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https://www.readbyqxmd.com/read/28545127/improvement-of-alt-decay-kinetics-by-all-oral-hcv-treatment-role-of-ns5a-inhibitors-and-differences-with-ifn-based-regimens
#1
Valeria Cento, Thi Huyen Tram Nguyen, Domenico Di Carlo, Elisa Biliotti, Laura Gianserra, Ilaria Lenci, Daniele Di Paolo, Vincenza Calvaruso, Elisabetta Teti, Maddalena Cerrone, Dante Romagnoli, Michela Melis, Elena Danieli, Barbara Menzaghi, Ennio Polilli, Massimo Siciliano, Laura Ambra Nicolini, Antonio Di Biagio, Carlo Federico Magni, Matteo Bolis, Francesco Paolo Antonucci, Velia Chiara Di Maio, Roberta Alfieri, Loredana Sarmati, Paolo Casalino, Sergio Bernardini, Valeria Micheli, Giuliano Rizzardini, Giustino Parruti, Tiziana Quirino, Massimo Puoti, Sergio Babudieri, Antonella D'Arminio Monforte, Massimo Andreoni, Antonio Craxì, Mario Angelico, Caterina Pasquazzi, Gloria Taliani, Jeremie Guedj, Carlo Federico Perno, Francesca Ceccherini-Silberstein
BACKGROUND: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. STUDY DESIGN: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR...
2017: PloS One
https://www.readbyqxmd.com/read/28530647/stage-of-liver-fibrosis-in-patients-with-congenital-bleeding-disorders-and-infected-with-hepatitis-c-virus
#2
Marta Kucharska, Urszula Zaleska-Dorobisz, Aleksandra Szymczak, Marcin Inglot, Weronika Rymer, Małgorzata Zalewska, Krzysztof Małyszczak, Małgorzata Kuliszkiewicz-Janus, Małgorzata Inglot
INTRODUCTION    Hepatitis C virus (HCV) is the major cause of chronic liver disease in patients with hemophilia. As liver biopsy should not be routinely used in them, possibilities of accurate assessment of the fibrosis stage have been very limited until recently. OBJECTIVES    The aim of the study was to determine the stage of liver fibrosis in HCV-infected hemophiliacs with use of non-invasive methods of fibrosis assessment and to analyze the influence of risk factors on liver fibrosis.  PATIENTS AND METHODS    The study included 71 HCV-infected patients with hemophilia and other congenital bleeding disorders...
May 22, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28513591/zinc-is-a-potent-and-specific-inhibitor-of-ifn-%C3%AE-3-signalling
#3
Scott A Read, Kate S O'Connor, Vijay Suppiah, Chantelle L E Ahlenstiel, Stephanie Obeid, Kristina M Cook, Anthony Cunningham, Mark W Douglas, Philip J Hogg, David Booth, Jacob George, Golo Ahlenstiel
Lambda interferons (IFNL, IFN-λ) are pro-inflammatory cytokines important in acute and chronic viral infection. Single-nucleotide polymorphisms rs12979860 and rs8099917 within the IFNL gene locus predict hepatitis C virus (HCV) clearance, as well as inflammation and fibrosis progression in viral and non-viral liver disease. The underlying mechanism, however, is not defined. Here we show that the rs12979860 CC genotype correlates with increased hepatic metallothionein expression through increased systemic zinc levels...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507081/reversion-of-anergy-signatures-in-clonal-cd21low-b-cells-of-mixed-cryoglobulinemia-after-clearance-of-hcv-viremia
#4
Martina Del Padre, Laura Todi, Milica Mitrevski, Ramona Marrapodi, Stefania Colantuono, Massimo Fiorilli, Milvia Casato, Marcella Visentini
Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM(+)CD27(+) B cells. These cells display both the features of anergy induced by continual engagement of the B cell receptor (BCR), such as high expression of phosphorylated extracellular signal regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion such as CD21(low) phenotype and defective response to ligation of BCR and Toll-like receptor 9 (TLR9). Usually MC regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28487083/hcv-clearance-after-direct-acting-antivirals-in-patients-with-cirrhosis-by-stages-of-liver-impairment-the-ital-c-network-study
#5
Antonio Massimo Ippolito, Michele Milella, Vincenzo Messina, Fabio Conti, Raffaele Cozzolongo, Filomena Morisco, Giuseppina Brancaccio, Michele Barone, Teresa Santantonio, Chiara Masetti, Paolo Tundo, Antonina Smedile, Vito Carretta, Pietro Gatti, Antonio Patrizio Termite, Maria Rosa Valvano, Giuseppe Bruno, Claudia Fabrizio, Pietro Andreone, Marianna Zappimbulso, Giovanni Battista Gaeta, Nicola Napoli, Luca Fontanella, Gianfranco Lauletta, Giuseppe Cuccorese, Antonio Metrangolo, Ruggiero Francavilla, Emanuela Ciracì, Salvatore Rizzo, Angelo Andriulli
BACKGROUND: Sustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D'Amico might provide new insights on timing for antiviral therapy. METHODS: We investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n=575) or cirrhosis (n=2037)...
April 8, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28480234/estimating-the-time-to-diagnosis-and-the-chance-of-spontaneous-clearance-during-acute-hepatitis-c-in-human-immunodeficiency-virus-infected-individuals
#6
Romain Ragonnet, Sylvie Deuffic-Burban, Christoph Boesecke, Marguerite Guiguet, Karine Lacombe, Jeremie Guedj, Jürgen K Rockstroh, Yazdan Yazdanpanah
BACKGROUND: Hepatitis C virus (HCV) infection is often asymptomatic, and the date of infection is almost impossible to determine. Furthermore, spontaneous clearance (SC) may occur, but little is known about its time of occurrence. METHODS: Data on human immunodeficiency virus (HIV)-HCV coinfected individuals were used to inform a stochastic simulation model of HCV viral load kinetics, alanine aminotransferase (ALT), and HCV antibodies during acute hepatitis C. The dates of diagnosis and potential SC were estimated through a Bayesian approach...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28478826/novel-aspects-of-defensins-involvement-in-virus-induced-autoimmunity-in-the-central-nervous-system
#7
Evangelos I Kazakos, Jannis Kountouras, Stergios A Polyzos, Georgia Deretzi
Recent research on re-circulation of interstitial fluid from the brain parenchyma to the periphery and its inferred importance in immune surveillance dysregulation are changing our conceptualization of the pathophysiology of virus-induced autoimmunity. In this context, it is necessary to reassess the immunomodulatory properties of human defensins that are variably expressed by cerebral microglia, astrocytes and choroid plexus epithelial cells and exhibit complex and often confounding roles in neuroinflammatory processes...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28472191/spontaneous-clearance-of-chronic-hepatitis-c-is-rare-in-hiv-infected-patients-after-effective-use-of-combination-antiretroviral-therapy
#8
Mario Frias, Antonio Rivero-Juarez, Francisco Tellez, Monserrat Perez-Perez, Angela Camacho, Isabel Machuca, Sandra Lorenzo-Moncada, Pedro Lopez-Lopez, Antonio Rivero
OBJECTIVE: To evaluate the rate of spontaneous resolution of chronic hepatitis C (CHC) infection in a cohort of HIV-infected patients. METHODS: A retrospective analysis of 509 HIV-infected patients with chronic HCV infection was performed at two reference hospitals in Andalusia. The main variable of the study was spontaneous clearance of CHC, defined as a negative HCV RNA result after at least two previous quantitative measurements of HCV RNA separated by a minimum of 12 months...
2017: PloS One
https://www.readbyqxmd.com/read/28470815/efficacy-of-12-or-18-weeks-of-elbasvir-plus-grazoprevir-with-ribavirin-in-treatment-na%C3%A3-ve-non-cirrhotic-hcv-genotype-3-infected-patients
#9
Edward Gane, Ronald Nahass, Velimir Luketic, Ernest Asante-Appiah, Peggy Hwang, Michael Robertson, Janice Wahl, Eliav Barr, Barbara Haber
Elbasvir (EBR; HCV NS5A inhibitor) and grazoprevir (GZR; HCV NS3/4A protease inhibitor) are approved as a fixed-dose combination to treat patients chronically infected with HCV genotypes 1 and 4. During the development program and supported by in vitro potency, the efficacy of EBR + GZR was assessed in HCV GT3-infected patients. This study's aim was to determine the efficacy and tolerability of 12 or 18 weeks of EBR+GZR with ribavirin (RBV) in treatment-naïve, non-cirrhotic HCV GT3-infected patients. Randomized patients received open-label EBR (50 mg once daily) + GZR (100 mg once daily) + RBV...
May 4, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28469084/broadly-neutralizing-antibodies-with-few-somatic-mutations-and-hepatitis-c-virus-clearance
#10
Justin R Bailey, Andrew I Flyak, Valerie J Cohen, Hui Li, Lisa N Wasilewski, Anna E Snider, Shuyi Wang, Gerald H Learn, Nurgun Kose, Leah Loerinc, Rebecca Lampley, Andrea L Cox, Jennifer M Pfaff, Benjamin J Doranz, George M Shaw, Stuart C Ray, James E Crowe
Here, we report the isolation of broadly neutralizing mAbs (bNAbs) from persons with broadly neutralizing serum who spontaneously cleared hepatitis C virus (HCV) infection. We found that bNAbs from two donors bound the same epitope and were encoded by the same germline heavy chain variable gene segment. Remarkably, these bNAbs were encoded by antibody variable genes with sparse somatic mutations. For one of the most potent bNAbs, these somatic mutations were critical for antibody neutralizing breadth and for binding to autologous envelope variants circulating late in infection...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28468011/overcoming-cd8-t-cell-exhaustion-in-viral-hepatitis-lessons-from-the-mouse-model-and-clinical-perspectives
#11
Dominik Wieland, Maike Hofmann, Robert Thimme
About 500 million people all over the world are chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) and are thus at high risk of developing liver fibrosis, cirrhosis or hepatocellular carcinoma. While in adults about 90% of acutely HBV-infected patients clear the virus, only 30% of acute HCV infections clear spontaneously. Several mechanisms contribute to the failure in viral clearance. The main factors responsible for the chronification of HBV and HCV infection are, on the one hand, viral escape mutations leading to lack of recognition by antiviral immune cells and, on the other hand, loss of antiviral effector functions of virus-specific CD8+ T cells, called T-cell exhaustion...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28456591/polymorphisms-of-chemokine-receptor-genes-and-clearance-of-hepatitis-c-virus-infection-in-chinese-population
#12
Mingzhu Chen, Yinan Yao, Ming Yue, Feng Zang, Mei Liu, Jie Wang, Hongbo Chen, Yun Zhang, Jun Li, Peng Huang, Rongbin Yu
BACKGROUND: Chemokine genes play an essential role in both spontaneous clearance in acute infection and therapy of HCV. We investigated whether several CXC family-related genes associated with HCV spontaneous clearance and response to treatment. METHODS: The current study genotyped four SNPs, respectively are CXCR6 rs2234358, CXCL12 rs1801157, CXCL9 rs10336, rs3733236 to assess their associations with HCV spontaneous clearance and response to treatment in a two stage study (668 chronic and 400 resolvers in discovery group, meanwhile 333 chronic and 199 resolver in replication group), and a treatment cohort of HCV with 282 patients...
April 26, 2017: Gene
https://www.readbyqxmd.com/read/28440692/both-hepatitis-c-virus-specific-t-cell-responses-and-il28b-rs12979860-single-nucleotide-polymorphism-genotype-influence-antihepatitis-c-virus-treatment-outcome-in-patients-with-chronic-hepatitis-c
#13
José M Benito, Javier García-Samaniego, Marcial García, Antonio Madejón, Luz Martín-Carbonero, Alfonso Cabello, Beatriz Álvarez, Miguel Górgolas, Norma Rallón
Despite new treatments for hepatitis C virus (HCV) infection, IFNα-based regimens still have clinical relevance in special populations of patients and remain the only therapeutic option for many patients. We sought to elucidate the interplay between two relevant factors (IL28B polymorphism and T cell immune responses) involved in the outcome of this therapy in HCV-infected patients. We evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who were undergoing a full course of pegIFNα/RBV therapy...
April 25, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28439936/hiv-positive-men-who-have-sex-with-men-are-at-high-risk-of-development-of-significant-liver-fibrosis-after-an-episode-of-acute-hepatitis-c
#14
K Steininger, A Boyd, S Dupke, I Krznaric, A Carganico, M Munteanu, S Neifer, M Schuetze, M Obermeier, K Arasteh, A Baumgarten, P Ingiliz
Acute hepatitis C virus infection remains a major health concern in human immunodeficiency virus(HIV)-infected men who have sex with men (MSM). New direct-acting antiviral agent (DAA) combination therapy has not yet been approved for the treatment for acute hepatitis C virus(HCV), thereby potentially causing deferral of HCV treatment. Therefore, we aimed to study the course of liver disease after an episode of acute HCV. This study is a retrospective single-centre cohort of HIV-positive MSM with acute HCV infection...
April 25, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28430385/significant-reductions-in-alcohol-use-after-hepatitis-c-treatment-results-from-the-french-anrs-co13-hepavih-cohort
#15
Rod Knight, Perrine Roux, Antoine Vilotitch, Fabienne Marcellin, Eric Rosenthal, Laure Esterle, François Boué, David Rey, Lionel Piroth, Stéphanie Dominguez, Philippe Sogni, Dominique Salmon-Ceron, Bruno Spire, Maria Patrizia Carrieri
BACKGROUND AND AIMS: Few data exist on changes to substance use patterns before and after hepatitis C virus (HCV) treatment. We used longitudinal data of HIV-HCV co-infected individuals to examine whether receiving Peg-interferon (Peg-IFN)-based therapy irrespective of HCV clearance could modify tobacco, cannabis and alcohol use. DESIGN: A prospective cohort of HIV-HCV co-infected individuals was enrolled from 2006. Participants' clinical data were retrieved from medical records and socio-demographic and behavioral characteristics were collected by yearly self-administered questionnaires...
April 21, 2017: Addiction
https://www.readbyqxmd.com/read/28419488/interferon-%C3%AE-3-gene-il28b-is-associated-with-spontaneous-or-treatment-induced-viral-clearance-in-hepatitis%C3%A2-c-virus-infected-multitransfused-patients-with-thalassemia
#16
Aritra Biswas, Rushna Firdaus, Debanjali Gupta, Monika Ghosh, Kallol Saha, Prosanto Chowdhury, Maitreyee Bhattacharyya, Provash C Sadhukhan
BACKGROUND: Hepatitis C virus (HCV) is the major posttransfusion infection in multitransfused individuals in India with thalassemia major. To our knowledge, this study is the first conducted to correlate and comprehend the effects of the host interleukin (IL)28B gene polymorphism at loci rs12979860 and rs8099917 in spontaneous or interferon (IFN)-induced treatment response in the HCV-seroreactive individuals with thalassemia major. STUDY DESIGN AND METHODS: A total of 557 HCV-seroreactive individuals with thalassemia were processed for HCV viral genotyping and host IL28B single-nucleotide polymorphism analysis at loci rs12979860 and rs8099917...
April 16, 2017: Transfusion
https://www.readbyqxmd.com/read/28414896/nk-cells-in-self-limited-hcv-infection-exhibit-a-more-extensively-differentiated-but-not-memory-like-repertoire
#17
Rik A de Groen, Zwier M A Groothuismink, Gertine van Oord, Neeltje A Kootstra, Harry L A Janssen, Maria Prins, Janke Schinkel, André Boonstra
Natural killer (NK) cells have long been thought of as a purely innate immune cell population, but increasing reports have described developmental and functional qualities of NK cells that are commonly associated with cells of the adaptive immune system. Of these features, the ability of NK cells to acquire functional qualities associated with immunological memory and continuous differentiation resulting in the formation of specific NK cell repertoires has recently been highlighted in viral infection settings...
April 17, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28413215/successful-withdrawal-of-insulin-therapy-after-post-treatment-clearance-of-hepatitis-c-virus-in-a-man-with-type-2-diabetes
#18
Timothy M E Davis, Wendy A Davis, Gary Jeffrey
BACKGROUND Chronic hepatitis C virus (HCV) infection is associated with increased insulin resistance and risk of type 2 diabetes. Successful antiviral treatment can improve insulin resistance and allow a reduction in blood glucose-lowering treatment. There have been case reports of a reduced insulin requirement in this situation, although 1 case in which insulin was stopped exhibited a subsequent deterioration in glycemic control. CASE REPORT A 55-year-old Italian man was diagnosed with HCV infection in 2000 at the age of 39 years and with type 2 diabetes 6 years later...
April 17, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28412292/hla-bw4-80-t-and-multiple-hla-bw4-copies-combined-with-kir3dl1-associate-with-spontaneous-clearance-of-hcv-infection-in-people-who-inject-drugs
#19
Christine Thöns, Tina Senff, Theresa J Hydes, Angela R Manser, Falko M Heinemann, Andreas Heinold, Martin Heilmann, Arthur Y Kim, Markus Uhrberg, Norbert Scherbaum, Georg M Lauer, Salim I Khakoo, Jörg Timm
BACKGROUND AND AIMS: NK cell function is regulated by inhibitory and activating receptors including killer-cell immunoglobulin-like receptors (KIRs). Here, we analyzed the impact of different KIR/KIR-ligand genotypes on the outcome of HCV infection in people who inject drugs (PWID). KIR/KIR-ligand genotypes associated with spontaneous clearance of HCV infection were identified in a cohort of PWID from Germany (n=266) and further validated in a second anti-HCV positive cohort of PWID recruited in North America (n=342)...
April 12, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28404135/incidence-risk-factors-and-prevention-of-hepatitis-c-reinfection-a-population-based-cohort-study
#20
Nazrul Islam, Mel Krajden, Jean Shoveller, Paul Gustafson, Mark Gilbert, Jane A Buxton, Jason Wong, Mark W Tyndall, Naveed Zafar Janjua
BACKGROUND: People remain at risk of reinfection with hepatitis C virus (HCV), even after clearance of the primary infection. We identified factors associated with HCV reinfection risk in a large population-based cohort study in British Columbia, Canada, and examined the association of opioid substitution therapy and mental health counselling with reinfection. METHODS: We obtained data from the British Columbia Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV at the British Columbia Centre for Disease Control Public Health Laboratory during 1990-2013 (when data were available)...
March 2017: Lancet. Gastroenterology & Hepatology
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