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https://www.readbyqxmd.com/read/28635671/rab33b-controls-hepatitis-b-virus-assembly-by-regulating-core-membrane-association-and-nucleocapsid-processing
#1
Christina Bartusch, Tatjana Döring, Reinhild Prange
Many viruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Using RNA interference (RNAi), we demonstrate that the Golgi/autophagosome-associated Rab33B is required for hepatitis B virus (HBV) propagation in hepatoma cell lines. While Rab33B is dispensable for the secretion of HBV subviral envelope particles, its knockdown reduced the virus yield to 20% and inhibited nucleocapsid (NC) formation and/or NC trafficking. The overexpression of a GDP-restricted Rab33B mutant phenocopied the effect of deficit Rab33B, indicating that Rab33B-specific effector proteins may be involved...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28635668/the-role-of-cccdna-in-hbv-maintenance
#2
REVIEW
Lena Allweiss, Maura Dandri
Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide; it can cause various degrees of liver damage and is strongly associated with the development of liver cirrhosis and hepatocellular carcinoma. The molecular mechanisms determining HBV persistence are not fully understood, but these appear to be multifactorial and the unique replication strategy employed by HBV enables its maintenance in infected hepatocytes. Both the stability of the HBV genome, which forms a stable minichromosome, the covalently closed circular DNA (cccDNA) in the hepatocyte nucleus, and the inability of the immune system to resolve chronic HBV infection are believed to be key mechanisms of HBV chronicity...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28635613/association-of-the-s267f-variant-on-ntcp-gene-and-treatment-response-to-pegylated-interferon-in-patients-with-chronic-hepatitis-b-a-multicentre-study
#3
Kessarin Thanapirom, Sirinporn Suksawatamnuay, Wattana Sukeepaisarnjaroen, Sombat Treeprasertsuk, Tawesak Tanwandee, Phunchai Charatcharoenwitthaya, Satawat Thongsawat, Apinya Leerapun, Teerha Piratvisuth, Rattana Boonsirichan, Chalermrat Bunchorntavakul, Chaowalit Pattanasirigool, Bubpha Pornthisarn, Supoj Tuntipanichteerakul, Ekawee Sripariwuth, Woramon Jeamsripong, Teeranan Sanpanjit, Yong Poovorawan, Piyawat Komolmit
BACKGROUND: Sodium taurocholate co-transporting polypeptide (NTCP) is a cell receptor for hepatitis B virus (HBV). The S267F variant on the NTCP gene is inversely associated with the chronicity of HBV infection, progression to cirrhosis and hepatocellular carcinoma in East Asian populations. This aim of this study was to determine whether the S267F variant was associated with response to pegylated interferon (Peg-IFN) in patients with chronic HBV infection. METHODS: Two hundred and fifty-seven patients with chronic HBV, treated with Peg-IFN for 48 weeks, were identified from 13 tertiary hospitals included in the hepatitis B database of the Thai Association for the Study of the Liver (THASL)...
June 21, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28634723/combinational-use-of-hepatitis-b-viral-antigens-predicts-responses-to-nucleos-t-ide-analogue-peg-interferon-sequential-therapy
#4
Akihiro Matsumoto, Shuhei Nishiguchi, Hirayuki Enomoto, Jong-Hon Kang, Yasuhito Tanaka, Noboru Shinkai, Masayuki Kurosaki, Masaru Enomoto, Tatsuo Kanda, Osamu Yokosuka, Hiroshi Yatsuhashi, Shinya Nagaoka, Chiaki Okuse, Tatehiro Kagawa, Tetsuya Mine, Koichi Takaguchi, Satoru Saito, Keisuke Hino, Fusao Ikeda, Shotaro Sakisaka, Daisuke Morihara, Shiho Miyase, Masataka Tsuge, Kazuaki Chayama, Naoki Hiramatsu, Yoshiyuki Suzuki, Kazumoto Murata, Eiji Tanaka
BACKGROUND: This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy. METHODS: A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks. RESULTS: Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN...
June 20, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28634402/enhanced-antiviral-and-antifibrotic-effects-of-short-hairpin-rnas-targeting-hbv-and-tgf-%C3%AE-in-hbv-persistent-mice
#5
Lei Ye, Fangming Kan, Tao Yan, Jiaqi Cao, Leiliang Zhang, Zhijian Wu, Wuping Li
The hepatitis B virus (HBV) causes acute and chronic liver infection, which may lead to liver cirrhosis and hepatocellular carcinoma. Current treatments including interferons and nucleotide analogs, have limited therapeutic effects, underscoring the need to identify effective therapeutic options to inhibit HBV replication and prevent complications. Previous animal models mimicking chronic HBV infection do not faithfully reflect disease progression in humans. Here, we used our established HBV-persistent mouse line with liver fibrosis to evaluate the efficacy of novel therapies...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634352/differences-in-sequences-between-hbv-relaxed-circular-dna-and-covalently-closed-circular-dna
#6
Magda Rybicka, Anna Woziwodzka, Tomasz Romanowski, Piotr Stalke, Marcin Dręczewski, Krzysztof Piotr Bielawski
The hepatitis B virus (HBV) genome exists in two forms: circular covalently closed DNA (cccDNA) and relaxed circular DNA (RCDNA). Here, we investigated the presence of differences in the sequences of both forms in paired samples of serum and liver tissue. The serum and liver biopsy samples were collected at the same time from 67 chronically infected patients. The genotyping of the RCDNA and cccDNA was performed using mass spectrometry analysis. The HBV mutations located in the HBV pol (P) and the HBV basal core promoter/pre-core (BCP/PC) regions were included...
June 21, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28633998/changes-in-risk-behaviours-during-and-following-treatment-for-hepatitis-c-virus-infection-among-people-who-inject-drugs-the-activate-study
#7
Håvard Midgard, Behzad Hajarizadeh, Evan B Cunningham, Brian Conway, Markus Backmund, Philip Bruggmann, Julie Bruneau, Stefan Bourgeois, Adrian Dunlop, Graham R Foster, Margaret Hellard, Geert Robaeys, Maria C Thurnheer, Martin Weltman, Janaki Amin, Philippa S Marks, Sophie Quiene, Gregory J Dore, Olav Dalgard, Jason Grebely
BACKGROUND: The risk of hepatitis C virus (HCV) reinfection due to continued injecting risk behaviours might remain a barrier to HCV treatment among people who inject drugs. We aimed to evaluate changes in risk behaviours during and following HCV treatment among people with ongoing injecting drug use or receiving opioid substitution treatment (OST). METHODS: ACTIVATE was an international multicentre clinical trial conducted between 2012 and 2014. Participants with HCV genotypes 2/3 infection were treated with peg-interferon/ribavirin for 12 or 24 weeks and completed a self-administered behavioural questionnaire at each study visit...
June 17, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28633989/efficacy-and-cytotoxicity-in-cell-culture-of-novel-%C3%AE-hydroxytropolone-inhibitors-of-hepatitis-b-virus-ribonuclease-h
#8
Elena Lomonosova, Jil Daw, Aswin K Garimallaprabhakaran, Nana B Agyemang, Yashkumar Ashani, Ryan P Murelli, John E Tavis
Chronic Hepatitis B virus (HBV) infection is a major worldwide public health problem. Current direct-acting anti-HBV drugs target the HBV DNA polymerase activity, but the equally essential viral ribonuclease H (RNaseH) activity is unexploited as a drug target. Previously, we reported that α-hydroxytropolone compounds can inhibit the HBV RNaseH and block viral replication. Subsequently, we found that our biochemical RNaseH assay underreports efficacy of the α-hydroxytropolones against HBV replication. Therefore, we conducted a structure-activity analysis of 59 troponoids against HBV replication in cell culture...
June 17, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28633899/discovery-of-bms-961955-an-allosteric-inhibitor-of-the-hepatitis-c-virus-ns5b-polymerase
#9
Barbara Zhizhen Zheng, Stanley V D'Andrea, Umesh Hanumegowda, Jay O Knipe, Kathy Mosure, Xiaoliang Zhuo, Julie A Lemm, Mengping Liu, Karen L Rigat, Ying-Kai Wang, Hua Fang, Chris Poronsky, Jingfang Cutrone, Dauh-Rurng Wu, Pirama Nayagam Arunachalam, T J Balapragalathan, Arunachalam Arumugam, Arvind Mathur, Nicholas A Meanwell, Min Gao, Susan B Roberts, John F Kadow
The synthesis, structure-activity relationship (SAR) data, and further optimization of the metabolic stability and pharmacokinetic (PK) properties for a previously disclosed class of cyclopropyl-fused indolobenzazepine HCV NS5B polymerase inhibitors are described. These efforts led to the discovery of BMS-961955 as a viable contingency backup to beclabuvir which was recently approved in Japan for the treatment of HCV as part of a three drug, single pill combination marketed as Ximency(TM).
June 11, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28633871/high-fat-diet-induced-plasma-protein-and-liver-changes-in-obese-rats-can-be-attenuated-by-melatonin-supplementation
#10
Prapimpun Wongchitrat, Paul Klosen, Supitcha Pannengpetch, Kuntida Kitidee, Piyarat Govitrapong, Chartchalerm Isarankura-Na-Ayudhya
Obesity triggers changes in protein expression in various organs that might participate in the pathogenesis of obesity. Melatonin has been reported to prevent or attenuate such pathological protein changes in several chronic diseases. However, such melatonin effects on plasma proteins have not yet been studied in an obesity model. Using a proteomic approach, we investigated the effect of melatonin on plasma protein profiles after rats were fed a high-fat diet (HFD) to induce obesity. We hypothesized that melatonin would attenuate abnormal protein expression in obese rats...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28633752/rituximab-administration-in-a-patient-with-pemphigus-vulgaris-following-reactivation-of-occult-hepatitis-b-virus-infection
#11
Soheil Tavakolpour, Tahereh Soori, Pedram Noormohammadpour, Kamran Balighi, Hamidreza Mahmoudi, Maryam Daneshpazhooh
Immunosuppressive drugs are the milestone of treatment of autoimmune diseases, but they can lead to serious complications, including hepatitis B virus reactivation in HBV carriers as well as in patients with occult HBV infection (OBI). A 36-year-old man with OBI was diagnosed with pemphigus vulgaris. He was prescribed prednisolone and his hepatitis B surface antigen turned positive. Viral replication was successfully controlled by lamivudine and adefovir. Mycophenolate mofetil and intravenous immunoglobulin  were not effective in controlling the pemphigus vulgaris...
June 20, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28632974/hcv-positive-donor-organs-in-solid-organ-transplantation-mind-the-gap
#12
EDITORIAL
J A Fishman, X Forns
The shortage of organs for transplantation is a major impediment to access to life-saving therapy. The availability of antiviral therapies that control hepatitis B (HBV) and HIV, or cure hepatitis C (HCV), have changed traditional equations in transplantation, allowing infected individuals access to transplantation without unimpeded viral replication during immunosuppression. The availability of these therapies also permits use of organs from donors actively or potentially infected with these viruses. This article is protected by copyright...
June 20, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28632964/long-term-follow-up-of-patients-triply-infected-with-hiv-and-hepatitis-b-and-c-viruses-in-a-comprehensive-hospital-in-central-china
#13
Rongrong Yang, Xien Gui, Yong Xiong, Shicheng Gao
The clinical characteristics of patients triply infected with HIV, HBV and HCV are notable. From January 2005 to June 2014, a total of 115 cART-naive HIV/HBV/HCV infected individuals were studied and 91 of them were followed-up consecutively after cART with 3TC. After cART with 3TC, the HBV-DNA positive rate decreased from 37.4% (43/115) to 9.9% (9/91) (P<0.001), whereas the HCV-RNA positive rate increased from 53.9% (62/115) to 70.3% (64/91) (P=0.016), and HCV-RNA level increased from 3.52 log10 copies/ml to 4...
June 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28632958/decreased-portal-vein-velocity-is-predictive-of-the-development-of-portal-vein-thrombosis-a-matched-case-control-study
#14
Jonathan G Stine, Jennifer Wang, Puja M Shah, Curtis K Argo, Nicolas Intagliata, Andre Uflacker, Stephen H Caldwell, Patrick G Northup
BACKGROUND & AIMS: Portal vein thrombosis (PVT) in cirrhosis may lead to hepatic decompensation and increased mortality. We aimed to investigate if decreased portal vein (PV) velocity is associated with future PVT. METHODS: Data on adult patients with cirrhosis and PVT between January 1, 2005 and July 30, 2015 were obtained. Cases with PVT were matched by age, gender and Model for End stage Liver Disease (MELD) score to corresponding controls without PVT. Cox proportional hazards models, receiver operator curves and Kaplan Meier curves were constructed...
June 20, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28632923/comparing-the-risk-of-hepatitis-b-virus-reactivation-between-direct-acting-antiviral-therapies-and-interferon-based-therapies-for-hepatitis-c
#15
Naoki Kawagishi, Goki Suda, Masahiro Onozawa, Megumi Kimura, Osamu Maehara, Masatsugu Ohara, Takaaki Izumi, Machiko Umemura, Jun Ito, Masato Nakai, Takuya Sho, Mitsuteru Natsuizka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
BACKGROUND: Hepatitis B virus (HBV)-reactivation has been reported during anti-hepatitis C treatment in patients with hepatitis C virus (HCV) and HBV co-infection. We aimed to evaluate the frequency and risk factors of HBV-reactivation during anti-HCV therapy and compared those between interferon (IFN)-free direct-acting antiviral (DAA)-therapies and IFN-based therapies. METHODS: 322 patients with HCV infection receiving anti-HCV therapy were retrospectively screened...
June 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28632898/hbsag-loss-after-peginterferon-and-nucleotide-combination-treatment-in-chronic-hepatitis-b-patients-5-years-of-follow-up
#16
Femke Stelma, Meike H van der Ree, Louis Jansen, Martine W Peters, Harry L A Janssen, Hans L Zaaijer, R Bart Takkenberg, Hendrik W Reesink
BACKGROUND AND AIMS: Combining peginterferon alfa-2a (pegIFN) with a nucleotide analogue can result in higher rates of HBsAg loss than either therapy given alone. Here we investigated the durability of the response to combination therapy in chronic hepatitis B (CHB) patients after 5 years of follow-up. METHODS: In the initial study, 92 CHB patients (44 HBeAg positive, 48 HBeAg negative) with HBV DNA > 100,000 c/mL (~20,000 IU/mL) and active hepatitis were treated for 48 weeks with pegIFN 180 μg/week and 10 mg adefovir dipivoxil daily...
June 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28632794/migrants-healthy-worker-effect-and-mortality-trends-in-the-gulf-cooperation-council-countries
#17
Karima Chaabna, Sohaila Cheema, Ravinder Mamtani
The Gulf Cooperation Council (GCC) countries namely, Bahrain, Kuwait, Oman, Qatar, United Arab Emirates (UAE), and Saudi Arabia, have experienced unique demographic changes. The major population growth contributor in these countries is young migrants, which has led to a shift in the population age pyramid. Migrants constitute the vast proportion of GCC countries' population reaching >80% in Qatar and UAE. Using Global Burden of Disease Study 2015 (GBD 2015) and United Nations data, for the GCC countries, we assessed the association between age-standardized mortality and population size trends with linear and polynomial regressions...
2017: PloS One
https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#18
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28632181/spirulina-protects-against-hepatic-inflammation-in-aging-an-effect-related-to-the-modulation-of-the-gut-microbiota
#19
Audrey M Neyrinck, Bernard Taminiau, Hannah Walgrave, Georges Daube, Patrice D Cani, Laure B Bindels, Nathalie M Delzenne
Aging predisposes to hepatic dysfunction and inflammation that can contribute to the development of non-alcoholic fatty liver disease. Spirulina, a cyanobacterium used as a food additive or food supplement, has been shown to impact immune function. We have tested the potential hepatoprotective effect of a Spirulina in aged mice and to determine whether these effects can be related to a modulation of the gut microbiota. Old mice have been fed a standard diet supplemented with or without 5% Spirulina for six weeks...
June 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28631698/-hepatitis-c-virus-associated-cryoglobulinemic-vasculitis-a-20-year-experience-with-treatment
#20
T M Ignatova, L V Kozlovskaya, N B Gordovskaya, O A Chernova, S Yu Milovanova, P I Novikov, T P Nekrasova, T V Beketova, N A Mukhin
AIM: To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV). SUBJECTS AND METHODS: Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25...
2017: Terapevticheskiĭ Arkhiv
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