Article
Chemistry, Multidisciplinary
Xiaoyu Shao, Shujing Xu, Xufeng Wan, Yang Zhou, Shuo Wang, Shuo Wu, Yuhuan Li, Xinyong Liu, Peng Zhan
Summary: Despite improving vaccine coverage, hepatitis B remains a severe global public health problem with over 250 million patients infected. Current therapies control replication but fail to eliminate cccDNA and achieve a cure. The HBV core protein is an attractive target for new anti-HBV therapies, and this article provides a concise report on the medicinal chemistry strategies involved in the latest research (2018–2022) of HBV CpAMs, offering guidance for the development of new and effective drugs.
CHINESE CHEMICAL LETTERS
(2023)
Article
Gastroenterology & Hepatology
Marc G. Ghany, Wendy C. King, Mauricio Lisker-Melman, Anna S. F. Lok, Norah Terrault, Harry L. A. Janssen, Mandana Khalili, Raymond T. Chung, William M. Lee, Daryl T. Y. Lau, Gavin A. Cloherty, Richard K. Sterling
Summary: The study found that HBV RNA and HBcrAg are moderately strongly correlated with HBV DNA levels, and the levels of these two markers also have certain correlations with clinical disease indicators for both HBeAg+ and HBeAg- phases of chronic hepatitis B patients.
Article
Gastroenterology & Hepatology
Daryl T. Y. Lau, Lilia Ganova-Raeva, Junyao Wang, Douglas Mogul, Raymond T. Chung, Mauricio Lisker-Melman, Kyong-Mi Chang, Obaid S. Shaikh, Harry L. A. Janssen, Abdus S. Wahed, Anna S. Lok
Summary: The study found that hepatitis B virus variants can be present in genotype A and are usually associated with C1858T, which preserves the pregenome encapsidation sequence. Additionally, participants with PC and BCP variants progressed significantly faster to the HBeAg(-) phase of chronic HBV infection.
Article
Gastroenterology & Hepatology
Won Sohn, Yoosoo Chang, Yong Kyun Cho, Yun Soo Hong, Seungho Ryu
Summary: This study investigated whether isolated hepatitis B core antibody (anti-HBc) positivity is a risk factor for long-term liver-related outcomes in Korean adults. The study found that isolated anti-HBc positivity is associated with liver-related and liver cancer mortality, especially when accompanied by a high fibrosis score.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Virology
Bonolo B. Phinius, Motswedi Anderson, Margaret Mokomane, Irene Gobe, Wonderful T. Choga, Tsholofelo Ratsoma, Basetsana Phakedi, Gorata Mpebe, Doreen Ditshwanelo, Rosemary Musonda, Joseph Makhema, Sikhulile Moyo, Simani Gaseitsiwe
Summary: A high prevalence of an atypical serology profile for hepatitis B virus (HBV) was found among people with HIV-1 in Botswana. This suggests that current HBV testing algorithms may underestimate the prevalence of HBV.
Article
Immunology
Jen-Min Huang, Shih-Yun Wang, Mei-Ru Lai, Yu-Kai Tseng, Ya-Hui Chi, Li-Min Huang
Summary: The study successfully constructed, expressed, and purified a recombinant RSV vaccine candidate (HRØ24) which, when administered in combination with HBc VLPs, induced antibody production and provided partial protection against RSV disease in mice.
Article
Chemistry, Medicinal
Weixing Zhang, Lei Guo, Haixia Liu, Guolong Wu, Houguang Shi, Mingwei Zhou, Zhisen Zhang, Buyu Kou, Taishan Hu, Zheng Zhou, Zhiheng Xu, Xue Zhou, Yuan Zhou, Xiaojun Tian, Guang Yang, John A. T. Young, Hongxia Qiu, Giorgio Ottaviani, Jianxun Xie, Alexander Mayweg, Hong C. Shen, Wei Zhu
Summary: This paper presents the first disclosure of Linvencorvir (RG7907), a clinical compound used for the treatment of chronic HBV infection. RG7907 was rationally designed with drug-like features, including low CYP3A4 induction, potent antiHBV activity, high metabolic stability, low hERG liability, and favorable animal pharmacokinetic (PK) profiles. The strategy used to mitigate CYP3A4 induction by introducing a large, rigid, and polar substituent at a position with less interaction with the therapeutic target (HBV core proteins) is of interest in medicinal chemistry. RG7907 showed favorable animal PK, pharmacodynamics, and safety profiles, supporting its clinical development.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Buyu Kou, Zhisen Zhang, Xingchun Han, Zheng Zhou, Zhiheng Xu, Xue Zhou, Fang Shen, Yuan Zhou, Xiaojun Tian, Guang Yang, John A. T. Young, Hongxia Qiu, Giorgio Ottaviani, Alexander Mayweg, Wei Zhu, Hong C. Shen, Haixia Liu, Taishan Hu
Summary: Hepatitis B Virus core protein allosteric modulators are potential therapeutic agents for treating Hepatitis B. This study describes the discovery of a series of compounds as potential HBV CpAMs and demonstrates their inhibitory effect on HBV viral load in a mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Jieying Zang, Min Liu, Huan Liu, Lina Ding
Summary: This study used molecular simulation techniques to analyze the binding mechanism between phthalazinone compounds and HBV core protein. The results identified van der Waals force as the main driving force and determined key residues. The findings provide important insights for the design and optimization of phthalazinone compounds.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Cell Biology
Pei-Yi Su, Shin-Chwen Bruce Yen, Ching-Chun Yang, Chih-Hsu Chang, Wen-Chang Lin, Chiaho Shih
Summary: This study discovered that the tip of the spike of HBV core particles contains a complex sensor for the secretion of virions and naked capsids. The secretion of HBV virions is highly dependent on CRM1 and microtubules, unlike the secretion of naked capsids.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Review
Public, Environmental & Occupational Health
William M. McFadden, Stefan G. Sarafianos
Summary: Hepatitis B virus (HBV) is a small DNA virus that infects liver tissue and can cause chronic hepatitis B (CHB), a life-long infection associated with significant risks of liver disease. HBV is a global health problem affecting hundreds of millions of people. Current strategies to prevent or inhibit HBV are effective, but a cure for CHB has been elusive. Capsid assembly modulators (CAMs), which target the HBV core protein (Cp), have shown potential to cure CHB by decreasing the cccDNA pools.
GLOBAL HEALTH & MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Yuan-Hung Kuo, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu, Tsung-Hui Hu, Chien-Hung Chen
Summary: The study found that the end-of-treatment HBsAg level is an independent predictor of virological relapse in HBeAg-negative patients after stopping tenofovir disoproxil fumarate (TDF) therapy. Combining EOT HBsAg and baseline HBcrAg levels could further reduce the risk of HBV relapse.
HEPATOLOGY INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Hussein Mukasa Kafeero, Dorothy Ndagire, Ponsiano Ocama, Charles Drago Kato, Eddie Wampande, Abdul Walusansa, Henry Kajumbula, David Kateete, Hakim Sendagire
Summary: This study evaluated the prevalence of HBV serological markers and associated socio-demographic factors among HBsAg seronegative individuals in eastern Uganda. The study found that age, gender, marital status, contact with HBV infected individuals, and blood transfusion were associated with the risk of HBV infection.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Xiang-An Zhao, Jian Wang, Jiacheng Liu, Guangmei Chen, Xiaomin Yan, Bei Jia, Yue Yang, Yong Liu, Da Gu, Zhaoping Zhang, Xiaoxing Xiang, Rui Huang, Chao Wu
Summary: The study found that the baseline serum anti-HBc level in HBeAg-positive CHB patients was a promising indicator for predicting HBeAg seroconversion after antiviral treatment.
ANTIVIRAL RESEARCH
(2021)
Review
Virology
Ivana Lazarevic, Ana Banko, Danijela Miljanovic, Maja Cupic
Summary: The management of HBV infection relies on monitoring viral activity, disease progression and treatment response. Traditional biomarkers have limitations in predicting outcomes. Quantitation of qAnti-HBc is a new biomarker that can solve multiple diagnostic problems. However, it should be combined with other biomarkers for better diagnostic and prognostic power. The availability of commercial qAnti-HBc kits still needs improvement.
Article
Gastroenterology & Hepatology
Harry L. A. Janssen, Jinlin Hou, Tarik Asselah, Henry L. Y. Chan, Fabien Zoulim, Yasuhito Tanaka, Ewa Janczewska, Ronald G. Nahass, Stefan Bourgeois, Maria Buti, Pietro Lampertico, Oliver Lenz, Thierry Verbinnen, Joris Vandenbossche, Willem Talloen, Ronald Kalmeijer, Maria Beumont, Michael Biermer, Umesh Shukla
Summary: The study evaluated the efficacy and safety of JNJ-56136379 in patients with chronic hepatitis B. The results showed that JNJ-56136379+NA significantly reduced HBV DNA and HBV RNA levels, but had limited effects on HBsAg or HBeAg declines in HBeAg-positive patients. Overall, JNJ-56136379 did not demonstrate clear superiority over NA in terms of efficacy.
Article
Gastroenterology & Hepatology
Lena Allweiss, Barbara Testoni, Mei Yu, Julie Lucifora, Chunkyu Ko, Bingqian Qu, Marc Luetgehetmann, Haitao Guo, Stephan Urban, Simon P. Fletcher, Ulrike Protzer, Massimo Levrero, Fabien Zoulim, Maura Dandri
Summary: A major goal of hepatitis B virus (HBV) treatments is to reduce or inactivate intrahepatic viral covalently closed circular DNA (cccDNA). There are different methods for cccDNA quantification, such as Southern blot (SB) and quantitative PCR (qPCR). This study compared various protocols for cccDNA isolation and qPCR quantification in liver tissues and cell cultures, aiming to develop evidence-based guidance for best practices.
Editorial Material
Gastroenterology & Hepatology
Fabien Zoulim, Barbara Testoni
JOURNAL OF HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Jil A. Schrader, Thomas L. Burkard, Yannick Brueggemann, Andre Goemer, Toni L. Meister, Rebecca M. Fu, Ann-Kathrin Mehnert, Viet L. Dao Thi, Patrick Behrendt, David Durantel, Ruth Broering, Florian W. R. Vondran, Daniel Todt, Volker Kinast, Eike Steinmann
Summary: This study identified the EGF receptor (EGFR) as a novel host factor for HEV and revealed the significance of EGFR for the HEV entry process. It was found that EGFR itself and its ligand-binding domain, rather than its signaling function, is responsible for the proviral effect. These findings provide new insights into the life cycle of HEV and identify EGFR as a potential target for future antiviral strategies against HEV.
Article
Virology
Caroline Charre, Hadrien Regue, Paul Deny, Laurence Josset, Isabelle Chemin, Fabien Zoulim, Caroline Scholtes
Summary: This study presents a workflow to amplify, sequence, and analyze the whole HDV genome in a single fragment. The HDV genome was successfully amplified and fully sequenced, allowing accurate subtyping and identification of a new HDV genotype 1 subtype. This workflow overcomes genome assembly issues and helps to identify modifications throughout the whole HDV genome.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Gastroenterology & Hepatology
Clemence Moreau, Marine Roux, Jeremie Riou, Clemence M. Canivet, Etienne Audureau, Clovis Lusivika-Nzinga, Pierre Nahon, Fabrice Carrat, Jerome Boursier
Summary: This study aimed to evaluate whether the dynamics of multiple measurements of simple parameters after sustained viral response (SVR) enable the development of a personalized prediction of prognosis in patients with hepatitis C virus (HCV) chronic infection. The study found that FIB4 was a biomarker associated with liver-related complications (LRC) occurrence after SVR. The results suggest that dynamic modeling using repeated measurements of simple parameters predicts the individual residual risk of LRC and improves personalized medicine after SVR in HCV patients.
JOURNAL OF VIRAL HEPATITIS
(2023)
Article
Gastroenterology & Hepatology
Armando A. Roca A. Suarez, Enkhtuul Batbold, Birke Bartosch, Naranjargal Dashdorj, Barbara Testoni, Fabien Zoulim
Summary: Hepatitis delta virus (HDV) is a satellite RNA virus that requires hepatitis B virus (HBV) for replication. Co-infection with HDV/HBV leads to faster disease progression compared to HBV mono-infection. Developing antiviral therapies targeting HDV is crucial. Evaluating promising HDV-specific drugs and combination therapies, as well as exploring anti-HBV drugs with potential effects against HDV, are key areas of research.
LIVER INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Sarah Duponchel, Lea Monnier, Jennifer Molle, Nadia Bendridi, Muhammad Rizwan Alam, Ahmed Gaballah, Boyan Grigorov, Alexander Ivanov, Marcel Schmiel, Margarete Odenthal, Michel Ovize, Jennifer Rieusset, Fabien Zoulim, Birke Bartosch
Summary: Chronic HCV infection causes cellular stress, fibrosis, and predisposes to hepatocarcinogenesis. Mitochondria play key roles in orchestrating stress responses. The study revealed that HCV proteins associate with mitochondria and alter the composition of mitochondrial subdomains, which are crucial for efficient viral replication.
Letter
Gastroenterology & Hepatology
Tangui Barre, David Zucman, Fabienne Marcellin, Clemence Ramier, Camelia Protopopescu, Raphaelle Tardieu, Karine Ory, Dominique Salmon-Ceron, Patrizia Carrieri
JOURNAL OF VIRAL HEPATITIS
(2023)
Review
Gastroenterology & Hepatology
Ievgeniia Chicherova, Charlotte Hernandez, Fanny Mann, Fabien Zoulim, Romain Parent
Summary: The liver is a neurovascular organ that develops various chronic liver diseases (CLD). Axon guidance cues (AGCs) play a role in the physiological development of the nervous system, but their expression can also be reinduced in diseases such as CLD. This review discusses the impact of AGCs on fibrosis regulation, immune functions, viral/host interactions, angiogenesis, and cell growth in CLD and HCC, and proposes future research directions.
LIVER INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Barbara Testoni, Armando Andres Roca Suarez, Arianna Battisti, Marie-Laure Plissonnier, Marintha Heil, Thierry Fontanges, Francois Villeret, Yasmina Chouik, Massimo Levrero, Upkar Gill, Patrick Kennedy, Fabien Zoulim
Summary: This study validated the possibility to quantify cccDNA and assess its transcriptional activity in patients with chronic hepatitis B by combining FNA and droplet digital PCR. The use of FNA in clinical trials to evaluate the intrahepatic viral reservoir during the development of new antivirals and immunomodulatory agents is supported.
Article
Gastroenterology & Hepatology
Fabienne Marcellin, Sylvie Bregigeon-Ronot, Clemence Ramier, Camelia Protopopescu, Camille Gilbert, Vincent Di Beo, Claudine Duvivier, Morgane Bureau-Stoltmann, Eric Rosenthal, Linda Wittkop, Dominique Salmon-Ceron, Patrizia Carrieri, Philippe Sogni, Tangui Barre
Summary: This study aimed to investigate the prevalence of moderate-to-severe depression in people living with HIV and HCV after successful HCV treatment, and identify associated socio-behavioral factors. Through descriptive and logistic regression analyses of data from 398 participants, it was found that 23.9% of HCV-cured individuals had moderate-to-severe depression. Female sex, unhealthy alcohol use, sedentary lifestyle, and unhealthy eating behaviors were associated with increased odds of moderate-to-severe depression.
Article
Surgery
Paolo Angelo Cortesi, Raffaella Vigano, Sara Conti, Ilaria Lenci, Riccardo Volpes, Silvia Martini, Mario Angelico, James Fung, Maria Buti, Audrey Coilly, Francois Durand, Constantino Fondevila, Pascal Lebray, Frederik Nevens, Wojciech G. Polak, Mario Rizzetto, Fabien Zoulim, Giovanni Perricone, Marina Berenguer, Lorenzo Giovanni Mantovani, Christophe Duvoux, Luca Saverio Belli
Summary: The European Liver and Intestine Transplant Association (ELITA) held a Consensus Conference involving experts worldwide to update guidelines on HBV prophylaxis in liver transplant candidates and recipients. A simulation model was developed to compare the economic impact of implementing the new ELITA guidelines. The model showed that the guidelines could save around euro 235.65 million after 5 years and euro 540.73 million after 10 years. These savings could be used to allocate resources to different needs.
TRANSPLANT INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Xiaoqi Yu, Qiming Gong, Demin Yu, Yongyan Chen, Ying Jing, Fabien Zoulim, Xinxin Zhang
Summary: Active HBV integration events are present in the liver tissue of patients with chronic HBV infection, including those with HBsAg loss. Antiviral treatment can decrease the number and extent of transcriptionally active viral integrations, suggesting that early treatment intervention may further reduce the risk of HBV infection.
Article
Respiratory System
Thomas El Jammal, Francois Dhelft, Pierre Pradat, Francois Bailly, Fabien Zoulim, Arnaud Hot, Maxime Fauter, Ayoub Drissi-Bakhkhat, Isabelle Durieu, Jean-Christophe Lega, Yvan Jamilloux, Pascal Seve
Summary: This study suggests that lymphopenia and sACE may be valuable biomarkers for sarcoidosis diagnosis in patients with granulomatous hepatitis when combined, especially in younger patients.
SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES
(2023)