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interferon lambda

Maryam Keshvari, Seyed Moayed Alavian, Bita Behnava, Ali Pouryasin, Heidar Sharafi
BACKGROUND: A dinucleotide variant rs368234815 in interferon lambda 4 (IFNL4) gene was recently found to be associated with the hepatitis C virus (HCV) treatment response. This study aimed to assess the impact of IFNL4 rs368234815 polymorphism on treatment response to pegylated-IFN alpha (Peg-IFN-α) and ribavirin (RBV) in hemophilic patients with chronic hepatitis C (CHC). MATERIALS AND METHODS: In this retrospective study, 92 hemophilic patients with CHC who were treated with Peg-IFN-α/RBV were investigated...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
Samir R Shah, P N Rao, Shiv K Sarin, Abhijit Chowdhury, Shobna Bhatia, Rajesh Dharamsi, B D Goswami, Dharmesh Kapoor, Rosang Luaia, Rajiv Mehta, Shrikant Mukewar, V G Mohan Prasad, Ramesh Roop Rai, Sanjiv Saigal, Devendra Singh, Nirupama Trehanpati, Sandra Chen, Anuj Gaggar, Steven J Knox, G Mani Subramanian, Shivaram Prasad Singh, Ajit Sood, Joy Varghese, Raj Vigna Venugopal
BACKGROUND AND AIMS: Although chronic hepatitis C virus (HCV) infection affects millions of people in India, few studies have assessed host, viral, and disease characteristics of chronically infected patients at national and regional levels. Such information is critical to support large scale screening and treatment initiatives for chronic HCV infection in India. METHODS: Patients with known chronic HCV infection making routine or for-cause visits to the participating study centers were enrolled in this observational study...
November 15, 2016: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
Adina Maria Kamal, Paul MitruŢ, Kamal Constantin Kamal, Oana Sorina Tica, Mihaela Niculescu, Dragoş Ovidiu Alexandru, Andrei Adrian Tica
Globally, over 4% of the world population is affected by hepatitis C virus (HCV) infection. The current standard of care for hepatitis C infection is combination therapy with pegylated interferon and ribavirin for 48 weeks, which yield a sustained virological response in only a little over half of the patients with genotype 1 HCV. We investigated the clinical importance of pharmacogenetics in treatment efficacy and prediction of hematotoxicity. A total of 148 patients infected with HCV were enrolled. All patients were treated for a period of 48 weeks or less with pegylated interferon and ribavirin...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
Seyed Moayed Alavian, Mohammad Saeid Rezaee-Zavareh
CONTEXT: Direct acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus (HCV) infection, which is a major public health problem. Among the known DAAs, daclatasvir (DCV), an inhibitor of the non-structural 5A protein, has been used in combination with several drugs for treatment of infection with HCV of different genotypes under different conditions. We conducted a systematic review and meta-analysis of combination therapy with DCV...
September 2016: Hepatitis Monthly
Yunhua Li, Luhua Yang, Kaihui Sha, Tonggang Liu, Liguo Zhang
BACKGROUND: Interferon-lambda 4 (IFNL4) ss469415590 is a newly discovered polymorphism that could predict the treatment response in hepatitis C virus (HCV)-infected patients. This meta-analysis was performed in order to clarify its specific effect on the treatment response and to compare it with interleukin 28b (IL28B). METHOD: The commonly used literature databases were searched. Meta-analyses were performed with fixed/random-effects models using Stata 12.0. The sustained virological response (SVR) rate was summarized using R software...
October 31, 2016: International Journal of Infectious Diseases: IJID
MeeAe Hong, Johannes Schwerk, Chrissie Lim, Alison Kell, Abigail Jarret, Joseph Pangallo, Yueh-Ming Loo, Shuanghu Liu, Curt H Hagedorn, Michael Gale, Ram Savan
Interferon (IFN) lambdas are critical antiviral effectors in hepatic and mucosal infections. Although IFNλ1, IFNλ2, and IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism. Intriguingly, human IFNL4 harbors a genetic variant that introduces a premature stop codon. We performed a molecular and biochemical characterization of IFNλ4 to determine its role and regulation of expression...
November 14, 2016: Journal of Experimental Medicine
Robert Flisiak, Mitchell Shiffman, Juan Arenas, Hugo Cheinquer, Igor Nikitin, Yuping Dong, Khurram Rana, Subasree Srinivasan
BACKGROUND: A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. METHODS: Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks...
2016: PloS One
Maryam Keshvari, Seyed Moayed Alavian, Bita Behnava, Ali Pouryasin, Johanna C Craig, Heidar Sharafi
BACKGROUND: The aim of this study was to determine whether two polymorphisms of the human interferon lambda 4 (IFNL4) gene (rs12979860 and rs8099917) can predict sustained virologic response (SVR) following antiviral therapy in patients with inherited bleeding disorder and chronic hepatitis C (CHC). METHODS: This retrospective study was conducted on 294 patients with congenital bleeding disorder and CHC who were treated with Peg-Interferon-α (PegIFN) and Ribavirin (RBV)...
October 13, 2016: Journal of Clinical Laboratory Analysis
Sujin Kim, Min-Ji Kim, Chang-Hoon Kim, Ju Wan Kang, Ha Kyung Shin, Dong-Young Kim, Tae-Bin Won, Doo Hee Han, Chae Seo Rhee, Joo-Heon Yoon, Hyun Jik Kim
RATIONALE AND OBJECTIVES: Here we studied the interferon (IFN)-regulated innate immune response against influenza A virus (IAV) infection in the mouse lung and the therapeutic effect of IFN-λ2/3 in acute IAV lung infection. . METHODS: For viral infections, IAV (WS/33, H1N1, PR8 H1N1, H5N1) were inoculated into WT mice by intranasal delivery and IAV mRNA level and viral titer were measured. To compare the antiviral effect of IFNs in vivo lung, neutralizing antibodies and recombinant IFNs were used...
September 15, 2016: American Journal of Respiratory Cell and Molecular Biology
Aoife Kelly, Mark W Robinson, Gerard Roche, Christine A Biron, Cliona O'Farrelly, Elizabeth J Ryan
The interferon lambda (IFN-λ) cytokines have well-known antiviral properties, yet their contribution to immune regulation is not well understood. Epithelial cells represent the major target cell of IFN-λ; peripheral blood mononuclear cells are generally considered nonresponsive, with the exception of plasmacytoid dendritic cells (pDCs). In this study we aimed to define the potential for discrete subpopulations of cells to directly respond to IFN-λ. Analysis of peripheral blood leukocytes reveals that, while pDCs uniformly express the highest levels of IFN-λ receptor, a small proportion of B cells and monocytes also express the receptor...
December 2016: Journal of Interferon & Cytokine Research
Graham R Foster, Kazuaki Chayama, Wan-Long Chuang, Hugo Fainboim, Martti Farkkila, Adrian Gadano, Giovanni B Gaeta, Christophe Hézode, Yukiko Inada, Jeong Heo, Hiromitsu Kumada, Sheng-Nan Lu, Patrick Marcellin, Christophe Moreno, Stuart K Roberts, Simone I Strasser, Alexander J Thompson, Joji Toyota, Seung Woon Paik, John M Vierling, Anna L Zignego, David Cohen, Fiona McPhee, Megan Wind-Rotolo, Subasree Srinivasan, Matthew Hruska, Heather Myler, Simon D Portsmouth
BACKGROUND AND PURPOSE: Peginterferon Lambda was being developed as an alternative to alfa interferon for the treatment of chronic hepatitis C virus (HCV) infection. We compared peginterferon Lambda-1a plus ribavirin (Lambda/RBV) and Lambda/RBV plus daclatasvir (DCV; pangenotypic NS5A inhibitor) with peginterferon alfa-2a plus RBV (alfa/RBV) in treatment-naive patients with HCV genotype 2 or 3 infection. METHODS: In this multicenter, double-blind, phase 3 randomized controlled trial, patients were assigned 2:2:1 to receive 24 weeks of Lambda/RBV, 12 weeks of Lambda/RBV + DCV, or 24 weeks of alfa/RBV...
2016: SpringerPlus
Camila Fernanda da Silveira Alves, Camila Schultz Grott, Vagner Ricardo Lunge, Jorge Umberto Béria, Daniela Cardoso Tietzmann, Airton Tetelbom Stein, Daniel Simon
Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism...
July 2016: Genetics and Molecular Biology
Camila Fernanda da Silveira Alves, Camila Schultz Grott, Vagner Ricardo Lunge, Jorge Umberto Béria, Daniela Cardoso Tietzmann, Airton Tetelbom Stein, Daniel Simon
Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism...
July 25, 2016: Genetics and Molecular Biology
Yu-Lin Hsu, Mei-Yi Wang, Ling-Jun Ho, Jenn-Haung Lai
A marked increase in the rate of dengue virus (DENV) infection has resulted in more than 212 deaths in Taiwan since the beginning of 2015, mostly from fatal outcomes such as dengue hemorrhagic fever and dengue shock syndrome. The pathogenic mechanisms of these fatal manifestations are poorly understood. Cytokines induce an overwhelming immune reaction and thus have crucial roles. Interferon-lambda (IFN-λ), a newly identified IFN subtype, has antiviral effects, but its immunologic effects in DENV infection have not been investigated...
2016: Scientific Reports
Ahmed Lasfar, Helen Gogas, Andrew Zloza, Howard L Kaufman, John M Kirkwood
Interferon-lambda (IFN-λ) is a new IFN type, related to IFN-α, that is commonly used in the clinic. However, significant side effects accompanying IFN-α treatment limit enthusiasm for IFN-α. In this review, we discuss the current landscape of IFN-α use in oncology and describe the biologic characteristics of IFN-λ. IFN-λ offers unique advantages, including a more tumor cell selective targeting, lower off-target binding and an ability to generate both innate and adaptive immune responses. IFN-λ has also demonstrated therapeutic benefit in murine cancer models...
July 2016: Immunotherapy
Zaigham Abbas, Javed Yakoob, Muhammad A Umer, Ali A Azeem, Saeed S Hamid, Wasim Jafri
OBJECTIVE: To assess the role of single nucleotide polymorphisms (SNPs) near the interferon lambda-3 (IFNλ3) (formal IL-28B) gene rs12979860 in predicting sustained virologic response (SVR) in hepatitis-C virus genotype-3 (HCV-3). STUDY DESIGN: Descriptive, analytical study. PLACE AND DURATION OF STUDY: Department of Medicine, The Aga Khan University Hospital, Karachi, from July 2012 to June 2014. METHODOLOGY: Patients with HCV-3 were classified as sustained virologic response (SVR), relapsers and non-responders...
June 2016: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
E Santagostino, S Pol, A Olveira, H W Reesink, K van Erpecum, P Bogomolov, D Xu, L Critelli, S Srinivasan, E Cooney
AIM: This study explores the potential role of a novel interferon-containing regimen for treatment of patients with chronic hepatitis C (CHC) and underlying haemophilia. METHODS: This trial (NCT01741545) was an open-label, non-randomized phase 3 study, which included adult haemophiliacs with hepatitis C virus (HCV). Patients with HCV genotypes (GT)-2 or -3 were treated with Lambda-IFN/ribavirin (RBV)/daclatasvir (DCV) for 12 weeks (cohort A). Patients with HCV GT-1b or -4 were treated with Lambda-IFN/RBV/DCV for 12 weeks, followed by Lambda-IFN/RBV for an additional 12 weeks (cohort B)...
September 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
K S O'Connor, S A Read, M Wang, S Schibeci, M Eslam, A Ong, M D Weltman, M W Douglas, A Mazzola, A Craxì, S Petta, G J Stewart, C Liddle, J George, G Ahlenstiel, D R Booth
Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals...
September 2016: Genes and Immunity
Weiguo Fan, Shiqi Xie, Xinhao Zhao, Nan Li, Chong Chang, Li Li, Ge Yu, Xiumei Chi, Yu Pan, Junqi Niu, Jin Zhong, Bing Sun
The recently discovered interferon lambda 4 (IFN-λ4) is a new member of the human type III interferons which could induce a strong antiviral effect through the JAK-STAT cascade. However, hepatitis C virus (HCV) patients who are capable of expressing IFN-λ4 usually have poor response to IFN-α treatment, and the mechanism behind this paradox remains unknown. Here, we reported that IFN-λ4 desensitized IFN-α-stimulated JAK-STAT signalling. Microarray analysis revealed that IFN-λ4 could induce ubiquitin specific peptidase 18 (USP18), a known inhibitor of the type I IFN signalling pathway, in a more sustained pattern compared with type I interferon induction...
September 2016: Journal of General Virology
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