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Ahmad Ayadi, Amir Hossein Nafari, Fatemeh Sakhaee, Kimia Rajabi, Yaser Ghaderi, Fatemeh Rahimi Jamnani, Farzam Vaziri, Seyed Davar Siadat, Abolfazl Fateh
AIM: Although the presence of occult hepatitis C virus (HCV) infection (OCI) is still controversial, however, this infection cannot be ignored. Therefore, the current study aimed at assessing the OCI frequency in patients on chronic hemodialysis (CHD) and also evaluating the association between OCI incidence with clinical parameters and interferon lambda 3/4 (IFNL3/4) gene polymorphisms. METHODS: A total of 515 patients on CHD and HCV negative markers were selected...
March 1, 2019: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Ahmad Ayadi, Amir Hossein Nafari, Shiva Irani, Elham Mohebbi, Fahimeh Mohebbi, Fatemeh Sakhaee, Farzam Vaziri, Seyed Davar Siadat, Abolfazl Fateh
Occult hepatitis C virus (HCV) infection (OCI) is described as the presence of viral genome in both hepatocytes and peripheral blood mononuclear cells (PBMCs) despite constant negative results on serum HCV RNA tests. Beta-thalassemia major (BTM) describes a group of inherited blood diseases. Patients with BTM require repeated blood transfusions, increasing the risk of exposure to infectious agents. We aimed to assess the prevalence of OCI in Iranian BTM patients and to identify the role of host factors in OCI positivity...
February 18, 2019: Journal of Cellular Biochemistry
Ikram Sghaier, Etienne Brochot, Besma Y Loueslati, Wassim Y Almawi
HCV has been associated with a pro-inflammatory state, which predisposes to hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on HCC progression remain unclear. Although HCV infection illustrates the potential role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment-induced HCV eradication. We studied the possible role of HCV infection in the processes of HCC initiation and performed a systematic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein-proteins interactions (PPI) networks...
March 2019: Reviews in Medical Virology
Katerina Kassela, Ioannis Karakasiliotis, Eleni Kokkiou, Fani Souvalidou, Panayotis Mimidis, Stavroula Veletza, Maria Panopoulou, John Koskinas, Konstantinos Mimidis, Penelope Mavromara
Background: Intergenotypic recombinant hepatitis C virus (HCV) strains emerge rarely during coinfection of the same individual with two HCV genotypes. Few recombinant HCV strains have been identified to date and only one, CRF01 2k/1b, has become a worldwide concern. This study reevaluated the genotyping of three HCV genotype 2 strains from a group of patients with an unusually low rate of sustained virological response after pegylated interferon/ribavirin treatment. In addition, genetic determinants of host interferon resistance were evaluated...
January 2019: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
Candelaria Vergara, Chloe L Thio, Eric Johnson, Alex H Kral, Thomas R O'Brien, James J Goedert, Alessandra Mangia, Valeria Piazzolla, Shruti H Mehta, Gregory D Kirk, Arthur Y Kim, Georg M Lauer, Raymond T Chung, Andrea L Cox, Marion G Peters, Salim I Khakoo, Laurent Alric, Matthew E Cramp, Sharyne M Donfield, Brian R Edlin, Michael P Busch, Graeme Alexander, Hugo R Rosen, Edward L Murphy, Rachel Latanich, Genevieve L Wojcik, Margaret A Taub, Ana Valencia, David L Thomas, Priya Duggal
BACKGROUND & AIMS: Spontaneous clearance of hepatitis C virus (HCV) occurs in approximately 30% of infected persons and less often in populations of African ancestry. Variants in major histocompatibility complex (MHC) and in interferon lambda genes are associated with spontaneous HCV clearance but there have been few studies of these variants in persons of African ancestry. We performed a dense multi-ancestry genome-wide association study of spontaneous clearance of HCV, focusing on individuals of African ancestry...
December 26, 2018: Gastroenterology
Javier Brahm, Alvaro Urzúa, Jaime Poniachik, Dante D Cáceres, Laura Carreño, Mauricio Venegas
BACKGROUND: Host genetic predispositions may be important determinants of liver fibrosis in patients with chronic hepatitis C (CHC). The association between Interferon-L 4 (IFNL4) rs12979860 C>T polymorphism and risk of liver fibrosis in CHC is contradictory. AIM: To evaluate the impact of IFNL4 rs12979860 polymorphism on the risk of fibrosis in patients with CHC. MATERIAL AND METHODS: One hundred fifty patients with CHC aged 50 ± 11 years (89 females) were genotyped for IFNL4 rs12979860 using real time PCR...
July 2018: Revista Médica de Chile
Tsion Zewdu Minas, Wei Tang, Cheryl J Smith, Olusegun O Onabajo, Adeola Obajemu, Tiffany H Dorsey, Symone V Jordan, Obadi M Obadi, Bríd M Ryan, Ludmila Prokunina-Olsson, Christopher A Loffredo, Stefan Ambs
Sexually transmitted infections can reach the prostate gland where their harmful effects are mediated by innate immunity, including interferons. Humans are polymorphic for the germline dinucleotide variant, rs368234815-TT/ΔG, in the IFNL4 gene encoding interferon λ4. Since the IFNL4- ΔG allele has been linked to impaired viral clearance, we hypothesized that potential exposure to sexually transmitted pathogens, as assessed by the number of lifetime sexual partners, may increase prostate cancer risk in an IFNL4- ΔG-dependent manner...
2018: Communications Biology
Claudia Jaimes-Bernal, Norma Rallón, José M Benito, Mohamed Omar Mohamed-Balghata, María Amparo Gómez-Vidal, Francisco José Márquez, Beatriz Sánchez-Arcas, Monte Trujillo, José Luis Royo, Irma Saulle, Mara Biasin, Antonio Rivero-Juárez, Antonio Caruz
The IFNL4 knock-out allele (rs368234815-TT) is associated with spontaneous and IFNA-dependent cure of HCV. The role of this polymorphism in susceptibility to HIV-1 infection is controversial. This study is aimed to assess the association of this knock-out IFNL4 gene variant and sexually transmitted HIV-1 infection. 228 HIV-1 positive and 136 HIV-exposed seronegatives were investigated for their association with IFNL4 rs368234815 genotypes. The IFNL4 G functional allele is associated to increased susceptibility to HIV-1 infection through sexual route OR: 2...
October 5, 2018: Journal of Infectious Diseases
A E Grzegorzewska, M K Swiderska, W Warchol
BACKGROUND: IFNL4 polymorphisms are associated with circulating IFN-λ3, and higher plasma IFN-λ3 are associated with higher production of antibodies to HBV surface antigen (anti-HBs). The IFNL4 rs8099917 T allele and anti-HBs development in response to HBV vaccine are associated with better survival in hemodialysis (HD) patients. OBJECTIVE: To show whether plasma IFN-λ3 is also a predictor of survival in HD patients. METHOD: Plasma IFN-λ3 was measured in 135 HD patients who were followed-up for 2...
September 26, 2018: Current Molecular Medicine
Stéphanie Bibert, Agnieszka Wójtowicz, Patrick Taffé, Philip E Tarr, Enos Bernasconi, Hansjakob Furrer, Huldrych F Günthard, Matthias Hoffmann, Laurent Kaiser, Michael Osthoff, Jacques Fellay, Matthias Cavassini, Pierre-Yves Bochud
BACKGROUND: Kaposi's sarcoma, the most common AIDS-related cancer, represents a major public concern in resource-limited countries. Single nucleotide polymorphisms within the Interferon lambda 3/4 region (IFNL3/4) determine the expression, function of IFNL4, and influence the clinical course of an increasing number of viral infections. OBJECTIVES: To analyze whether IFNL3/4 variants are associated with susceptibility to AIDS-related Kaposi's sarcoma among MSM enrolled in the Swiss HIV Cohort Study (SHCS)...
November 28, 2018: AIDS
Enrico Galmozzi, Roberta D'Ambrosio
No abstract text is available yet for this article.
June 2018: Hepatobiliary Surgery and Nutrition
Alicja E Grzegorzewska
Genetic polymorphisms within the interferon λ (IFN-λ) chromosomal region, mainly rs12979860 of IFN-λ4 gene (IFNL4), are known as associated with spontaneous hepatitis C virus (HCV) resolution and sustained viral response to therapy with pegylated interferon-α and ribavirin. Strong linkage disequilibrium of IFNL4 rs12979860 with IFNL4 rs368234815, which is casually associated with HCV spontaneous and therapeutical eradication, at least partially explains favorable HCV outcomes attributed to major homozygosity in rs12979860...
July 19, 2018: Current Medicinal Chemistry
Wei Tang, Tiffany A Wallace, Ming Yi, Cristina Magi-Galluzzi, Tiffany H Dorsey, Olusegun O Onabajo, Adeola Obajemu, Symone V Jordan, Christopher A Loffredo, Robert M Stephens, Robert H Silverman, George R Stark, Eric A Klein, Ludmila Prokunina-Olsson, Stefan Ambs
Purpose: Men of African ancestry experience an excessive prostate cancer mortality that could be related to an aggressive tumor biology. We previously described an immune-inflammation signature in prostate tumors of African-American (AA) patients. Here, we further deconstructed this signature and investigated its relationships with tumor biology, survival, and a common germline variant in the IFNλ4 ( IFNL4 ) gene. Experimental Design: We analyzed gene expression in prostate tissue datasets and performed genotype and survival analyses...
November 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Alicja E Grzegorzewska, Monika K Świderska, Leszek Niepolski, Maciej Bura, Adrianna Mostowska, Małgorzata Łagiedo-Żelazowska, Paweł P Jagodziński
Introduction Factors associated with hepatitis E virus (HEV) infection are rarely recognized in patients on renal replacement therapy (RRT), and the results of studies are inconsistent. Objectives We aimed to search for determinants of HEV seroprevalence among polymorphisms of the interferon‑λ4 gene (IFNL4) associated with seroclearance of hepatotropic viruses (IFNL4 rs12979860, rs8099917 near IFNL4), circulating interferon λ3 (IFN‑λ3), and clinical variables of patients treated with hemodialysis (HD) in a HEV‑endemic region...
June 29, 2018: Polish Archives of Internal Medicine
Alicja E Grzegorzewska, Hanna Winnicka, Wojciech Warchoł, Adrianna Mostowska, Paweł P Jagodziński
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) contributes to maintaining immune homeostasis. Polymorphisms (SNPs) of the IDO encoding gene (IDO1) influence the IDO activity. Interferon (IFN)-λ3 induces IDO expression. We aimed to investigate whether IDO1 variants are associated with anti-HBs production in response to HBV vaccination or infection, interact with IFN-λ3 associated variants of IFNL4, and influence survival of hemodialysis (HD) patients. We also tested circulating IDO concerning IDO1 SNPs and plasma IFN-λ3 and anti-HBs levels...
July 16, 2018: Vaccine
Lisa I Backus, Troy A Shahoumian, Pamela S Belperio, Mark Winters, Ludmila Prokunina-Olsson, Thomas R O'Brien, Mark Holodniy
In direct acting antiviral (DAA)-treated HCV genotype 1, the sustained virologic response rate with the ∆G/∆G genotype of IFNL4 rs368234815 (86.8%) was significantly lower than with ∆G/TT (95.9%, P = 0.03) or TT/TT (98.6%, P = 0.01). The SVR odds ratio for ∆G/∆G compared to TT/TT was 0.10 (P = 0.03). IFNL4 genotype might predict DAA-response.
September 2018: Diagnostic Microbiology and Infectious Disease
Anand Bhushan, Sreedhar Chinnaswamy
Genetic variants at the interferon lambda (IFNL) locus have been associated with several human phenotypes in both disease and health. In chronic hepatitis C virus (HCV) infections, where the IFNL variants were first identified to be associated with response to interferon-α-ribavirin therapy, the available data clearly suggests that the causal variant could be the dinucleotide polymorphism rs368234815 that causes an open reading frame-shift in the IFNL4 gene resulting in expression of a functional IFN-λ4, a new type III IFN...
July 20, 2018: Gene
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
Fabiana Cannella, Carolina Scagnolari, Maura Statzu, Ilaria Sciandra, Nadia Recine, Gabriella d'Ettorre, Guido Antonelli, Alessandra Pierangeli
Interferon (IFN) lambdas are important specific components of the mucosal innate immune response. The IFN lambda 4 (IFNL4) dinucleotide polymorphism (ΔG/TT) determines the IFN lambdas and related Interferon-stimulated genes activation, in HCV and other chronic infections. Our group first reported that IFN Lambda response was impaired in high-risk Human Papillomavirus (HPV) cervical infections and in precancerous lesions. Accordingly, we sought to evaluate the possible role of the IFNL4 polymorphism in determining HPV infection outcome...
April 2018: Virus Genes
Brad R Rosenberg, Catherine A Freije, Naoko Imanaka, Spencer T Chen, Jennifer L Eitson, Rachel Caron, Skyler A Uhl, Marija Zeremski, Andrew Talal, Ira M Jacobson, Charles M Rice, John W Schoggins
Polymorphisms at IFNL4 strongly influence spontaneous resolution and interferon therapeutic response in hepatitis C virus (HCV) infection. In chronic HCV, unfavorable alleles are associated with elevated interferon (IFN)-stimulated gene (ISG) expression in the liver, but extrahepatic effects are less well characterized. We used RNA sequencing (RNA-Seq) to examine whether IFNL4 genetic variation (rs368234815) modulates ISG expression in peripheral blood mononuclear cells (PBMC) during chronic HCV infection. ISG expression was elevated in unstimulated PBMC homozygous for the unfavorable ΔG IFNL4 variant; expression following IFN-α stimulation was comparable across genotypes...
January 30, 2018: Journal of Infectious Diseases
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