Article
Immunology
Lorenzo Piermatteo, Stefano D'Anna, Ada Bertoli, Maria Bellocchi, Luca Carioti, Lavinia Fabeni, Mohammad Alkhatib, Simone La Frazia, Miriam Lichtner, Claudio Mastroianni, Giuseppe De Sanctis, Massimo Marignani, Caterina Pasquazzi, Nerio Iapadre, Giustino Parruti, Giuseppina Cappiello, Jacopo Vecchiet, Vincenzo Malagnino, Sandro Grelli, Francesca Ceccherini-Silbertein, Massimo Andreoni, Loredana Sarmati, Valentina Svicher, Romina Salpini
Summary: 17.7% of HBV-D infected patients carry at least one vaccine-escape mutation, and the proportion of patients with complex mutations is increasing over time. Complex mutations are associated with lower HBsAg levels and HBsAg negativity despite HBV-DNA positivity.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Gastroenterology & Hepatology
Milan J. Sonneveld, Shao-Ming Chiu, Jun Yong Park, Sylvia M. Brakenhoff, Apichat Kaewdech, Wai-Kay Seto, Yasuhito Tanaka, Ivana Carey, Margarita Papatheodoridi, Florian van Bommel, Thomas Berg, Fabien Zoulim, Sang Hoon Ahn, George N. Dalekos, Nicole S. Erler, Christoph Honer Zu Siederdissen, Heiner Wedemeyer, Markus Cornberg, Man-Fung Yuen, Kosh Agarwal, Andre Boonstra, Maria Buti, Teerha Piratvisuth, George Papatheodoridis, Chien-Hung Chen, Benjamin Maasoumy
Summary: The probability of HBsAg loss after NUC cessation varies according to patient ethnicity, HBV genotype and end-of-treatment viral antigen levels. Patients with low HBsAg and HBcrAg levels, particularly non-Asian or infected with HBV genotype C, may be the best candidates for treatment withdrawal.
JOURNAL OF HEPATOLOGY
(2022)
Article
Pharmacology & Pharmacy
Hsing Huang, Hsiu-Chen Huang, Wei-Chung Chiou, Lie-Chwen Lin, Jui-Chieh Chen, Hui-Kang Liu, Yu-Heng Lai, Cheng Huang
Summary: Hepatitis B virus (HBV) infection causes severe liver diseases, but current therapies are unable to eradicate the virus completely. The newly identified inhibitor EP targets the entry step of HBV infection and shows potential for fighting against HBV infection by interfering with the NTCP-LHBsAg interaction.
ANTIVIRAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Si-Yu Yuan, Hai-Bo Yu, Zhen Yang, Yi-Ping Qin, Ji-Hua Ren, Sheng-Tao Cheng, Fang Ren, Betty Yuen Kwan Law, Vincent Kam Wai Wong, Jerome P. L. Ng, Yu-Jiao Zhou, Xin He, Ming Tan, Zhen-Zhen Zhang, Juan Chen
Summary: This study identified pimobendan as a potential drug with strong antiviral activity against hepatitis B virus (HBV). Pimobendan inhibits HBV transcription, leading to reduced production of HBsAg. These findings provide a promising lead for the development of new anti-HBV agents.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Xin Liu, Shu-xiang Chen, Hui Liu, Jin-li Lou
Summary: This study analyzed the differences in T-lymphocyte subsets, cytokine levels, and HBV S gene sequences between HBsAg-negative and HBsAg-positive patients. The results showed that HBsAg-negative patients had superior cellular immune function compared to HBsAg-positive patients, with possible mutations and amino acid replacement sites in the HBV S region.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Mauricio Lisker-Melman, Abdus S. Wahed, Marc G. Ghany, Raymond T. Chung, Wendy C. King, David E. Kleiner, Atul K. Bhan, Mandana Khalili, Mamta K. Jain, Mark Sulkowski, David K. Wong, Gavin Cloherty, Richard K. Sterling
Summary: In patients coinfected with HBV and HIV, HBV RNA and HBcrAg can still be detected despite viral suppression, and their levels are associated with the extent of HBsAg and HBcAg staining in liver cells. This suggests that residual transcription and translation may contribute to liver pathology even when viral replication is suppressed.
Article
Chemistry, Medicinal
Xiaoyu Qin, Lu Yang, Xican Ma, Bin Jiang, Shuo Wu, Apeng Wang, Shijie Xu, Wenhao Wu, Huijuan Song, Na Du, Kai Lv, Yuhuan Li, Mingliang Liu
Summary: RG7834, a DHQ candidate developed by Roche Pharma, was dismissed in phase I clinical trial due to its neurotoxicity. In this study, new DHQ derivatives containing a cyclic ether or benzo-fused ether moiety were designed, synthesized and evaluated for their in vitro activity. Many of them exhibited potent inhibition activity against HBV and showed potential improvement in neurotoxicity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Li Zhang, Xingfeng Ge, Hui Jin, Dandan Lu, Shuo Chen, Yang Zhang, Xiaojin Wang, Hongjiang Xu, Wangwei Ao, Yinsheng Zhang
Summary: A series of tetrahydropyridine derivatives were synthesized and evaluated in this study, and compound 17i was found to be a potent inhibitor of HBsAg production and HBV DNA activity. It showed excellent in vitro anti-HBV potency and low toxicity, with favorable in vitro/in vivo DMPK properties in mice. Additionally, 17i significantly reduced serum HBsAg and HBV DNA levels in HBV transgenic mice.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Virology
Runal John Steve, Arul Prakash, Suresh Ponnuvel, Calvin John Dickson, Karthick Nandan, Bakthalal Singh, Gift Ajay Sam, Ashish Goel, Uday George Zachariah, Chundamannil Eapen Eapen, Rajesh Kannangai, Priya Abraham, Gnanadurai John Fletcher
Summary: HBsAg Next assay (HBsAgNx) showed improved accuracy in detecting HBsAg without compromising specificity, and it could detect HBsAg in various phases of HBV infection. It is also amenable to in-house neutralization to confirm low HBsAg levels.
JOURNAL OF CLINICAL VIROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ilaria Montali, Andrea Vecchi, Marzia Rossi, Camilla Tiezzi, Amalia Penna, Valentina Reverberi, Diletta Laccabue, Gabriele Missale, Carolina Boni, Paola Fisicaro
Summary: Current treatment for chronic hepatitis B infection mainly relies on nucleos(t)ide analogues, which are often required for a patient's lifetime. However, there is a need to develop new therapeutic strategies to shorten antiviral treatments. Dysfunction of virus-specific T cell responses contributes to virus persistence, and immune modulation is considered a potential approach for HBV cure. However, the evidence for improving antiviral T cell functions by reducing viral antigen burden is currently lacking.
Review
Virology
Maryam Moini, Scott Fung
Summary: Despite the availability of vaccines and antiviral therapy, chronic hepatitis B remains a global health threat. The functional cure of HBV is rare and the current antiviral therapy has limited efficacy. Exciting developments in novel antiviral agents may improve the cure rate, but further research is needed. Improved detection methods and combination therapies are important for achieving a functional cure.
Article
Medicine, General & Internal
Shue Xiong, Dan Zhu, Boyun Liang, Mingyue Li, Wen Pan, Junyi He, Hua Wang, Kathrin Sutter, Ulf Dittmer, Mengji Lu, Di Liu, Dongliang Yang, Jia Liu, Xin Zheng
Summary: The desirable endpoint of treatment against chronic hepatitis B virus infection is to achieve a functional cure, characterized by HBsAg loss with or without anti-HBs seroconversion. This study found that cHBV patients with sAg-L display distinct CD4(+) and CD8(+) T cell phenotype fingerprints compared to sAg-R patients, with upregulated HLA-DR expression and potent HBcAg-specific CD8(+) T cell response. The onset of HBsAg decrease and subsequent loss in cHBV patients on treatment is associated with significant alterations of both CD4(+) and CD8(+) T cell phenotypes, which may serve as predictive factors for sAg-L.
Article
Gastroenterology & Hepatology
Abhishek Aggarwal, Pamela M. Odorizzi, Jens Brodbeck, Nicholas van Buuren, Christina Moon, Silvia Chang, MaryVic Adona, Silpa Suthram, Vithika Suri, Torsten Trowe, Scott Turner, Patrick Marcellin, Maria Buti, Anuj Gaggar, Simon P. Fletcher, Lauri Diehl, Becket Feierbach, Scott Balsitis
Summary: This study quantified the patterns of HBV antigen expression in liver biopsies from individuals with chronic hepatitis B using a novel four-plex immunofluorescence assay and image analysis. The findings revealed variations in HBV staining within individuals and the effects of disease stage and NUC treatment. Correlations between liver and peripheral viral biomarkers were observed, particularly in samples from HBeAg-positive individuals.
Article
Medicine, General & Internal
Yu Yu, Yingqiang Zhang, Yuzhu Dai, Qingyang Sun, Chun Jiang, Xujian Xu, Chuanzhong Mei, Jun Cheng
Summary: In this study, we detected HBsAg immune complex and sequenced the HBV S gene to investigate the association between sustained low-level expression of HBsAg and mutated S gene sequence characteristics. We found that there is a higher positive rate of HBsAg immune complex in the low-level HBsAg group, and there are correlations between HBsAg immune complex and HBsAg or HBV DNA. We also identified specific hot-spot mutations in the MHR of the S gene, which could affect the physicochemical properties and functions of HBsAg. Our findings suggest that these mutations may contribute to the formation of sustained low-level expression of HBsAg in HBV-infected individuals.
FRONTIERS IN MEDICINE
(2022)
Article
Virology
Carla S. S. Coffin, Sarah Haylock-Jacobs, Karen Doucette, Alnoor Ramji, Hin Hin Ko, David K. K. Wong, Magdy Elkhashab, Robert Bailey, Julia Uhanova, Gerald Minuk, Keith Tsoi, Alexander Wong, Mang M. M. Ma, Edward Tam, Mayur Brahmania, Carmine Nudo, Julie Zhu, Christopher F. F. Lowe, Carla Osiowy, B. Cord Lethebe, Stephen E. E. Congly, Eric K. H. Chan, Angelina Villasis-Keever, Urbano Sbarigia, Curtis L. L. Cooper, Scott Fung
Summary: Loss of Hepatitis B surface antigen (HBsAg) is associated with improved clinical outcomes in chronic hepatitis B (CHB) patients. This retrospective study of 844 CHB patients found that those who received antiviral therapy and/or achieved HBsAg loss had a lower risk of cirrhosis and hepatocellular carcinoma (HCC). Fibrosis was not associated with quantitative HBsAg levels in this diverse cohort.