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https://www.readbyqxmd.com/read/28441762/replication-and-oncolytic-activity-of-an-avian-orthoreovirus-in-human-hepatocellular-carcinoma-cells
#1
Robert A Kozak, Larissa Hattin, Mia J Biondi, Juan C Corredor, Scott Walsh, Max Xue-Zhong, Justin Manuel, Ian D McGilvray, Jason Morgenstern, Evan Lusty, Vera Cherepanov, Betty-Anne McBey, David Leishman, Jordan J Feld, Byram Bridle, Éva Nagy
Oncolytic viruses are cancer therapeutics with promising outcomes in pre-clinical and clinical settings. Animal viruses have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. We isolated an avian orthoreovirus (ARV-PB1), and tested it against a panel of hepatocellular carcinoma cells. We found that ARV-PB1 replicated well and induced strong cytopathic effects. It was determined that one mechanism of cell death was through syncytia formation, resulting in apoptosis and induction of interferon stimulated genes (ISGs)...
April 24, 2017: Viruses
https://www.readbyqxmd.com/read/28441386/graft-derived-cell-free-dna-a-noninvasive-early-rejection-and-graft-damage-marker-in-liver-transplantation-a-prospective-observational-multicenter-cohort-study
#2
Ekkehard Schütz, Anna Fischer, Julia Beck, Markus Harden, Martina Koch, Tilo Wuensch, Martin Stockmann, Björn Nashan, Otto Kollmar, Johannes Matthaei, Philipp Kanzow, Philip D Walson, Jürgen Brockmöller, Michael Oellerich
BACKGROUND: Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection...
April 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28441362/real-world-experiences-with-the-combination-treatment-of-ledipasvir-plus-sofosbuvir-for-12-weeks-in-hcv-genotype-1-infected-japanese-patients-achievement-of-a-sustained-virological-response-in-previous-users-of-peginterferon-plus-ribavirin-with-hcv-ns3-4a-inhibitors
#3
Tatsuo Kanda, Shin Yasui, Masato Nakamura, Eiichiro Suzuki, Makoto Arai, Yoshihiko Ooka, Sadahisa Ogasawara, Tetsuhiro Chiba, Tomoko Saito, Yuki Haga, Koji Takahashi, Reina Sasaki, Shuang Wu, Shingo Nakamoto, Akinobu Tawada, Hitoshi Maruyama, Fumio Imazeki, Naoya Kato, Osamu Yokosuka
The aim of this study was to characterize the treatment response and serious adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12 weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among treatment-naïve patients, SVR12 was achieved in 136 of 138 (98...
April 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28441176/long-term-nitrite-inhalant-exposure-and-cancer-risk-in-msm
#4
Anupriya Dutta, Hajime Uno, Alex Holman, David R Lorenz, Steven M Wolinsky, Dana Gabuzda
OBJECTIVES: Nitrite inhalants (poppers) are commonly used recreational drugs among MSM and were previously associated with elevated rates of high-risk sexual behavior, HIV and human herpesvirus type 8 (HHV-8) seroconversion, and transient immunosuppressive effects in experimental models. Whether long-term popper use is associated with cancer risk among MSM in the HAART era is unclear. DESIGN: Prospective cohort study of cancer risk in 3223 HIV-infected and uninfected MSM in the Multicenter AIDS Cohort Study from 1996-2010...
May 15, 2017: AIDS
https://www.readbyqxmd.com/read/28441174/increased-incidence-of-cancer-observed-in-hiv-hepatitis-c-virus-coinfected-patients-versus-hiv-monoinfected
#5
Héctor Meijide, Sonia Pértega, Iria Rodríguez-Osorio, Ángeles Castro-Iglesias, Josefa Baliñas, Guillermo Rodríguez-Martínez, Álvaro Mena, Eva Poveda
BACKGROUND: Cancer is a growing problem in persons living with HIV infection (PLWH) and hepatitis C virus (HCV) coinfection could play an additional role in carcinogenesis. Herein, all cancers in an HIV-mono and HIV/HCV-coinfected cohort were evaluated and compared to identify any differences between these two populations. METHODS: A retrospective cohort study was conducted including all cancers in PLWH between 1993 and 2014. Cancers were classified in two groups: AIDS-defining cancer (ADC) and non-AIDS-defining cancer (NADC)...
May 15, 2017: AIDS
https://www.readbyqxmd.com/read/28440885/a-comparison-of-direct-sequencing-and-invader-assay-for-y93h-mutation-and-response-to-interferon-free-therapy-in-hepatitis-c-virus-genotype-1b
#6
Kazuhiko Hayashi, Masatoshi Ishigami, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Hiroki Kawashima, Tetsuya Ishikawa, Yoshihiko Tachi, Masashi Hattori, Yoshiaki Katano, Hidemi Goto, Yoshiki Hirooka
BACKGROUND AND AIM: Virologic failure of interferon (IFN)-free therapy has been associated with Y93H mutation in the NS5A region in hepatitis C virus (HCV) genotype 1b, and screening is recommended. A simple assay based on Q-Invader technology was developed for Y93H mutant screening to reduce cost and effort. The present study sought to compare two methods of detection of Y93H mutation and to evaluate the effect of Y93H mutation on response to IFN free therapy. METHODS: Y93H mutation was examined in 258 patients with HCV genotype 1b using both direct sequencing analysis and the PCR-Invader assay...
April 25, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28440785/impacts-of-hbv-rth55r-polymerase-substitution-on-viral-replication-and-rtm204i-v-resistance-to-nucleoside-nucleotide-antiviral-drugs
#7
Kuan-Hui Xiang, Cheng-Yu Zhao, Shuai Wang, Yao Li, Ming-Ze Su, Qiang-Yi Wang, Xi-Zhan Xu, Juan Deng, Hui Zhuang, Tong Li
BACKGROUND: High genetic variability at reverse transcriptase (RT) region of hepatitis B virus (HBV) could confer resistance to nucleos(t)ide analogues (NUCs). The aim of this study was to identify new RT amino acid (AA) substitutions related to NUCs resistance. METHODS: HBV RT sequences of genotype C from 501 chronic hepatitis B (CHB) patients were analyzed to identify potential RT substitutions related to NUCs resistance. In vitro studies without and with NUCs were performed in HepG2 cell line transfected by clones with RT harboring wild-type or substituted AA(s) of interest...
April 25, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28440692/both-hepatitis-c-virus-specific-t-cell-responses-and-il28b-rs12979860-single-nucleotide-polymorphism-genotype-influence-antihepatitis-c-virus-treatment-outcome-in-patients-with-chronic-hepatitis-c
#8
José M Benito, Javier García-Samaniego, Marcial García, Antonio Madejón, Luz Martín-Carbonero, Alfonso Cabello, Beatriz Álvarez, Miguel Górgolas, Norma Rallón
Despite new treatments for hepatitis C virus (HCV) infection, IFNα-based regimens still have clinical relevance in special populations of patients and remain the only therapeutic option for many patients. We sought to elucidate the interplay between two relevant factors (IL28B polymorphism and T cell immune responses) involved in the outcome of this therapy in HCV-infected patients. We evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who were undergoing a full course of pegIFNα/RBV therapy...
April 25, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28440681/discovery-and-preclinical-development-of-dasabuvir-for-the-treatment-of-hepatitis-c-infection
#9
Mohamed El Kassas, Tamer Elbaz, Enas Hafez, Mohamed Naguib Wifi, Gamal Esmat
Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality. Positively, the introduction of new directly-acting antivirals (DAAs) have led to dramatic improvements in response rates to antiviral therapy. Furthermore, newer generations of DAAs have demonstrated better safety profiles as well as efficacy than older generations. Current treatment recommendations are based on different combinations of DAAs. Current combination therapies rely on agents that target the different steps of viral replication by using different molecules from various DAAs families...
April 25, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28440304/the-natural-history-of-severe-acute-liver-injury
#10
David G Koch, J L Speiser, V Durkalski, R J Fontana, T Davern, B McGuire, R T Stravitz, A M Larson, I Liou, O Fix, M L Schilsky, T McCashland, J E Hay, N Murray, O S Shaikh, D Ganger, A Zaman, S B Han, R T Chung, R S Brown, S Munoz, K R Reddy, L Rossaro, R Satyanarayana, A J Hanje, J Olson, R M Subramanian, C Karvellas, B Hameed, A H Sherker, W M Lee, A Reuben
OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death. METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2...
April 25, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28440303/hcv-genotype-6-increased-the-risk-for-hepatocellular-carcinoma-among-asian-patients-with-liver-cirrhosis
#11
Mei-Hsuan Lee, Tiffany I Hsiao, Shreenidhi R Subramaniam, An K Le, Vinh D Vu, Huy N Trinh, Jian Zhang, Mingjuan Jin, Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Mindie H Nguyen
OBJECTIVES: Hepatitis C virus (HCV) infection is a well-documented risk factor for hepatocellular carcinoma (HCC). Seven HCV genotypes have been classified, and the genotypes show a great variety of geographic distribution. HCV genotype 6 is prevalent in Southeast Asia and has been less studied than the other genotypes. METHODS: This follow-up study was designed to evaluate the natural history of HCV genotype 6. The cohort enrolled 851 Asian patients consisting of 222 with HCV genotype 6 and 629 with other genotypes...
April 25, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28439936/hiv-positive-men-who-have-sex-with-men-are-at-high-risk-of-development-of-significant-liver-fibrosis-after-an-episode-of-acute-hepatitis-c
#12
K Steininger, A Boyd, S Dupke, I Krznaric, A Carganico, M Munteanu, S Neifer, M Schuetze, M Obermeier, K Arasteh, A Baumgarten, P Ingiliz
Acute hepatitis C virus infection remains a major health concern in human immunodeficiency virus(HIV)-infected men who have sex with men (MSM). New direct-acting antiviral agent (DAA) combination therapy has not yet been approved for the treatment for acute hepatitis C virus(HCV), thereby potentially causing deferral of HCV treatment. Therefore, we aimed to study the course of liver disease after an episode of acute HCV. This study is a retrospective single-centre cohort of HIV-positive MSM with acute HCV infection...
April 25, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28439915/treatment-of-chronic-hepatitis-c-with-direct-acting-antivirals-in-patients-with-%C3%AE-thalassaemia-major-and-advanced-liver-disease
#13
Emmanouil Sinakos, Dimitrios Kountouras, John Koskinas, Kalliopi Zachou, Stylianos Karatapanis, Christos Triantos, Themistoklis Vassiliadis, Ioannis Goulis, Alexandra Kourakli, Efthymia Vlachaki, Barbara Toli, Maria Tampaki, Pinelopi Arvaniti, Georgios Tsiaoussis, Aristea Bellou, Antonis Kattamis, Konstantinos Maragkos, Foteini Petropoulou, George N Dalekos, Evangelos Akriviadis, George V Papatheodoridis
Interferon-based regimens for chronic hepatitis C (CHC) were often deferred in patients with β-thalasaemia major (β-TM) due to poor efficacy and tolerance. Current guidelines recommend direct-acting antivirals (DAAs) for these patients. The aim of this study was to assess the safety and efficacy of DAAs in patients with β-TM and advanced liver disease due to CHC. Patients were recruited from eight liver units in Greece. The stage of liver disease was assessed using transient elastography and/or liver histology...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439747/management-of-cirrhotic-patients-after-successful-hcv-eradication
#14
REVIEW
Ryan M Kwok, Tram T Tran
Chronic hepatitis C (HCV) is a hepatotropic virus which, when untreated, can lead to progressive inflammation and fibrosis resulting in cirrhosis, hepatocellular carcinoma (HCC), and decompensations related to end-stage liver disease. The relatively recent introduction of all oral, interferon-free, direct-acting antiviral medications against HCV has transformed the management of these patients. Previous treatment regimens were prolonged, poorly tolerated, and frequently did not result in cure. Current therapies achieve sustained viral response (SVR) in the vast majority of patients including those with decompensated liver disease; a previously challenging population to treat...
April 24, 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28439730/physiological-and-therapeutic-regulation-of-pcsk9-activity-in-cardiovascular-disease
#15
REVIEW
Simon Glerup, Rainer Schulz, Ulrich Laufs, Klaus-Dieter Schlüter
Ischemic heart disease is the main cause of death worldwide and is accelerated by increased levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL-C through its ability to induce degradation of the LDL receptor (LDLR) in the lysosome of hepatocytes. Only in the last few years, a number of breakthroughs in the understanding of PCSK9 biology have been reported illustrating how PCSK9 activity is tightly regulated at several levels by factors influencing its transcription, secretion, or by extracellular inactivation and clearance...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28439409/serial-deletion-reveals-structural-basis-and-stability-for-the-core-enzyme-activity-of-human-glutaminase-1-isoforms-relevance-to-excitotoxic-neurodegeneration
#16
Yuju Li, Justin Peer, Runze Zhao, Yinghua Xu, Beiqing Wu, Yi Wang, Changhai Tian, Yunlong Huang, Jialin Zheng
BACKGROUND: Glutaminase 1 is a phosphate-activated metabolic enzyme that catalyzes the first step of glutaminolysis, which converts glutamine into glutamate. Glutamate is the major neurotransmitter of excitatory synapses, executing important physiological functions in the central nervous system. There are two isoforms of glutaminase 1, KGA and GAC, both of which are generated through alternative splicing from the same gene. KGA and GAC both transcribe 1-14 exons in the N-terminal, but each has its unique C-terminal in the coding sequence...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28439184/systemic-inflammation-and-viral-exposure-among-young-mexican-american-women-nativity-related-differences
#17
Natalya Rosenberg, Martha L Daviglus, Holli A DeVon, Chang Gi Park, Kamal Eldeirawi
BACKGROUND: Factors contributing to elevated inflammation in racial/ethnic minority populations are not well understood. We examined the association of viral exposure with C-reactive protein (CRP) in young Mexican American women. METHODS AND RESULTS: Participants (N=1,141) were currently non-pregnant women of Mexican background, aged 18-39 years, from the cross-sectional National Health and Nutrition Examination Survey (NHANES) 1999-2010. Viral exposure was defined as seropositive status for hepatitis B, and herpes simplex types 1 and 2, and classified as seronegative, seropositive for any one agent, and seropositive for 2 or 3 agents...
2017: Ethnicity & Disease
https://www.readbyqxmd.com/read/28438952/recommendations-on-hepatitis-c-screening-for-adults
#18
(no author information available yet)
No abstract text is available yet for this article.
April 24, 2017: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
https://www.readbyqxmd.com/read/28438950/toward-ending-hepatitis-c-virus-infection-what-are-the-next-steps
#19
Geneviève Cadieux, Herveen Sachdeva
No abstract text is available yet for this article.
April 24, 2017: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
https://www.readbyqxmd.com/read/28438835/il-1%C3%AE-transcriptionally-activates-hepcidin-by-inducing-c-ebp%C3%AE-expression-in-hepatocytes
#20
Yohei Kanamori, Masaru Murakami, Makoto Sugiyama, Osamu Hashimoto, Tohru Matsui, Masayuki Funaba
Hepcidin is a liver-derived hormone that negatively regulates serum iron levels and is mainly regulated at the transcriptional level. Previous studies have clarified that in addition to hepatic iron levels, inflammation also efficiently increases hepatic hepcidin expression. The principle regions responsible for efficient hepcidin transcription are bone morphogenetic protein-responsive elements (BMP-REs) 1 and 2 as well as the signal transducer and activator of transcription 3-binding site (STAT-BS). Here, we show that the proinflammatory cytokine interleukin-1β (IL-1β) efficiently increases hepcidin expression in human HepG2 liver-derived cells and primary mouse hepatocytes...
April 24, 2017: Journal of Biological Chemistry
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