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Monika Lindemann, Marina Zaslavskaya, Melanie Fiedler, Benjamin Wilde, Falko M Heinemann, Andreas Heinold, Peter A Horn, Oliver Witzke
Approximately 70% of kidney transplant recipients are non-responders to conventional hepatitis B virus (HBV) vaccines. We examined whether Fendrix(™) , an HBV vaccine containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) as adjuvant, could induce HBV immunity in these patients and compared their vaccination efficacy with healthy controls tested previously by the same assays. We selected 35 kidney transplant recipients who had been vaccinated at least thrice against HBV but had never displayed anti-HBs antibodies...
October 20, 2016: Scandinavian Journal of Immunology
Kenichi Morikawa, Tomoe Shimazaki, Rei Takeda, Takaaki Izumi, Machiko Umumura, Naoya Sakamoto
Hepatitis B virus (HBV) infection is a serious health threat around the world. Despite the availability of an effective hepatitis B vaccine, the number of HBV carriers is estimated to be as high as 240 million worldwide. Global mortality due to HBV-related liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) may be as high as 1 million deaths per year. HBV is transmitted via blood and body fluids, and is much more infectious than both human immunodeficiency virus (HIV) and hepatitis C virus...
September 2016: Annals of Translational Medicine
Monica A Konerman, Anna S Lok
Chronic hepatitis B virus (HBV) infection has a significant public health impact. There are currently 7 approved therapies for chronic HBV, including standard and pegylated interferon (IFN)-α, and 5 nucleos(t)ide analogs (NUCs). IFN offers benefits over NUCs, including a finite duration of therapy and a higher rate of clearance of hepatitis Be antigen and surface antigen. These benefits need to be weighed against the potential adverse effects of IFN therapy. Some patients should not receive IFN because of advanced liver disease or comorbidities...
November 2016: Clinics in Liver Disease
Sukriti Sukriti, Nirupma Trehanpati, Manoj Kumar, Chandana Pande, Syed S Hissar, Shiv Kumar Sarin
BACKGROUND: Dendritic cells (DCs) promote pathogen recognition, uptake and presentation of antigen through DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and toll-like receptors (TLRs). AIMS AND OBJECTIVES: We aimed to study temporal changes in DCs, TLRs and DC-SIGN during acute viral hepatitis B (AVHB) infection and compare them to chronic (CHB) and to investigate the earliest time point of activated pathogen recognition receptors in hepatitis B viral infection...
September 22, 2016: Hepatology International
Takahisa Kouwaki, Yoshimi Fukushima, Takuji Daito, Takahiro Sanada, Naoki Yamamoto, Edin J Mifsud, Chean Ring Leong, Kyoko Tsukiyama-Kohara, Michinori Kohara, Misako Matsumoto, Tsukasa Seya, Hiroyuki Oshiumi
UNLABELLED: The innate immune system is essential for controlling viral infection. Hepatitis B virus (HBV) persistently infects human hepatocytes and causes hepatocellular carcinoma. However, the innate immune response to HBV infection in vivo remains unclear. Using a tree shrew animal model, we showed that HBV infection induced hepatic interferon (IFN)-γ expression during early infection. Our in vitro study demonstrated that hepatic NK cells produced IFN-γ in response to HBV only in the presence of hepatic F4/80(+) cells...
2016: Frontiers in Immunology
Chean Ring Leong, Kenji Funami, Hiroyuki Oshiumi, Deng Mengao, Hiromi Takaki, Misako Matsumoto, Hussein H Aly, Koichi Watashi, Kazuaki Chayama, Tsukasa Seya
Hepatitis B virus (HBV) barely induces host interferon (IFN)-stimulated genes (ISGs), which allows efficient HBV replication in the immortalized mouse hepatocytes as per human hepatocytes. Here we found that transfection of Isg20 plasmid robustly inhibits the HBV replication in HBV-infected hepatocytes irrespective of IRF3 or IFN promoter activation. Transfection of Isg20 is thus effective to eradicate HBV in the infected hepatocytes. Transfection of HBV genome or ε-stem of HBV pgRNA (active pgRNA moiety) failed to induce Isg20 in the hepatocytes, while control polyI:C (a viral dsRNA analogue mimic) activated MAVS pathway leading to production of type I IFN and then ISGsg20 via the IFN-α/β receptor (IFNAR)...
September 8, 2016: Oncotarget
Alicja E Grzegorzewska, Monika K Świderska, Adrianna Mostowska, Wojciech Warchoł, Paweł P Jagodziński
AIM: To investigate circulating IFN-λ3 and IFNL3 polymorphisms in hemodialysis (HD) patients differing in HBV surface antigen antibody (anti-HBs) production. METHODS: The study included 106 HBV-vaccinated HD patients (88 developed anti-HBs) and 36 HBV-infected HD subjects (27 developed anti-HBs). Plasma IFN-λ3 (enzyme-linked immunosorbent assay) and rs12979860 (C>T) and rs8099917 (T>G) in IFNL3 (high-resolution melting curve analysis) were analyzed with regard to the association with anti-HBs production in response to HBV vaccination or infection...
September 22, 2016: Vaccine
G P Caviglia, M L Abate, D Noviello, A Olivero, C Rosso, G Troshina, A Ciancio, M Rizzetto, G M Saracco, A Smedile
AIM: To evaluate Hepatitis B core-related antigen (HBcrAg) correlation with HBV DNA and hepatitis B surface antigen (HBsAg) levels and to investigate HBcrAg kinetic during nucleos(t)ide analogues (NAs) or pegylated-interferon (PEG-IFN)-α treatment in a cohort of chronic hepatitis B (CHB)-genotype-D patients. METHODS: One-hundred-thirty-eight sequential serum samples were collected from 28 Hepatitis B e antigen (HBeAg)-negative CHB-genotype-D patients (20 M/8 F; median age 54 [47-58] years), who underwent NAs (n = 20) or PEG-IFN-α (n = 8) treatment...
August 30, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Xiaoyan Li, Min Zhang, Jing Liu, Zhanlian Huang, Qiyi Zhao, Yuehua Huang, Xu Li, Zhiliang Gao
BACKGROUND: Although numerous epidemiological studies indicate that hepatitis B virus-related liver fibrosis (HBV-LF), particularly cirrhosis, represents the main risk factor for liver cancer development, the mechanisms determining the persistence of fibrosis and liver cancer pathogenesis are still poorly defined. Few studies have investigated the status of NK cells during different stages of HBV-LF. METHODS: Liver tissues at least 3 cm away from the tumour site and peripheral blood were obtained simultaneously from 32 HBV-infected patients undergoing surgery for HCC at the medical centre of Sun Yat-sen University...
October 2016: European Journal of Clinical Investigation
Kyle E Korolowicz, Radhakrishnan P Iyer, Stefanie Czerwinski, Manasa Suresh, Junming Yang, Seetharamaiyer Padmanabhan, Anjaneyulu Sheri, Rajendra K Pandey, Jeffrey Skell, Judith K Marquis, Bhaskar V Kallakury, Robin D Tucker, Stephan Menne
SB 9200, an oral prodrug of the dinucleotide SB 9000, is being developed for the treatment of chronic hepatitis B virus (HBV) infection and represents a novel class of antivirals. SB 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) resulting in interferon (IFN) mediated antiviral immune responses in virus-infected cells. Additionally, the binding of SB 9200 to these sensor proteins could also sterically block the ability of the viral polymerase to access pre-genomic RNA for nucleic acid synthesis...
2016: PloS One
Carla Osiowy, Carla Coffin, Anton Andonov
There are only two currently approved classes of hepatitis B virus (HBV) antiviral agents, pegylated interferon (Peg-IFN), and nucleos(t)ide analogs (NAs) for chronic HBV infection. Although Peg-IFN is used for a finite 48-week duration and offers a greater chance of sustained off-treatment virological response, it is poorly tolerated and can only be offered to selected patients. The NAs are well tolerated but require prolonged therapy due to risk of relapse with treatment cessation. There is evolving data that novel virological assays (e...
2016: Current Treatment Options in Infectious Diseases
Hui-Lin Wu, Tzu-Hung Hsiao, Pei-Jer Chen, Siao-Han Wong, Jia-Horng Kao, Ding-Shinn Chen, Jo-Yang Lu, Tzu-Pin Lu, Yidong Chen, Eric Y Chuang, Hui-Chu Tu, Chun-Jen Liu
The natural course of chronic hepatitis B (CHB) infection and treatment response are determined mainly by the genomic characteristics of the individual. We investigated liver gene expression profiles to reveal the molecular basis associated with chronic hepatitis B and IFN-alpha (IFNα) treatment response in CHB patients. Expression profiles were compared between seven paired liver biopsy samples taken before and 6 months after successful IFNα treatment or between pretreatment biopsy samples of 11 IFNα responders and 11 non-responders...
August 22, 2016: Scientific Reports
Florian A Lempp, Yi Ni, Stephan Urban
Chronic hepatitis D is the most severe form of viral hepatitis, affecting ∼20 million HBV-infected people worldwide. The causative agent, hepatitis delta virus (HDV), is a unique human pathogen: it is the smallest known virus; it depends on HBV to disseminate its viroid-like RNA; it encodes only one protein (HDAg), which has both structural and regulatory functions; and it replicates using predominantly host proteins. The failure of HBV-specific nucleoside analogues to suppress the HBV helper function, and the limitations of experimental systems to study the HDV life cycle, have impeded the development of HDV-specific drugs...
October 2016: Nature Reviews. Gastroenterology & Hepatology
Anette Pietrzak-Nguyen, Keti Piradashvili, Michael Fichter, Leah Pretsch, Fred Zepp, Frederik R Wurm, Katharina Landfester, Stephan Gehring
Chronic hepatitis B virus (HBV) infection is the most prevalent serious liver infection in the world. A frequent route of infection represents mother-to-child transmission. Efficient control of HBV replication depends on antigen-specific cellular immune response mediated by dendritic cells (DCs). Aim of the present study was to evaluate optimized adjuvant combinations, efficiently maturing monocyte-derived neonatal and adult dendritic cells (moDCs). In addition, the potential of polymeric HBsAg-nanocapsules (HBsAg-NCs) was investigated regarding up-take by moDCs and the subsequent induction of specific T cell responses in a human co-culture model...
August 8, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Junhua Yang, Fangfang Qi, Yang Yang, Qunfang Yuan, Juntao Zou, Kaihua Guo, Zhibin Yao
The immune system plays a vital role in brain development. The hepatitis B vaccine (HBV) is administered to more than 70% of neonates worldwide. Whether this neonatal vaccination affects brain development is unknown. Newborn C57BL/6 mice were injected intraperitoneally with HBV or phosphate-buffered saline. HBV induced impaired behavioral performances and hippocampal long-term potentiation at 8 weeks (w) of age without influence at 4 or 12w. At 6w, there was decreased neurogenesis, M1 microglial activation and a neurotoxic profile of neuroimmune molecule expression [increased tumor necrosis factor-α and reduced interferon (IFN)-γ, brain-derived neurotrophic factor and insulin-like growth factor-1] in the hippocampus of the HBV-vaccinated mice...
November 2016: Psychoneuroendocrinology
Jin-A Lee, Yun-Mi Kim, Tae-Hoon Kim, Sang-Ho Lee, Cho-A Lee, Cheong-Weon Cho, Jong-Woon Jeon, Jin-Kyu Park, Sang-Ki Kim, Bock-Gie Jung, Bong-Joo Lee
Nasal delivery is a convenient and acceptable route for drug administration, and has been shown to elicit a much more potent local and systemic response compared with other drug delivery routes. We previously demonstrated that rectal administration of poly(lactide-co-glycolide)-encapsulated honeybee venom (P-HBV) could enhance systemic Th 1-specific immune responses. We therefore synthesized chitosan-coated P-HBV (CP-HBV) and then evaluated the immune-boosting efficacy of nasally administered CP-HBV on systemic and local intestinal immunity compared with non-chitosan-coated P-HBV...
October 1, 2016: Veterinary Immunology and Immunopathology
Nourhan H AbdelAllah, Nourtan F Abdeltawab, Abeer A Boseila, Magdy A Amin
Hepatitis B viral (HBV) infections represent major public health problem and are an occupational hazard for healthcare workers. Current alum-adjuvanted HBV vaccine is the most effective measure to prevent HBV infection. However, the vaccine has some limitations including poor response in some vaccinee and being a frost-sensitive suspension. The goal of our study was to use an alternative natural adjuvant system strongly immunogenic allowing for a reduction in dose and cost. We tested HBV surface antigen (HBsAg) adjuvanted with chitosan (Ch) and sodium alginate (S), both natural adjuvants, either alone or combined with alum in mouse model...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Z W Chen, Y H Guan, L N Ma, X Y Liu, Y X Yang, H D Hu, X C Ding, P Hu
OBJECTIVE: To investigate the role of glucose-6-phosphate dehydrogenase (G6PD) in hepatitis B virus (HBV) replication and its possible mechanism of action. METHODS: Tissue microarray, quantitative real-time PCR, and Western blot were performed to analyze the differences in G6PD expression levels in the HBV-positive and HBV-negative liver tissues, HepG2.2.15 cells, and HepG2 cells. The siRNA transfection technique was used to knock down G6PD gene in HepG2.2.15 cells for 48 hours...
May 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
X D Luo, X P Chen, R Chen, X F Chen, J Huang
OBJECTIVE: To investigate the efficacy and safety of 104-week sequential therapy with telbivudine or entecavir in HBeAg-positive chronic hepatitis B (CHB) patients with suboptimal responses to 24-week pegylated interferon-α-2a (PEG-IFN-α-2a) therapy. METHODS: A total of 130 HBeAg-positive CHB patients with HBV DNA≥5.0 lg IU/ml and a reduction in HBsAg quantitation < 1 lg IU/ml compared with baseline who received PEG-IFN-α-2a therapy for 24 weeks were enrolled and randomly divided into telbivudine group and entecavir group, and 5 of them were lost...
April 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Seiji Tsunematsu, Goki Suda, Kazushi Yamasaki, Megumi Kimura, Takaaki Izumi, Machiko Umemura, Jun Ito, Fumiyuki Sato, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Yasuhito Tanaka, Koichi Watashi, Takaji Wakita, Naoya Sakamoto
Hepatitis B Virus (HBV) causes liver cirrhosis and hepatocellular carcinoma. Standard therapy includes treatment with interferon (IFN); however, its efficacy is limited. HBV has been reported to impair IFN signaling; however, the mechanism is unclear. Here, the relationship between HBV X protein (HBx) and IFN signaling was investigated by establishing HepG2 cells, stably expressing HBx (HepG2/HBx) via retrovirus-mediated gene transfer. Subsequently, IFN negative-regulator expression and its mechanism were studied...
July 26, 2016: Journal of Medical Virology
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