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https://www.readbyqxmd.com/read/28622951/population-approach-to-efavirenz-therapy
#1
Hélder Duarte, João Paulo Cruz, Natália Aniceto, Ana Clara Ribeiro, Ana Fernandes, Paulo Paixão, Francisco Antunes, José Morais
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor commonly used as first line therapy in the treatment of human immunodeficiency virus, with a narrow therapeutic range and a high between-subject variability which can lead to central nervous system toxicity or therapeutic failure. To characterize the sources of variability and better predict EFV steady state plasma concentrations, a population pharmacokinetic model was developed form 96 HIV positive individuals, using a nonlinear mixed effect method with Monolix® software...
June 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28614389/immunological-dynamics-associated-with-rapid-virological-response-during-the-early-phase-of-type-i-interferon-therapy-in-patients-with-chronic-hepatitis-c
#2
Jae-Won Lee, Won Kim, Eun-Kyung Kwon, Yuri Kim, Hyun Mu Shin, Dong-Hyun Kim, Chan-Ki Min, Ji-Yeob Choi, Won-Woo Lee, Myung-Sik Choi, Byeong Gwan Kim, Nam-Hyuk Cho
Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV)...
2017: PloS One
https://www.readbyqxmd.com/read/28605503/behavioural-not-biological-factors-drive-the-hcv-epidemic-among-hiv-positive-msm-hcv-and-hiv-modelling-analysis-including-hcv-treatment-as-prevention-impact
#3
Louis MacGregor, Natasha K Martin, Christinah Mukandavire, Ford Hickson, Peter Weatherburn, Matthew Hickman, Peter Vickerman
Background: Uncertainty surrounds why hepatitis C virus (HCV) is concentrated among HIV-positive men who have sex with men (MSM). We used mathematical modelling to explore reasons for these infection patterns, and implications for HCV treatment-as-prevention. Methods: Using a joint MSM HIV/HCV transmission model parameterized with UK behavioural data, we considered how biological (heightened HCV infectivity and reduced spontaneous clearance among HIV-positive MSM) and/or behavioural factors (preferential sexual mixing by HIV status and risk heterogeneity) could concentrate HCV infection in HIV-positive MSM as commonly observed (5-20 times the HCV prevalence in HIV-negative MSM; defined as the HCV ratio)...
June 12, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28598970/seroprevalence-and-clinical-characteristics-of-viral-hepatitis-in-transfusion-dependent-thalassemia-and-hemophilia-patients
#4
Tyng-Yuan Jang, Pei-Chin Lin, Ching-I Huang, Yu-Mei Liao, Ming-Lun Yeh, Yu-Sheng Zeng, Po-Cheng Liang, Wan-Yi Hsu, Shih-Pien Tsai, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Chia-Yen Dai, Chung-Feng Huang, Shyh-Shin Chiou, Wan-Long Chuang, Ming-Lung Yu
BACKGROUND/AIMS: Transfusion dependent subjects are at a great risk of viral hepatitis infection. We aimed to evaluate the prevalence and factors associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among transfusion-dependent patients in Taiwan. METHODS: A total of 140 patients (67 thalassemic patients, 70 hemophilic patients, two patients with hereditary spherocytosis and one patient with von Willebrand disease) were prospectively enrolled to evaluate the prevalence and factors associated with viral hepatitis and spontaneous HCV clearance...
2017: PloS One
https://www.readbyqxmd.com/read/28595541/evaluating-the-role-of-interleukin-12-b-gene-polymorphism-in-prediction-of-disease-progression-in-patients-with-chronic-hepatitis-c-virus-infection
#5
Nadia Elwan, Khalda Amr, Sahar Elyamany, Walaa Elkhalawany, Shaimaa Soliman, Mohamed Ziada, Sherief Abd-Elsalam
Background &Aims: Cell-mediated immunity plays a critical role in viral clearance and disease progression during Hepatitis C virus (HCV) infection. Interleukin (IL)-12 is a cytokine that has been shown to be a potent antiviral cytokine. The aim of this work is to investigate the association of IL-12 B gene polymorphism with the progression of liver disease in chronic HCV patients. METHODS: This cross sectional study was carried out in tropical medicine department, Tanta university hospital, Egypt, on 120 chronic HCV patients with various stages of liver disease and 30 healthy subjects served as control...
June 5, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28587866/digging-more-in-the-genetic-risk-prediction-of-hepatitis-c-virus-epidemic-in-egypt-apoptosis-genes-polymorphisms-in-the-susceptibility-of-hepatitis-c-virus-and-association-with-viral-load
#6
Rania H Khalifa, Rasha Mohamad Hosny Shahin, Reham Emad Eldin Aboukhalil, Mohamed A Marie, Amr M El-Deeb, Nermine Magdi Riad
Egypt is confronted with the highest hepatitis C virus (HCV) epidemic. Apoptosis and cellular immune responses are crucial to the clearance or persistence of viral infections. This case-control study was carried out to detect whether apoptosis genes single nucleotide polymorphisms (SNPs) confer risk to HCV in a cohort of Egyptian patients and to explore their association with viral load. One hundred and ninety six blood samples were withdrawn from 96 HCV patients and 100 controls. The Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) -1525G>A and FasL-844T>C SNPs were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)...
June 3, 2017: Virus Research
https://www.readbyqxmd.com/read/28578937/active-hcv-infection-is-associated-with-increased-circulating-levels-of-interferon-gamma-ifn-%C3%AE-inducible-protein-10-ip-10-soluble-cd163-and-inflammatory-monocytes-regardless-of-liver-fibrosis-and-hiv-coinfection
#7
Claudia Mascia, Miriam Lichtner, Paola Zuccalà, Serena Vita, Tiziana Tieghi, Raffaella Marocco, Stefano Savinelli, Raffaella Rossi, Marco Iannetta, Michela Campagna, Francesco Schiavone, Fabio Mengoni, Gianluca Russo, Claudio Maria Mastroianni, Vincenzo Vullo
BACKGROUND AND OBJECTIVE: Interferon-gamma (IFN-γ)-inducible protein-10 (IP-10), soluble (s) CD163 and sCD14 play an important role in the pathogenesis of HCV and HIV infection and are involved in inflammation and liver fibrosis. The aim of the present study was to evaluate at a single time point, plasma soluble biomarkers and inflammatory monocytes subsets in different groups of subjects: (i) HIV monoinfected patients on suppressive ART; (ii) HIV/HCV coinfected patients on ART, with undetectable HIV viremia (including either subjects who had active HCV replication or those who cleared HCV); (iii) HCV monoinfected individual with active viral replication...
May 31, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28574439/the-evolving-interplay-among-abundant-adipokines-in-patients-with-hepatitis-c-during-viral-clearance
#8
Ming-Ling Chang, Chen-Ming Hsu, Cheng-Hui Lin, Cheng-Yu Lin, Chia-Jung Kuo, Shu-Wei Huang, Chun-Wei Chen, Hao-Tsai Cheng, Chau-Ting Yeh, Cheng-Tang Chiu
How hepatatitis C virus (HCV) infection affects the interplay among abundant adipokines in the host remains unclear. A prospective study was conducted with 450 consecutive genotype 1 (G1) and G2 HCV patients who completed a course of anti-HCV therapy and underwent pre-therapy and 24-week post-therapy surveys to assess various profiles and levels of abundant adipokines, including leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1). Before anti-HCV therapy, multivariate analyses showed gender to be associated with leptin and adiponectin levels, and BMI with leptin and PAI-1 levels...
June 2, 2017: Nutrients
https://www.readbyqxmd.com/read/28567493/epidemiologic-features-of-348-children-with-hepatitis-c-virus-infection-over-a-30-year-period-a-nationwide-survey-in-japan
#9
Tatsuki Mizuochi, Tomoko Takano, Tadahiro Yanagi, Kosuke Ushijima, Mitsuyoshi Suzuki, Yoko Miyoshi, Yoshinori Ito, Ayano Inui, Hitoshi Tajiri
BACKGROUND: Although the epidemiology of hepatitis C virus (HCV) infection among children may be rapidly changing, few reports have characterized large nationwide cohorts of children with HCV infection. We, therefore, sought to clarify the epidemiology and natural history of HCV infection in Japanese children born over the last three decades. METHODS: Sixty-five pediatric centers retrospectively and prospectively recruited consecutive, otherwise-healthy HCV-infected children born during 1986 to 2015...
May 31, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28567042/hepatitis-c-virus-and-human-cytomegalovirus-natural-killer-cell-subsets-in-persistent-viral-infections
#10
REVIEW
Julia Pollmann, Alexander Rölle, Maike Hofmann, Adelheid Cerwenka
Hepatitis C virus (HCV) and human cytomegalovirus (HCMV) are prominent examples of RNA and DNA viruses, respectively, that establish a persistent infection in their host. HCV affects over 185 million patients worldwide, who are at high risk for developing liver fibrosis, liver cirrhosis, and ultimately hepatocellular carcinoma. Recent breakthroughs in HCV therapy, using direct-acting antivirals have provided the opportunity to monitor natural killer (NK) cells after clearance of a chronic infection. There is now increasing evidence that the individual NK cell repertoire before infection is predictive for the course of disease...
2017: Frontiers in Immunology
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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