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https://www.readbyqxmd.com/read/28927676/a-pilot-study-to-expand-treatment-of-chronic-hepatitis-c-in-resource-limited-settings
#1
REVIEW
Poonam Mathur, Emily Comstock, Edward McSweegan, Natalia Mercer, Nongthombam Suraj Kumar, Shyamasundaran Kottilil
The past five years have seen a revolution in the treatment of chronic hepatitis C, as short duration oral regimens of direct-acting antiviral drugs (DAAs), with nearly 100% cure rates for all genotypes, have replaced longer courses of ribavirin and injected interferon. Although initially very expensive, these DAAs are now becoming available in generic equivalents in countries with large numbers of chronically infected people, such as India. However, a number of obstacles may hinder the delivery of these drugs in resource-limited settings, including lack of access to diagnostic testing and the restriction of treatment to a small number of medical specialists...
September 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28926120/glecaprevir-pibrentasvir-for-hcv-genotype-3-patients-with-cirrhosis-and-or-prior-treatment-experience-a-partially-randomized-phase-iii-clinical-trial
#2
David Wyles, Fred Poordad, Stanley Wang, Laurent Alric, Franco Felizarta, Paul Y Kwo, Benedict Maliakkal, Kosh Agarwal, Tarek Hassanein, Frank Weilert, Samuel S Lee, Jens Kort, Sandra S Lovell, Ran Liu, Chih-Wei Lin, Tami Pilot-Matias, Preethi Krishnan, Federico J Mensa
BACKGROUND: This study assessed the efficacy and safety of ribavirin (RBV)-free coformulated glecaprevir/pibrentasvir (G/P) in patients with hepatitis C virus (HCV) genotype (GT) 3 infection with either prior treatment experience and/or compensated cirrhosis, a patient population with limited treatment options. METHODS: SURVEYOR-II, Part 3 was a partially-randomized, open-label, multicenter, phase 3 study. Treatment-experienced (prior interferon (IFN) or pegIFN ± ribavirin or SOF plus ribavirin ± pegIFN therapy) patients without cirrhosis were randomized 1:1 to receive 12 or 16 weeks of G/P (300 mg/120 mg) once daily...
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28925824/can-we-go-for-a-shorter-treatment-course-in-chronic-hepatitis-c-more-inspiring-cases
#3
Rosa Zampino, Martina Vitrone, Antonio Parrella, Enrico Ragone, Emanuele Durante-Mangoni
Current interest in HCV therapy with direct acting antivirals is focused on shortening treatment length. We managed two cirrhotics who achieved virological cure after 4 weeks of ombitasvir/paritaprevir/ritonavir, dasabuvir, ribavirin treatment. Analysis to identify potential predictive factors for a successful outcome with a shorter treatment course was conducted.
September 19, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28925068/when-and-how-can-nephrologists-treat-hepatitis-c-virus-infection-in-dialysis-patients
#4
REVIEW
Maya I Davis, Donald F Chute, Raymond T Chung, Meghan E Sise
Hepatitis C virus (HCV) infection, a major cause of end-stage liver disease, is a common comorbidity in patients on dialysis and causes increased morbidity and mortality. Historically HCV has been extremely difficult to cure with interferon and ribavirin-based therapies, which are also associated with significant side effects, and few dialysis patients ever received HCV treatment. However, in the last 4 years, interferon-free direct-acting antiviral therapies have been approved, and several combinations have been studied in dialysis patients...
September 18, 2017: Seminars in Dialysis
https://www.readbyqxmd.com/read/28923637/ledipasvir%C3%A2-sofosbuvir-for-liver-transplant-recipients-with-recurrent-hepatitis-c-a-systematic-review-and-meta-analysis
#5
H-T Liao, P Tan, J-W Huang, K-F Yuan
INTRODUCTION: Studies focusing on the efficacy and safety of ledipasvir (LDV) + sofosbuvir (SOF) therapy in liver transplant (LT) recipients with hepatitis C virus (HCV) recurrence are still limited. Therefore, the aim of our work was to perform a systematic review and meta-analysis to evaluate outcome data of LDV + SOF therapy in LT recipients. METHODS: Multiple databases were systematically searched for eligible studies. We included studies reporting sustained virological response 12 weeks after treatment (SVR12) and treatment-related adverse events (AEs) in LT recipients treated with LDV + SOF ± ribavirin (RBV) for HCV recurrence...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28922464/molecular-dynamics-simulation-revealed-binding-of-nucleotide-inhibitors-to-zikv-polymerase-over-444-nanoseconds
#6
Abdo A Elfiky, Wael M Elshemey
In the year 2015, new Zika virus (ZIKV) broke out in Brazil and spread away in more than 80 countries. Scientists directed their efforts toward viral polymerase in attempt to find inhibitors that might interfere with its function. In this study, molecular dynamics simulation (MDS) was performed over 444 ns for a ZIKV polymerase model. Molecular docking (MD) was then performed every 10 ns during the MDS course to ensure the binding of small molecules to the polymerase over the entire time of the simulation...
September 18, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28921807/the-italian-compassionate-use-of-sofosbuvir-in-hcv-patients-waitlisted-for-liver-transplantation-a-national-real-life-experience
#7
Silvia Martini, Maria Francesca Donato, Chiara Mazzarelli, Maria Rendina, Ubaldo Visco-Comandini, Daniela Filì, Alice Gianstefani, Stefano Fagiuoli, Mario Melazzini, Simona Montilla, Luca Pani, Sandra Petraglia, Pierluigi Russo, Maria Paola Trotta, Paola Carrai, Paolo Caraceni
BACKGROUND & AIMS: This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. METHODS: Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. RESULTS: Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for <4 weeks or still viremic at transplant: 34 patients continued treatment after LT (bridging therapy) (SVR12: 88%), while 15 stopped treatment (SVR12: 53%)...
September 16, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28919791/pegylated-interferon-plus-ribavirin-treatment-does-not-alter-the-prevalence-of-resistance-associated-substitutions-to-direct-acting-antivirals-in-hcv-genotype-1a-patients
#8
Zhi-Wei Chen, Xi-Chen Pang, Zhao Li, Hong Ren, Peng Hu
BACKGROUND: Direct-acting antiviral (DAA) resistance-associated substitutions (RASs) can jeopardize the effectiveness of DAAs in patients with hepatitis C virus (HCV). The selection pressure by pegylated-interferon (Peg-IFN) plus ribavirin (P/R) treatment may enhance HCV genome variation. However, whether P/R treatment alters the rate of change of RASs is still unclear. MATERIALS AND METHODS: We retrieved the genomic sequences of HCV genotype (GT) 1a patients from GenBank, which included patients naïve to P/R (pre-IFN group) and those previously treated with P/R (post-IFN group)...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28918403/successful-twice-interrupted-therapy-of-hcv-infection-in-patients-with-cirrhosis-with-hepatocellular-carcinoma-before-and-after-liver-transplantation
#9
Anna Szymanek-Pasternak, Karolina Rostkowska, Krzysztof Simon
We are presenting the case study of the patient diagnosed at the age of 37 with liver cirrhosis due to genotype 1b hepatitis C virus infection. At the age of 46, he was diagnosed with hepatocellular carcinoma with subsequent resection of the tumour in May 2015. In December 2015, the treatment was started with ombitasvir, paritaprevir/ritonavir and dasabuvir (3D) with ribavirin (RBV) 1000 mg per day. After 24 days of this treatment, the patient received a deceased donor liver transplantation, followed by 18-day interruption of 3D therapy...
September 15, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28916737/determining-ribavirin-s-mechanism-of-action-against-lassa-virus-infection
#10
Paola Carrillo-Bustamante, Thi Huyen Tram Nguyen, Lisa Oestereich, Stephan Günther, Jeremie Guedj, Frederik Graw
Ribavirin is a broad spectrum antiviral which inhibits Lassa virus (LASV) replication in vitro but exhibits a minor effect on viremia in vivo. However, ribavirin significantly improves the disease outcome when administered in combination with sub-optimal doses of favipiravir, a strong antiviral drug. The mechanisms explaining these conflicting findings have not been determined, so far. Here, we used an interdisciplinary approach combining mathematical models and experimental data in LASV-infected mice that were treated with ribavirin alone or in combination with the drug favipiravir to explore different putative mechanisms of action for ribavirin...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900714/efficacy-of-peginterferon-plus-ribavirin-in-patients-receiving-opioid-substitution-therapy-final-results-of-the-austrian-peghope-study
#11
Michael Gschwantler, Hermann Laferl, Wolfgang Vogel, Wolfgang Korak, Stephan Moser, Harald Hofer, Bernhard Bauer, Michael Schleicher, Barbara Bognar, Martin Bischof, Rudolf Stauber, Andreas Maieron, Peter Ferenci
BACKGROUND: Patients with a history of intravenous drug abuse included in an official opioid substitution program represent an important subgroup of patients with chronic hepatitis C. The objective of this study was to assess the efficacy of and adherence to treatment with peginterferon and ribavirin in Austrian patients on stable opioid substitution therapy (OST). METHODS: This prospective, multicenter, observational, non-interventional trial (clinicaltrials...
September 12, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28892235/beclabuvir-in-combination-with-asunaprevir-and-daclatasvir-for-hepatitis-c-virus-genotype-1-infection-a-systematic-review-and-meta-analysis
#12
Ali Mahmoud Ahmed, Mohamed Fahmy Doheim, Omar Mohamed Mattar, Nourin Ali Sherif, Duy Hieu Truong, Pham Thi Le Hoa, Kenji Hirayama, Nguyen Tien Huy
Daclatasvir, asunaprevir, and beclabuvir are direct-acting antivirals for patients with hepatitis C virus genotype 1 infection. This systematic review and meta-analysis investigating the efficacy and safety of this three-drug combination in HCV genotype 1 infection. Eleven electronic search engines were searched for relevant publications. Studies were screened for eligibility and data was extracted. The outcomes were pooled as event rate and risk ratio. The protocol was registered in PROSPERO (CRD42017054391)...
September 11, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28890388/dhea-prevents-ribavirin-induced-anemia-via-inhibition-of-glucose-6-phosphate-dehydrogenase
#13
Lynda Handala, Barbara Domange, Hakim Ouled-Haddou, Loïc Garçon, Eric Nguyen-Khac, Francois Helle, Sandra Bodeau, Gilles Duverlie, Etienne Brochot
Ribavirin has been widely used for antiviral therapy. Unfortunately, ribavirin-induced anemia is often a cause of limiting or interrupting treatment. Our team has observed that dehydroepiandrosterone (DHEA) has a protective effect against in vitro and in vivo ribavirin-induced hemolysis. The aim of this study was to better understand this effect as well as the underlying mechanism(s). DHEA was able to reduce in vitro intraerythrocytic ATP depletion induced by ribavirin. Only 1% of ATP remained after incubation with ribavirin (2 mM) at 37 °C for 24 h vs...
September 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28883690/direct-acting-antiviral-agents-against-hepatitis-c-virus-and-lipid-metabolism
#14
EDITORIAL
Tatsuo Kanda, Mitsuhiko Moriyama
Hepatitis C virus (HCV) infection induces steatosis and is accompanied by multiple metabolic alterations including hyperuricemia, reversible hypocholesterolemia and insulin resistance. Total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels are increased by peginterferon and ribavirin combination therapy when a sustained virologic response (SVR) is achieved in patients with HCV. Steatosis is significantly more common in patients with HCV genotype 3 but interferon-free regimens are not always effective for treating HCV genotype 3 infections...
August 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28881052/asunaprevir-and-daclatasvir-for-recurrent-hepatitis-c-after-liver-transplantation-a-japanese-multicenter-experience
#15
Toru Ikegami, Yoshihide Ueda, Nobuhisa Akamatsu, Kohei Ishiyama, Ryoichi Goto, Akihiko Soyama, Kaori Kuramitsu, Masaki Honda, Masahiro Shinoda, Tomoharu Yoshizumi, Hideaki Okajima, Yuko Kitagawa, Yukihiro Inomata, Yonson Ku, Susumu Eguchi, Akinobu Taketomi, Hideki Ohdan, Norihiro Kokudo, Mitsuo Shimada, Katsuhiko Yanaga, Hiroyuki Furukawa, Shinji Uemoto, Yoshihiko Maehara
The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) has not been evaluated in Japan. A multicenter study of LT recipients (n=74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated-interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n=1) in the NS3, and at L31 (n=4), Y93 (n=4), and L31/Y93 (n=1) in the NS5A region of the HCV genome...
September 7, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28881031/ribavirin-steady-state-plasma-level-is-a-predictor-of-sustained-virological-response-in-hepatitis-c-infected-patients-treated-with-direct-acting-antivirals
#16
M van Tilborg, F I Lieveld, E J Smolders, K J van Erpecum, C T M M de Kanter, R Maan, M van der Valk, J E Arends, A S M Dofferhoff, H Blokzijl, M Bijmolen, J P H Drenth, R J de Knegt, D M Burger
BACKGROUND: In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients. AIM: To assess the association between RBV steady-state plasma levels and sustained virological response (SVR). METHODS: Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled...
September 7, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28879707/analysis-of-hepatitis-c-virus-ns5a-region-in-patients-with-cirrhosis-using-an-ultra-deep-pyrosequencing-method
#17
Fahriye Keskin, Sevgi Ciftci, Filiz Akyuz, Neslihan Abaci, Aris Cakiris, Umit Akyuz, Kadir Demir, Fatih Besisik, Duran Ustek, Sabahattin Kaymakoglu
BACKGROUND: HCV (Hepatitis C Virus) is genetically more diverse than HBV and HIV (Human Immunodeficiency Virus) and exists as quasispecies within infected individuals. This is due to the lack of efficient proofreading of the viral RNA-dependent RNA polymerase. Consequently, quasispecies emerge depending on the mutation rate of the viral polymerase, which may display a high level of genetic variability in a population. In infected individuals, HCV replicates and circulates as quasispecies composed of a complex mixture of different but closely related genomes that undergoes continuous change due to competitive selection and cooperation between arising mutants...
September 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28879699/interleukin-20-gene-polymorphism-rs1518108-is-not-associated-with-sustained-virological-response-in-iranian-patients-with-hepatitis-c-virus-infection
#18
Mona S Larijani, Seyed M Sadat, Mehri Nikbin, Nasir Mohajel
METHODS: This case-control study, was performed on 136 blood samples based on 81 patients with chronic HCV genotypes 1 and 3 including 64 SVR positive and 17 negative and 55 healthy individual controls. DNA was isolated from the samples and the frequency of the polymorphism was analyzed using a PCR-RFLP method. Finally, the products were detected on 3.5% agarose gel electrophoresis. RESULTS: The analysis of the data for C/T polymorphism indicated that the CC genotype was found in 19 of 64 patients who achieved SVR, while the TT genotype was detected in 3 patients and SVR was achieved in 2...
September 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28878911/severe-autoimmune-hemolytic-anemia-during-pegylated-interferon-plus-ribavirin-treatment-for-chronic-hepatitis-c-a-case-report
#19
Shasha Wang, Eryun Qin, Yixiao Zhi, Rui Hua
We report a rare case of severe autoimmune hemolytic anemia triggered by pegylated interferon during combination therapy for chronic HCV. This case demonstrated that interferon can de novo induce autoimmune hemolytic anemia during therapy for chronic hepatitis C in a previously healthy patient.
September 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28877086/retreatment-of-chronic-hepatitis-c-virus-infection-after-unsuccessful-therapy-with-all-oral-direct-acting-antiviral-regimens-a-real-life-experience
#20
Laura Milazzo, Carlo Magni, Fosca Niero, Monica Schiavini, Alessia Lai, Valeria Cento, Francesca Binda, Spinello Antinori, Salvatore Sollima
OBJECTIVE: Few real-life data are available on the retreatment of patients who failed direct-acting antiviral (DAA)-regimens. We reported the outcome of retreatment with approved DAA regimens in a real-life cohort of patients who previously failed an all-oral DAAs combination and we analyzed the association with resistance substitutions (RASs) performed at the time of virological failure. AIM AND METHODS: Next-generation sequencing of the NS3, NS5A, and NS5B regions was performed by Illumina deep sequencing...
September 4, 2017: European Journal of Gastroenterology & Hepatology
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