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"Hepatitis C"

Anna Hojka-Osinska, Lucyna Budzko, Agnieszka Zmienko, Agnieszka Rybarczyk, Patrick Maillard, Agata Budkowska, Marek Figlerowicz, Paulina Jackowiak
Hepatitis C virus (HCV) infection is one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury and host-virus interactions are still not well recognized. To better understand these processes we determined the changes in the host gene expression that occur during HCV infection of Huh-7.5 cells. As a result, we identified genes that may contribute to the immune and metabolic cellular responses to infection. Pathway enrichment analysis indicated that HCV induced an increased expression of genes involved in mitogen-activated protein kinases signaling, adipocytokine signaling, cell cycle and nitrogen metabolism...
October 25, 2016: Acta Biochimica Polonica
Jun Itakura, Masayuki Kurosaki, Chitomi Hasebe, Yukio Osaki, Kouji Joko, Hitoshi Yagisawa, Shinya Sakita, Hiroaki Okushin, Takashi Satou, Hiroyuki Hisai, Takehiko Abe, Keiji Tsuji, Takashi Tamada, Haruhiko Kobashi, Akeri Mitsuda, Yasushi Ide, Chikara Ogawa, Syotaro Tsuruta, Kouichi Takaguchi, Miyako Murakawa, Yasuhiro Asahina, Nobuyuki Enomoto, Namiki Izumi
BACKGROUNDS & AIMS: We aimed to clarify the characteristics of resistance-associated substitutions (RASs) after treatment failure with NS5A inhibitor, daclatasvir (DCV) in combination with NS3/4A inhibitor, asunaprevir (ASV), in patients with chronic hepatitis C virus genotype 1b infection. METHODS: This is a nationwide multicenter study conducted by the Japanese Red Cross Liver Study Group. The sera were obtained from 68 patients with virological failure after 24 weeks of DCV/ASV treatment...
2016: PloS One
Sabrina J Merat, Richard Molenkamp, Koen Wagner, Sylvie M Koekkoek, Dorien van de Berg, Etsuko Yasuda, Martino Böhne, Yvonne B Claassen, Bart P Grady, Maria Prins, Arjen Q Bakker, Menno D de Jong, Hergen Spits, Janke Schinkel, Tim Beaumont
Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug user who spontaneously cleared HCV infection 25 years ago. CD27+IgG+ memory B cells were immortalized using BCL6 and Bcl-xL. These immortalized B cells were used to study antibody-mediated immunity against the HCV E1E2 glycoproteins...
2016: PloS One
Emmanuel Fortier, Maryam Alavi, Julie Bruneau, Michelle Micallef, Jacinta Perram, Sanjeev Sockalingam, Adrian J Dunlop, Annie C Balcomb, Carolyn A Day, Carla Treloar, Nicky Bath, Paul S Haber, Gregory J Dore, Jason Grebely
OBJECTIVE: The aims of this study were to assess symptoms of depression, anxiety, and stress and associated sociodemographic factors among people living with chronic hepatitis C virus (HCV) infection with a history of injecting drug use and to assess the association between symptoms of depression, anxiety, or stress and HCV treatment intent, specialist assessment, or treatment uptake. METHODS: The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings was an observational cohort study evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from 9 community health centers and opioid substitution therapy (OST) clinics (New South Wales, Australia)...
October 21, 2016: Journal of Addiction Medicine
Feng Su, Pamela K Green, Kristin Berry, George N Ioannou
: Black race and Hispanic ethnicity were associated with lower rates of sustained virologic response (SVR) to interferon (IFN)-based treatments for chronic hepatitis C virus (HCV) infection whereas Asian race was associated with higher SVR rates compared to white patients. We aimed to describe the association between race/ethnicity and effectiveness of new direct-acting antiviral (DAA) regimens in the Veterans Affairs (VA) healthcare system nationally. We identified 21,095 HCV-infected patients (11,029 [52%] white, 6,171 [29%] black, 1,187 [6%] Hispanic, 348 [2%] Asian/Pacific Islander/American Indian/Alaska Native [Asian/PI/AI/AN] and 2,360 [11%] declined/missing race or ethnicity) who initiated antiviral treatment with regimens containing sofosbuvir (SOF), simeprevir + sofosbuvir (SMV+SOF), ledipasvir/sofosbuvir (LDV/SOF) or paritaprevir/ombitasvir/ritonavir/dasabuvir (PrOD), during the 18-month period from 01/01/2014 to 06/30/2015...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Hongbo Chen, Yinan Yao, Yifan Wang, Hua Zhou, Tianxiang Xu, Jing Liu, Guocheng Wang, Yongfeng Zhang, Xiang Chen, Qingwei Liu, Peng Huang, Rongbin Yu
BACKGROUND: HLA-DM gene, which is related to antigen processing and presentation and located in the non-classical class-II region of human leukocyte antigen (HLA) region, may play a crucial role in chronic hepatitis C virus (HCV) infection treatment outcomes. The study was conducted to evaluate the role of the variant of several single nucleotide polymorphisms (SNPs) in HLA-DM gene in HCV treatment outcomes. METHODS: We genotyped four SNPs from the candidate genes (HLA-DMA and DMB) in 336 patients who were treated with pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV)...
October 20, 2016: International Journal of Environmental Research and Public Health
Usama W Hawas, Radwan Al-Farawati, Lamia T Abou El-Kassem, Adnan J Turki
The endophytic fungus Fusarium equiseti was isolated from the brown alga Padina pavonica, collected from the Red Sea. The fungus was identified by its morphology and 18S rDNA. Cultivation of this fungal strain in biomalt-peptone medium led to isolation of 12 known metabolites of diketopeprazines and anthraquinones. The organic extract and isolated compounds were screened for their inhibition of hepatitis C virus NS3/4A protease (HCV PR). As a result, the fungal metabolites showed inhibition of HCV protease (IC50 from 19 to 77 μM), and the fungus was subjected to culture on Czapek's (Cz) media, with a yield of nine metabolites with potent HCV protease inhibition ranging from IC50 10 to 37 μM...
October 20, 2016: Marine Drugs
Brian P Charrette, Mark A Boerneke, Thomas Hermann
Crystal structure analysis revealed key interactions of a 2-amino-benzimidazole viral translation inhibitor that captures an elongated conformation of an RNA switch target in the internal ribosome entry site (IRES) of hepatitis C virus (HCV). Here, we have designed and synthesized quinazoline derivatives with improved shape complementarity at the ligand binding site of the viral RNA target. A spiro-cyclopropyl modification aimed at filling a pocket in the back of the RNA binding site led to a fivefold increase of ligand affinity while a slightly more voluminous dimethyl substitution at the same position did not improve binding...
October 24, 2016: ACS Chemical Biology
María Luján Cuestas
Since the British scientist Michael Houghton along with George Kuo, Qui-Lim Choo (Chiron Corporation Emeryville), and Daniel W. Bradley (Centers for Disease Control and Prevention) co-discovered the causative agent of hepatitis C in 1989, so much progress has been made for the screening of blood donors and management of this chronic liver disease. In this regard, direct-acting antiviral agents (DAAs) have emerged as the potential "cure" of this slowly progressing and devastating disease. However, improvements are still clearly required since the anti-hepatitis C drugs currently available in the market are so extremely expensive (i...
October 19, 2016: Mini Reviews in Medicinal Chemistry
Hyun-Ji Park, Eun Je Jeon, Jung Seung Lee, Sang Hyeon Hong, Ann-Na Cho, Joan Lee, Jae-Su Moon, Kyeong-Eun Jung, Jong-Won Oh, Haeshin Lee, Seung-Woo Cho
Small interfering RNA (siRNA) delivery can provide an effective therapy for treating viral diseases by silencing genes involved in viral replication. In this study, a liver-targeting formulation of lipidoid nanoparticle for delivery of siRNA that targets protein kinase C-related kinase 2 (PRK2) to inhibit hepatitis C virus (HCV) replication is reported. The most effective, minimally cytotoxic lipidoid for siRNA delivery to hepatic cells is identified from a small library of alkyl epoxide-polyamine conjugates...
October 24, 2016: Advanced Healthcare Materials
Rebecca J Winter, Bethany White, Stuart A Kinner, Mark Stoové, Rebecca Guy, Margaret E Hellard
OBJECTIVES: Testing is the first step in treatment and care for blood-borne viruses (BBVs) and sexually transmitted infections (STIs). As new treatments for viral hepatitis emerge, it is important to document effective models for BBV/STI testing. A nurse-led intervention was implemented across three prisons in Victoria to improve BBV/STI testing. We evaluated the impact of the intervention on BBV/STI testing rates and hepatitis B (HBV) vaccination for reception prisoners. METHODS: BBV/STI testing and HBV vaccination data were collected from the medical files of 100 consecutive reception prisoners at three prisons (n=300) prior to and after the intervention was implemented...
October 23, 2016: Australian and New Zealand Journal of Public Health
Chiara Vendramin, Siobhan McGuckin, Ferras Alwan, John-Paul Westwood, Mari Thomas, Marie Scully
BACKGROUND: Patients presenting with acute episodes of thrombotic microangiopathies (TMAs) require urgent access to plasma exchange (PEX). OctaplasLG, a solvent/detergent fresh-frozen plasma product that has undergone viral inactivation and prion reduction step, has been used in our institution since 2013, replacing Octaplas. STUDY DESIGN AND METHODS: We prospectively reviewed 981 PEX procedures where OctaplasLG was the replacement fluid in 90 patients admitted acutely with a TMA presentation within our institution from January 1, 2013, to December 31, 2015...
October 23, 2016: Transfusion
Dana Tedesco, Manoj Thapa, Sanjeev Gumber, Elizabeth J Elrod, Khalidur Rahman, Chris C Ibegbu, Joseph F Magliocca, Andrew B Adams, Frank Anania, Arash Grakoui
: Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to non-functional intrahepatic CD8+ T cell responses. In light of dampened CD8+ T cell responses, liver disease often manifests systemically as Ig-related syndromes due to aberrant B cell functions. These two opposing yet co-existing phenomena implicate the potential of altered CD4+ T cell help. Elevated CD4+ Foxp3+ T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Lize Cuypers, Guangdi Li, Christoph Neumann-Haefelin, Supinya Piampongsant, Pieter Libin, Kristel Van Laethem, Anne-Mieke Vandamme, Kristof Theys
Despite significant progress in hepatitis C (HCV) treatment, global viral eradication remains a challenge. An in-depth map of its genome diversity within the context of structural and immunological constraints could contribute to the design of pan-genotypic antivirals and preventive vaccines. For such analyses, extensive information is only available for the highly prevalent HCV genotypes (GT) 1a and 1b. Using 647 GT1a and 408 GT1b full-genome sequences obtained from the Los Alamos database, we found that respectively 3 per cent and 82 per cent of all codon positions are under positive and negative selective pressure, suggesting variation mainly accumulates due to random genetic drift...
July 2016: Virus Evolution
Satoru Noji, Noriyoshi Seki, Takaki Maeba, Takayuki Sakai, Eiichi Watanabe, Katsuya Maeda, Kyoko Fukushima, Toru Noguchi, Kazuya Ogawa, Yukiyo Toyonaga, Tamotsu Negoro, Hisashi Kawasaki, Makoto Shiozaki
In typical kinase inhibitor programs, a hinge binder showing best potency with preferential specificity is initially selected, followed by fine-tuning of the accompanying substituents on its core module. A shortcoming of this approach is that the exclusive focus on a single chemotype can endanger all the analogues in the series if a critical shortcoming is revealed. Thus, an early evaluation of structure-activity relationships (SARs) can mitigate unforeseen outcomes within a series of multiple compounds, although there have been very few examples to follow such a policy...
October 13, 2016: ACS Medicinal Chemistry Letters
Daisuke Ikeda, Makiko Sugawa, Kazuo Kawahara
Nucleic acid amplification test (NAT), which was introduced by the Japanese Red Cross Society in October 1999, began to be performed for screening of blood transfusion formulations in Japan in August 2014. In this study, the precision of immunological screenings of hepatitis B (HBsAg, HBcAb, and HBsAb), hepatitis C (HCVAb), and human immunodeficiency (HIVAb) virus antigens in donated blood were evaluated. In addition, the sensitivity of the alanine aminotransferase (ALT) test for detection of the hepatitis B and C viruses was re-evaluated...
2016: Journal of Medical and Dental Sciences
Takashi E Komatsu, Sarita Boyd, Adam Sherwat, LaRee Tracy, Lisa K Naeger, Julian J O'Rear, Patrick R Harrington
BACKGROUND & AIMS: Elbasvir (an NS5A inhibitor) and grazoprevir (an NS3/4A protease inhibitor) are direct-acting antiviral agents recently approved in the US for treatment of chronic hepatitis C virus (HCV) genotype 1 and 4 infections, as a fixed-dose combination. Trials of elbasvir and grazoprevir, with or without ribavirin, demonstrated high rates of sustained virologic response 12 weeks after treatment ended (SVR12). However, 12 weeks of treatment with elbasvir and grazoprevir failed in a small proportion of patients with HCV genotype 1 infection...
October 20, 2016: Gastroenterology
Nandan S Gokhale, Alexa B R McIntyre, Michael J McFadden, Allison E Roder, Edward M Kennedy, Jorge A Gandara, Sharon E Hopcraft, Kendra M Quicke, Christine Vazquez, Jason Willer, Olga R Ilkayeva, Brittany A Law, Christopher L Holley, Mariano A Garcia-Blanco, Matthew J Evans, Mehul S Suthar, Shelton S Bradrick, Christopher E Mason, Stacy M Horner
The RNA modification N6-methyladenosine (m(6)A) post-transcriptionally regulates RNA function. The cellular machinery that controls m(6)A includes methyltransferases and demethylases that add or remove this modification, as well as m(6)A-binding YTHDF proteins that promote the translation or degradation of m(6)A-modified mRNA. We demonstrate that m(6)A modulates infection by hepatitis C virus (HCV). Depletion of m(6)A methyltransferases or an m(6)A demethylase, respectively, increases or decreases infectious HCV particle production...
October 18, 2016: Cell Host & Microbe
Kathleen O Degnan, Emily A Blumberg
Patients infected with human immunodeficiency virus (HIV) are living longer, healthier lives on highly active antiretroviral therapy and, as a result, interest in kidney transplantation for HIV-infected patients with end-stage renal disease has increased. HIV is no longer considered a contraindication to solid-organ transplantation and the number of kidney transplants performed in HIV-infected patients each year is increasing steadily. HIV-infected kidney transplant recipients have had excellent outcomes overall, but there are still significant challenges, including high rates of acute rejection, drug-drug interactions, and poor outcomes in patients co-infected with hepatitis C virus...
September 2016: Seminars in Nephrology
Nimish Bhatt, J Mark Sloan, Carl J O'Hara, Roy Oommen, Katrina Steiling, Virginia R Litle
We describe two patients with hepatitis C and a diagnosis of pulmonary extranodal marginal zone B cell lymphoma. Both patients demonstrated a chronic nonproductive cough without hemoptysis. Diagnosis was obtained after a computed tomographic chest scan and flexible bronchoscopic biopsy. We discuss the staging and prognosis of this disease, its correlation with hepatitis C, and potential benefits of treating the associated hepatitis C.
November 2016: Annals of Thoracic Surgery
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