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Julie Lynch, Scott L DuVall, Brygida Berse, Angela Whatley, Cathy St Pierre, Omobonike Oloruntoba, Christine M Hunt
We assessed implementation of precision medicine within the Veterans Health Administration. We analyzed the use of interleukin-28B (IL28B) pharmacogenetic test, which predicts interferon-α treatment response in patients with hepatitis C. Patients with favorable CC genotype exhibit a two-fold higher response than patients with less favorable genotypes (CT and TT). Linking IL28B tests to Veterans Health Administration clinical data, we analyzed test use, concordance with guidelines, subsequent interferon-α treatment, and site variations...
October 2016: Military Medicine
Yone-Han Mah, Chen-Hua Liu, Chi-Ling Chen, Tai-Chung Tseng, Chun-Jen Liu, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
BACKGROUND/PURPOSE: Clinical implications of IL28B gene in Taiwanese chronic hepatitis C (CHC) patients remain unknown. We thus investigated the prevalence and clinical implications of IL28B rs8099917 genotypes in CHC patients with different hepatitis C virus (HCV) genotypes and healthy controls. METHODS: A total of 200 HCV genotype 1 patients and 200 HCV genotype 2 patients who received liver biopsy, as well as 197 healthy controls were enrolled to determine the frequencies of IL28B rs8099917 genotypes...
October 14, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Maribel Rodriguez-Torres, Eric Lawitz, Bienvenido Yangco, Lennox Jeffers, Steven-Huy Han, Paul J Thuluvath, Vinod Rustgi, Stephen Harrison, Reem Ghalib, John M Vierling, Velimir Luketic, Philippe J Zamor, Natarajan Ravendhran, Timothy R Morgan, Brian Pearlman, Christopher O'Brien, Hicham Khallafi, Nikolaos Pyrsopoulos, George Kong, Fiona McPhee, Philip D Yin, Eric Hughes, Michelle Treitel
:  Background. Patient race and ethnicity have historically impacted HCV treatment response. This phase 3 study evaluated daclatasvir with peginterferon-alfa-2a/ribavirin (pegIFN alfa-2a/RBV) in treatment-naive black/African American (AA), Latino, and white non-Latino patients with chronic HCV genotype 1 infection. MATERIAL AND METHODS: In this single-arm, open-label study, 246 patients received daclatasvir plus pegIFN alfa-2a and weight-based RBV. Patients with an extended rapid virologic response (eRVR; undetectable HCV-RNA at treatment weeks 4 and 12) received 24 weeks of treatment; those without eRVR received an additional 24 weeks of treatment with pegIFN alfa-2a/RBV...
November 2016: Annals of Hepatology
Camelia Sultana, Gabriela Oprişan, Monica Delia Teleman, Sorin Dinu, Cristiana Oprea, Mihai Voiculescu, Simona Ruta
AIM: To determine whether hepatitis C virus (HCV) core substitutions play a role in the response to interferon-based treatment in Caucasian patients. METHODS: One hundred eight HCV chronically infected patients initiating treatment with pegylated IFN plus ribavirin for 48 wk were tested for baseline substitutions at codons 70 and 91 of the viral core protein (BigDye Terminator vers.3.1, Applied Biosystems,) and for genetic polymorphisms in host IL28B gene rs12979860 (Custom TaqMan 5' allelic discrimination assay; Applied Biosystems)...
October 7, 2016: World Journal of Gastroenterology: WJG
Marwa K Ibrahim, Hosny Salama, Mohamad Abd El Rahman, Reham M Dawood, Noha G Bader El Din, Heba F Salem, Mohamed E A Abdelrahim, Dalia Omran, Moataza H Omran, Khaled Helmi El-Wakeel, Tawfeek H Abdelhafez, Ahmed Khedr, Mostafa K El Awady
Hepatitis C virus (HCV) is the leading cause of liver fibrosis and hepatocellular carcinoma (HCC). At present, there is no predictive biomarker for the patients at high risk of developing HCC. In this study, we examined the association between single-nucleotide polymorphisms (SNPs) in 3 innate immunity genes [2'-5'oligoadenylate synthetase 1 (OAS1) rs10774671, interleukin 28B (IL28B) rs12979860, and low molecular mass polypeptide 7 (LMP-7) at codon 49] besides cytomegalovirus (CMV) coinfection and susceptibility to HCC in genotype 4 (GT4) chronically infected Egyptian patients...
October 11, 2016: Journal of Interferon & Cytokine Research
Akira Sato, Toshiya Ishii, Kayo Adachi, Hideaki Takahashi, Fumiaki Sano, Nobuyuki Matsumoto
Following interferon-based therapy for chronic hepatitis C, the negativity of hepatitis C virus RNA is essential to achieve viral clearance at the end of treatment. We report a case of clearance of chronic hepatitis C virus infection following early discontinuation (at 6 weeks) of peginterferon plus ribavirin therapy, without negativity for hepatitis C virus RNA during the treatment period. The patient was a 76-year-old Japanese male infected with hepatitis C virus genotype 1b and TT of IL28B rs8099917. Hepatitis C virus RNA remained positive at persistently low levels for more than 2 months after the cessation of therapy and became negative at 7 months after the discontinuation of therapy...
May 2016: Case Reports in Gastroenterology
Parvaneh Sedighimehr, Shiva Irani, Fatemeh Sakhaee, Farzam Vaziri, Mohammadreza Aghasadeghi, Seyed Mehdi Sadat, Fatemeh Rahimi Jamnani, Abolfazl Fateh, Seyed Davar Siadat
Single-nucleotide polymorphisms (SNPs) in the Interleukin-28B (IL28B) gene and rs4273729 in the human leukocyte antigen (HLA) gene in chronic hepatitis C (CHC) virus infection are important for predicting treatment outcome. In this study, the distribution of IL28B SNPs (rs12979860 and rs12980275) and HLA rs4273729 in rapid virologic response (RVR), complete early virologic response (cEVR) and sustained virologic response (SVR) in HCV Iranian patients with CHC virus infection was assessed. IL28B genotyping and rs4273729 were performed using the amplification refractory mutation system (ARMS)-PCR and direct sequencing in 190 CHC virus infections, respectively...
October 6, 2016: Archives of Virology
Y Morán-Auth, M Penna-Martinez, D Perner, S Susser, S Wicker, S Zeuzem, C Sarrazin, K Badenhoop
Type 2 Diabetes (T2D) develops, when ß-cell insulin response fails to compensate for insulin resistance. Recent studies reported associations between the IL28B polymorphisms (rs12979860 and rs8099917) and T2D development in hepatitis C virus (HCV) patients. To identify possible association with T2D independent from virus infection, we investigated both IL28B polymorphisms in T2D patients and healthy controls (HC). No association was found comparing the genotype and allele frequencies of both IL28B polymorphisms between T2D patients and HC...
September 21, 2016: Human Immunology
Arielle Klepper, Francis J Eng, Erin H Doyle, Ahmed El-Shamy, Adeeb H Rahman, M Isabel Fiel, Gonzalo Carrasco Avino, Moonju Lee, Fei Ye, Sasan Roayaie, Meena B Bansal, Margaret R MacDonald, Thomas D Schiano, Andrea D Branch
: Hepatitis C virus (HCV) is unique among RNA viruses in its ability to establish chronic infection in the majority of exposed adults. HCV persists in the liver despite interferon-stimulated gene (ISG) induction; robust induction actually predicts treatment failure and viral persistence. It is unclear which forms of HCV RNA are associated with ISG induction and interferon resistance during natural infections. To thoroughly delineate HCV RNA populations, we developed conditions that fully separate the strands of long double-stranded (ds)RNA and allow the released RNAs to be quantified in reverse transcription/polymerase chain reaction (qRT/PCR) assays...
September 19, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Markus H Heim, Pierre-Yves Bochud, Jacob George
Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability...
October 2016: Journal of Hepatology
Dilek Arpaci, Sevim Karakas Celik, Murat Can, Gunes Cakmak Genc, Fatih Kuzu, Mustafa Unal, Taner Bayraktaroglu
Hashimoto's thyroiditis (HT) is thought to result from decreased T helper type 2 (Th2) responses, leading to the progressive destruction of thyrocytes. IFN-λ1, -λ2, and -λ3 (also known as IL-29, IL-28A, and IL-28B, respectively) are recently described members of the IFN-λ family and have been shown to decrease the production of Th2 cytokines in vitro. However, the role and mechanism of IFN-λ1 in HT remain unknown. The purpose of this study was to examine whether IL29 and IL28B gene polymorphisms are susceptibility genes for the development of HT...
October 2016: Immunological Investigations
E Apostolou, E K Kapsogeorgou, O D Konsta, I Giotakis, M I Saridaki, E Andreakos, A G Tzioufas
Type III interferons (IFNs) or IFN-λs (IFN-λ1/IL29, IFN-λ2/interleukin (IL)-28A and IFN-λ3/IL-28B) consist of a recently identified group of IFNs, implicated initially in several human diseases, including cancer and autoimmunity. In this study, we sought to investigate the expression of type III IFNs and their common receptor IFN-λR1/IL-28Ra in Sjögren's syndrome (SS). Type III IFN expression was examined in minor salivary gland tissues (MSG), peripheral blood mononuclear cells (PBMCs), sera and resting or Toll-like receptor (TLR)-stimulated salivary gland epithelial cells (SGEC) from SS patients and sicca-complaining controls...
September 10, 2016: Clinical and Experimental Immunology
Lucio Boglione, Jessica Cusato, Giovanni Di Perri, Antonio D''Avolio
No abstract text is available yet for this article.
September 8, 2016: Intervirology
Aryn A Price, Dana Tedesco, Mona R Prasad, Kimberly A Workowski, Christopher M Walker, Mehul S Suthar, Jonathan R Honegger, Arash Grakoui
Maternal innate and adaptive immune responses are modulated during pregnancy to concurrently defend against infection and tolerate the semiallogeneic fetus. The restoration of these systems after childbirth is poorly understood. We reasoned that enhanced innate immune activation may extend beyond gestation while adaptive immunity recovers. To test this hypothesis, the transcriptional profiles of total peripheral blood mononuclear cells following delivery in healthy women were compared with those of nonpregnant control subjects...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
Hui-Lian Wang, Xi Lu, Xudong Yang, Nan Xu
BACKGROUND & AIMS: Daclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b infection. A definite conclusion about efficacy and safety of DCV + ASV in patients with HCV genotype 1b is not available. A meta-analysis was conducted to evaluate outcomes of all-oral treatment with DCV + ASV in terms of sustained virological response at 12 (SVR12 ) , 24 (SVR24 ) weeks and adverse effects (AEs) after the end of treatment...
September 6, 2016: Journal of Gastroenterology and Hepatology
Isabel Corrales, Carlos Solano, Paula Amat, Estela Giménez, Rafael de la Cámara, José Nieto, Javier López, Ana García-Noblejas, José Luis Piñana, David Navarro
A single nucleotide polymorphism (SNP), 3 kbp upstream of the IL28B gene (rs12979860; C/T), has been shown to influence the dynamics of cytomegalovirus (CMV) replication in allogeneic stem cell transplant recipients (Allo-SCT). We investigated whether this SNP had any effect on the dynamics of CMV-specific T-cell immunity in these patients. CMV pp65/IE-1 IFN-γ CD8(+) and CD4(+) T cells were enumerated by flow cytometry in 85 patients with no prior CMV DNAemia (group A) and in 57 after the onset of CMV DNAemia (group B)...
September 3, 2016: Journal of Medical Virology
Ching-Sheng Hsu, Shih-Jer Hsu, Wei-Liang Liu, Ding-Shinn Chen, Jia-Horng Kao
The scavenger receptor type B class I(SR-BI) is a receptor for high-density lipoproteins(HDL) and one of entry factors for hepatitis C virus(HCV). We examined the association of single nucleotide polymorphisms(SNPs) of the SCARB1 gene, which encodes SR-BI, with virologic responses to pegylated interferon-based treatment in Asian chronic hepatitis C(CHC) patients. Human genomic and clinical data were collected from 156 consecutive Taiwanese HCV genotype 1 or 2 patients who received pegylated interferon plus ribavirin therapy and 153 non-HCV healthy subjects...
2016: Scientific Reports
Minesh Mehta, Helal F Hetta, Enass A Abdel-Hameed, Susan D Rouster, MdMonir Hossain, Mohamed A Mekky, Nasr K Khalil, Wegdan A Mohamed, Mohamed A El-Feky, Shabaan H Ahmed, Enas A Daef, Mohamed A El-Mokhtar, Sayed F Abdelwahab, Ahmed Medhat, Kenneth E Sherman, Mohamed Tarek M Shata
The IL28B gene is associated with spontaneous or treatment-induced HCV viral clearance. However, the mechanism by which the IL28B single nucleotide polymorphism (SNP) affects the extra-hepatic HCV immune responses and its relationship to HCV pathogenesis have not been thoroughly investigated. To examine the mechanism by which IL28B affects HCV clearance. Forty Egyptian patients with chronic HCV infection receiving an Interferon/ribavirin treatment regimen were enrolled into this study. There were two groups: non-responders (NR; n = 20) and sustained virologic responders (SVR; n = 20)...
November 2016: Archives of Virology
Ming-Ying Lu, Ching-I Huang, Ming-Yen Hsieh, Tusty-Juan Hsieh, Edward Hsi, Pei-Chien Tsai, Yi-Shan Tsai, Ching-Chih Lin, Meng-Hsuan Hsieh, Po-Cheng Liang, Yi-Hung Lin, Nai-Jen Hou, Ming-Lun Yeh, Chung-Feng Huang, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. We hypothesized that dynamic gene expression in PBMCs might impact the treatment efficacy of peginterferon/ribavirin in HCV patients. PBMCs were collected at baseline, 1st week and 4th week of treatment from 27 chronic HCV-1 patients with 48-week peginterferon/ribavirin therapy (screening dataset n = 7; validation dataset n = 20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after end-of-treatment...
August 17, 2016: Oncotarget
Yoko Yamagiwa, Mai Asano, Youhei Kawasaki, Masaaki Korenaga, Kazumoto Murata, Tatsuya Kanto, Masashi Mizokami, Naohiko Masaki
AIM: Telaprevir (TVR) remarkably improves the efficacy of interferon treatment for chronic hepatitis C. Interleukin-28B (IL28B) genotype and interferon-gamma-inducible protein-10 (IP-10) level predict virologic response to peg-interferon (Peg-IFN)/ribavirin (RBV) therapy. We aimed to investigate the usefulness of pretreatment serum IP-10 levels and IL28B genotyping in predicting sustained virologic response (SVR) to TVR-based triple therapy. METHODS: In this multi-center study, patients infected with hepatitis C virus genotype 1 with high viral load (⩾5...
December 2016: Cytokine
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