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https://www.readbyqxmd.com/read/29154807/rational-design-of-antiviral-drug-combinations-based-on-equipotency-using-hcv-subgenomic-replicon-as-an-in-vitro-model
#1
Mohamed Mandour, Inge Vliegen, Jan Paeshuyse, Johan Neyts
Combination therapy of directly acting antivirals (DAA's) for the treatment of chronic HCV infections has proven to be a highly effective strategy to cure chronic infections with this virus. Here we studied, using HCV as an example, how to best design in vitro studies that explore the combined antiviral efficiency of combinations of three or more DAA's. To that end we used a HCV NS3 protease inhibitor, a NS5A targeting compound and two non-nucleoside NS5B polymerase inhibitors (each one targeting a different drug binding site)...
November 14, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29149205/kir-content-genotypes-associate-with-carriage-of-hepatitis-b-surface-antigen-e-antigen-and-hbv-viral-load-in-gambians
#2
Louis-Marie Yindom, Maimuna Mendy, Christopher Bodimeade, Caroline Chambion, Peter Aka, Hilton C Whittle, Sarah L Rowland-Jones, Robert Walton
BACKGROUND: Hepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation...
2017: PloS One
https://www.readbyqxmd.com/read/29149077/rna-virus-evolution-via-a-quasispecies-based-model-reveals-a-drug-target-with-a-high-barrier-to-resistance
#3
Richard J Bingham, Eric C Dykeman, Reidun Twarock
The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly...
November 17, 2017: Viruses
https://www.readbyqxmd.com/read/29135030/hepatitis-c-virus-clearance-in-older-adults
#4
Antonio Massimo Ippolito, Angelo Iacobellis, Michele Milella, Fabio Conti, Vincenzo Messina, Maria Rosa Valvano, Grazia Anna Niro, Filomena Morisco, Michele Barone, Antonio Patrizio Termite, Giuseppina Brancaccio, Angelo Andriulli
OBJECTIVES: To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct-acting antiviral therapy. PARTICIPANTS: Individuals aged 80 and older with chronic HCV infection (N = 253; n = 213 with cirrhosis, n = 40 with advanced fibrosis). MEASUREMENTS: We investigated the efficacy, safety, and global clinical effect of treatment with different combinations of direct antiviral agents (DAAs)...
November 14, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/29113002/-acute-liver-failure-as-a-rare-case-of-a-frequent-disease
#5
Angela Marie Thiel, Jürgen Rissland, Frank Lammert, Markus Casper
Here we report the case of a 63-year-old female patient who was admitted with acute liver failure. The etiology turned out to be an acute fulminant hepatitis caused by hepatitis C virus (HCV) infection of unknown origin. Fulminant hepatitis due to acute hepatitis C is very rare and hardly reported but a potential cause of acute liver failure due to massive hepatic necrosis, which may lead to encephalitis and multi-organ-failure. During follow-up spontaneous virological clearance was observed. The case illustrates that acute HCV infection, which is confirmed by the detection of HCV-RNA, has to be considered in the differential diagnosis of acute liver failure...
November 7, 2017: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/29100993/hepatitis-c-virus-induced-natural-killer-cell-proliferation-involves-monocyte-derived-cells-and-the-ox40-ox40l-axis
#6
Julia Pollmann, Jana-Julia Götz, Daniel Rupp, Otto Strauss, Markus Granzin, Oliver Grünvogel, Pascal Mutz, Catharina Kramer, Felix Lasitschka, Volker Lohmann, Niklas K Björkström, Robert Thimme, Ralf Bartenschlager, Adelheid Cerwenka
BACKGROUND AND AIMS: Natural killer (NK) cells are found at increased frequencies in hepatitis C virus (HCV)-infected patients. NK cell activation was shown to correlate with HCV clearance and to predict favourable treatment response. The aim of our study was to dissect mechanisms leading to NK cell activation and proliferation in response to HCV. METHODS: NK cell phenotype, proliferation, and function were assessed after six-day co-culture of human peripheral blood mononuclear cells (PBMCs) with HCV-replicon containing Huh6 hepatoblastoma cells or HCV-infected Huh7...
October 31, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29084399/hepatitis-c-treatment-with-sofosbuvir-and-ledipasvir-accompanied-by-immediate-improvement-in-hemoglobin-a1c
#7
Atsuyuki Ikeda, Kaori Ikeda, Atsushi Takai, Ken Takahashi, Yoshihide Ueda, Hiroyuki Marusawa, Horoshi Seno, Nobuya Inagaki, Hiroyuki Kokuryu
BACKGROUND/AIMS: Direct-acting antiviral agents (DAAs) have increased the sustained viral response rate with minimal adverse effects and short treatment duration. In addition, recent data suggest the possibility that hepatitis C virus (HCV) clearance results in rapid improvement in metabolic pathways. The aim of the present study was to evaluate whether the DAA treatment without ribavirin lowers hemoglobin A1c (HbA1c) at 12 weeks after therapy completion. METHODS: We performed an observational study to assess the effect of sofosbuvir and ledipasvir (SOF/LED) treatment on glycemic control...
October 30, 2017: Digestion
https://www.readbyqxmd.com/read/29084265/mirna-independent-hepacivirus-variants-suggest-a-strong-evolutionary-pressure-to-maintain-mir-122-dependence
#8
Yingpu Yu, Troels K H Scheel, Joseph M Luna, Hachung Chung, Eiko Nishiuchi, Margaret A Scull, Natalia Echeverría, Inna Ricardo-Lax, Amit Kapoor, Ian W Lipkin, Thomas J Divers, Douglas F Antczak, Bud C Tennant, Charles M Rice
Hepatitis C virus (HCV) requires the liver specific micro-RNA (miRNA), miR-122, to replicate. This was considered unique among RNA viruses until recent discoveries of HCV-related hepaciviruses prompting the question of a more general miR-122 dependence. Among hepaciviruses, the closest known HCV relative is the equine non-primate hepacivirus (NPHV). Here, we used Argonaute cross-linking immunoprecipitation (AGO-CLIP) to confirm AGO binding to the single predicted miR-122 site in the NPHV 5'UTR in vivo. To study miR-122 requirements in the absence of NPHV-permissive cell culture systems, we generated infectious NPHV/HCV chimeric viruses with the 5' end of NPHV replacing orthologous HCV sequences...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29084047/infection-by-htlv-1-is-associated-with-high-levels-of-pro-inflammatory-cytokines-in-hiv-hcv-coinfected-patients
#9
Carlos Brites, Marcos Abrahão, Patrícia Bozza, Eduardo M Netto, André Lyra, Fabianna Bahia
OBJECTIVES: HIV, HCV, and HTLV-1 share the same routes of infection, making coinfection by these viruses a frequent finding in endemic areas. However, there is scarce information on the clinical / immunological consequences of triple infection. Coinfection by HTLV-1 is able to modulate cytokine´s production in HIV patients, but there is no data on the immune response of HIV-HCV-HTLV-1 infected patients METHODS:: we compared the plasma levels of 25 different cytokines in HIV-HCV patients, according to their serostatus to HTLV-1 infection...
October 27, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29080244/impaired-patient-reported-outcomes-persist-in-hiv-hcv-co-infected-patients-and-in-cirrhotic-patients-despite-hcv-clearance
#10
Fabienne Marcellin, Philippe Morlat, Linda Wittkop, Dominique Salmon-Ceron, Maria Patrizia Carrieri
Dirks et al.(1) 's recent study provides greater insight into the neuropsychiatric symptoms experienced by HCV infected patients and questions how these symptoms are associated with HCV clearance. The authors show that in HCV infected patients with mild liver disease, none of the following outcomes depend on HCV clearance: cognitive function, mood alteration, health-related quality of life (HRQL) and fatigue (FIS scores). However, these results may not be generalizable to HIV-HCV co-infected patients and cirrhotic patients, who were excluded from the study and who are generally more concerned by fatigue and neuropsychiatric symptoms...
October 27, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29075676/direct-acting-antivirals-in-kidney-transplant-patients-successful-hepatitis-c-treatment-and-short-term-reduction-in-urinary-protein-creatinine-ratios
#11
Michael R Goetsch, Ashutosh Tamhane, Mohit Varshney, Anuj Kapil, Edgar T Overton, Graham C Towns, Ricardo A Franco
BACKGROUND: The role of Hepatitis C Virus (HCV) clearance in kidney graft survival is unknown. We examined short-term trends of protein/creatinine (P/C) ratios in HCV-infected kidney transplant recipients treated with direct-acting antivirals (DAAs). METHODS: This is a retrospective study of 19 kidney transplant patients with HCV infection treated with DAAs at the University of Alabama at Birmingham between January 2013 and June 2016. Markers of glomerular damage were assessed using average urinary protein/creatinine (P/C) ratios measured pretreatment and posttreatment...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/29071045/repeated-spontaneous-clearance-of-hepatitis-c-virus-infection-in-the-setting-of-long-term-non-progression-of-hiv-infection
#12
Genevieve Kerkerian, Arshia Alimohammadi, Tyler Raycraft, Brian Conway
Hepatitis C Virus (HCV) and human immunodeficiency virus (HIV) are global pandemics that affect 170 million and 35 million individuals, respectively. Up to 45% of individuals infected with HCV clear their infections spontaneously - correlating to factors like aboriginal descent and some host specific immune factors. HIV, however, establishes true latency in infected cells and cannot be cured. In the setting of longterm non-progressors (LTNPs) of HIV, a state of immune preservation and low circulating viral load is established...
October 2, 2017: Infectious Disease Reports
https://www.readbyqxmd.com/read/29070670/ifn-%C3%AE-4-attenuates-antiviral-responses-by-enhancing-negative-regulation-of-ifn-signaling
#13
Adeola A Obajemu, Nina Rao, Kari A Dilley, Joselin M Vargas, Faruk Sheikh, Raymond P Donnelly, Reed S Shabman, Eric G Meissner, Ludmila Prokunina-Olsson, Olusegun O Onabajo
Type III IFNs are important mediators of antiviral immunity. IFN-λ4 is a unique type III IFN because it is produced only in individuals who carry a dG allele of a genetic variant rs368234815-dG/TT. Counterintuitively, those individuals who can produce IFN-λ4, an antiviral cytokine, are also less likely to clear hepatitis C virus infection. In this study, we searched for unique functional properties of IFN-λ4 that might explain its negative effect on hepatitis C virus clearance. We used fresh primary human hepatocytes (PHHs) treated with recombinant type III IFNs or infected with Sendai virus to model acute viral infection and subsequently validated our findings in HepG2 cell line models...
October 25, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29055921/hepatitis-c-and-its-metabolic-complications-in-kidney-disease
#14
Fabrizio Fabrizi, Francesca M Donato, Piergiorgio Messa
INTRODUCTION: Evidence has been accumulated during the last decade showing that HCV infection plays an important activity at hepatic and extra-hepatic level. Chronic HCV is associated with a large spectrum of extra-hepatic manifestations including lympho-proliferative diseases and metabolic abnormalities (such as insulin resistance and fatty liver disease). MATERIAL AND METHODS: We have performed an extensive review of the medical literature regarding the increased risk of cardiovascular and kidney disease that has been observed in various groups of HCV-infected patients...
October 16, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/29040985/serum-ifn-%C3%AE-3-levels-correlate-with-serum-hepatitis-c-virus-rna-levels-in-symptomatic-patients-with-acute-hepatitis-c
#15
Susumu Imoto, Soo Ryang Kim, Keisuke Amano, Etsuko Iio, Seitetsu Yoon, Shigeya Hirohata, Yoshihiko Yano, Toru Ishikawa, Shinji Katsushima, Toshiki Komeda, Toyokazu Fukunaga, Hobyung Chung, Hiroyuki Kokuryu, Yutaka Horie, Takashi Hatae, Aya Fujinami, Soo Ki Kim, Masatoshi Kudo, Yasuhito Tanaka
BACKGROUND: Recent genome-wide association studies demonstrated that 2 single nucleotide polymorphisms (SNPs), upstream of the interferon-λ (IFNL) 3 gene, are associated with the spontaneous clearance of hepatitis C virus (HCV) in symptomatic patients with acute hepatitis C (AHC). Although these 2 SNPs, rs8099917 and rs12979860, have established their significant roles in the innate immunity response to spontaneously clear HCV in patients with AHC, the detailed mechanisms of their roles remain largely unknown...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/29040318/rapid-reversal-of-innate-immune-dysregulation-in-blood-of-patients-and-livers-of-humanized-mice-with-hcv-following-daa-therapy
#16
Matthew A Burchill, Justin A Roby, Nanette Crochet, Megan Wind-Rotolo, Amy E Stone, Michael G Edwards, Rachael J Dran, Michael S Kriss, Michael Gale, Hugo R Rosen
RESULTS: First, in patients receiving two different combinations of DAAs, we found that DAAs induced not only rapid viral clearance, but also a re-setting of antiviral immune responses in the peripheral blood. Specifically, we see a rapid decline in the expression of genes associated with chronic IFN stimulation (IFIT3, USP18, IFIT1) as well as a rapid decline in genes associated with inflammation (IL1β, CXCL10, CXCL11) in the peripheral blood that precedes the complete removal of virus from the blood...
2017: PloS One
https://www.readbyqxmd.com/read/29039469/the-association-of-lmp7-and-tap2-gene-polymorphisms-with-treatment-response-to-interferon-ribavirin-in-patients-with-genotype-1-chronic-hepatitis-c
#17
Feng Zang, Yinan Yao, Mei Liu, Haozhi Fan, Ming Yue, Mingzhu Chen, Jie Wang, Rongbin Yu, Peng Huang
Previous studies have highlighted the important role of genes related to antigen presentation in the spontaneous clearance of hepatitis C virus. The present study aimed to explore the association between TAP, LMP and tapasin gene polymorphism and treatment response in chronic hepatitis C virus (CHC) patients. Six single nucleotide polymorphisms in TAP, LMP and tapasin genes were genotyped among 352 Chinese genotype 1 CHC patients with pegylated interferon-α and ribavirin (pegIFN-α/RBV) treatment. There were 232 cases achieving sustained virological response (SVR), which yielded an SVR rate of 65...
October 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29024739/direct-antiviral-agents-daas-a-new-age-in-the-treatment-of-hepatitis-c-virus-infection
#18
REVIEW
Ulrich Spengler
Hepatitis C virus (HCV) is a global health problem, because infection frequently leads to chronic hepatitis C eventually progressing to liver cirrhosis and liver cancer. Improved insights into the HCV replication cycle and the role of HCV non-structural proteins have recently enabled to identify drugs directly acting on specific HCV target structures. Agents from three drug classes have been developed and approved by the health authorities. Combinations of two or more drugs from different classes achieve high (>90%) HCV clearance rates and are well tolerated...
October 10, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29022122/association-of-interferon-lambda-polymorphisms-with-elevated-baseline-viral-loads-in-chronic-hepatitis-c-virus-genotype-6-infection
#19
Linh Thuy Nguyen, Dzung Van Nguyen, Michael J Carr, William W Hall, Lan Anh Nguyen
Globally, hepatitis C virus (HCV) is one of the major causes of hepatocellular carcinoma and liver cirrhosis. For clinical decision making, genetic variation in the interferon-λ (IFNL) cluster has been utilised as a baseline predictor of natural and interferon-based treatment-induced viral clearance. In Vietnam, where HCV genotypes 1 (g1) and g6 predominate, no prior studies have been conducted investigating associations of IFNL3/4 polymorphisms with spontaneous clearance (SC) or HCV viral load (VL) in chronic infection...
October 11, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28960366/portal-pressure-and-liver-stiffness-measurements-in-the-prediction-of-fibrosis-regression-after-svr-in-recurrent-hepatitis-c
#20
Ezequiel Mauro, Gonzalo Crespo, Carla Montironi, Maria-Carlota Londoño, Virginia Hernández-Gea, Pablo Ruiz, Lydia Sastre, Julissa Lombardo, Zoe Mariño, Alba Díaz, Jordi Colmenero, Antoni Rimola, Juan Carlos Garcia-Pagan, Mercé Brunet, Xavier Forns, Miquel Navasa
Sustained virological response (SVR) improves survival in post liver transplant (LT) recurrent hepatitis C. However, the impact of SVR on fibrosis regression is not well defined. In addition, the performance of noninvasive methods to evaluate the presence of fibrosis and portal hypertension after SVR has been scarcely evaluated. We aimed to investigate the degree of fibrosis regression (decrease ≥1 METAVIR stage) after SVR and its associated factors in recurrent hepatitis C, as well as the diagnostic capacity of noninvasive methods in the assessment of liver fibrosis and portal hypertension after viral clearance...
September 27, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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