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HBV IFN

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https://www.readbyqxmd.com/read/28879707/analysis-of-hepatitis-c-virus-ns5a-region-in-patients-with-cirrhosis-using-an-ultra-deep-pyrosequencing-method
#1
Fahriye Keskin, Sevgi Ciftci, Filiz Akyuz, Neslihan Abaci, Aris Cakiris, Umit Akyuz, Kadir Demir, Fatih Besisik, Duran Ustek, Sabahattin Kaymakoglu
BACKGROUND: HCV (Hepatitis C Virus) is genetically more diverse than HBV and HIV (Human Immunodeficiency Virus) and exists as quasispecies within infected individuals. This is due to the lack of efficient proofreading of the viral RNA-dependent RNA polymerase. Consequently, quasispecies emerge depending on the mutation rate of the viral polymerase, which may display a high level of genetic variability in a population. In infected individuals, HCV replicates and circulates as quasispecies composed of a complex mixture of different but closely related genomes that undergoes continuous change due to competitive selection and cooperation between arising mutants...
September 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28872283/impact-of-selected-predictive-factors-on-sustained-virologic-response-in-hcv-genotype-4-infected-patients-treated-with-pegylated-interferon-alpha-and-ribavirin
#2
Dorota Kozielewicz, Anna Grabińska, Grzegorz Madej, Magdalena Wietlicka-Piszcz
BACKGROUND: Dual therapy (PegIFN and ribavirin) (DT) had been the standard of care in patients infected with HCV genotype 4 (HCV-4) until 2014. Thereafter, new treatment options were available including IFNbased and other IFN-free regimens. Objectives: The aim was to assess the efficacy (SVR24) of DT and a selection of predictive factors of SVR in HCV-4 infected patients. METHODS: 112 patients (62 men) of median age 23 years were treated with DT for 48/72 weeks (107/5)...
2017: Przegla̧d Epidemiologiczny
https://www.readbyqxmd.com/read/28855902/different-adjuvants-induce-common-innate-pathways-that-are-associated-with-enhanced-adaptive-responses-against-a-model-antigen-in-humans
#3
Wivine Burny, Andrea Callegaro, Viviane Bechtold, Frédéric Clement, Sophie Delhaye, Laurence Fissette, Michel Janssens, Geert Leroux-Roels, Arnaud Marchant, Robert A van den Berg, Nathalie Garçon, Robbert van der Most, Arnaud M Didierlaurent
To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18-45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4(+) T-cell and antibody responses at day 44...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28854883/addition-of-nucleoside-analogues-to-peg-ifn%C3%AE-2a-enhances-virological-response-in-chronic-hepatitis-b-patients-without-early-response-to-peg-ifn%C3%AE-2a-a-randomized-controlled-trial
#4
Yan Xu, Xu Wang, Zhenhua Liu, Changyu Zhou, Wenqian Qi, Jian Jiao, Fan Yu, Honghua Guo, Ping Zhao, Jiangbin Wang
BACKGROUND: Current treatments for chronic hepatitis B (CHB) include pegylated interferon alpha (PEG-IFN-α) which is an immune modulator, and nucleos(t)ide analogs (NAs) which directly inhibit HBV DNA polymerase. With the limited efficacy of PEG-IFN-α and prolonged treatment periods associated with NAs, there is an urgent need for novel therapeutic strategies, especially for patients with a poor early response to anti-viral therapy. METHODS: In this study, 178 patients with chronic hepatitis B (n = 131) and compensated (n = 47) HBV-induced cirrhosis were enrolled, 120 patients with HBeAg (+)...
August 30, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28838891/interaction-effects-among-ifn-%C3%AE-874-il-2-330-il-10-1082-il-10-592-and-il-4-589-polymorphisms-on-the-clinical-progression-of-subjects-infected-with-hepatitis-b-virus-and-or-hepatitis-c-virus-a-retrospective-nested-case-control-study
#5
Qiu-Ju Gao, Jia-Xin Xie, Li-Min Wang, Qiang Zhou, Shi-Yong Zhang
BACKGROUND: The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood. OBJECTIVES: To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes...
August 23, 2017: BMJ Open
https://www.readbyqxmd.com/read/28827021/toward-cure-chronic-hepatitis-b-infection-and-hepatocellular-carcinoma-prevention-lessons-learned-from-nucleos-t-ide-analogues-therapy
#6
REVIEW
Soheil Tavakolpour, Hajar Sadat Mirsafaei, Somayeh Elkaei Behjati, Mojtaba Ghasemiadl, Meisam Akhlaghdoust, Shahnaz Sali
Nucleos(t)ide analogues (NAs) could successfully suppress hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB). However, due to probable development of drug resistance or low/delayed response, these treatments may not be satisfactory. In addition to the HBV DNA polymerase inhibiting activity, these drugs could lead to changes in cytokines profiles. It is important to monitor these changes so that they could be used as target of treatment. Evaluating the previously reported immune responses due to NAs treatments, it was concluded that interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), and IL-12 increase after the treatment...
August 5, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28819561/factors-associated-with-the-decrease-in-hepatitis-b-surface-antigen-titers-following-interferon-therapy-in-patients-with-chronic-hepatitis-b-is-interferon-and-adefovir-combination-therapy-effective
#7
Yoshihiko Yano, Yasushi Seo, Hiroki Hayashi, Yuri Hatazawa, Hirotaka Hirano, Akihiro Minami, Yuki Kawano, Masaya Saito, Toshiaki Ninomiya, Masahiko Sugano, Hajime Yamada, Naoto Kitajima, Seitetsu Yoon, Yoshitake Hayashi
The purpose of antiviral therapy in chronic hepatitis B (CHB) is generally to achieve a decrease and ultimately disappearance of HBs antigen (HBsAg). Interferon (IFN) therapy of CHB appears to be less effective in Asian countries than in European countries, and the advantage of IFN and nucleotide(s) analog (NA) combination therapy has yet to be fully investigated. The present study focused on the factors associated with a decrease in HBs antigen following IFN monotherapy or IFN + NA combination therapy. A total of 35 patients with CHB who received IFN-based therapy (mean ± standard deviation age 36...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28801732/evaluation-of-the-relationship-between-alopecia-areata-and-viral-antigen-exposure
#8
Christopher T Richardson, Matthew S Hayden, Elaine S Gilmore, Brian Poligone
BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by non-scarring alopecia with T-cell infiltration at the affected hair follicle. OBJECTIVE: Our aim was to study the potential link between hepatitis B virus (HBV) antigen exposure and AA. METHODS: Two pediatric patients with AA following hepatitis B vaccination were identified in a general dermatology clinic. A bioinformatics analysis and an electronic medical record (EMR) database query were performed at the University of Rochester Medical Center to identify patients with AA, coexisting viral infections, vaccinations, or interferon (IFN) therapy in order to determine if the presence of AA and these conditions was higher than in AA patients without these associated conditions or therapy...
August 11, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28774415/new-treatments-to-reach-functional-cure-virological-approaches
#9
REVIEW
David Durantel
Current therapies of chronic hepatitis B (CHB) remain limited to pegylated-interferon-alpha (pegIFN-α) or any of the five approved nucleos(t)ide analogues (NA). If viral suppression can be achieved in the majority of patients with the high-barrier-to-resistance new-generation of NA, i.e. entecavir and tenofovir, HBsAg loss is achieved by PEG-IFN-α and/or NA in only 10% of patients, after a 5-year follow-up. Attempts to improve the response by administering two different NA or a combination of NA and PEG-IFN-α have not provided a dramatic increase in the rate of "functional cure"...
June 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28774414/hepatitis-delta-infection-current-and-new-treatment-options
#10
REVIEW
Menashe Elazar, Christopher Koh, Jeffrey S Glenn
In humans, hepatitis D virus (HDV) infection only occurs in the presence of a concomitant hepatitis B virus (HBV) infection, and induces the most severe form of human viral hepatitis. Even though HDV is spread worldwide and is endemic in some regions, screening and treatment has been often neglected in part due to the lack of an effective therapy. Moreover, HDV prevalence rates are increasing in many countries driven by immigration from areas of high endemicity. Currently, no FDA-approved anti-HDV therapy is available, although interferon (IFN) alpha therapy has demonstrated benefit in a minority of patients...
June 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28765875/quantum-dot-pmhc-multimers-vs-phycoerythrin-pmhc-tetramers-for-identification-of-hla-a-0201-restricted-phbv-core-antigen18-27-specific-t-cells
#11
Jianmeng Zhu, Yong Huang, Jing Su, Jian He, Yating Yu, Yongxiang Zhao, Xiaoling Lu
Detection of human leukocyte antigens-A2-restricted p-hepatitis B virus (HBV) core antigen‑specific cytotoxic T lymphocytes (CTLs) is important in the study of HBV immunopathogenesis and vaccine design. Currently, major histocompatibility complex (MHC) class I/peptide‑(p) MHCI tetramers are considered the optimal tools to detect antigen‑specific CTLs. However, the MHC‑tetramer technique also has certain drawbacks and is under continuous development. The quantum dot (QD) bioconjugates nanotechnology with its unique inorganic‑biological properties has been developing fast...
August 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28757610/the-il-1r-tlr-signaling-pathway-is-essential-for-efficient-cd8-t-cell-responses-against-hepatitis-b-virus-in-the-hydrodynamic-injection-mouse-model
#12
Zhiyong Ma, Jia Liu, Weimin Wu, Ejuan Zhang, Xiaoyong Zhang, Qian Li, Gennadiy Zelinskyy, Jan Buer, Ulf Dittmer, Carsten J Kirschning, Mengji Lu
The outcome of hepatitis B viral (HBV) infection is determined by the complex interactions between replicating HBV and the immune system. While the role of the adaptive immune system in the resolution of HBV infection has been studied extensively, the contribution of innate immune mechanisms remains to be defined. Here we examined the role of the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signaling pathway in adaptive immune responses and viral clearance by exploring the HBV mouse model. Hydrodynamic injection with a replication-competent HBV genome was performed in wild-type mice (WT) and a panel of mouse strains lacking specific innate immunity component expression...
July 31, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28754258/viral-minority-variants-in-the-core-promoter-and-precore-region-identified-by-deep-sequencing-are-associated-with-response-to-peginterferon-and-adefovir-in-hbeag-negative-chronic-hepatitis-b-patients
#13
Louis Jansen, Matthijs R A Welkers, Karel A van Dort, R Bart Takkenberg, Uri Lopatin, Hans L Zaaijer, Menno D de Jong, Hendrik W Reesink, Neeltje A Kootstra
BACKGROUND AND AIM: Precore (PC) and basal core promoter (BCP) mutations are associated with responses to interferon-based treatment in HBeAg-positive chronic hepatitis B (CHB) patients. Here, we identify viral minority variants in these regions and assess association with response to peginterferon-alfa (Peg-IFN) and adefovir combination therapy. PATIENTS AND METHODS: Ultra-deep pyrosequencing analysis of the BCP and PC region was performed for 89 CHB patients (42 HBeAg-positive; 47 HBeAg-negative), at baseline and during treatment...
July 25, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28753426/methyltransferase-setd2-mediated-methylation-of-stat1-is-critical-for-interferon-antiviral-activity
#14
Kun Chen, Juan Liu, Shuxun Liu, Meng Xia, Xiaomin Zhang, Dan Han, Yingming Jiang, Chunmei Wang, Xuetao Cao
Interferon-α (IFNα) signaling is essential for antiviral response via induction of IFN-stimulated genes (ISGs). Through a non-biased high-throughput RNAi screening of 711 known epigenetic modifiers in cellular models of IFNα-mediated inhibition of HBV replication, we identified methyltransferase SETD2 as a critical amplifier of IFNα-mediated antiviral immunity. Conditional knockout mice with hepatocyte-specific deletion of Setd2 exhibit enhanced HBV infection. Mechanistically, SETD2 directly mediates STAT1 methylation on lysine 525 via its methyltransferase activity, which reinforces IFN-activated STAT1 phosphorylation and antiviral cellular response...
July 27, 2017: Cell
https://www.readbyqxmd.com/read/28750917/predictive-role-of-serum-hbsag-and-hbcrag-kinetics-in-patients-with-hbeag-negative-chronic-hepatitis-b-receiving-pegylated-interferon-based-therapy
#15
Natthaya Chuaypen, Nawarat Posuwan, Salyavit Chittmittraprap, Nattiya Hirankarn, Sombat Treeprasertsuk, Yasuhito Tanaka, Noboru Shinkai, Yong Poovorawan, Pisit Tangkijvanich
OBJECTIVES: To investigate the role of serum hepatitis B core-related antigen (HBcrAg) kinetics in predicting long-term outcome of pegylated interferon (PEG-IFN)-based therapy in patients with HBeAg-negative chronic hepatitis B (CHB). METHODS: 121 Thai patients with HBeAg-negative CHB recruited from a previous randomized trial of 48-week PEG-IFN alone or combined with entecavir were enrolled. HBsAg and HBcrAg levels were serially examined. Paired biopsies at baseline and post-treatment were assessed for intrahepatic cccDNA...
July 24, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28748854/ratios-of-t-helper-2-cells-to-t-helper-1-cells-and-cytokine-levels-in-patients-with-hepatitis-b
#16
Ming-Hui Li, Dan Zhang, Lu Zhang, Xiao-Jing Qu, Yao Lu, Ge Shen, Shu-Ling Wu, Min Chang, Ru-Yu Liu, Lei-Ping Hu, Hong-Xiao Hao, Wen-Hao Hua, Shu-Jing Song, Gang Wan, Shun-Ai Liu, Yao Xie
BACKGROUND: Hepatitis B is an immune response-mediated disease. The aim of this study was to explore the differences of ratios of T-helper (Th) 2 cells to Th1 cells and cytokine levels in acute hepatitis B (AHB) patients and chronic hepatitis B virus (HBV)-infected patients in immune-tolerance and immune-active phases. METHODS: Thirty chronic HBV-infected patients in the immune-tolerant phase (IT group) and 50 chronic hepatitis B patients in the immune-active (clearance) phase (IC group), 32 AHB patients (AHB group), and 13 healthy individuals (HI group) were enrolled in the study...
August 5, 2017: Chinese Medical Journal
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
#17
Enrico Galmozzi, Floriana Facchetti, Glenda Grossi, Alessandro Loglio, Mauro Viganò, Giovanna Lunghi, Massimo Colombo, Pietro Lampertico
BACKGROUND & 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
#18
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
#19
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-hepatitis-b-virus-markers-in-serum-without-cellular-immunity-by-combination-of-peginterferon-and-entecavir-therapy-in-humanized-mice
#20
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 peginterferon (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...
September 2017: Antimicrobial Agents and Chemotherapy
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