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https://www.readbyqxmd.com/read/28732143/ifnl4-rs368234815-and-rs117648444-variants-predict-off-treatment-hbsag-seroclearance-in-ifn-treated-hbeag-negative-chronic-hepatitis-b-patients
#1
Enrico Galmozzi, Floriana Facchetti, Glenda Grossi, Alessandro Loglio, Mauro Vigano, Giovanna Lunghi, Massimo Colombo, Pietro Lampertico
BACKGROUND AND AIM: Robust baseline predictors of interferon (IFN) response in HBeAg negative chronic hepatitis B (CHB) patients are not currently available. The recently described rs368234815 TT/ΔG dinucleotide and rs117648444 nonsynonymous P70S polymorphisms in IFN lambda 4 (IFNL4) gene, which are strongly associated with response to IFN in hepatitis C virus (HCV) infection, could be also useful in IFN treated CHB patients. Here we assessed whether IFNL4 rs368234815 and rs117648444 polymorphisms predict IFN induced HBsAg clearance in CHB patients...
July 21, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28725013/baseline-value-of-intrahepatic-hbv-dna-over-cccdna-predicts-patient-s-response-to-interferon-therapy
#2
Di Mu, Fang-Chao Yuan, Yu Chen, Xiao-Yan Jiang, Liang Yan, Ling-Yu Jiang, Jian-Ping Gong, Da-Zhi Zhang, Hong Ren, Yong Liao
Methodology for accurate quantification of intra-hepatic cccDNA has long been a technical challenge, yet it is highly desired in the clinic. Here, we developed a sensitive method for quantification of intrahepatic cccDNA in liver biopsies from patients, which allowed to predict patient's response to interferon therapy at baseline. Twenty-five patients with HBeAg+ CHB were recruited and liver biopsies were obtained at baseline and 1-year after interferon treatment, respectively. Both intrahepatic cccDNA and HBV DNA were absolutely quantified by a droplet digital PCR amplification system...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709686/toxicologic-evaluations-of-recombinant-liver-targeting-interferon-ifn-csp-genotoxicity-and-tegenicratoity
#3
Wenting Zeng, Chunxu Wu, Jie Wang, Lingjie Cao, Xiaobao Jin, Jiayong Zhu, Xuemei Lu
Interferon alpha as the one of FDA recommended drugs for Hepatitis B virus (HBV) infection has many side effects. Targeting IFNα to the liver may be a strategy to increase its efficacy locally and may increase efficacy of IFNα-based therapy of HBV infection. We have prepared a novel liver-targeting fusion interferon (IFN-CSP) combining IFN α2b with plasmodium region I peptide and have revealed it may be an excellent candidate as a liver-targeting anti-HBV agent. In this study, we investigated the genotoxic and teratogenic effects of IFN-CSP...
July 11, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28696237/persistent-loss-of-hbv-markers-in-serum-without-cellular-immunity-by-combination-of-peg-ifn-plus-etv-therapy-in-humanized-mice
#4
Takuro Uchida, Michio Imamura, C Nelson Hayes, Nobuhiko Hiraga, Hiromi Kan, Masataka Tsuge, Hiromi Abe-Chayama, Yizhou Zhang, Grace Naswa Makokha, Hiroshi Aikata, Daiki Miki, Hidenori Ochi, Yuji Ishida, Chise Tateno, Kazuaki Chayama
Nucleot(s)ide analogues and peg-interferon (PEG-IFN) treatment are the only approved therapies for chronic hepatitis B virus (HBV) infection. However, complete eradication of the virus, as indicated by persistent loss of hepatitis B surface antigen (HBsAg), is rare among treated patients. This is due to long-term persistence of the HBV genome in infected hepatocytes in the form of covalently closed circular DNA (cccDNA). In this study, we investigated whether administration of a large dose of a nucleoside analogue in combination with PEG-IFN can achieve long term loss of HBsAg in human hepatocyte chimeric mice...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28673589/hepatitis-b-vaccine-non-response-a-predictor-of-latent-autoimmunity
#5
M D Raffaella Mormile
Unresponsiveness to Hepatitis B virus (HBV) vaccine has been associated with interleukins involved with Th1 functioning including Interleukin-8 (IL-18) and Interferon-γ (IFN-γ). IL-18 and IFN-γ have also been implicated in the onset of different types of immune-mediate inflammatory conditions such as Type 1 Diabetes (T1D), Celiac disease (CD), rheumatoid arthritis (RA), obesity and systemic lupus erythematosus (SLE). Taking into account that HBV vaccination is provided in the 1st year of life worldwide, I propose that all babies should be tested for anti-HBs response after completion of the vaccine series...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28665004/hepatitis-b-virus-evades-innate-immunity-of-hepatocytes-but-activates-cytokine-production-by-macrophages
#6
Xiaoming Cheng, Yuchen Xia, Elisavet Serti, Peter Daniel Block, Michelle Chung, Kazuaki Chayama, Barbara Rehermann, T Jake Liang
Hepatitis B virus (HBV) infects hepatocytes specifically and causes immune mediated liver damage. How HBV interacts with the innate immunity at the early phase of infection, either with the hepatocytes or other cells in the liver remains controversial. To address this question, we utilized various cell culture models and humanized Alb-uPA/SCID mice. All these models were unable to mount an interferon (IFN) response despite robust HBV replication. To elucidate the mechanisms involved in the lack of IFN response, we examined whether HBV actively inhibits innate immune functions of hepatocytes...
June 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28654775/hepatitis-b-virus-reactivation-among-hepatitis-c-patients-treated-with-direct-acting-antiviral-therapies-in-routine-clinical-practice
#7
Elisabetta Loggi, Stefano Gitto, Silvia Galli, Mario Minichiello, Fabio Conti, Elena Grandini, Alessandra Scuteri, Giovanni Vitale, Roberto Di Donato, Carmela Cursaro, Giuliano Furlini, Pietro Andreone
BACKGROUND: Hepatitis B (HBV) reactivation in chronic hepatitis C (CHC) patients treated with IFN-free direct acting antiviral (DAA) therapies has recently emerged as a potential risk. Given the potential burden of this issue, further data are needed to establish its actual clinical impact. OBJECTIVES: The aim of the present study was to analyze the occurrence of HBV reactivation in a cohort of CHC patient treated with DAAs in routine clinical practice. STUDY DESIGN: Consecutive CHC patients with different genotypes, treated with DAA between January 2015 and January 2016 were included in the study...
August 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
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
#8
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/28632923/comparing-the-risk-of-hepatitis-b-virus-reactivation-between-direct-acting-antiviral-therapies-and-interferon-based-therapies-for-hepatitis-c
#9
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/28627791/no-evidence-of-hepatitis-b-virus-reactivation-in-patients-with-resolved-infection-treated-with-direct-acting-antivirals-for-hepatitis-c-in-a-large-real-world-cohort
#10
V T Mücke, M M Mücke, K-H Peiffer, N Weiler, T M Welzel, C Sarrazin, S Zeuzem, A Berger, J Vermehren
BACKGROUND: Hepatitis B virus (HBV) reactivation has been observed following interferon (IFN)-based treatment in HBV/hepatitis C virus (HCV) co-infected patients. Recent reports suggest that reactivation may also occur in both hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative patients during HCV treatment with direct-acting antivirals (DAAs). AIM: To investigate the rate of patients with HBV reactivation during IFN-based and IFN-free HCV treatment in a large real-world cohort...
June 19, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28624460/identification-of-kx2-391-as-an-inhibitor-of-hbv-transcription-by-a-recombinant-hbv-based-screening-assay
#11
Keisuke Harada, Hironori Nishitsuji, Saneyuki Ujino, Kunitada Shimotohno
Antiviral therapies for chronic hepatitis B virus (HBV) infection that are currently applicable for clinical use are limited to nucleos(t)ide analogs targeting HBV polymerase activity and pegylated interferon alpha (PEG-IFN). Towards establishing an effective therapy for HBV related diseases, it is important to develop a new anti-HBV agent that suppresses and eradicates HBV. This study used recombinant HBV encoding NanoLuc to screen anti-HBV compounds from 1827 US Food and Drug Administration approved compounds and identified several compounds that suppressed HBV infection...
August 2017: Antiviral Research
https://www.readbyqxmd.com/read/28623307/both-interferon-alpha-and-lambda-can-reduce-all-intrahepatic-hdv-infection-markers-in-hbv-hdv-infected-humanized-mice
#12
Katja Giersch, Maria Homs, Tassilo Volz, Martina Helbig, Lena Allweiss, Ansgar W Lohse, Jörg Petersen, Maria Buti, Teresa Pollicino, Camille Sureau, Maura Dandri, Marc Lütgehetmann
Co-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effect of pegylated interferon alpha (peg-IFNα) and lambda (peg-IFNλ), compared to the HBV-polymerase inhibitor entecavir (ETV) on all HDV infection markers using human liver chimeric mice and novel HDV strand-specific qRT-PCR and RNA in situ hybridization assays, which enable intrahepatic detection of HDV RNA species...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611778/peg-interferon-lambda-treatment-induces-robust-innate-and-adaptive-immunity-in-chronic-hepatitis-b-patients
#13
Sandra Phillips, Sameer Mistry, Antonio Riva, Helen Cooksley, Tanya Hadzhiolova-Lebeau, Slava Plavova, Krum Katzarov, Marieta Simonova, Stephan Zeuzem, Clive Woffendin, Pei-Jer Chen, Cheng-Yuan Peng, Ting-Tsung Chang, Stefan Lueth, Robert De Knegt, Moon-Seok Choi, Heiner Wedemeyer, Michael Dao, Chang-Wook Kim, Heng-Chen Chu, Megan Wind-Rotolo, Roger Williams, Elizabeth Cooney, Shilpa Chokshi
IFN-lambda (IFNλ) is a member of the type III IFN family and is reported to possess anti-pathogen, anti-cancer, and immunomodulatory properties; however, there are limited data regarding its impact on host immune responses in vivo. We performed longitudinal and comprehensive immunosurveillance to assess the ability of pegylated (peg)-IFNλ to augment antiviral host immunity as part of a clinical trial assessing the efficacy of peg-IFNλ in chronic hepatitis B (CHB) patients. These patients were pretreated with directly acting antiviral therapy (entecavir) for 12 weeks with subsequent addition of peg-IFNλ for up to 32 weeks...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611343/hbsag-clearance-in-chronic-hepatitis-b-patients-with-add-on-pegylated-interferon-alfa-2a-to-ongoing-tenofovir-treatment-a-randomized-controlled-study
#14
Hamad Al Ashgar, Musthafa C Peedikayil, Mohammed Al Quaiz, Fahad Al Sohaibani, Abdulrahman Al Fadda, Mohammed Q Khan, Einar Thoralsson, Sahar Al Thawadi, Ahmed Al Jedai, Khalid Al Kahtani
BACKGROUND/AIMS: The ideal end point of treatment for chronic hepatitis B virus (HBV) infection is sustained off-therapy hepatitis B surface antigen (HBsAg) loss with or even without seroconversion to anti-HBs. We investigated the role of adding PEGylated interferon (PEG IFN) to ongoing tenofovir treatment in chronic HBV patients for achieving HBsAg clearance. PATIENTS AND METHODS: In this randomized controlled trial, chronic HBV patients who have been receiving tenofovir for >6 months with HBV viral load <2000 IU/ml were randomized into two groups...
May 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/28606013/decrease-of-cd69-levels-on-tcr-v%C3%AE-7-2-cd4-innate-like-lymphocytes-is-associated-with-impaired-cytotoxic-functions-in-chronic-hepatitis-b-virus-infected-patients
#15
Yean K Yong, Hong Y Tan, Alireza Saeidi, Mohamed Rosmawati, Nadia Atiya, Abdul W Ansari, Jayakumar Rajarajeswaran, Jamuna Vadivelu, Vijayakumar Velu, Marie Larsson, Esaki M Shankar
Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2(+)CD4(+)T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA(+) and nine were HBV DNA(-)...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28603234/what-to-start-with-in-first-line-treatment-of-chronic-hepatitis-b-patients-an-italian-multicentre-observational-cohort-hbv-rer-study-group
#16
Gianluca Cuomo, Vanni Borghi, Tiziana Giuberti, Pietro Andreone, Marco Massari, Erica Villa, Antonello Pietrangelo, Gabriella Verucchi, Fabio Levantesi, Carlo Ferrari
Treatment options for chronic hepatitis B (CHB) are pegylated interferon (Peg-IFN) in minimal-mild liver fibrosis and nucleot(s)ide analogues (NUC) in more advanced disease. Since little is known about their use in daily clinical practice, we conducted a multicentre prospective study to investigate treatment regimens applied to naïve CHB patients in real life. HBV-RER is an observational multicentre Italian network that collect clinic and virologic data of patients with CHB. Among the 2527 CHB patients seen during the study period (2009 - 2012), 502 patients started a first line antiviral treatment...
June 1, 2017: Le Infezioni in Medicina
https://www.readbyqxmd.com/read/28562554/effectiveness-of-entecavir-or-telbivudine-therapy-in-patients-with-chronic-hepatitis-b-virus-infection-pre-treated-with-interferon-compared-with-de-novo-therapy-with-entecavir-and-telbivudine
#17
COMPARATIVE STUDY
Shaohang Cai, Jiawei Cao, Tao Yu, Muye Xia, Jie Peng
Little is known about the optimal treatment following the initial failure of interferon therapy and the potential different efficacy with de novo therapy with entecavir (ETV) or telbivudine (LDT) and following the interferon therapy failure.ETV or LDT therapy following the interferon therapy failure was compared with that of de novo therapy with ETV or LDT in patients with chronic hepatitis B virus (HBV) infection. Treatment parameters included virological response, hepatitis B e antigen (HBeAg) seroconversion, and alanine aminotransferase (ALT) normalization...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28551415/interferon-%C3%AE-response-is-impaired-by-hepatitis-b-virus-infection-in-tupaia-belangeri
#18
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Haiying Chi, Takahiro Sanada, Naoki Yamamoto, Bouchra Kitab, Takumi Haraguchi, Rika Matsuyama, Chimène Nze Nkogue, Hitoshi Hatai, Noriaki Miyoshi, Shuko Murakami, Yasuhito Tanaka, Jun-Ichiro Takano, Yumiko Shiogama, Yasuhiro Yasutomi, Michinori Kohara, Kyoko Tsukiyama-Kohara
To date, the chimpanzee has been used as the natural infection model for hepatitis B virus (HBV). However, as this model is very costly and difficult to use because of ethical and animal welfare issues, we aimed to establish the tupaia (Tupaia belangeri) as a new model for HBV infection and characterized its intrahepatic innate immune response upon HBV infection. First, we compared the propagation of HBV genotypes A2 and C in vivo in tupaia hepatocytes. At 8-10days post infection (dpi), the level of HBV-A2 propagation in the tupaia liver was found to be higher than that of HBV-C...
May 25, 2017: Virus Research
https://www.readbyqxmd.com/read/28540167/t-cell-associated-immunoregulation-and-antiviral-effect-of-oxymatrine-in-hydrodynamic-injection-hbv-mouse-model
#19
Xiuxiu Sang, Ruilin Wang, Yanzhong Han, Cong'en Zhang, Honghui Shen, Zhirui Yang, Yin Xiong, Huimin Liu, Shijing Liu, Ruisheng Li, Ruichuang Yang, Jiabo Wang, Xuejun Wang, Zhaofang Bai, Xiaohe Xiao
Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV) in vitro, limited research has been done with this drug in vivo. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg)...
May 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28527664/a-new-hdv-mouse-model-identifies-mitochondrial-antiviral-signaling-protein-mavs-as-a-key-player-in-ifn-%C3%AE-induction
#20
Lester Suárez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Frias, Rafael Aldabe, Gloria González-Aseguinolaza
BACKGROUND & AIMS: Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the limited availability of small animal models. Here a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented. METHODS: HDV and hepatitis B virus (HBV) replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV; AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection...
May 18, 2017: Journal of Hepatology
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