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https://www.readbyqxmd.com/read/28339489/human-subtilisin-kexin-isozyme-1-ski-1-site-1-protease-s1p-regulates-cytoplasmic-lipid-droplet-abundance-a-potential-target-for-indirect-acting-anti-dengue-virus-agents
#1
Anastasia Hyrina, Fanrui Meng, Steven J McArthur, Sharlene Eivemark, Ivan R Nabi, François Jean
Viral hijacking and manipulation of host-cell biosynthetic pathways by human enveloped viruses are shared molecular events essential for the viral lifecycle. For Flaviviridae members such as hepatitis C virus and dengue virus (DENV), one of the key subsets of cellular pathways that undergo manipulation is the lipid metabolic pathways, underlining the importance of cellular lipids and, in particular, lipid droplets (LDs) in viral infection. Here, we hypothesize that targeting cellular enzymes that act as key regulators of lipid homeostasis and LD formation could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with all DENV serotypes (1-4) circulating around the world...
2017: PloS One
https://www.readbyqxmd.com/read/28332729/transplantation-of-kidneys-from-hepatitis-c-positive-donors-into-hepatitis-c-virus-infected-recipients-followed-by-early-initiation-of-direct-acting-antiviral-therapy-a-single-center-retrospective-study
#2
Kalyan Ram Bhamidimarri, Marco Ladino, Fernando Pedraza, Giselle Guerra, Adela Mattiazzi, Linda Chen, Gaetano Ciancio, Warren Kupin, Paul Martin, George Burke, David Roth
The availability of direct acting antiviral agents (DAA) has transformed the treatment of hepatitis C virus (HCV) infection. The current study is a case series that reports the outcomes from a cohort of twenty-five HCV-infected ESRD patients who received a kidney from an anti-HCV-positive deceased organ donor followed by treatment with DAAs in the early post-transplant period. Time to transplantation and the efficacy of DAA therapy as measured by sustained viral response at 12 weeks were assessed. The median waiting time from original date of activation on the UNOS waiting list until transplantation was 427 days, however, the median time from entering the patient into UNet(sm) for a HCV positive offer until transplantation was only 58 days...
March 23, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28332476/new-onset-hepatitis-c-virus-associated-glomerulonephritis-following-sustained-virologic-response-with-direct-acting-antiviral-therapy%C3%A2
#3
Muriel Ghosn, Matthew B Palmer, Catherine E Najem, Danny Haddad, Peter A Merkel, Jonathan J Hogan
Glomerulonephritis (GN) is an important extra-hepatic manifestation of infection with hepatitis C virus (HCV). HCV-associated GN occurs due to HCV-induced lymphoproliferation, leading to the generation of pathogenic immune complexes, including complexes containing cryoglobulins. The management of HCV-associated extra-hepatic disease is focused on viral eradication, with direct-acting antiviral agents leading to high rates of sustained virologic remission. There have been a few reports of relapsing cryoglobulinemic vasculitis after sustained virologic remission was achieved with interferon-based therapies...
March 23, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28324595/recent-advances-in-developing-antiviral-therapies-for-respiratory-syncytial-virus
#4
REVIEW
Brian C Shook, Kai Lin
Respiratory syncytial virus (RSV) infection presents a significant health challenge in small children, the elderly and immunocompromised patients. There is still a high unmet medical need among patients with RSV infection, and no specific antiviral therapy is available. The only approved agents are palivizumab, which has to be given prophylactically, mainly in high-risk infants, and ribavirin, which is rarely used due to toxicity concerns and questionable benefits. Efforts to develop new antiviral agents have been hampered by the perceived need for high safety hurdles in pediatric patient populations use and the lack of well-characterized druggable targets...
April 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28321163/optimizing-hepatitis-c-virus-treatment-through-pharmacist-interventions-identification-and-management-of-drug-drug-interactions
#5
Jacob A Langness, Matthew Nguyen, Amanda Wieland, Gregory T Everson, Jennifer J Kiser
AIM: To quantify drug-drug-interactions (DDIs) encountered in patients prescribed hepatitis C virus (HCV) treatment, the interventions made, and the time spent in this process. METHODS: As standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral (DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir (LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir (OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV)...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28320588/herpes-zoster-reactivation-in-patients-with-chronic-hepatitis-c-under-treatment-with-directly-acting-antiviral-agents-a-case-series
#6
Mohamed El Kassas, Mohamed Naguib Wifi, Reem Mahdy, Shimaa Afify, Enas Hafez, Yasmeen Abd El Latif, Marwa Ezzat, Adel El Tahan, Naglaa Youssef, Gamal Esmat
We report a series of cutaneous Herpes Zoster (HZ) reactivation cases in patients with hepatitis C virus (HCV) infection treated with directly acting antiviral (DAA) agents. Five cases were detected among 2133 treated patients with DAAs at one of the specialized viral hepatitis treatment centers in Egypt. A control group including 2300 age and sex matched HCV patients who were previously treated with pegylated interferon and ribavirin did not show any HZ reactivation reports while on treatment. None of cases had an evidence of immunosuppression or a risk factor for HZ reactivation...
March 17, 2017: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
https://www.readbyqxmd.com/read/28319996/oral-direct-acting-agent-therapy-for-hepatitis-c-virus-infection-a-systematic-review
#7
Oluwaseun Falade-Nwulia, Catalina Suarez-Cuervo, David R Nelson, Michael W Fried, Jodi B Segal, Mark S Sulkowski
Background: Rapid improvements in hepatitis C virus (HCV) therapy have led to the approval of multiple oral direct-acting antiviral (DAA) regimens by the U.S. Food and Drug Administration (FDA) for treatment of chronic HCV infection. Purpose: To summarize published literature on the efficacy and safety of oral DAAs for treatment of persons with chronic HCV infection. Data Sources: MEDLINE and EMBASE from inception through 1 November 2016. Study Selection: 42 English-language studies from controlled and single-group registered clinical trials of adults with HCV infection that evaluated at least 8 weeks of an FDA-approved interferon-free HCV regimen that included at least 2 DAAs...
March 21, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28315743/treatment-with-peg-ifn-and-ribavirin-in-patients-with-chronic-hepatitis-c-low-grade-of-hepatic-fibrosis-genotype-1-and-4-and-favorable-ifnl3-genotype-a-pharmacogenetic-prospective-study
#8
Lucio Boglione, Chiara Simona Cardellino, Jessica Cusato, Amedeo De Nicolò, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio
The new direct-acting antivirals agents (DAAs) rapidly changed the treatment approach in chronic hepatitis C (CHC); however, the interferon (IFN)-free therapies availability is currently different in some countries, due to higher costs of these drugs. Naïve treated patients, who are not eligible for IFN-free therapies, could be selected for standard dual treatment with pegylated (PEG)-IFN and ribavirin (RBV), through IFN lambda 3 gene polymorphisms and fibrosis stage evaluation. Inclusion criteria were: naïve treated CHC patients with GT1 or GT4, without major contraindication to PEG-IFN or RBV, with fibrosis stage F0-F2 and IFNL3 rs8099917/rs12979860 TT/CC genotypes...
March 15, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28293974/treatment-of-hepatitis-c-virus-infection-updated-swedish-guidelines-2016
#9
Martin Lagging, Rune Wejstål, Gunnar Norkrans, Olle Karlström, Soo Aleman, Ola Weiland, Maria Castedal, Johan Westin
In a recent expert meeting, Swedish recommendations for the treatment of hepatitis C virus (HCV) infection were updated. An interferon-free combination of direct-acting antiviral agents is considered and indicated for all patients with chronic HCV infection, but the ability to treat all is limited primarily by high cost of medication. The group of patients prioritized for therapeutic intervention has been extended to also include fertile women desiring to become pregnant. A more thorough discussion of treatment for people who inject drugs (PWIDs) in order to diminish transmission is included, and the clinical significance of baseline NS5A resistance associated variants (RAVs), also known as resistance associated substitutions (RASs), for the treatment of HCV genotype 1a or 3 infection is discussed...
March 15, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28293834/synthesis-and-evaluation-of-novel-hcv-replication-inhibitors
#10
David C McGowan, Mourad D Khamlichi, Alex De Groot, Frederik Pauwels, Frédéric Delouvroy, Kristof Van Emelen, Kenneth Simmen, Pierre Raboisson
Direct acting antiviral agents to cure hepatitis C virus (HCV) infection has emerged as the gold standard therapy. Along with protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors, the inhibition of NS5a has proved to be an effective way to treat HCV patients. Here we report on novel HCV NS5a inhibitors which were synthesized and evaluated in the HCV replicon assay. A series of inhibitors were formed by a cycloaddition reaction in parallel to establish new leads and explore the effects of unsymmetrical cap substitution...
March 14, 2017: Molecular Diversity
https://www.readbyqxmd.com/read/28293407/thrombocytopenia-in-patients-with-chronic-hepatitis-c-virus-infection
#11
REVIEW
Sumit Dahal, Smrity Upadhyay, Rashmi Banjade, Prajwal Dhakal, Nabin Khanal, Vijaya Raj Bhatt
Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28288715/hepatitis-c-virus-associated-marginal-zone-lymphoma
#12
REVIEW
Marine Armand, Caroline Besson, Olivier Hermine, Frédéric Davi
The link between hepatitis C virus (HCV) infection and the development of B-cell non-Hodgkin lymphoma is now well established and based on a number of epidemiological studies. It is further supported by the observation of lymphoma regression after HCV eradication by antiviral treatment. The far most frequent entities are marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). MZL usually emerge on a background of mixed cryoglobulinemia, a low-grade lymphoproliferation, and often transform into DLBCL, thereby following a multistep oncogenesis process...
March 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/28287204/-biliary-and-kidney-lithiasis-during-treatment-with-daclatasvir-sofosbuvir-ribavirin-and-atazanavir-ritonavir-abacavir-lamivudine-in-an-hiv-hcv-genotype-4-infected-patient-a-case-report
#13
Andrea Vavassori, Paola Lanza, Ilaria Izzo, Salvatore Casari, Silvia Odolini, Serena Zaltron, Elena Festa, Francesco Castelli
New Direct-acting Antiviral Agents (DAA)-based anti-HCV therapies currently provide extraordinary opportunities to cure patients. Drug-drug interactions are however a real challenge during treatment. In particular, in HIV-infected patients in cART, DAA choice is limited by such interactions, which can result both in reduced efficacy and toxicity. We report the case of a HIV-infected patient on cART with atazanavir/ritonavir/abacavir/lamivudine, who presented kidney and biliary lithiasis, the latter treated with endoscopic retrograde cholangiopancreatography and endoscopic biliary sphincterotomy, after beginning anti-HCV treatment with daclatasvir/sofosbuvir/ribavirin...
February 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28286567/grazoprevir-elbasvir-combination-therapy-for-hcv-infection
#14
REVIEW
Anaïs Vallet-Pichard, Stanislas Pol
Interferon-free regimens combine different second-wave direct-acting antiviral agents (DAAs), which target the main viral proteins involved in the replication cycle of hepatitis C virus (HCV): NS3/4A protease inhibitors (simeprevir or paritaprevir boosted by ritonavir), NS5B nucleos(t)idic (sofosbuvir) and nonnucleos(t)idic (dasabuvir) polymerase inhibitors, NS5A replication complex inhibitors (daclatasvir, ledipasvir, elbasvir, velpatasvir). Combinations of two or three DAAs, given for 8-24 weeks reach sustained virology response (SVR) rates greater than 90% with good tolerance...
January 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28286560/prevalence-of-end-of-treatment-rna-positive-sustained-viral-response-in-hcv-patients-treated-with-sofosbuvir-combination-therapies
#15
Miguel Malespin, Tamara Benyashvili, Susan L Uprichard, Alan S Perelson, Harel Dahari, Scott J Cotler
BACKGROUND: Some chronic hepatitis C virus (HCV), genotype 1 infected patients treated with direct antiviral agents (DAAs) remain viremic at end of treatment (EOT+), yet go on to achieve sustained virological response 12 weeks after completion of therapy (SVR12). The incidence of EOT+/SVR in patients with genotype 1 and other genotypes, as well as whether such patients achieve SVR24 remain in question. The aims of this study were to evaluate the frequency and durability of EOT+/SVR12&24 and other response categories in HCV genotype 1, 2, or 3 infected patients treated with DAA in clinical practice...
January 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28273391/liver-transplantation-for-fulminant-genotype-2a-c-hepatitis-c-virus-marked-by-a-rapid-recurrence-followed-by-cure
#16
Brett Tracy, Roshan Shrestha, Lance Stein, Devina Bhasin, Harrison Pollinger, Raymond A Rubin
Although chronic hepatitis C is still the leading indication for liver transplantation (LT) in the United States and Europe, acute liver failure caused by to hepatitis C is distinctly uncommon and transplantation for fulminant hepatitis C virus (HCV) has not been documented in the United States. We present a case report of fulminant hepatic failure caused by genotype 2a/c HCV not only treated with LT, but also complicated by severe, rapid recurrence of HCV within 6 days of transplantation. The risk factor for the infection was likely sexual, as there were no other concomitant causes of liver disease pre-transplant or explanations for acute hepatitis post-transplant...
March 8, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28272163/real-world-efficacy-of-daclatasvir-and-sofosbuvir-with-and-without-ribavirin-in-hiv-hcv-co-infected-patients-with-advanced-liver-disease-in-a-french-early-access-cohort
#17
Karine Lacombe, Hélène Fontaine, Catherine Dhiver, Sophie Metivier, Eric Rosenthal, Teresa Antonini, Marc Antoine Valantin, Patrick Miailhes, Stanislas Harent, Dominique Batisse, Georges-Philippe Pageaux, Julie Chas, Hugues Aumaitre, Stephanie Dominguez, Thierry Allegre, Alain Lafeuillade, Eric Billaud, Pierre De Truchis, Philippe Perre, Vincent Leroy, Victor De Ledinghen, Philippe Sogni, Francois Dabis, Yue Zhao, Anne Filipovics, Larysa Fedchuk, Raoudha Akremi, Yacia Bennai, Dominique Salmon Ceron
BACKGROUND: Efficacious, well-tolerated direct antiviral agents have drastically changed the prognosis of hepatitis C virus (HCV) disease, but real-world data for oral treatments are limited in key populations such as human immunodeficiency virus (HIV)/HCV co-infection with advanced liver disease. Daclatasvir (DCV) efficacy and safety was assessed in the French "Autorisation Temporaire d'Utilisation" (ATU) program providing DCV ahead of market authorization to patients with advanced HCV disease without other treatment options...
March 6, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28271521/transformation-of-hepatitis-c-antiviral-treatment-in-a-national-healthcare-system-following-the-introduction-of-direct-antiviral-agents
#18
A M Moon, P K Green, K Berry, G N Ioannou
BACKGROUND: Highly effective direct antiviral agents (DAAs) for hepatitis C virus (HCV) were introduced recently. Their utilisation has been limited by high cost and low access to care. AIM: To describe the effect of DAAs on HCV treatment and cure rates in the United States Veterans Affairs (VA) national healthcare system. METHODS: We identified all HCV antiviral treatment regimens initiated from 1 January 1999 to 31 December 2015 (n = 105 369) in the VA national healthcare system, and determined if they resulted in sustained virological response (SVR)...
March 8, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28270038/inf-free-sofosbuvir-based-treatment-of-post-transplant-hepatitis-c-relapse-a-swedish-real-life-experience
#19
Castedal Maria, Segenmark Michael, Cederberg Susanne, Skoglund Catarina, Weiland Ola
BACKGROUND: Relapse of hepatitis C virus (HCV) infection after liver transplantation has been universal, and the fibrosis progression faster than in non-transplanted patients. Interferon (IFN)-free treatment with direct antiviral agents (DAA) has improved the treatment outcome dramatically. We here report on the outcome of IFN-free treatment for HCV relapse after liver transplantation in a real life setting in Sweden. MATERIAL: In total, 93 patients with a mean age of 60 years (range 32-80) with HCV relapse after liver transplantation were given sofosbuvir-based treatment in combination with a protease inhibitor (simeprevir) or a NS5A inhibitor (daclatasvir or ledipasvir) with or without addition of ribavirin (RBV), or sofosbuvir and RBV only...
May 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28263457/ombitasvir-paritaprevir-ritonavir-and-dasabuvir-drug-interactions-with-antiretroviral-agents-and-drugs-forsubstance-abuse
#20
Jennifer R King, Rajeev M Menon
AbbVie's 3 direct-acting antiviral (3D) regimen containing ombitasvir, paritaprevir, ritonavir, and dasabuvir with and without ribavirin is approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection. Safe and efficacious antiviral regimens resulting in minimal to no drug-drug interactions (DDIs) with antiretrovirals are needed to ensure that patients coinfected with HCV and the human immunodeficiency virus (HIV) achieve 12-week sustained virologic response rates similar to HCV-monoinfected patients...
March 2017: Clinical Pharmacology in Drug Development
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