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https://www.readbyqxmd.com/read/29444493/modulators-of-innate-immunity-as-novel-therapeutics-for-treatment-of-chronic-hepatitis-b
#1
REVIEW
Aleksei Suslov, Stefan Wieland, Stephan Menne
The first line defense mechanisms against viral infection are mediated by the innate immune system. Viral components are detected by infected cells and/or innate immune cells that express different sensory receptors. They in turn mediate induction of direct antiviral mechanisms and further modulation of innate and adaptive immune responses. For evading the innate system, most viruses have evolved efficient mechanisms to block sensing and/or antiviral functions of the innate response. Interestingly, hepatitis B virus (HBV) seems to act like a stealth virus that escapes cell intrinsic antiviral mechanisms through avoiding recognition by the innate system rather than blocking its effector functions...
February 11, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29444087/safety-and-efficacy-of-anti-pd-l1-therapy-in-the-woodchuck-model-of-hbv-infection
#2
Scott Balsitis, Volodymyr Gali, Pamela J Mason, Susan Chaniewski, Steven M Levine, Michael J Wichroski, Michael Feulner, Yunling Song, Karen Granaldi, James K Loy, Chris M Thompson, Jacob A Lesniak, Catherine Brockus, Narendra Kishnani, Stephan Menne, Mark I Cockett, Renuka Iyer, Stephen W Mason, Daniel J Tenney
Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters...
2018: PloS One
https://www.readbyqxmd.com/read/29443737/effect-of-tenofovir-on-renal-function-in-patients-with-chronic-hepatitis-b
#3
Woo Jin Jung, Jae Young Jang, Won Young Park, Soung Won Jeong, Hee Jeong Lee, Sang Joon Park, Sae Hwan Lee, Sang Gyune Kim, Sang-Woo Cha, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim, Suyeon Park, Baigal Baymbajav
Tenofovir disoproxil fumarate (TDF) is widely used to treat patients with hepatitis B virus (HBV) infection. We investigated the effect of TDF on renal insufficiency in patients with chronic hepatitis B (CHB).A consecutive cohort analysis was applied to CHB patients taking prescribed TDF from January 2012 to May 2016 at Soonchunhyang University Seoul Hospital. Alterations over time in corrected calcium, phosphate, creatinine, and estimated glomerular filtration rate (eGFR) were analyzed using the generalized estimating equation method...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29443655/is-interferon-based-treatment-of-viral-hepatitis-c-genotype-3-infection-still-of-value-in-the-era-of-direct-acting-antivirals
#4
Dorota Zarębska-Michaluk, Robert Flisiak, Jerzy Jaroszewicz, Ewa Janczewska, Agnieszka Czauż-Andrzejuk, Hanna Berak, Andrzej Horban, Agnieszka Staniaszek, Andrzej Gietka, Magdalena Tudrujek, Krzysztof Tomasiewicz, Dorota Dybowska, Waldemar Halota, Anna Piekarska, Marek Sitko, Aleksander Garlicki, Iwona Orłowska, Krzysztof Simon, Teresa Belica-Wdowik, Barbara Baka-Ćwierz, Włodzimierz Mazur, Jolanta Białkowska, Łukasz Socha, Marta Wawrzynowicz-Syczewska, Łukasz Laurans, Zbigniew Deroń, Beata Lorenc, Beata Dobracka, Olga Tronina, Małgorzata Pawłowska
The aim of the study is to analyze treatments available for patients infected with genotype (G) 3 hepatitis C virus (HCV) in Poland at the beginning of the interferon (IFN)-free era and evaluate the efficacy and safety of different therapeutic options administered in a real-world setting. We analyzed data of 198 patients who started antiviral therapy after July 1, 2015, and completed it before December 31, 2016; 57.6% of them had liver cirrhosis and 46% were treatment experienced. Fifty percent of patients were assigned to sofosbuvir (SOF)+pegylated IFN alfa (PegIFNa)+ribavirin (RBV), 9% to PegIFNa+RBV, 36% received SOF+RBV, and 5% SOF+daclatasvir (DCV)±RBV...
February 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29443378/hepatitis-c-virus-e2-envelope-glycoprotein-induces-an-immunoregulatory-phenotype-in-macrophages
#5
Young-Chan Kwon, Keith Meyer, Guangyong Peng, Soumya Chatterjee, Daniel F Hoft, Ranjit Ray
A comprehensive strategy to control HCV infection needs a vaccine. Our phase I study with recombinant HCV E1/E2 EnvGPs as a candidate vaccine did not induce a strong immune response in volunteers. We analyzed the interactions of HCV EnvGPs with human monocyte derived macrophages as antigen presenting cells. HCV E2 induced immune regulatory cytokine IL-10 and sCD163 protein expression in macrophages from 7 of 9 blood donors tested. Further, HCV E2 enhanced Stat3 and suppressed Stat1 activation, reflecting macrophage polarization towards M2 phenotype...
February 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29442296/first-report-of-the-presence-of-hepatitis-e-virus-in-scottish-harvested-shellfish-purchased-at-retail-level
#6
Zoe O'Hara, Claire Crossan, John Craft, Linda Scobie
Shellfish samples (n = 310) purchased from local supermarkets were analysed for the presence of hepatitis E virus (HEV) by nested RT-PCR and real-time qRT-PCR. Overall, 2.9% of samples tested positive for the presence of HEV. Phylogenetic analysis of HEV sequences revealed all as being genotype 3 HEV. This is the first report of the detection of HEV in commercially sold shellfish in Scotland. These findings may encourage further research that will help address the gaps in the knowledge in respect to foodborne transmission of HEV in Scotland and the rest of the United Kingdom...
February 13, 2018: Food and Environmental Virology
https://www.readbyqxmd.com/read/29442226/molecular-evolution-and-phylodynamics-of-hepatitis-b-virus-infection-circulating-in-iran
#7
Sayed-Hamidreza Mozhgani, Seyed Amir Malekpour, Mehdi Norouzi, Fatemeh Ramezani, Seyed Abdolrahim Rezaee, Vahdat Poortahmasebi, Mehdi Sadeghi, Seyed Moayed Alavian, Mohadeseh Zarei-Ghobadi, Azam Ghaziasadi, Hadi Karimzadeh, Reza Malekzadeh, Masood Ziaee, Farshid Abedi, Behrooz Ataei, Majid Yaran, Babak Sayad, Hamid Reza Jahantigh, Mohammad Hossein Somi, Gholamreza Sarizadeh, Ismail Sanei-Moghaddam, Fariborz Mansour-Ghanaei, Hossein Keyvani, Ebrahim Kalantari, Zahra Fakhari, Babak Geravand, Seyed Mohammad Jazayeri
Previous local and national Iranian publications indicate that all Iranian hepatitis B virus (HBV) strains belong to HBV genotype D. The aim of this study was to analyze the evolutionary history of HBV infection in Iran for the first time, based on an intensive phylodynamic study. The evolutionary parameters, time to most recent common ancestor (tMRCA), and the population dynamics of infections were investigated using the Bayesian Monte Carlo Markov chain (BMCMC). The effective sample size (ESS) and sampling convergence were then monitored...
February 13, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29441983/microrna-137-promotes-hepatitis-b-virus-gene-expression-and-replication-via-targeting-the-protein-inhibitor-of-activated-stat-2
#8
Yongjie Pan, Jinhua Dai, Yufeng Liao, Qiuyun Yu
Hepatitis B virus (HBV) infection is one of the most important infectious diseases in China. In this study, we investigated the functional role of miR-137 in HBV infection to further elucidate the mechanism underlying the associated pathology. Viral replication was determined after transfection of HEK293 cells with the replication-competent vector pHBV1.3 and miR137 mimics or inhibitors. Expression of HBV genes was determined by quantitative real-time PCR (qRT-PCR). Expression of miR-137 and protein inhibitor of activated STAT 2 (PIAS2) was determined by qRT-PCR and Western blotting...
September 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29441690/hepatitis-e-virus-infection-of-slaughtered-healthy-pigs-in-brazil
#9
A R Amorim, G S Mendes, G P A Pena, N Santos
Hepatitis E virus (HEV) is an emerging pathogen that can be transmitted through contaminated raw or undercooked meat derived from domestic pigs. HEV infections have been documented among pig herds, pig products and environmental samples raising concern about the spread of the virus. HEV genotypes 3 and 4 are considered zoonotic and have been linked to human cases. HEV was detected in 51 of 335 bile samples (15.2%) from healthy pigs in Minas Gerais, Brazil. Phylogenetic analysis of partial sequences from ORF1 and ORF2 regions yielded discordant results, assigning isolates to subtypes 3c and 3i, respectively, suggesting intragenotypic HEV recombination...
February 13, 2018: Zoonoses and Public Health
https://www.readbyqxmd.com/read/29441589/dissecting-the-decline-of-hepatitis-c-in-first-time-donors-in-england-and-wales
#10
C A Reynolds, K L Davison, N Andrews, P Patel, A Kitchen, S R Brailsford
BACKGROUND AND OBJECTIVES: The rate of confirmed hepatitis C virus (HCV) cases, in first-time donors, is much lower in 2015 than 20 years ago. We investigate reasons for the decline. MATERIALS AND METHODS: HCV rates were analysed by gender and birth cohort for 1996 to 2015 and ethnic group for 2006 to 2015. Variables for confirmed positive cases were compared for two ten-year periods (1996 to 2005 and 2006 to 2015) including genotyping data for 2006 to 2015. RESULTS: There were 2007 confirmed HCV cases identified between 1996 and 2015...
February 14, 2018: Vox Sanguinis
https://www.readbyqxmd.com/read/29441587/transfusion-transmitted-hepatitis-b-virus-hbv-infection-from-an-individual-donation-nucleic-acid-id-nat-non-reactive-donor
#11
N O'Flaherty, I Ushiro-Lumb, L Pomeroy, S Ijaz, F Boland, C De Gascun, J Fitzgerald, J O'Riordan
Lookback was initiated upon notification of an acute HBV infection in a repeat Irish donor, 108 days post-donation. The donation screened non-reactive by individual-donation nucleic acid testing (ID-NAT) using the Procleix Ultrio Elite multiplex assay and again when the archived sample was retested, but the discriminatory assay for HBV was reactive. The immunocompromised recipient of the implicated red cell component was tested 110 days post-transfusion, revealing a HBV DNA viral load of 470 IU/ml. Genotype C2 sequences identical across two regions of the HBV genome were found in samples from the donor and recipient...
February 14, 2018: Vox Sanguinis
https://www.readbyqxmd.com/read/29440324/natural-history-clinical-manifestations-and-pathogenesis-of-hepatitis-a
#12
Eui-Cheol Shin, Sook-Hyang Jeong
Hepatitis A virus (HAV) is transmitted by the fecal-oral route and is a major cause of acute viral hepatitis. The clinical manifestations of HAV infection range from asymptomatic infection to acute liver failure (ALF), but do not include progression to chronic hepatitis. Risk factors for severe acute hepatitis A are older age (>40 years) and preexisting liver disease. Some patients may show atypical clinical features such as relapsing hepatitis, prolonged cholestasis, or extrahepatic manifestations. Almost all hepatitis A patients spontaneously recover with supportive care...
February 12, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29439971/sofosbuvir-and-ribavirin-liver-pharmacokinetics-in-patients-infected-with-hepatitis-c-virus
#13
Darius Babusis, Michael P Curry, Brian Kirby, Yeojin Park, Eisuke Murakami, Ting Wang, Anita Mathias, Nezam Afdhal, John G McHutchison, Adrian S Ray
Sofosbuvir and ribavirin exert their anti-hepatitis C virus (HCV) activity following metabolic activation in the liver. However, intrahepatic concentrations of the pharmacologically active nucleotide metabolites in humans are poorly characterized due to the inaccessibility of tissue and technical challenges with measuring nucleotide levels. A clinical study assessing the efficacy of sofosbuvir and ribavirin administered prior to liver transplant to prevent HCV reoccurrence provided a unique opportunity to quantify nucleotide concentrations in human liver...
February 12, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29439751/impact-of-hepatitis-b-vaccination-on-acute-hepatitis-b-epidemiology-in-european-union-european-economic-area-countries-2006-to-2014
#14
Alessandro Miglietta, Chantal Quinten, Pier Luigi Lopalco, Erika Duffell
Hepatitis B prevention in European Union/European Economic Area (EU/EEA) countries relies on vaccination programmes. We describe the epidemiology of acute hepatitis B virus (HBV) at country and EU/EEA level during 2006-2014. Using a multi-level mixed-effects Poisson regression model we assessed differences in the acute HBV infection notification rates between groups of countries that started universal HBV vaccination before/in vs after 1995; implemented or not a catch-up strategy; reached a vaccine coverage ≥ 95% vs < 95% and had a hepatitis B surface antigen prevalence ≥ 1% vs < 1%...
February 2018: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/29439720/plant-derived-antivirals-against-hepatitis-c-virus-infection
#15
REVIEW
Ana Carolina Gomes Jardim, Jacqueline Farinha Shimizu, Paula Rahal, Mark Harris
Hepatitis C virus (HCV) infection is a worldwide public health burden and it is estimated that 185 million people are or have previously been infected worldwide. There is no effective vaccine for prevention of HCV infection; however, a number of drugs are available for the treatment of infection. The availability of direct-acting antivirals (DAAs) has dramatically improved therapeutic options for HCV genotype 1. However, the high costs and potential for development of resistance presented by existing treatment demonstrate the need for the development of more efficient new antivirals, or combination of therapies that target different stages of the viral lifecycle...
February 13, 2018: Virology Journal
https://www.readbyqxmd.com/read/29439653/unexplained-chronic-liver-disease-in-ethiopia-a-cross-sectional-study
#16
Stian Magnus Staurung Orlien, Nejib Yusuf Ismael, Tekabe Abdosh Ahmed, Nega Berhe, Trine Lauritzen, Borghild Roald, Robert David Goldin, Kathrine Stene-Johansen, Anne Margarita Dyrhol-Riise, Svein Gunnar Gundersen, Marsha Yvonne Morgan, Asgeir Johannessen
BACKGROUND: Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development. METHODS: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia...
February 13, 2018: BMC Gastroenterology
https://www.readbyqxmd.com/read/29439266/effect-of-the-opioid-crisis-on-the-donor-pool-for-kidney-transplantation-an-analysis-of-national-kidney-deceased-donor-trends-from-2010-2016
#17
Donald F Chute, Meghan E Sise
BACKGROUND: The opioid crisis has led to a dramatic increase in the number of drug overdose deaths in the United States. Little is known about the effect of the opioid crisis on the kidney transplant donor pool, particularly on hepatitis C virus (HCV)-infected donors. METHODS: This is a retrospective analysis of the data from the Organ Procurement and Transplantation Network from 2010 to 2016. We determined the changes in characteristics of kidney transplant donors and evaluated which changes may be directly related to the opioid crisis...
February 13, 2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/29438889/recent-progress-in-potential-anti-hepatitis-b-virus-agents-structural-and-pharmacological-perspectives
#18
Dejuan Sun, Lingjuan Zhu, Dahong Yao, Lixia Chen, Leilei Fu, Liang Ouyang
Hepatitis B virus (HBV) infections affect about 240 million patients worldwide and increase the risk of liver cirrhosis and hepatocellular carcinoma. It is estimated that about 686 thousand people died annually of liver damage resulted from HBV infections. At present, two classes of antiviral drugs have been approved by the Food and Drug Administration (FDA) for the treatment of hepatitis B, immunomodulators (interferon [IFN]-a and pegylated-interferon [PEG-IFN]-a) and nucleos(t)ide analogs (lamivudine, telbivudine, adefovir, tenofovir [TDF], and entecavir [ETV])...
February 5, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29438748/neuregulin-1-discovered-as-a-cleavage-target-for-the-hcv-ns3-4a-protease-by-a-microfluidic-membrane-protein-array
#19
Nika Schwartz, Michal Pellach, Yair Glick, Reuven Gil, Gahl Levy, Dorit Avrahami, Efrat Barbiro-Michaely, Yaakov Nahmias, Doron Gerber
The hepatitis C virus (HCV) non-structural protein 3 (NS3) is essential for HCV maturation. The NS3/4A protease is a target for several HCV treatments and is a well-known target for HCV drug discovery. The protein is membrane associated and thus probably interacts with other membrane proteins. However, the vast majority of known NS3 host partners are soluble proteins rather than membrane proteins, most likely due to lack of appropriate platforms for their discovery. Utilization of an integrated microfluidics platform enables analysis of membrane proteins in their native form...
February 10, 2018: New Biotechnology
https://www.readbyqxmd.com/read/29438402/haiku-new-paradigm-for-the-reverse-genetics-of-emerging-rna-viruses
#20
Thérèse Atieh, Miriam Diala El Ayoubi, Fabien Aubry, Stéphane Priet, Xavier de Lamballerie, Antoine Nougairède
Reverse genetics is key technology for producing wild-type and genetically modified viruses. The ISA (Infectious Subgenomic Amplicons) method is a recent versatile and user-friendly reverse genetics method to rescue RNA viruses. The main constraint of its canonic protocol was the requirement to produce (e.g., by DNA synthesis or fusion PCR) 5' and 3' modified genomic fragments encompassing the human cytomegalovirus promoter (pCMV) and the hepatitis delta virus ribozyme/simian virus 40 polyadenylation signal (HDR/SV40pA), respectively...
2018: PloS One
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