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Hepatitis C genotype 3

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
Muhammad Shoaib Siddique, Alvia Saad, Sana Shoaib
OBJECTIVE: To determine the change in rapid virological response for chronic hepatitis C by qualitative PCR testing after treatment with sofosbuvir. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Memon Medical Institute Hospital, Karachi, from January to September 2016. METHODOLOGY: The study population consisted of patients above 18 years, till 80 years of age, of both genders, having chronic infection with HCV...
March 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
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
Bangari Haldipur, Prudhvi Lal Bhukya, Vidya Arankalle, Kavita Lole
Molecular mechanisms of liver pathology and clinical disease in HEV infection remain unclear. MicroRNAs are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection. In silico predictions using genotype 1, 2, 3 and 4 HEV sequences showed that majority of genomes (203/222) harbor at least one miR-122/miR-122* target site...
March 14, 2018: Journal of Virology
J von Felden, J Vermehren, P Ingiliz, S Mauss, T Lutz, K G Simon, H W Busch, A Baumgarten, K Schewe, D Hueppe, C Boesecke, J K Rockstroh, M Daeumer, N Luebke, J Timm, J Schulze Zur Wiesch, C Sarrazin, S Christensen
BACKGROUND: Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. AIM: To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting...
March 14, 2018: Alimentary Pharmacology & Therapeutics
Jennifer S Husson, Bharath Ravichandran, Srijana Jonchhe, Shyamasundaran Kottilil, Eleanor Wilson
Short treatment duration of ledipasvir/sofosbuvir (LDV/SOF) has been successfully used to treat hepatitis C virus (HCV) genotype 1 infection in treatment-naive noncirrhotic patients with viral loads (VLs) under 6 million IU/mL. However, this short duration has not been studied in renal transplant recipients (RTRs), a patient population on lifelong immunosuppression. Here, we describe 3 RTRs who received 8 weeks of LDV/SOF, meeting the standard criteria for shortened treatment duration. All 3 patients tolerated treatment well and achieved sustained virologic response at 12 weeks (SVR 12)...
December 2017: Transplantation Direct
Narayan Ramamurthy, Emanuele Marchi, M Azim Ansari, Vincent Pedergnana, Angela Mclean, Emma Hudson, Rory Bowden, Chris C A Spencer, Ellie Barnes, Paul Klenerman
New directly acting antivirals (DAAs) provide very high cure rates in most patients infected by hepatitis C virus (HCV). However, some patient groups have been relatively harder to treat including those with cirrhosis or infected with HCV genotype 3. In the recent BOSON trial, genotype 3, cirrhotic patients receiving a 16 week course of sofosbuvir and ribavirin had a sustained virologic response rate (SVR) of around 50%. In cirrhotic patients, IFNL4 CC genotype was significantly associated with SVR. This genotype was also associated with a lower interferon-stimulated gene (ISG) signature in peripheral blood and in liver at baseline...
March 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
P Kashyap, M Deka, S Medhi, S Dutta, K Kashyap, N Kumari
Hepatitis A virus (HAV) which causes liver disease is recognized by Toll-like receptors (TLRs) through the viral nucleic acid, initiating the host defense response. The study aims to analyze the role of TLR4 rs11536889 polymorphism in the pathogenesis of hepatitis A cases from Assam. There was significant correlation between TLR4 SNP G/C (rs11536889) and between acute viral hepatitis (AVH) A cases and controls. The correlation of the 3 different genotypes GG, GC and CC of TLR4 rs11536889 with the TLR4 mRNA expression level in all the HAV cases groups have been found to be statistically significant (p <0...
2018: Acta Virologica
Varun Chauhan, Mini P Singh, Radha K Ratho
Hepatitis C virus (HCV) infects almost 150 million people and is a leading cause of liver disease worldwide. It has been classified into seven genotypes; the most common genotype affecting Indian population is genotype 3 (60-70%). Currently there is no vaccine for any genotype of HCV. In order to develop peptide based vaccine against HCV, it is important to identify the conservancy in the circulating genotypes, along with the Human Leucocyte Antigen (HLA) alleles in the target population. The present study aims to identify conserved CD4 and CD8 T cells and B cell epitopes against Indian HCV-genotype-3a using an in silico analysis...
March 5, 2018: Biologicals: Journal of the International Association of Biological Standardization
Joseph D Yao, Stephen Young, Gabrielle M Heilek, Enrique Marino, Ellen E Paxinos, Ed G Marins, Alexandra Valsamakis
BACKGROUND AND OBJECTIVES: Accurate, sensitive, and specific tests for detection and monitoring of hepatitis C virus (HCV) RNA concentrations are essential for diagnosis and management of HCV infections. We evaluated the next-generation reverse-transcription real-time PCR test, cobas® HCV test for use with the cobas® 6800/8800 systems ("cobas HCV") by determining its analytical performance characteristics and clinical utility for the diagnosis and therapeutic monitoring of chronic HCV infections...
February 24, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
Ching-I Huang, Chung-Feng Huang, Ming-Lun Yeh, Yi-Hung Lin, Po-Cheng Liang, Shang-Yin Vanson Liu, Meng-Hsuan Hsieh, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Reports of the role of host interleukin 28B (IL-28B) genetic variants in liver disease severity in patients with chronic hepatitis C (CHC) have obtained conflicting results. The impact of IL-28B in Asian patients with different viral genotypes remains elusive.We try to elucidate the effect of IL-28B genetic variants in a large Asian cohort with different viral genotypes.The association between the IL-28B rs8099917 genotype and liver fibrosis was investigated in 1288 patients with biopsy-proven CHC.Patients with hepatitis C virus genotype 1 (HCV-1) infection comprised 59...
March 2018: Medicine (Baltimore)
Sathej Gopalakrishnan, Sven Mensing, Rajeev M Menon, Jiuhong Zha
BACKGROUND: The clinical development program of the direct-acting antiviral (DAA) combination therapy of paritaprevir (coadministered with ritonavir) and ombitasvir, with and without dasabuvir (3-DAA [3D] and 2-DAA [2D] regimens, respectively) used in the treatment of chronic hepatitis C infection has generated a robust dataset across various dosing regimens and patient populations. OBJECTIVE: The current analysis aimed to characterize the population pharmacokinetics in patients without cirrhosis ('non-cirrhotic') and with compensated cirrhosis ('cirrhotic'), while accounting for differences across hepatitis C virus (HCV) genotypes (GT) 1, 2, and 4, multiple regimens (3D regimen ± ribavirin for GT1 in global studies, 2D regimen for subgenotype 1b in Japan, 2D regimen + ribavirin for GT2 in Japan, and 2D regimen + ribavirin for GT4), and ethnicities...
March 7, 2018: Clinical Pharmacokinetics
Bo Wang, Dominik Harms, C Patrick Papp, Sandra Niendorf, Sonja Jacobsen, Marc Lütgehetmann, Sven Pischke, Heiner Wedermeyer, Jörg Hofmann, C-Thomas Bock
Autochthonous Hepatitis E virus genotype 3 (HEV-3) infections in industrialized countries are more frequent than previously assumed. HEV-3 is zoonotic and the causal pathogen of chronic hepatitis E. According to the latest classification of the family Hepeviridae , 10 HEV-3 designated subtypes (HEV-3a to HEV-3j) and 7 unassigned HEV-3 subtypes are proposed. In order to identify and characterize HEV-3 variants in circulation, we developed a molecular approach combining a sensitive HEV-specific real-time RT-PCR targeting HEV ORF2/3 region and two newly designed consensus nested RT-PCRs targeting HEV ORF1 and ORF2 genes, respectively...
March 7, 2018: Journal of Clinical Microbiology
Cirley Maria de Oliveira Lobato, Natalia Balassiano, Elodie Bomfim Hyppolito, Rafaela Liz Pellegrim Sanchez-Lermen, Izabelle Venturini Signorelli, Miguel Yasuo Tomita Nicacio, Alberto Pereira Firmino Filho, Thais Guaraná de Andrade, José Milton de Castro Lima, Talita Amorim de Arruda, Fernanda Schwanz Coutinho, Everton Felipe do Vale Araujo, Ticiana Mota Esmeraldo, Erlon Cortez, Rafaela Lorenzon Aragão Capeli, Melquior Brunno Mateus de Matos, Francisco Sérgio Rangel Pessoa, Hélder Cássio de Oliveira, Érico Antônio Gomes de Arruda, Patrícia Lofêgo Gonçalves, Antônio Haroldo Araújo Filho, Eliane Bordalo Cathalá Esberard, Francisco José Dutra Souto
INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol...
January 2018: Revista da Sociedade Brasileira de Medicina Tropical
N Y Mapoure, M N Budzi, S A F B Eloumou, A Malongue, C Okalla, H N Luma
BACKGROUND: Chronic hepatitis C infection is a major public health concern, with a high burden in Sub-Saharan Africa. There is growing evidence that chronic hepatitis C virus (HCV) infection causes neurological complications. This study aimed at assessing the prevalence and factors associated with neurological manifestations in chronic hepatitis C patients. METHODS: Through a cross-sectional design, a semi-structured questionnaire was used to collect data from consecutive chronic HCV infected patients attending the outpatient gastroenterology unit of the Douala General Hospital (DGH)...
2018: PloS One
Filomena Morisco, Rocco Granata, Silvia Camera, Antonio Ippolito, Michele Milella, Fabio Conti, Chiara Masetti, Antonella Smedile, Paolo Tundo, Teresa Santantonio, Maria Rosa Valvano, Antonio Termite, Pietro Gatti, Vincenzo Messina, Angelo Iacobellis, Marta Librandi, Nicola Caporaso, Angelo Andriulli
Background and aim: Direct antiviral agents (DAAs) have led to high sustained virological responses (SVR) in hepatitis C virus (HCV) patients. However, genotype 3 patients respond to treatment in a suboptimal way. This study aims to identify which of the several treatment schedules recommended for genotype 3 would constitute the best option. Methods: Twenty-four Italian centers were involved in this real-life study of HCV genotype 3 patients treated with DAAs. To expand the number of cases, we conducted a systematic review of the literature on the outcome of genotype 3 patients treated with DAAs...
March 2018: United European Gastroenterology Journal
Christine M Durand, Mary G Bowring, Diane M Brown, Michael A Chattergoon, Guido Massaccesi, Nichole Bair, Russell Wesson, Ashraf Reyad, Fizza F Naqvi, Darin Ostrander, Jeremy Sugarman, Dorry L Segev, Mark Sulkowski, Niraj M Desai
Background: Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource. Objective: To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R- transplantation)...
March 6, 2018: Annals of Internal Medicine
Eve Todesco, Alessandra Mazzola, Sepideh Akhavan, Florence Abravanel, Thierry Poynard, Anne-Marie Roque-Afonso, Gilles Peytavin, Anne-Geneviève Marcelin, Yvon Calmus, Lucien Lecuyer, Romain Guillemain, Filomena Conti
Hepatitis E Virus can induce chronic infections in the case of immunosuppression, which are sometimes not cured with ribavirin. Furthermore, Sofosbuvir is a highly potent inhibitor of Hepatitis C virus polymerase and was shown to inhibit Hepatitis E Virus (HEV) genotype 3 replication in vitro.We report here the outcome of sofosbuvir/ribavirin therapy on a chronic HEV infection in a heart transplant recipient non responder to ribavirin. After 24 weeks, the regimen failed to cure the persistent HEV infection, highlighting the need of therapeutic options for HEV-infected immunosuppressed patients...
March 5, 2018: Antiviral Therapy
Norio Akuta, Joji Toyota, Yoshiyasu Karino, Fusao Ikeda, Akio Ido, Katsuaki Tanaka, Koichi Takaguchi, Atsushi Naganuma, Eiichi Tomita, Kazuaki Chayama, Shigetoshi Fujiyama, Yukiko Inada, Hitoshi Yoshiji, Hideaki Watanabe, Hiroki Ishikawa, Fiona McPhee, Stephanie Noviello, Hiromitsu Kumada
BACKGROUND: In the UNITY-3 study, 96% sustained virologic response (SVR12) rate was observed in Japanese patients with hepatitis C virus (HCV) genotype (GT)-1 infection treated for 12 weeks with fixed-dose daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO). As HCV clearance may improve liver outcomes, we assessed hepatic fibrosis and alpha-fetoprotein (AFP), a hepatocellular carcinoma risk marker, pre- and post-treatment in UNITY-3. METHODS: Treatment-naive or interferon-experienced UNITY-3 patients with HCV GT-1 who received twice-daily DCV-TRIO were assessed for fibrosis [FibroTest; FibroScan; fibrosis-4 index (FIB-4), aspartate-aminotransferase-to-platelet-ratio index] and AFP at baseline and Weeks 4 (FIB-4 only), 12 or 24 post-treatment...
March 2, 2018: Journal of Gastroenterology
Natalia Freitas, Tetyana Lukash, Sumedha Gunewardena, Benjamin Chappell, Betty L Slagle, Severin O Gudima
Five matching sets of non-malignant liver tissues and HCCs from individuals chronically infected with hepatitis B virus (HBV) were examined. The HBV genomic sequences were determined using overlapping PCR amplicons covering the entire viral genome. Four pairs of tissues were infected with HBV of genotype C, while one pair - with genotype B. HBV replication markers were found in all tissues. In majority of HCC samples, the levels of pre-genomic/pre-core RNA (pgRNA) and covalently closed circular DNA (cccDNA) were lower than those of liver tissue counterparts...
February 28, 2018: Journal of Virology
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