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HBsAg Clearance

Xiaowen Wang, Qingyang Dong, Qian Li, Yuanyuan Li, Dianyuan Zhao, Jinjie Sun, Junliang Fu, Fanping Meng, Hu Lin, Junjie Luan, Biao Liu, Min Wang, Fusheng Wang, Fuchu He, Li Tang
BACKGROUND & AIMS: Production of neutralizing antibodies against hepatitis B surface antigen (HBsAg) is dysregulated in patients with persistent hepatitis V virus (HBV) infection. We investigated mechanisms by which this immune response to the virus is disrupted and whether it can be restored to promote clearance of HBV. METHODS: Immune-competent C57BL/6N and C57BL/6J, as well as mice deficient in follicular helper T cells (Tfh cell-deficient), B cells, or Foxp3+ T-regulatory cells (Treg cell-deficient), were given hydrodynamic injections of pAAV/HBV1...
March 12, 2018: Gastroenterology
Wen-Han Yu, Cormac Cosgrove, Christoph T Berger, Patrick C Cheney, Marina Krykbaeva, Arthur Y Kim, Lia Lewis-Ximenez, Georg M Lauer, Galit Alter
Background: Hepatitis B virus (HBV) affects up to 400 million people worldwide and accounts for approximately one million deaths per year from liver pathologies. Current treatment regimens are effective in suppressing viremia but usually have to be taken indefinitely, warranting research into new therapeutic approaches. Acute HBV infection in adults almost universally results in resolution of viremia, with the exception of immunocompromised persons, suggesting that the immune response can functionally cure or even eradicate HBV infection...
2018: Pathogens & Immunity
Liwen Chen, Chuanwu Zhu, Fengdi Li, Yun Wang, Rebecca Bao, Zhujun Cao, Xiaogang Xiang, Lei Yan, Lanyi Lin, Gangde Zhao, Qing Xie, Shisan Bao, Hui Wang
Background: Chronic hepatitis B (CHB) remains a global health dilemma with high morbidity and mortality. Human males absent on the first (hMOF) (a histone acetyltransferase) is responsible for DNA damage repair, tumorigenesis and cell cycle regulation. Persistence of HBV DNA contributes to cirrhosis and hepatocellular carcinoma (HCC) in CHB patients. Histone acetyltransferase enhances HBV replication, however the precise underlying mechanism of hMOF in HBV replication in CHB patients remains to be explored...
2018: Cell & Bioscience
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
Conar R O'Neil, Stephen E Congly, M Sarah Rose, Samuel S Lee, Meredith A Borman, Carmen L Charlton, Carla Osiowy, Mark G Swain, Kelly W Burak, Carla S Coffin
INTRODUCTION: Quantitative hepatitis B surface antigen (qHBsAg) combined with HBV DNA may be useful for predicting chronic hepatitis B (CHB) activity and nucleoside analogue (NA) response. MATERIAL AND METHODS: In this retrospective cohort study we evaluated qHBsAg levels according to CHB disease phase and among patients on treatment. Random effect logistic regression analysis was used to analyze qHBsAg change with time in the NA-treated cohort. RESULTS: 545 CHB carriers [56% M, median age 48 y (IQR 38-59), 73% Asian] had qHBsAg testing...
March 1, 2018: Annals of Hepatology
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
Satoru Hagiwara, Naoshi Nishida, Tomohiro Watanabe, Hiroshi Ida, Toshiharu Sakurai, Kazuomi Ueshima, Masahiro Takita, Yoriaki Komeda, Norihiro Nishijima, Yukio Osaki, Masatoshi Kudo
BACKGROUND: Although the efficacy of combination therapy with lamivudine or tenofovir and pegylated-interferon (Peg-IFN) has been reported in patients with chronic hepatitis B (CHB), the long-term effect of the combination based on the observation of clinical course remains to be clarified. We previously reported the efficacy of combination therapy with entecavir (ETV) and Peg-IFN. Here, we investigated the long-term effect of this combination in patients with CHB. METHODS: We administered both ETV and Peg-IFN α-2a or -2b simultaneously to 26 patients with hepatitis B virus genotype C infection...
February 13, 2018: Antiviral Therapy
Jiannis Vlachogiannakos, George V Papatheodoridis
As current treatment options almost never achieve eradication of hepatitis B virus (HBV), the most realistic goal for HBV treatment is persistent inhibition of viral replication and ALT normalization. Thus, the decision to start treatment should be based on careful patient selection and individualized decisions. Treatment is generally indicated in chronic hepatitis B patients with HBV DNA >2000 IU/mL, elevated ALT and/or at least moderate histological lesions, while all patients with cirrhosis and detectable HBV DNA should be treated...
February 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Lucio Boglione, Giuseppe Cariti, Valeria Ghisetti, Elisa Burdino, Giovanni Di Perri
An alternative approach in the treatment of chronic hepatitis B (CHB) with pegylated (PEG)-interferon (IFN) is the prolonged course to 96 weeks of therapy, with higher sustained response (SR) than patients treated for 48 weeks. This result was confirmed in patients with CHB and D genotype, while no data are currently available about the prolonged course of PEG-IFN in E genotype. This retrospective analysis reported the role of different treatment duration of PEG-IFN on the SR in patients affected by CHB and E genotype...
January 31, 2018: Journal of Medical Virology
Song Feng, Lu Gao, Xinchun Han, Taishan Hu, Yimin Hu, Haixia Liu, Andrew William Thomas, Zhipeng Yan, Song Yang, John A T Young, Hongying Yun, Wei Zhu, Hong C Shen
The chronic infection of hepatitis B virus (HBV) inflicts 250 million people worldwide representing a major public health threat. A significant sub-population of chronically infected HBV patients eventually develop cirrhosis and hepatocellular carcinoma (HCC) which aggravate the issues caused by hepatitis alone. Unfortunately, none of the current standard therapies for chronic Hepatitis B (CHB) result in a satisfactory clinical cure rate. Driven by a highly unmet medical need for novel and more effective treatments of HBV infection, multiple pharmaceutical companies and research institutions have been engaged in drug discovery and development to improve the CHB functional cure rate, which is defined by sustainable viral suppression and HBsAg clearance after a finite treatment...
January 25, 2018: ACS Infectious Diseases
Shanshan Wu, Xiaohua Chen, Yuyan Tang, Yi Zhang, Dan Li, Jie Chen, Jieling Wang, Zhenghao Tang, Guoqing Zang, Yongsheng Yu
Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) play a vital role in viral control and clearance. Recent studies have elucidated that Tapasin, an endoplasmic reticulum chaperone, is a well-known molecule that appears to be essential in peptide-loading process. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway plays an important role in immune response regulation and cytokines secretion. We have previously verified that fusion protein CTP-HBcAg18-27-Tapasin could facilitate the maturation of bone marrow derived dendritic cells and enhance specific CTLs responses in vitro, which might be associated with the activation of JAK/STAT signaling pathway...
January 11, 2018: Acta Biochimica et Biophysica Sinica
Xuerui Yi, Youcheng Yuan, Na Li, Lu Yi, Cuiling Wang, Ying Qi, Liang Gong, Guangze Liu, Xiangping Kong
BACKGROUND: Viral clearance of human HBV infection largely depends on the age of exposure. Thus, a mouse model with age-dependent immune response and immune-tolerance for HBV infection was established. METHODS: HBVRag1 mice were generated by crossing Rag1-/- mice with HBV-Tg mice. Following adoptive transfer of splenocytes adult (8-9 weeks old) and young (3 weeks old) HBVRag1 mice were named as HBVRag-ReA and HBVRag-ReY mice respectively. The biochemical parameters that were associated with viral load and immune function, as well as the histological evaluation of the liver tissues between the two mouse models were detected...
January 3, 2018: Vaccine
Terry Cheuk-Fung Yip, Vincent Wai-Sun Wong, Henry Lik-Yuen Chan, Yee-Kit Tse, Alice Pik-Shan Kong, Kelvin Long-Yan Lam, Grace Chung-Yan Lui, Grace Lai-Hung Wong
BACKGROUND & AIMS: Diabetes is associated with a 2-fold increase in risk of hepatocellular carcinoma (HCC) among patients with chronic hepatitis B virus (HBV) infection. However, we know little about the effect of diabetes on HCC risk after seroclearance of hepatitis B surface antigen (HBsAg). We evaluated the effect of diabetes and glycemic control on HCC development after HBsAg seroclearance in a population-wide study in Hong Kong. METHODS: We performed a retrospective study of 4568 patients with chronic HBV infection who cleared HBsAg from January 2000 through August 2016, using the Clinical Data Analysis and Reporting System of the Hospital Authority, Hong Kong...
December 12, 2017: Clinical Gastroenterology and Hepatology
Alicja E Grzegorzewska, Monika K Świderska, Adrianna Mostowska, Paweł P Jagodziński
The IFN- λ 3 gene (IFNL3) plays a role in HCV clearance. We investigated circulating IFN- λ 3 and IFNL3 SNPs in haemodialysis patients who differed in their response to HBV vaccination and their HBV/HCV infection status. In 201 patients, plasma IFN- λ 3 was determined using ELISA. IFNL3 SNPs (rs12979860, rs8099917) were genotyped using HRM analysis. Differences in IFN- λ 3 levels were shown between responders and nonresponders to HBV vaccination and between HBsAg-positive patients and those who developed anti-HBs after infection and became HBsAg negative...
2017: BioMed Research International
Zhan-Qing Zhang, Xiao-Nan Zhang, Wei Lu, Yan-Bing Wang, Qi-Cheng Weng, Yan-Ling Feng
BACKGROUND: The current clinical practice on chronic hepatitis B (CHB) requires better on-treatment monitoring of viral persistence. Quantified assays for hepatitis B surface antigen (HBsAg) and core-related antigen (HBcrAg) hold promise for further optimization of therapy. Here, we aimed to characterize HBcrAg during the natural course of CHB. METHODS: Four-hundred and forty four treatment naïve CHB patients, who all underwent liver histology examination, were enrolled in this cross-sectional study...
December 4, 2017: BMC Gastroenterology
Xue-Ping Gao, Yang Zhou, Xin-Chun Zheng, Xuan Yi, Li-Bo Tang, Jin-Lin Hou, Yong-Yin Li
OBJECTIVE: To investigate the effect of an adenovirus vector containing murine interleukin-21 gene (Ad-GFP-mIL-21) in virus clearance and on the production of HBV-specific antibodies in mice with persistent HBV infection. METHODS: ELISA and Western blot analysis were used to detect the expression of mIL-21 in the supernatant and cytoplasm of cultured HepG2.2.15 cells after infection by Ad-GFP-mIL-21. Mouse models of chronic HBV infection established by in vivo transduction with rAAV8-1...
November 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Louis-Marie Yindom, Maimuna Mendy, Christopher Bodimeade, Caroline Chambion, Peter Aka, Hilton C Whittle, Sarah L Rowland-Jones, Robert Walton
BACKGROUND: Hepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation...
2017: PloS One
X-J Ma, X-F Chen, W-L Chen, R Chen, J Huang, X-D Luo, J-Y Liao, X-P Chen
OBJECTIVE: To study the alteration of CD8+ memory T cell subsets under different immune statuses during the spontaneous clearance of hepatitis B virus (HBV) in Chinese patients with chronic HBV infection. PATIENTS AND METHODS: We analyzed Chinese patients with chronic HBV infection including 10 patients with Hepatitis B surface Antigen (HBsAg) spontaneous seroconversion, 25 patients with Hepatitis B virus e Antigen (HBeAg) spontaneous seroconversion, 25 patients with chronic hepatitis B (CHB), and 25 chronic HBV carriers...
October 2017: European Review for Medical and Pharmacological Sciences
Wen-Juei Jeng, Yi-Cheng Chen, Rong-Nan Chien, I-Shyan Sheen, Yun-Fan Liaw
Hepatitis B s antigen (HBsAg) loss is a rare event during nucleos(t)ide analogue (Nuc) therapy. Limited data suggest that stopping Nuc therapy may increase HBsAg loss rate in hepatitis B e antigen (HBeAg) negative patients. A large study was conducted to investigate this issue in more detail. Of the 1075 HBeAg-negative patients treated with Nuc for 156 (61-430) weeks, 6 showed HBsAg seroclearance during treatment at an estimated annual incidence of 0.15%. Of the patients who remained HBsAg seropositive, 691 (52...
November 6, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
X D Luo, X F Chen, Y Zhou, X P Chen
The purpose of the study was to compare the efficacy and safety of 208-week sequential therapy with telbivudine and entecavir in HBeAg-positive chronic hepatitis B (CHB) patients with suboptimal responses to 24 weeks of Peg-IFNα-2a therapy. This was an open-label, randomized, controlled, "real-life" trial. HBeAg-positive CHB patients with serum HBV DNA ≥5.0 lg IU/mL and a < 1 lg IU/mL decline of HBsAg level from baseline who underwent at least 24 weeks of Peg-IFNα-2a therapy were included. Enrolled patients were randomized to receive either telbivudine (600 mg/d, n = 95) or entecavir (0...
November 2017: Journal of Viral Hepatitis
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