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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 7, 2018: Journal of Hepatology
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
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...
March 3, 2018: Antiviral Research
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 1, 2018: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
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...
February 28, 2018: Experimental Cell Research
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
Piero Colombatto, Cristiana Barbera, Flavia Bortolotti, Anna M Maina, Francesco Moriconi, Daniela Cavallone, Pierluigi Calvo, Filippo Oliveri, Ferruccio Bonino, Maurizia R Brunetto
BACKGROUND: 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. METHODS: 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...
February 28, 2018: Journal of Medical Virology
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
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
Jianwei Zhou, Cui Kong, Bo Ban, Haixin Dong, Chengqiang Jin
INTRODUCTION: Chronic hepatitis B (CHB) is still a public health problem and its mechanism remains unclear. In this study, we detect the skewness of T cell receptor beta chain variable gene (TCR Vβ) in peripheral blood lymphocytes (PBL) and the liver infiltrating lymphocytes (LIL) of patients with CHB; and hope to provide information for further research on the pathogenic mechanism of CHB. MATERIAL AND METHODS: Fifteen patients with CHB, ten healthy volunteers and three patients with liver cysts were recruited as the subjects...
March 1, 2018: Annals of Hepatology
Yingying Wu, Yongbin Zeng, Wennan Wu, Jinpiao Lin, Qishui Ou
BACKGROUND: Host single nucleotide polymorphisms were associated with antiviral therapy in CHB patients. The CYP27B1 gene, encoding 25(OH)D3 -1α hydroxylase, might activate 25(OH)D3 to 1,25(OH)2 D3 in kidney resulted in influencing the efficacy of interferon (IFN). The aim of the study was to investigate the association between CYP27B1 polymorphisms and the response to IFN in HBeAg-positive patients. METHODS: Eighty-seven HBeAg-positive CHB patients infected with HBV genotype B or C were included in the study...
February 18, 2018: Journal of Clinical Laboratory Analysis
Shishu Zhu, Hongfei Zhang, Yi Dong, Limin Wang, Zhiqiang Xu, Weiwei Liu, Yu Gan, Hongmei Tang, Dawei Chen, Fuchuan Wang, Pan Zhao
BACKGROUND & AIM: Chronic infection with hepatitis B virus (HBV) in children possesses a serious health problem worldwide. It remains unresolved how children with immune-tolerant chronic hepatitis B should be treated, who were commonly characterized by HBeAg positivity, high viral load, normal or mildly elevated ALT and no or minimal inflammation in liver histology. This trial aims to study the benefits of antiviral therapy in children with these characters. METHODS: This is a pilot open-lable randomized controlled study...
February 13, 2018: Journal of Hepatology
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
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
Mauro Viganò, Glenda Grossi, Alessandro Loglio, Pietro Lampertico
The treatment of chronic hepatitis B (CHB) patients is based on monotherapy with pegylated-interferon (Peg-IFN) or with one of the three most potent nucleot(s)ide analogues (NUCs) with the best resistance profiles, i.e. entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). Long-term NUCs treatment can achieve virological suppression in almost all patients. However, this requires lifelong therapy, is costly and the rate of hepatitis B surface antigen (HBsAg) seroclearance is low...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Qian Zhang, Binbin Zhao, Xin Chen, Nan Song, Jing Wu, Guangchao Li, Pin Yu, Yunlin Han, Jiangning Liu, Chuan Qin
Human enterovirus 71 (EV71) is the second most common cause of hand, foot, and mouth disease (HFMD), which can occur as a severe epidemic especially among children under 5-years old. New and improved treatment strategies to control EV71 infection are therefore urgently required. The heterocyclic compound GS-9620, a potent and selective agonist of Toll-like receptor 7 (TLR7), has been reported to activate plasmacytoid dendritic cells (pDCs), and suppress HBV as well as HIV replication. In this study, we indicated that GS-9620 also could inhibit EV71 replication in the mouse model of EV71 infection...
February 6, 2018: Antiviral Research
Sha She, Min Yang, Huaidong Hu, Peng Hu, Yixuan Yang, Hong Ren
BACKGROUND/AIMS: Hepatitis B virus (HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma. Therefore, we aimed to obtain further information on HBV pathogenesis, and to search for novel putative molecules for anti-HBV therapy. METHODS: We utilized Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) to identify the secretory proteins that are differentially expressed in the HBV DNA-transfected HepG2.2.15 cell line and its parental HepG2 cell line...
February 1, 2018: Cellular Physiology and Biochemistry
Pascal Mutz, Philippe Metz, Florian A Lempp, Silke Bender, Bingqian Qu, Katrin Schöneweis, Stefan Seitz, Thomas Tu, Agnese Restuccia, Jamie Frankish, Christopher Dächert, Benjamin Schusser, Ronald Koschny, Georgios Polychronidis, Peter Schemmer, Katrin Hoffmann, Thomas F Baumert, Marco Binder, Stephan Urban, Ralf Bartenschlager
BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is sensitive to interferon (IFN)-based therapy whereas HBV infection is not. It is unclear whether HBV escapes detection by the IFN-mediated immune response or actively suppresses it. Moreover, little is known on how HBV and HCV influence each other in co-infected cells. We investigated interactions between HBV and the IFN-mediated immune response using HepaRG cells and primary human hepatocytes (PHHs). We analyzed the effects of HBV on HCV replication, and vice versa, at the single-cell level...
January 31, 2018: Gastroenterology
Aleksei Suslov, Tujana Boldanova, Xueya Wang, Stefan Wieland, Markus H Heim
BACKGROUND AND AIMS: Most viruses are detected at early stages of cell infection and induce an innate immune response mediated by production interferons (IFNs). IFNs induce expression of hundreds of IFN-stimulated genes (ISGs). Infection of chimpanzees with hepatitis C virus, but not hepatitis B virus (HBV), induces ISG expression in the liver. HBV might not induce an innate immune response because it is not detected by pattern recognition receptors (the stealth properties of HBV) or because HBV suppresses IFN production or signaling despite detection by pattern recognition receptors...
February 2, 2018: Gastroenterology
Junling Gong, Xing Liu
The effect of hepatitis B immune globulin (HBIG) combined with hepatitis B vaccine on blocking hepatitis B virus (HBV) transmission between mother and infant and its effect on immune cells were studied. Ninety newborn infants confirmed to be HBV surface antigen (HBsAg)-positive were divided equally into three groups. Group A newborns received the hepatitis B vaccine at 0, 1 and 6 months after birth (10 µg/time). Group B newborns received an intramuscular injection of 100 IU HBIG 2 h after birth before the same treatment as group A...
January 2018: Experimental and Therapeutic Medicine
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