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HCV immunity

Fernanda Cristina Winckler, Aline Marcia Marques Braz, Vanessa Nogueira da Silva, Marjorie de Assis Golim, Vanessa Gutierrez de Andrade, Paulo Eduardo de Abreu Machado, Liciana Vaz de Arruda Silveira, Giovanni Faria Silva
INTRODUCTION: Chronic hepatitis C is a leading cause of liver disease. Infection triggers an immediate immune response in the host that is mediated by humoral/cellular mechanisms. T cells respond to infection via secretion of cytokines, which inhibit or stimulate one another, leading to cytokine imbalance and ultimately affecting treatment. Studies using interferon (IFN) and ribavirin (RBV) showed that TCD8+ cells and cytokine levels are associated with sustainable virological response (SVR)...
November 2018: Revista da Sociedade Brasileira de Medicina Tropical
Kerstin Rauwolf, Heidi Herbrüggen, Stefan Zöllner, Heike Thorer, Olga Makarova, Thomas Kaiser, Aleksandra Pettke, Claudia Rossig, Birgit Burkhardt, Andreas H Groll
Chronic hepatitis C virus (HCV) infection carries increased risks for morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) but has become curable through the advent of directly acting antiviral compounds. Current guidelines of the American Society for Blood and Marrow Transplantation (ASBMT) recommend that HCV-infected HSCT candidates preferably start and complete therapy prior to transplant. However, this is often not feasible due to time constraints or treatment limiting comorbidities, conditions and treatments...
December 5, 2018: Journal of Viral Hepatitis
Mohamed Abdel Wahab, Ahmed Shehta, Eman M Ibrahim, Rehab T Eldesoky, Ahmed A Sultan, Khaled R Zalata, Omar Fathy, Mohamed Elshoubary, Tarek Salah, Amr M Yassen, Mohamed Elmorshedi, Ahmed Monier, Ahmed Farouk, Usama Shiha
INTRODUCTION: The adrenal gland is a rare site for hepatocellular carcinoma (HCC) recurrence after living-donor liver transplantation (LDLT). Solitary adrenal recurrence can be managed by surgical excision, with expected better survival outcomes. We describe a rare case of successful left adrenalectomy of solitary recurrent HCC in the left adrenal gland 5 years after LDLT. PRESENTATION: 59 years male patient with HCC complicating chronic HCV infection received a right hemi-liver graft from his son...
November 27, 2018: International Journal of Surgery Case Reports
Yu Yang, Zheng-Kun Tu, Xing-Kai Liu, Ping Zhang
The mononuclear phagocyte system (MPS), which consists of monocytes, dendritic cells (DCs), and macrophages, plays a vital role in the innate immune defense against pathogens. Hepatitis C virus (HCV) is efficient in evading the host immunity, thereby facilitating its development into chronic infection. Chronic HCV infection is the leading cause of end-stage liver diseases, liver cirrhosis, and hepatocellular carcinoma. Acquired immune response was regarded as the key factor to eradicate HCV. However, innate immunity can regulate the acquired immune response...
November 28, 2018: World Journal of Gastroenterology: WJG
Lucy A Eddowes, Kinda Al-Hourani, Narayan Ramamurthy, Jamie Frankish, Hannah T Baddock, Cynthia Sandor, John D Ryan, Dahlene N Fusco, João Arezes, Eleni Giannoulatou, Sara Boninsegna, Stephane Chevaliez, Benjamin M J Owens, Chia Chi Sun, Paolo Fabris, Maria Teresa Giordani, Diego Martines, Slobodan Vukicevic, John Crowe, Herbert Y Lin, Jan Rehwinkel, Peter J McHugh, Marco Binder, Jodie L Babitt, Raymond T Chung, Matthew W Lawless, Andrew E Armitage, Caleb Webber, Paul Klenerman, Hal Drakesmith
Understanding the control of viral infections is of broad importance. Chronic hepatitis C virus (HCV) infection causes decreased expression of the iron hormone hepcidin, which is regulated by hepatic bone morphogenetic protein (BMP)/SMAD signalling. We found that HCV infection and the BMP/SMAD pathway are mutually antagonistic. HCV blunted induction of hepcidin expression by BMP6, probably via tumour necrosis factor (TNF)-mediated downregulation of the BMP co-receptor haemojuvelin. In HCV-infected patients, disruption of the BMP6/hepcidin axis and genetic variation associated with the BMP/SMAD pathway predicted the outcome of infection, suggesting that BMP/SMAD activity influences antiviral immunity...
December 3, 2018: Nature Microbiology
Silvia Piconese, Ilenia Cammarata, Vincenzo Barnaba
In the present review, we analyzed the various overlapping and non-mutually exclusive mechanisms that intersect and form complex and highly flexible immunological networks allowing the defense against liver infections and tumors. Liver immunity results from the combination of the skills of systemic and local immune system(s) to sense and recognize pathogen or tumor antigens, to sensitize a wide range of innate and adaptive immune cells, and to clear the "invaders", through the establishment of a transient liver immunopathology state undergoing resolution/control of infections or tumors, and memory development...
December 2018: Journal of Autoimmunity
Monika Rau, Johannes Schmitt, Thomas Berg, Andreas E Kremer, Bruno Stieger, Katharina Spanaus, Bertram Bengsch, Marta R Romero, Jose J Marin, Verena Keitel, Hartwig Klinker, Hans-Peter Tony, Beat Müllhaupt, Andreas Geier
BACKGROUND & AIMS: Serum interferon-gamma-inducible protein-10 (IP-10) is elevated in cholestatic liver diseases and predicts response to antiviral therapy in patients with chronic hepatitis C virus (HCV) infection. Dipeptidylpeptidase 4 (DPPIV) cleaves active IP-10 into an inactive form, which inhibits recruitment of CXCR3+ T cells to the liver. In this study the link between IP-10 levels, DPPIV activity in serum and CXCR3+ T cells is analysed in cholestatic and non-cholestatic liver patients...
2018: PloS One
Sara M El-Sayed, Mohamed A M Ali, Bahaa El-Dien M El-Gendy, Samar S Dandash, Yvette Issac, Reda Saad, Mohamed M Azab, Mohamed R Mohamed
Background Hepatitis C virus (HCV) infection poses a considerable threat to the public health. The current standard of care treatment with pegylated interferon-alpha in combination with ribavirin (PEG-IFN-α+RBV) is associated with significant side effects, poorly tolerated, and provides limited efficacy. The development of direct-acting antiviral agents (DAAs) targeting key viral enzymes essential for viral replication represents a significant milestone in the treatment of chronic HCV infection. Given its critical role in the viral polyprotein processing and the evasion of the host innate immunity, the NS3/4A protease has emerged as a promising drug target for the development of anti-HCV therapies...
December 3, 2018: Current Pharmaceutical Design
Nico Buettner, Robert Thimme
The incidence of viral hepatitis B or C (HBV/HCV) infection and hepatocellular carcinoma is higher in male compared to female populations, showing a faster disease progression and results in a worse overall survival. Indeed, women are in general better protected from viral infections and show a lower risk of death from malignant cancer in comparison to men. Females mount stronger innate and adaptive immune responses than males, and therefore, most of the autoimmune diseases occur predominantly in females. Next to occupational and/or behavioral factors, cellular and molecular differences between the two sexes contribute to this observation...
November 29, 2018: Seminars in Immunopathology
Jacqueline B Henson, Meghan E Sise
Hepatitis C virus (HCV) infection is not only an important cause of chronic liver disease, but extrahepatic manifestations are common and include chronic kidney disease (CKD). HCV is classically associated with cryoglobulinemic glomerulonephritis in the context of mixed cryoglobulinemia syndrome, but other glomerular diseases also occur and may be significantly under-recognized. HCV may cause glomerular disease by immune complex deposition; however, other potential mechanisms by which HCV promotes CKD include a direct cytopathic effect of the virus on renal tissue, and by its association with accelerated atherosclerosis, insulin resistance, and chronic inflammation...
November 29, 2018: Seminars in Dialysis
Andreas Baranyi, Andreas Meinitzer, Hans-Bernd Rothenhäusler, Omid Amouzadeh-Ghadikolai, Dirk V Lewinski, Robert J Breitenecker, Markus Herrmann
BACKGROUND: The aim of this study was to identify previously unrecognised biological pathways and biomarkers that might expand the inflammatory hypothesis of depression. METHODS: Broad metabolomics analyses in plasma samples from 31 chronic hepatitis C-infected patients with and without immune-related depression were carried out using the Absolute IDQ p180 kit-a targeted metabolomics approach of combined direct flow injection and liquid chromatography that measures acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, and sugars...
2018: PloS One
Raffaele Bruno, Valentina Zuccaro
No abstract text is available yet for this article.
December 2018: Alimentary Pharmacology & Therapeutics
Gregory R Hart, Andrew L Ferguson
Hepatitis C virus (HCV) afflicts 170 million people and kills 700 000 annually. Vaccination offers the most realistic and cost effective hope of controlling this epidemic, but despite 25 years of research, no vaccine is available. A major obstacle is HCV's extreme genetic variability and rapid mutational escape from immune pressure. Coupling maximum entropy inference with population dynamics simulations, we have employed a computational approach to translate HCV sequence databases into empirical landscapes of viral fitness and simulate the intrahost evolution of the viral quasispecies over these landscapes...
November 28, 2018: Physical Biology
Alireza Saeidi, Keivan Zandi, Yi Ying Cheok, Hamidreza Saeidi, Won Fen Wong, Chalystha Yie Qin Lee, Heng Choon Cheong, Yean Kong Yong, Marie Larsson, Esaki Muthu Shankar
T-cell exhaustion is a phenomenon of dysfunction or physical elimination of antigen-specific T cells reported in human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections as well as cancer. Exhaustion appears to be often restricted to CD8+ T cells responses in the literature, although CD4+ T cells have also been reported to be functionally exhausted in certain chronic infections. Although our understanding of the molecular mechanisms associated with the transcriptional regulation of T-cell exhaustion is advancing, it is imperative to also explore the central mechanisms that control the altered expression patterns...
2018: Frontiers in Immunology
Wen-Xiu Bian, Yan Xie, Xiao-Ning Wang, Guo-Hua Xu, Bo-Shi Fu, Shu Li, Gang Long, Xiang Zhou, Xiao-Lian Zhang
Hepatitis C virus (HCV) infection is a major cause of human chronic liver disease and hepatocellular carcinoma. G-quadruplex (G4) is an important four-stranded secondary structure of nucleic acids. Recently, we discovered that the core gene of HCV contains a G4 RNA structure; however, the interaction between the HCV core RNA G4 and host cellular proteins, and the roles of the HCV core RNA G4 in HCV infection and pathogenesis remain elusive. Here, we identified a cellular protein, nucleolin (NCL), which bound and stabilized the HCV core RNA G4 structure...
November 20, 2018: Nucleic Acids Research
Hendrik Luxenburger, Christoph Neumann-Haefelin, Robert Thimme, Tobias Boettler
Hepatitis C virus (HCV)-specific T cell responses are closely linked to the clinical course of infection. While T cell responses in self-limiting infection are typically broad and multi-specific, they display several distinct features of functional impairment in the chronic phase. Moreover, HCV readily adapts to immune pressure by developing escape mutations within epitopes targeted by T cells. Much of our current knowledge on HCV-specific T cell responses has been gathered under the assumption that this might eventually pave the way for a therapeutic vaccine...
November 17, 2018: Viruses
Jacinta A Holmes, Charles Carlton-Smith, Arthur Y Kim, Emily O Dumas, Joelle Brown, Jenna L Gustafson, Georg M Lauer, Sakuni T Silva, Maxwell Robidoux, Daniel Kvistad, Nadia Alatrakchi, Pierre Tonnerre, Daniel E Cohen, Hongtao Zhang, Nancy S Shulman, Raymond T Chung
The role of the endogenous interferon (IFN) system has been well characterized during IFN-based therapy for chronic hepatitis C virus (HCV) infection; less is known for direct-acting antivirals (DAAs). In this phase 3b open-label study, we assessed changes in IFN-stimulated genes (ISGs) in non-cirrhotic treatment-naïve or pegIFN/RBV-experienced HCV-GT1a-infected patients receiving paritaprevir/ritonavir/ombitasvir+dasabuvir+ribavirin (PrOD+R) for 12 weeks. ISG expression was quantified from PBMCs at baseline, treatment weeks (TW)2, TW4, TW8, end-of-treatment (EOT) and at post-treatment week 12...
November 19, 2018: Journal of Viral Hepatitis
Arkadiusz Urbanowicz, Radosław Zagożdżon, Michał Ciszek
The treatment of patients with chronic hepatitis C virus (HCV) infection has changed tremendously over the past 2 years, with an increasing variety of all-oral direct-acting antiviral (DAA) treatment regimens available for different HCV genotypes and distinct clinical settings. These treatments have significantly improved safety in patients with advanced liver disease compared with interferon (IFN)-based regimens. HCV modifies the human immune system to escape immunosurveillance via several mechanisms. One of the basic mechanisms of HCV is the ability to "switch" the immune response by reducing the activity of cells responsible for the elimination of virus-infected cells...
November 15, 2018: Archivum Immunologiae et Therapiae Experimentalis
Lei Chen, Shiqi Zhang, Xiaoyong Pan, XiaoHua Hu, Yu-Hang Zhang, Fei Yuan, Tao Huang, Yu-Dong Cai
Many complex diseases or traits are the results of both genetic and environmental factors. The environmental factors affect the human body by modifying its epigenetics, which controls the activity of genomes without mutating it. Viral infection is one of the common environmental factors for complex diseases. For example, the human immunodeficiency virus (HIV) infection can cause acquired immune deficiency syndrome (AIDS), HBV, and HCV infections are associated with hepatocellular carcinoma, and human papillomavirus infection is a causal factor in cervical carcinoma...
November 15, 2018: Gene Therapy
Tanvi Khera, Patrick Behrendt, Dorothea Bankwitz, Richard J P Brown, Daniel Todt, Mandy Doepke, Abdul Ghafoor Khan, Kai Schulze, John Law, Michael Logan, Darren Hockman, Jason Alexander Ji-Xhin Wong, Leona Dold, Victor Gonzalez-Motos, Ulrich Spengler, Abel Viejo-Borbolla, Luisa Ströh, Thomas Krey, Alexander W Tarr, Eike Steinmann, Michael P Manns, Florian Klein, Carlos A Guzman, Joseph Marcotrigiano, Michael Houghton, Thomas Pietschmann
BACKGROUND AND AIMS: Induction of cross-reactive antibodies targeting conserved epitopes of the envelope proteins E1E2 is a key requirement for an HCV vaccine. Conserved epitopes like the viral CD81-binding site are targeted by rare broadly neutralizing antibodies. However, these viral segments are occluded by variable regions and glycans. We aimed to identify antigens exposing conserved epitopes and to characterize their immunogenicity. METHODS: We created HCV variants with mutated glycosylation sites and/or hypervariable region 1 (HVR1)...
November 12, 2018: Journal of Hepatology
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