Remaining Challenges of HBV Infection: Pathogenesis, Immune Response, Diagnosis and Therapeutic Strategies

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 3326

Special Issue Editor


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Guest Editor
Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Interests: hepatitis viruses; HBV; viral genetic variability; antiviral resistance
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Special Issue Information

Dear Colleagues,

Viral hepatitis is a significant public health challenge of this decade, according to data collected from 187 countries by the World Health Organization (WHO). The majority of the global burden of viral hepatitis is associated with hepatitis B virus (HBV) due to its likelihood of causing chronic infection and its long-term consequences like liver cirrhosis and hepatocellular carcinoma (HCC). The current estimation is that worldwide 254 million people live with chronic HBV infection, 1.23 million get infected each year, and 1.1 million lives are lost annually due to this infection.

Early diagnosis, efficient monitoring and prognostic evaluation are the critical factors contributing to the efficient treatment of HBV-related diseases. Unfortunately, only 13.4% of people living with chronic hepatitis B are diagnosed, and only 2.6% are receiving antiviral therapy. The introduction of antiviral therapy has revolutionized the treatment of chronic hepatitis B infection by reducing liver inflammation and preventing liver-related complications. However, despite the efficient suppression of viral DNA replication, a complete (sterilizing) cure is not achievable by current therapeutic strategies since the persistence of viral covalently closed circular DNA (cccDNA) in the liver cells or the viral DNA integrated into the host genome is not affected. The surrogate treatment endpoint is HBV surface antigen (HBsAg) seroclearance, known as a functional cure. It is a feasible endpoint but is only achieved in a minority of patients. Thus, the current research is focused on developing new therapeutic options and a wider introduction of new non-invasive biomarkers capable of reflecting the virus's intrahepatic activity.

Although many fundamental problems regarding HBV immunopathogenesis have been solved, the phenomena of persistence, clearance, and recurrence of HBV still need to be elucidated. Evidently, some patients spontaneously control the infection, while it becomes chronic in others. Since HBV is not cytocidal, virus-induced liver damage results from a complex interplay between the virus replication and host defense. A better understanding of the role of different viral proteins in the light of viral genetic variability and the mechanisms behind immune-induced control of HBV infection continuously represent the challenges for researchers.

This Special Issue invites original research and review articles covering all unresolved aspects of hepatitis B pathogenesis, immune response, prevention, diagnosis, and therapy.

Prof. Dr. Ivana Lazarevic
Guest Editor

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Keywords

  • HBV
  • pathogenesis
  • immune response
  • clinical management
  • diagnostic methods
  • new biomarkers
  • antiviral therapy
  • new antiviral strategies
  • vaccines and prevention

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Published Papers (3 papers)

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Research

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21 pages, 2438 KiB  
Article
Development of Low-Cost In-House Assays for Quantitative Detection of HBsAg, HBeAg, and HBV DNA to Enhance Hepatitis B Virus Diagnostics and Antiviral Screening in Resource-Limited Settings
by Simmone D’souza, Layla Al-Yasiri, Annie Chen, Dan T. Boghici, Guido van Marle, Jennifer A. Corcoran, Trushar R. Patel and Carla S. Coffin
Pathogens 2025, 14(3), 258; https://doi.org/10.3390/pathogens14030258 - 5 Mar 2025
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Abstract
Globally, an estimated 254 million people are living with chronic hepatitis B virus (HBV) infection, yet only 10.5% have been diagnosed, underscoring the urgent need to expand testing to meet the World Health Organization’s HBV elimination targets by 2030. Many HBV diagnostic tests [...] Read more.
Globally, an estimated 254 million people are living with chronic hepatitis B virus (HBV) infection, yet only 10.5% have been diagnosed, underscoring the urgent need to expand testing to meet the World Health Organization’s HBV elimination targets by 2030. Many HBV diagnostic tests remain expensive and inaccessible in resource-limited settings. In this study, we demonstrate how individually sourced, commercially available reagents can be used to develop cost-effective in-house assays for total DNA isolation, HBV viral load quantification by (q)PCR, and qHBsAg and qHBeAg measurement using sandwich ELISA. These assays were validated using known HBV-positive and HBV-negative plasma samples (genotypes A–F) and HepAD38 cells treated with tenofovir disoproxil fumarate (TDF). DNA isolation using a commercial column-based kit was compared to a high-throughput, column-free method, allowing for HBV quantification from 50 µL of plasma with lower limits of detection (LLOD) of 1.8 × 103 and 1.8 × 104 HBV DNA copies IU/mL, respectively. Both commercial and in-house DNA isolation methods yielded comparable half-maximal effective concentration (EC50) values in TDF-treated HepAD38 cells. Additionally, in-house sandwich ELISA assays were developed for quantitative HBsAg and HBeAg detection, with LLOD values of 0.78 IU/mL and 0.38 PEI U/mL (Paul Ehrlich Institute), respectively. The in-house reagents for DNA isolation, molecular testing, and serological detection of HBV were estimated to be at least 10 times more cost-effective than commercially available kits, highlighting their potential for broader application in resource-limited regions. Full article
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13 pages, 4121 KiB  
Article
Contrasting Effect of Curcumin on Hepatitis B Virus Replication According to the Hepatoma Cell Line
by María Mercedes Elizalde, Pedro Fuentes, Diego Chiappetta and Diego Martín Flichman
Pathogens 2025, 14(2), 203; https://doi.org/10.3390/pathogens14020203 - 19 Feb 2025
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Abstract
In recent decades, considerable advances have been achieved in the treatment of chronic hepatitis B. However, the currently available drugs have shortcomings. In this context, several natural compounds have been proposed as potential agents to improve either the outcome of antiviral treatment or [...] Read more.
In recent decades, considerable advances have been achieved in the treatment of chronic hepatitis B. However, the currently available drugs have shortcomings. In this context, several natural compounds have been proposed as potential agents to improve either the outcome of antiviral treatment or the progression of chronic infection, with curcumin being one of the most evaluated compounds due to its pleiotropic antiviral activity. The aim of this study was to characterize the effect and mechanism of curcumin on hepatitis B virus (HBV) replication in two different experimental models. Treatment of HepG22.15 and HBV-transfected Huh7 cells with curcumin revealed that the phytochemical differentially modulated HBV replication in both cell lines. In HepG22.15 cells, the addition of curcumin had no effect on viral DNA, pregenomic RNA (pgRNA), and e antigen (HBeAg) levels, while it decreased Precore RNA and s antigen (HBsAg) levels. Conversely, in Huh-7 cells, curcumin significantly increased viral progeny more than tenfold, as well as HBV RNAs and viral antigens. Furthermore, the analysis of the cellular mechanisms associated with the modulation of viral replication revealed that in Huh-7 cells, curcumin-induced cell cycle arrest in the G2/M phase and the modulation of genes involved in proliferation, cell cycle progression, and apoptosis, whereas no changes in cell cycle progression and gene expression were observed in HepG22.15 cells. In conclusion, curcumin elicits a differential cellular response in two hepatoma cell lines, which, in the case of Huh-7 cells, would provide an optimal cellular setting that enhances HBV replication. Therefore, the antiviral effect of this phytochemical remains controversial. Full article
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16 pages, 675 KiB  
Review
Surveillance Following Hepatitis B Surface Antigen Loss: An Issue Requiring Attention
by Shuai-Wen Huang, Hong Long and Jia-Quan Huang
Pathogens 2025, 14(1), 8; https://doi.org/10.3390/pathogens14010008 - 27 Dec 2024
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Abstract
Due to the lack of agents that directly target covalently closed circular DNA and integrated HBV DNA in hepatocytes, achieving a complete cure for chronic hepatitis B (CHB) remains challenging. The latest guidelines recommend (hepatitis B surface antigen) HBsAg loss as the ideal [...] Read more.
Due to the lack of agents that directly target covalently closed circular DNA and integrated HBV DNA in hepatocytes, achieving a complete cure for chronic hepatitis B (CHB) remains challenging. The latest guidelines recommend (hepatitis B surface antigen) HBsAg loss as the ideal treatment target for improving liver function, histopathology, and long-term prognosis. However, even after HBsAg loss, hepatitis B virus can persist, with a risk of recurrence, reactivation, cirrhosis, and hepatocellular carcinoma. Therefore, follow-up and surveillance are still necessary. With increasing treatment options available for achieving HBsAg loss in patients with CHB, developing effective surveillance strategies has become crucial. Recent studies on outcomes following HBsAg loss provide new insights for refining current surveillance strategies, though further improvement is needed through long-term observation and follow-up. Full article
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