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https://www.readbyqxmd.com/read/29777955/perspectives-and-limitations-for-nucleo-t-side-analogs-in-future-hbv-therapies
#1
REVIEW
Massimo Levrero, Miroslava Subic, Francois Villeret, Fabien Zoulim
The latest generation of nucleo(t)side analogs (NAs) provide robust virus suppression with high barrier to resistance. Long term NAs treatment is associated with a partial restoration in HBV-specific T-cell functions, regression of fibrosis, no disease progression and a reduction of HCC risk but rarely lead to cure and life-long treatments is often required. New insights into the hepatitis B viral life cycle and the host immune response have expanded the potential targets for drug therapies with interesting antiviral candidates and novel immunotherapeutic approaches in early stage development...
May 16, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29766002/influence-of-vitamin-d-receptor-gene-polymorphisms-on-response-to-pegylated-interferon-in-chronic-hepatitis-b-egyptian-patients
#2
Gomaa Mostafa-Hedeab, Dina Sabry, Ghada Mostafa Abdelaziz, Manal Ewaiss, Nagla Adli, Wael Fathy
Background: We explored the effect of vitamin D receptor gene ( VDR ) polymorphisms in response to PEG-IFN treatment in Egyptian chronic hepatitis B (CHB) patients. Methods: Two hundred hepatitis B virus (HBV) patients (42.3±10.7 years) on PEG-IFN α-2a (180 µg /kg for 48 weeks) and one hundred control subjects (37.3 ±12 years) were enrolled in the study. Vitamin D levels and hepatitis B surface antigen (HBsAg) expression were assessed by ELISA. VDR polymorphisms FokI T>C (rs 10735810), BsmI A>G (rs 1544410), ApaI (rs7975253), and TaqI C>T (rs 731236), were genotyped using real-time PCR...
April 2018: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29753730/expression-and-significance-of-peripheral-myeloid-derived-suppressor-cells-in-chronic-hepatitis-b-patients
#3
Y Lv, M Cui, Z Lv, J Lu, X Zhang, Z Zhao, Y Wang, L Gao, N M Tsuji, H Yan
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) exert their suppressive effects on multiple immune response and contribute to the development of many diseases. However, limited data is available on the involvement of MDSCs in human chronic HBV infection. OBJECTIVE: To investigate whether the progression of chronic HBV infection was associated with imbalance of MDSCs. METHODS: The percentages of MDSCs, regulatory T (Treg), Th1 and Tc1 cells in the peripheral blood from chronic hepatitis B (CHB) patients and healthy controls (HC) were determined by flow cytometry...
May 9, 2018: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/29751499/survival-and-prognostic-factors-in-mixed-cryoglobulinemia-data-from-246-cases
#4
Cesare Mazzaro, Luigino Dal Maso, Endri Mauro, Valter Gattei, Michela Ghersetti, Pietro Bulian, Giulia Moratelli, Gabriele Grassi, Francesca Zorat, Gabriele Pozzato
INTRODUCTION: The clinical and therapeutic management of mixed cryoglobulinemia (MC) remains a subject of controversy. In addition, most studies have not recorded the long-term follow-up and the outcome of these cases. MATERIAL AND METHODS: We enrolled 246 patients affected by MC who were consecutively admitted to our Department from January 1993 to February 2013. Clinical and biological data had been recorded until June 2014. RESULTS: The median age (at diagnosis) was 60 years (range 26⁻83)...
May 3, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29739113/combination-of-micrornas-and-cytokines-a-method-for-better-evaluation-of-acute-on-chronic-liver-failure
#5
Chunwen Pu, Chunmeng Jiang, Lang Lang, Huang Hui, Zhidong Wang, Dapeng Ma, Yong Zhang
BACKGROUND: The aim was to establish expression profiles of microRNAs (miRNAs) in Peripheral Blood Mononuclear Cells (PBMC) and of plasma cytokines from the patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) and high-risk of acute-on-chronic liver failure (ACLF) patients as well as healthy people and to examine the relationships between these profiles and clinical features. METHODS: Herein, we collected PBMCs and plasma from peripheral blood of HBV-ACLF and ACLF patients as well as healthy people...
March 1, 2018: Clinical Laboratory
https://www.readbyqxmd.com/read/29720863/hepatitis-b-and-c-coinfection-in-a-real-life-setting-viral-interactions-and-treatment-issues
#6
Nikolaos Papadopoulos, Maria Papavdi, Anna Pavlidou, Dimitris Konstantinou, Hariklia Kranidioti, George Kontos, John Koskinas, George V Papatheodoridis, Spilios Manolakopoulos, Melanie Deutsch
Background: Only limited data concerning hepatitis B (HBV) and C viruses (HCV) coinfection are available. Direct-acting antivirals (DAAs) may be more effective for HCV clearance than interferon (IFN)-based regimens with a risk of HBV reactivation. Methods: We retrospectively enrolled 40 HBV/HCV-coinfected patients to evaluate their clinical profile and treatment outcomes. Results: Chronic dual infection was present in 25/40 (62.5%) patients, acute HCV superinfection in 5/40 (12...
May 2018: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/29643189/elevated-hepatic-cd1d-levels-coincide-with-invariant-nkt-cell-defects-in-chronic-hepatitis-b-virus-infection
#7
Xiaosheng Tan, Yajie Ding, Peng Zhu, Rui Dou, Zhihui Liang, Daofeng Yang, Zhiyong Huang, Wei Wang, Xiongwen Wu, Xiufang Weng
Activation of invariant NKT (iNKT) cells manifests antiviral immune responses in vivo. However, clinical trials have failed to show consistent hepatitis B virus (HBV) DNA reduction postadministration of iNKT cell-specific agonist α-galactosylceramide (α-GalCer). In this study, we aimed to investigate HBV infection-related iNKT cell defects and explore iNKT cell-based therapeutic potential for chronic hepatitis B (CHB). Liver specimens from 30 HBV-infected hepatocellular carcinoma patients were collected for CD1d/hepatitis B surface Ag (HBsAg) staining and/or intrahepatic iNKT cell assay...
April 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29627530/an-enriched-environment-restores-hepatitis-b-vaccination-mediated-impairments-in-synaptic-function-through-ifn-%C3%AE-arginase1-signaling
#8
Fangfang Qi, Zejie Zuo, Saisai Hu, Yucen Xia, Dan Song, Jiechen Kong, Yang Yang, Yingying Wu, Xiao Wang, Junhua Yang, Dandan Hu, Qunfang Yuan, Juntao Zou, Kaihua Guo, Jie Xu, Zhibin Yao
Activation of the neonatal immune system may contribute to deficits in neuronal plasticity. We have reported that neonatal vaccination with a hepatitis B vaccine (HBV) transiently impairs mood status and spatial memory involving a systemic T helper (Th) 2 bias and M1 microglial activation. Here, an EE induced microglial anti-inflammatory M2 polarization, as evidenced by selectively enhanced expression of the Arginase1 gene (Arg-1) in the hippocampus. Interestingly, knock-down of the Arg-1 gene prevented the effects of EE on restoring the dendritic spine density...
April 5, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29627062/immune-active-cells-with-4-1bb-signal-enhancement-inhibit-hepatitis-b-virus-replication-in-noncytolytic-manner
#9
Lili Wang, Yongxiang Yi, Wenxiu Jiang, Dandan Yin, Jing Fan, Wei Ye, Wei Zhao
Immune active cells (IACs) have been shown to be an alternative immunotherapy for CHB patients. However, there is a practical problem of different expansion rate and function of HBV inhibition as individual variability exists. Our previous studies have confirmed that the proliferation and cytolysis of IACs were significantly up-regulated by engineered cells for costimulatory enhancement (ECCE) delivering a 4-1BBζ activating signal. In this study, we aimed to investigate the contribution of ECCE to IACs from CHB patients...
April 2, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29602251/tim-3-blockade-promotes-inkt-cell-function-to-inhibit-hbv-replication
#10
Yong Xu, Zehua Wang, Xianhong Du, Yuan Liu, Xiaojia Song, Tixiao Wang, Siyu Tan, Xiaohong Liang, Lifen Gao, Chunhong Ma
Increased expression of T cell immunoglobulin and mucin domain-3 (Tim-3) on invariant natural killer T (iNKT) cells is reported in chronic hepatitis B virus (HBV) infection. However, whether Tim-3 regulates iNKT cells in chronic HBV condition remains unclear. In this study, our results showed that the expression of Tim-3 was up-regulated on hepatic iNKT cells from HBV-transgenic (Tg) mice or iNKT cells stimulated with α-galactosylceramide (α-Galcer). Compared with Tim-3- iNKT cells, Tim-3+ iNKT cells expressed more IFN-γ, IL-4 and CD107a, indicating a strong relationship between Tim-3 and iNKT cell activation...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29576222/blocking-tim-3-or-and-pd-1-reverses-dysfunction-of-tumor-infiltrating-lymphocytes-in-hbv-related-hepatocellular-carcinoma
#11
Furong Liu, Gucheng Zeng, Shaotang Zhou, Xiaoshun He, Nianfeng Sun, Xiaofeng Zhu, Anbin Hu
BACKGROUND: The immunosuppression of tumor-infiltrating lymphocytes (TILs) is associated with rapid progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). T cell Ig- and mucin-domain-containing molecule-3 (Tim-3) and programmed cell death 1 (PD-1) are important inhibitory molecules expressed on the surface of T cells, but their roles in the function of TILs in HBV-HCC are poorly understood. We aimed to study the roles of these two markers in HBV-HCC. METHODS: Ninety patients with pathologically confirmed HBV-associated HCC were enrolled in our study...
March 22, 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/29524530/hepatitis-d-virus-replication-is-sensed-by-mda5-and-induces-ifn-%C3%AE-%C3%AE-responses-in-hepatocytes
#12
Zhenfeng Zhang, Christina Filzmayer, Yi Ni, Holger Sültmann, Pascal Mutz, Marie-Sophie Hiet, Florian W R Vondran, Ralf Bartenschlager, Stephan Urban
BACKGROUND & AIMS: Hepatitis B virus (HBV) and D virus (HDV) co-infections cause the most severe form of viral hepatitis. HDV induces an innate immune response, but it is unknown how the host cell senses HDV and if this defense affects HDV replication. We aim to characterize interferon (IFN) activation by HDV, identify the responsible sensor and evaluate the effect of IFN on HDV replication. METHODS: HDV and HBV susceptible hepatoma cell lines and primary human hepatocytes (PHH) were used for infection studies...
March 8, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29523836/type-iii-interferon-induced-cbf%C3%AE-inhibits-hbv-replication-by-hijacking-hbx
#13
Fengchao Xu, Hongxiao Song, Qingfei Xiao, Na Li, Hong Zhang, Genhong Cheng, Guangyun Tan
Hepatitis B virus (HBV) and its associated chronic infection remain serious health threats worldwide. However, there is still no impactful approach for clinical treatment of hepatitis B patients. Therefore, developing a better understanding of the interactions between HBV and its host is particularly important. HBV infection has been reported to induce type-III but not type-I or type-II interferon (IFN). In this study, we identified CBFβ, an HIV enhancer, as an HBV restriction factor that is specifically induced by type-III IFN in the early stages of HBV infection...
March 9, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29510155/nasal-route-favors-the-induction-of-cd4-t-cell-responses-in-the-liver-of-hbv-carrier-mice-immunized-with-a-recombinant-hepatitis-b-surface-and-core-based-therapeutic-vaccine
#14
Maryline Bourgine, Sandrine Crabe, Yadira Lobaina, Gerardo Guillen, Julio Cesar Aguilar, Marie-Louise Michel
Immunization routes and number of doses remain largely unexplored in therapeutic vaccination. The aim of the present work is to evaluate their impact on immune responses in naïve and hepatitis B virus (HBV)-carrier mouse models following immunization with a non-adjuvanted recombinant vaccine comprising the hepatitis B surface (HBsAg) and core (HBcAg) antigens. Mice were immunized either by intranasal (i.n.), subcutaneous (s.c.) or simultaneous (i.n. + s.c.) routes. Humoral immunity was detected in all the animal models with the induction of a potent antibody (Ab) response against HBcAg, which was stronger than the anti-HBs response...
May 2018: Antiviral Research
https://www.readbyqxmd.com/read/29503077/the-prevalence-of-occult-hepatitis-b-in-chronic-hepatitis-c-patients-treated-with-interferon-based-antiviral-therapy
#15
Tayibe Bal, Yusuf Onlen
BACKGROUND AND STUDY AIMS: Occult hepatitis B infection (OBI) is known to be mostly prevalent in chronic hepatitis C (CHC) patients and OBI reactivation might be life-threatening in patients undergoing interferon (IFN)-free direct acting antiviral (DAA) therapy. As previous studies have revealed a relationship between OBI and non-response to IFN-based antiviral therapy, the aim of the current study was to determine if there was a higher prevalence of OBI in IFN non-responders than responders...
March 2018: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
https://www.readbyqxmd.com/read/29501568/circulating-regulatory-tfh-cells-are-enriched-in-patients-with-chronic-hepatitis-b-infection-and-induce-the-differentiation-of-regulatory-b-cells
#16
Rongxin Wang, Ruiling Xie, Zongchang Song
Chronic hepatitis B virus (HBV) infection is a complex disease with dysregulations in the immune system. Follicular helper T (Tfh) cells are professional B helper cells that are crucial to the development of antibody responses and are involved in a variety of diseases. In this study, we examined the circulating Tfh cells in patients with chronic HBV infection. We observed that CD3+ CD4+ CXCR5+ circulating Tfh cells contained a CD25+ Foxp3+ Treg-like subset that was significantly enriched in patients with chronic HBV infections...
April 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29493287/vitamin-d-serum-levels-and-receptor-genetic-polymorphisms-are-associated-with-hepatitis-b-virus-and-hiv-infections-and-ifn-%C3%AE-levels
#17
Wenfeng Gao, Rui Wang, Xiaojun Wang, Hao Wu, Yang Wang, Xiaofan Lu, Li Li, Jiasheng Zheng, Wei Li
AIM: Vitamin D is involved in antiviral/antitumor activities. Its associations to hepatitis B virus (HBV), HIV and hepatocellular carcinoma (HCC) are unclear. MATERIALS & METHODS: A retrospective study was conducted on 232 chronic hepatitis B (CHB) patients and 72 HIV-infected patients. The correlation between serum 25(OH)D3 and 25 vitamin D receptor single nucleotide polymorphisms to disease progression and interferons were evaluated. RESULTS: The 25(OH)D3 was associated with HBV infection and progression...
September 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/29488227/hbv-pre-core-mutant-in-genotype-d-infected-children-is-selected-during-hbeag-anti-hbe-seroconversion-and-leads-to-hbeag-negative-chronic-hepatitis-b-in-adulthood
#18
Piero Colombatto, Cristiana Barbera, Flavia Bortolotti, Anna M Maina, Francesco Moriconi, Daniela Cavallone, Pierluigi Calvo, Filippo Oliveri, Ferruccio Bonino, Maurizia R Brunetto
Selection of HBeAg defective HBV mutants (mt) during childhood might influence infection outcome in adults. Aim of this study was to correlate the dynamics of pre-core HBV mutant (pre-C mt) selection with virological/clinical outcomes in children followed-up until adulthood. Eighty subjects (50-M/30-F), 70 HBeAg-positive (87.5%), and 10 (12.5%) HBeAg-negative/anti-HBe-positive at the admission, mostly genotype D infected (91.2%), with median age of 6.5 (range: 0.2-17) years, were followed-up for 14.3 years (range: 1...
February 28, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29474139/levels-of-regulatory-b-cells-do-not-predict-serological-responses-to-hepatitis-b-vaccine
#19
Maria Bolther, Karen Lise Dahl Andersen, Martin Tolstrup, Kumar Visvanathan, Ian Woolley, Narelle Skinner, Rosemary Millen, Nadia Warner, Lars Østergaard, Søren Jensen-Fangel
This study investigated the immunomodulatory influence of IL10 producing B regulatory cells, Bregs (CD19+CD24hiCD38hi) to standard Twinrix® vaccination. We also investigated HBsAg specific T-cell mediated IFN-γ responses to Twinrix® which in theory could provide effective immunity despite low anti-HBs titer. A total of 309 hepatitis B negative health care students and workers completed a standard Twinrix® vaccination schedule (0, 1 and 6 months). Depending on the vaccination response the participants were divided in to non-, low- and high responders according to anti-HBs titer (<10, <100 and >1000 mIU/mL respectively) two months after completed vaccination schedule...
February 23, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29471567/targeting-hepatitis-d
#20
Mario Rizzetto
New therapeutic strategies to treat chronic hepatitis D are directed to deprive the hepatitis D virus (HDV) of functions necessary to complete its life cycle that are provided by the hepatitis B virus (HBV) and by the host. Current options are (1) the block by the synthetic peptide Myrcludex B of HBV surface antigen (HBsAg) entry into cells through the inhibition of the sodium taurocholate cotransporting receptor; (2) the inhibition with lonafarnib of the farnesylation of the large HD antigen, required for virion assembly; (3) the presumed reduction by the nucleic acid polymer REP 2139 of the release of the HBsAg and subviral HBV particles necessary for HD virion morphogenesis...
February 2018: Seminars in Liver Disease
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