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Hepatitis C therapy

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https://www.readbyqxmd.com/read/28732153/hepatitis-b-and-c-viruses-and-biologics
#1
P Grewal, R Sanghera
Hepatitis B virus (HBV) and hepatitis C virus (HCV) are common, worldwide viral illnesses that potentially impact the clinician's ability to manage patients with immunosuppressive medications such as biological therapy. In light of recent literature reviews, patients with HBV and HCV should be referred to a hepatologist or infectious disease expert prior to initiation of biological therapy.
July 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28731786/high-post-treatment-%C3%AE-fetoprotein-levels-and-aspartate-aminotransferase-to-platelet-ratio-index-predict-hepatocellular-carcinoma-in-hepatitis-c-virus-decompensated-cirrhotic-patients-with-sustained-virological-response-after-antiviral-therapy
#2
Fanpu Ji, Rui Zhou, Wenjun Wang, Dan Bai, Caini He, Zhifang Cai, Yuan Shen, Shengbang Wang, Hong Deng, Zongfang Li
Although eradication of hepatitis C virus (HCV) decreases the risk of hepatocellular carcinoma (HCC) development, a considerable level of risk remains in cirrhotic patients with advanced liver disease. Yet, data for the effect of serum markers on HCC development in this population after viral eradication are still lacking. Seventy-eight consecutive patients with HCV infection and decompensated cirrhosis were administered interferon-based regimens at our hospital between August 2008 and December 2013. Thirty-four achieved sustained virological response and were enrolled in the study...
July 21, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28730994/baseline-and-post-treatment-hepatitis-c-ns5a-resistance-in-relapsed-patients-from-a-multicentric-real-life-cohort
#3
Philippe Halfon, Caroline Scholtès, Jacques Izopet, Sylvie Larrat, Pascale Trimoulet, Fabien Zoulim, Laurent Alric, Sophie Métivier, Vincent Leroy, Denis Ouzan, Victor de Lédinghen, Sofiane Mohamed, Guillaume Pénaranda, Hacène Khiri, Marie-Ange Thélu, Anne Plauzolles, Laurent Chiche, Marc Bourlière, Florence Abravanel
BACKGROUND: Recent data have suggested that failure to achieve sustained virological response with direct-acting antiviral therapy is usually due to relapse and is primarily associated with the emergence of resistance-associated substitutions. The aim of this study was to investigate the prevalence and characterization of non-structural-5A resistance-associated substitutions in patients infected with hepatitis C virus genotypes 1, 3, and 4 treated by direct-acting antiviral therapy, including anti- non-structural-5A, and to characterize the preexisting resistance-associated substitutions in subjects treated with anti- non-structural-5A inhibitors...
July 21, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28729967/tesevatinib-ameliorates-progression-of-polycystic-kidney-disease-in-rodent-models-of-autosomal-recessive-polycystic-kidney-disease
#4
William E Sweeney, Philip Frost, Ellis D Avner
AIM: To investigate the therapeutic potential of tesevatinib (TSV), a unique multi-kinase inhibitor currently in Phase II clinical trials for autosomal dominant polycystic kidney disease (ADPKD), in well-defined rodent models of autosomal recessive polycystic kidney disease (ARPKD). METHODS: We administered TSV in daily doses of 7.5 and 15 mg/kg per day by I.P. to the well characterized bpk model of polycystic kidney disease starting at postnatal day (PN) 4 through PN21 to assess efficacy and toxicity in neonatal mice during postnatal development and still undergoing renal maturation...
July 6, 2017: World Journal of Nephrology
https://www.readbyqxmd.com/read/28729550/anti-tumor-activity-and-immunotherapeutic-potential-of-a-bisphosphonate-prodrug
#5
Yoshimasa Tanaka, Masashi Iwasaki, Kaoru Murata-Hirai, Kenji Matsumoto, Kosuke Hayashi, Haruki Okamura, Tomoharu Sugie, Nagahiro Minato, Craig T Morita, Masakazu Toi
Bisphosphonates have benefits in breast cancer and multiple myeloma patients and have been used with adoptive immunotherapy with γδ T cells expressing Vγ2 Vδ2 TCRs. Although treatment with γδ T cells is safe, it has shown limited efficacy. Present bisphosphonates stimulate γδ T cells but were designed to inhibit bone resorption rather than treating cancer and have limited oral absorption, tumor cell entry, and cause bone side effects. The development of phosphate and phosphonate nucleotide prodrugs has led to important drugs for hepatitis C and HIV...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729054/isosorbide-based-peptidomimetics-as-inhibitors-of-hepatitis-c-virus-serine-protease
#6
Aline C Portela, Thalita G Barros, Camilo H da S Lima, Luiza R S Dias, Pedro H R de A Azevedo, Anna Sophia C L Dantas, Ronaldo Mohana-Borges, Gustavo T Ventura, Sergio Pinheiro, Estela M F Muri
Hepatitis C infection is a cause of chronic liver diseases such as cirrhosis and carcinoma. The current therapy for hepatitis C has limited efficacy and low tolerance. The HCV encodes a serine protease which is critical for viral replication, and few protease inhibitors are currently on the market. In this paper, we describe the synthesis and screening of novel isosorbide-based peptidomimetic inhibitors, in which the compounds 1d, 1e, and 1i showed significant inhibition of the protease activity in vitro at 100µM...
July 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28727946/confounding-by-single-nucleotide-polymorphism-rs117648444-p70s-affects-the-association-of-interferon-lambda-locus-variants-with-response-to-interferon-%C3%AE-ribavirin-therapy-in-patients-with-chronic-genotype-3-hepatitis-c-virus-infection
#7
Anand Bhushan, Sumona Ghosh, Samsiddhi Bhattacharjee, Sreedhar Chinnaswamy
Genome-wide association studies discovered interferon lambda (IFNL or IFN-λ) locus on chromosome 19 to be involved in clearance of chronic hepatitis C virus (HCV) infection in patients following interferon-α-ribavirin (IFN-RBV) therapy. Subsequent studies established a dinucleotide polymorphism rs368234815, as the prime causal variant behind this association. The ΔG allele of this variant gives rise to a new IFNL gene, IFNL4, coding for IFN-λ4 whose activity paradoxically associates with lesser viral clearance rates...
July 20, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28725041/a-screen-for-novel-hepatitis-c-virus-rdrp-inhibitor-identifies-a-broad-spectrum-antiviral-compound
#8
Abhilasha Madhvi, Smita Hingane, Rajpal Srivastav, Nishant Joshi, Chandru Subramani, Rajagopalan Muthumohan, Renu Khasa, Shweta Varshney, Manjula Kalia, Sudhanshu Vrati, Milan Surjit, C T Ranjith-Kumar
Hepatitis C virus (HCV) is a global pathogen and infects more than 185 million individuals worldwide. Although recent development of direct acting antivirals (DAA) has shown promise in HCV therapy, there is an urgent need for the development of more affordable treatment options. We initiated this study to identify novel inhibitors of HCV through screening of compounds from the National Cancer Institute (NCI) diversity dataset. Using cell-based assays, we identified NSC-320218 as a potent inhibitor against HCV with an EC50 of 2...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723780/the-relationship-between-itpa-rs1127354-polymorphisms-and-efficacy-of-antiviral-treatment-in-northeast-chinese-chc-patients
#9
Zhenhua Liu, Song Wang, Wenqian Qi, Xu Wang, Derong Sun, Hongguang Wang, Yonggui Zhang, Zhongxie Li, Liying Zhu, Ping Zhao, Honghua Guo, Changyu Zhou, Jiangbin Wang
This prospective study investigated the relationship between 2 inosine triphosphatase (ITPA) polymorphisms (rs7270101 and rs1127354) and the efficacy of ribavirin-based antiviral therapy in hepatitis C virus (HCV)-infected Chinese patients.A total of 906 patients diagnosed with chronic hepatitis C receiving pegylated interferon (PEG-IFN) plus ribavirin combination therapy between January 2011 and January 2014 from 5 hepatitis centers in Northeast China were enrolled. The patients were divided into genotype 1 and non-genotype 1 groups according to the genotype of infected HCV...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28723711/epidemiology-of-autoimmune-and-inflammatory-diseases-in-a-french-nationwide-hiv-cohort
#10
D Lebrun, M Hentzien, L Cuzin, D Rey, V Joly, L Cotte, C Allavena, P Dellamonica, A Servettaz, F Bani-Sadr
HIV infection and inflammatory and autoimmune diseases (IAD) are both related to immune dysfunction. Epidemiological data on IAD in patients living with HIV (PLHIV) are scarce. The aim of this study was thus to estimate the prevalence of 26 IAD among PLHIV followed in a large French multicenter cohort in the cART era (from January 2000 to July 2013), and to describe their occurrence according to cART onset, the immuno-virological status of patients and HCV and/or HBV co-infection.During the study period, 33 403 PLHIV were included in the Dat'AIDS cohort; 1381 patients with an IAD were identified...
July 18, 2017: AIDS
https://www.readbyqxmd.com/read/28722780/add-on-effects-of-fluvastatin-in-simeprevir-pegylated-interferon-ribavirin-combination-therapy-for-patients-with-genotype-1-hepatitis-c-virus-infection-a-randomized-controlled-study
#11
Goki Suda, Jun Ito, Atsushi Nagasaka, Yoshiya Yamamoto, Ken Furuya, Munenori Okamoto, Katsumi Terashita, Tomoe Kobayashi, Izumi Tsunematsu, Junichi Yoshida, Takashi Meguro, Masatsugu Ohara, Naoki Kawagishi, Megumi Kimura, Machiko Umemura, Takaaki Izumi, Yoko Tsukuda, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
BACKGROUND: The Japan Society of Hepatology guidelines indicate that HCV protease inhibitor combination therapy with simeprevir (SMV), pegylated-interferon (Peg-IFN), and ribavirin (RBV) is a therapeutic option for patients who fail to respond to a direct direct-acting antiviral (DAA) containing regimen. However, treatment outcomes have room for improvement. Fluvastatin (FLV) add-on treatment in Peg-IFN and RBV combination therapy for hepatitis C-infected patients significantly improved the sustained virological response (SVR), but the add-on effect of FLV on SMV combination therapy is not well understood...
July 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28722244/risk-of-liver-decompensation-with-cumulative-use-of-mitochondrial-toxic-nucleoside-analogues-in-hiv-hepatitis-c-virus-coinfection
#12
Vincent Lo Re Rd, Bret Zeldow, Michael J Kallan, Janet P Tate, Dena M Carbonari, Sean Hennessy, Jay R Kostman, Joseph K Lim, Matthew Bidwell Goetz, Robert Gross, Amy C Justice, Jason A Roy
PURPOSE: Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. METHODS: We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients...
July 19, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28719060/drug-use-and-phylogenetic-clustering-of-hepatitis-c-virus-infection-among-people-who-use-drugs-in-vancouver-canada-a-latent-class-analysis-approach
#13
Brendan Jacka, Bethany Bray, Tanya L Applegate, Brandon Dl Marshall, Viviane Dias Lima, Kanna Hayashi, Kora DeBeck, Jayna Raghwani, P Richard Harrigan, Mel Krajden, Julio Montaner, Jason Grebely
BACKGROUND: This study estimated latent classes (i.e., unobserved subgroups in a population) of people who use drugs in Vancouver, Canada and examined how these classes relate to phylogenetic clustering of hepatitis C virus (HCV) infection. METHODS: HCV antibody positive people who use drugs from two cohorts in Vancouver, Canada (1996-2012) with a Core-E2 sequence were included. Time-stamped phylogenetic trees were inferred and phylogenetic clustering was determined by time to most common recent ancestor...
July 18, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28719029/directly-observed-therapy-of-sofosbuvir-ribavirin-peginterferon-with-minimal-monitoring-for-the-treatment-of-chronic-hepatitis-c-in-people-with-a-history-of-drug-use-in-chennai-india-c-dot
#14
Sunil S Solomon, Mark S Sulkowski, Pradeep Amrose, Aylur K Srikrishnan, Allison M McFall, Balakrishnan Ramasamy, Muniratnam S Kumar, Santhanam Anand, David L Thomas, Shruti H Mehta
BACKGROUND AND AIMS: We assessed the feasibility of field-based directly observed therapy (DOT) with minimal monitoring to deliver HCV treatment to people with a history of drug use in Chennai, India. METHODS: 50 participants were randomized 1:1 to sofosbuvir + peginterferon alfa 2a + ribavirin (SOF+PR) for 12 weeks (Arm 1) vs. sofosbuvir + ribavirin (SOF+R) for 24 weeks (Arm 2). SOF+R was delivered daily at participant chosen venues and weekly peginterferon injections at the study clinic...
July 18, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28718673/ameliorative-effect-of-gallic-acid-in-doxorubicin-induced-hepatotoxicity-in-wistar-rats-through-antioxidant-defense-system
#15
Temidayo Olutayo Omobowale, Ademola Adetokunbo Oyagbemi, Uchechukwu Enwiwe Ajufo, Olumuyima Abiola Adejumobi, Olufunke Eunice Ola-Davies, Adeolu Alex Adedapo, Momoh Audu Yakubu
Hepatotoxicity has been found to be one of the main side effects associated with doxorubicin (Dox) administration in cancer therapy. The aim of the present study was to examine the ameliorative effect of gallic acid (GA) in Dox-induced hepatotoxicity. Sixty male Wistar rats of 10 rats per group were used in this study and were randomly divided into 6 experimental groups (A-F). Rats in Group A served as the control group and received distilled water orally for 7 days; Group B was given Dox at 15 mg/kg body weight intraperitoneally (IP) on Day 8...
July 18, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28715943/introducing-treat-to-target-strategies-of-autoimmune-extrahepatic-manifestations-of-chronic-hepatitis-c-virus-infection
#16
Soledad Retamozo, Pilar Brito-Zeron, Luca Quartuccio, Salvatore De Vita, Manuel Ramos-Casals
The hepatitis C virus (HCV) is recognized as one of the hepatic viruses most often associated with extrahepatic manifestations (EHMs). It is currently accepted that cryoglobulinemic vasculitis (CV) is the key autoimmune extrahepatic disease associated with HCV infection. Therapeutic approaches have mainly been based on the use of old antiviral interferon (IFN)-based regimens and immunosuppressive therapies, often with an inadequate balance between therapeutic benefits and excess side effects. AREAS COVERED...
July 18, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28715911/hepatitis-c-treatment-regimens-are-cost-effective-but-compared-with-what
#17
T Joseph Mattingly, Julia F Slejko, C Daniel Mullins
BACKGROUND: Numerous economic models have been published evaluating treatment of chronic hepatitis C virus (HCV) infection, but none provide a comprehensive comparison among new antiviral agents. OBJECTIVE: Evaluate the cost-effectiveness of all recommended therapies for treatment of genotypes 1 and 4 chronic HCV. METHODS: Using data from clinical trials, observational analyses, and drug pricing databases, Markov decision models were developed for HCV genotypes 1 and 4 to compare all recommended drugs from the perspective of the third-party payer over a 5-, 10-, and 50-year time horizon...
July 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28712788/antimalarial-agent-artesunate-protects-concanavalin-a-induced-autoimmune-hepatitis-in-mice-by-inhibiting-inflammatory-responses
#18
Xin Zhao, MingJiang Liu, JinGui Li, ShaoJie Yin, YangYang Wu, AnYuan Wang
The anti-malarial drug artesunate (ARS) has been shown to possess anti-inflammatory activity. Its effect on autoimmune hepatitis remains unclear. Concanavalin A (Con A)-induced hepatitis was used in this study to reveal the potential action of ARS and the related mechanism. Mice were pretreated with ARS followed by Con A challenge. Con A caused obvious hepatic injury with higher levels of liver enzymes, elevated pro-inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways...
July 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28711021/sensitizing-effects-of-an-organovanadium-compound-during-adjuvant-therapy-with-cyclophosphamide-in-a-murine-tumor-model
#19
Abhishek Basu, Arin Bhattacharjee, Prosenjit Ghosh, Amalesh Samanta, Sudin Bhattacharya
Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of vanadium. In addition, recent studies have also indicated the abilities of vanadium-based compounds to induce cell death selectively towards malignant cells. Therefore, the objective of the present investigation is to improve the therapeutic efficacy and toxicity profile of an alkylating agent, cyclophosphamide, by the concurrent use of an organovanadium compound, oxovanadium(IV)-l-cysteine methyl ester complex (VC-IV)...
July 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28710853/real-world-effectiveness-of-sofosbuvir-based-treatment-regimens-for-chronic-hepatitis-c-genotype-3-infection-results-from-the-multicenter-german-hepatitis-c-cohort-gecco-03
#20
Malte H Wehmeyer, Patrick Ingiliz, Stefan Christensen, Dietrich Hueppe, Thomas Lutz, Karl Georg Simon, Knud Schewe, Christoph Boesecke, Axel Baumgarten, Heiner Busch, Juergen Rockstroh, Guenther Schmutz, Torben Kimhofer, Florian Berger, Stefan Mauss, Julian Schulze Zur Wiesch
There are limited data regarding the real world effectiveness of direct acting antivirals (DAA) for the therapy of chronic genotype 3 hepatitis C virus (HCV) infection. All HCV genotype 3 infected patients from the German hepatitis C cohort (GECCO), which is a prospective database of nine German hepatitis C treatment centers, were included in the study. 342 chronically infected HCV genotype 3 patients were analyzed (253 males [74.0%], mean age 47.3 years, 127 cirrhotic patients [37.1%] mostly with Child A cirrhosis, 113 treatment experienced patients [37...
July 15, 2017: Journal of Medical Virology
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