime HCV Genotype II assay...
October 7, 2016: International Journal of Molecular Sciences
Maria Stepanova, Trevor Locklear, Nila Rafiq, Alita Mishra, Chapy Venkatesan, Zobair M Younossi
BACKGROUND: Chronic HCV infection is often considered a contraindication for receiving a heart transplantation. METHODS: From the Scientific Registry of Transplant Recipients, we selected all adults with and without HCV infection who underwent a single organ heart transplantation in 1995-2013; the mortality status was updated in September 2015. RESULTS: A total of 32,812 heart transplant recipients were included; N=756 (2.30%) HCV-positive...
October 14, 2016: Clinical Transplantation
Christoph Sarrazin, Vasily Isakov, Evguenia Svarovskaia, Charlotte Hedskog, Ross Martin, Krishna Chodavarapu, Diana M Brainard, Michael D Miller, Hongmei Mo, Jean-Michel Molina, Mark S Sulkowski
BACKGROUND:  Development of direct-acting antivirals in recent years has dramatically enhanced rates of viral eradication to >90% in patients with chronic hepatitis C virus (HCV) infection. To determine true treatment efficacy and to define the most appropriate retreatment, it is important to distinguish virologic relapse from reinfection where patients who achieve HCV eradication during treatment become infected with a new HCV strain posttreatment. METHODS:  Here, we investigated prevalence of late recurrent viremia (patients who achieved SVR12 but had detectable HCV RNA at follow up week 24) and used refined phylogenetic analysis of multiple HCV genes to distinguish virologic relapse from reinfection...
October 12, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
M P Economides, P Mahale, A Kyvernitakis, F Turturo, H Kantarjian, A Naing, J Hosry, T L Shigle, A Kaseb, H A Torres
BACKGROUND: Antiviral therapy improves hepatic outcomes in hepatitis C virus (HCV)-infected cancer patients. However, such patients are not treated simultaneously with antivirals and chemotherapy, owing to overlapping toxicities with previous standard of care treatment of pegylated interferon and ribavirin. AIM: To examine the safety and clinically-significant drug-drug interactions observed in patients who received simultaneous treatment with direct-acting antivirals (DAAs) and chemotherapy...
October 11, 2016: Alimentary Pharmacology & Therapeutics
Martín Bonacci, Sabela Lens, María-Carlota Londoño, Zoe Mariño, Maria C Cid, Manuel Ramos-Casals, Jose María Sánchez-Tapias, Xavier Forns, José Hernández-Rodríguez
BACKGROUND & AIMS: Cryoglobulins (circulating immune complexes of polyclonal IgG, monoclonal IgM, and rheumatoid factor) are detected in the circulation of 40%-60% of patients with chronic hepatitis C virus infection and cryoglobulinemic vasculitis (CV) is observed in approximately 10% of patients. We aimed to assess the clinical and immune effects of direct-acting antiviral (DAA) treatment. METHODS: We performed a prospective study of 64 patients with HCV infection with circulating cryoglobulins receiving direct-acting anti-viral therapy at a single center in Barcelona, Spain from January 2014 through April 2016...
October 7, 2016: Clinical Gastroenterology and Hepatology
Petr Husa
Extrahepatic manifestations of hepatitis C virus infection (HCV) are very common. The most common of these is mixed cryoglobulinaemia. Anti-HCV antibodies and viral ribonucleic acid, HCV RNA, can be found in the cryoprecipitates, together with the rheumatoid factor. Cryoglobulins consist of a complex of immunoglobulins that in vitro precipitate upon the cooling bellow the human body temperature. Vasculitis is caused by the deposition of such immune complexes in the small blood vessels. A link with the HCV infection is considered to be established with membranoproliferative glomerulonephritis, leukocytoclastic vasculitis, lymphoproliferative disorders (in particular B cell lymphoma), Sjögren and sicca syndrome, lichen planus, porfyria cutanea tarda and diabetes mellitus...
2016: Vnitr̆ní Lékar̆ství
Kerstin Herzer, Guido Gerken
Chronic hepatitis C virus (HCV) infection is one of the primary causes of hepatocellular carcinoma and liver transplantation (LT). Graft loss due to hepatitis C (HCV) recurrence is a serious problem after LT. Thus, the approval of interferon-free direct-acting antiviral (DAA) regimens has important implications in the LT setting. The findings of controlled trials have confirmed the safety and the excellent efficacy of most DAA combinations, and these findings have been confirmed by reports of high rates of sustained virologic response in the real-life setting...
August 2016: Visc Med
Reina Sasaki, Tatsuo Kanda, Masayuki Ohtsuka, Shin Yasui, Yuki Haga, Masato Nakamura, Masayuki Yokoyama, Shuang Wu, Shingo Nakamoto, Makoto Arai, Hitoshi Maruyama, Masaru Miyazaki, Osamu Yokosuka
Direct-acting antivirals (DAAs) are relatively safe and highly effective for the eradication of hepatitis C virus (HCV) in liver transplant recipients. In this case study, we present a female with a graft reinfected with HCV genotype 2 who was treated with a combination of sofosbuvir and ribavirin after living donor liver transplantation (LDLT). Because the graft was from a hepatitis B core antibody-positive donor, passive immunization with hyperimmune hepatitis B immunoglobulin (HBIG) and entecavir were also provided to prevent hepatitis B virus (HBV) reactivation...
May 2016: Case Reports in Gastroenterology
Xianzong Wang, Xiaolin Liu
BACKGROUND: Horizontal transfer (HT) of genetic materials is increasingly being found in both animals and plants and mainly concerns transposable elements (TEs). Many crustaceans have big genome sizes and are thus likely to harbor high TE contents. Their habitat might offer them ample opportunities to exchange genetic materials with organisms that are ecologically close but taxonomically distant to them. RESULTS: In this study, we analyzed the transcriptome of Pacific white shrimp (Litopenaeus vannamei), an important economic crustacean, to explore traces of HT events...
October 7, 2016: BMC Evolutionary Biology
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