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International Journal of Molecular... Jun 2024Hepatitis B virus (HBV) infects approximately 300 million people worldwide, causing chronic infections. The HBV X protein (HBx) is crucial for viral replication and...
Hepatitis B virus (HBV) infects approximately 300 million people worldwide, causing chronic infections. The HBV X protein (HBx) is crucial for viral replication and induces reactive oxygen species (ROS), leading to cellular damage. This study explores the relationship between HBx-induced ROS, p53 activation, and HBV replication. Using HepG2 and Hep3B cell lines that express the HBV receptor NTCP, we compared ROS generation and HBV replication relative to p53 status. Results indicated that HBV infection significantly increased ROS levels in p53-positive HepG2-NTCP cells compared to p53-deficient Hep3B-NTCP cells. Knockdown of p53 reduced ROS levels and enhanced HBV replication in HepG2-NTCP cells, whereas p53 overexpression increased ROS and inhibited HBV replication in Hep3B-NTCP cells. The ROS scavenger N-acetyl-L-cysteine (NAC) reversed these effects. The study also found that ROS-induced degradation of the HBx is mediated by the E3 ligase Siah-1, which is activated by p53. Mutations in p53 or inhibition of its transcriptional activity prevented ROS-mediated HBx degradation and HBV inhibition. These findings reveal a p53-dependent negative feedback loop where HBx-induced ROS increases p53 levels, leading to Siah-1-mediated HBx degradation and HBV replication inhibition. This study offers insights into the molecular mechanisms of HBV replication and identifies potential therapeutic targets involving ROS and p53 pathways.
Topics: Humans; Tumor Suppressor Protein p53; Hepatitis B virus; Reactive Oxygen Species; Virus Replication; Trans-Activators; Viral Regulatory and Accessory Proteins; Hep G2 Cells; Liver Neoplasms; Carcinoma, Hepatocellular; Ubiquitin-Protein Ligases; Nuclear Proteins; Cell Line, Tumor
PubMed: 38928309
DOI: 10.3390/ijms25126606 -
PloS One 2024Hepatitis B virus (HBV) constitutes a significant global health challenge, with more than 2 billion people infected globally and almost 291 million chronic cases. In...
Hepatitis B virus (HBV) constitutes a significant global health challenge, with more than 2 billion people infected globally and almost 291 million chronic cases. In Africa, coinfection of HBV with Human Immunodeficiency Virus (HIV) is high, yet the condition remains overlooked in many countries. While antiretroviral therapy (ART) has improved HIV survival, viral hepatitis continues to contribute to morbidity and mortality. Occult Hepatitis B infection (OBI), characterized by a low-level of HBV DNA in individuals with negative hepatitis B surface antigen (HBsAg), is an emerging concern among HIV seropositive individuals due to the risk of HBV reactivation and associated complications, especially hepatocellular carcinoma (HCC). Ghana has an estimated HBV/HIV coinfection prevalence of 13.6% making it important to also determine potential cases of OBI. This study aims to assess OBI prevalence in persons living with HIV (PLHIV). A cross-sectional study was conducted in five health facilities in the Cape Coast Metropolis. HBV-related serological markers were determined among 116 PLHIV using the Enzyme-Linked Immunosorbent Assay (ELISA) method. HBV DNA was extracted from 30 participants found to be HBsAg negative but positive for hepatitis B core antibody (HBcAb+). Nested PCR was employed in detecting HBV DNA and HBV viral load was performed using qPCR. The median age of the participants was 37 years (IQR 22-65). Serologically, 7.8% (n = 9, 95% CI: 3.5-22.7), 12.1% (n = 14), and 25.9% (n = 30) tested positive for solely HBsAg, HBsAb, and HBcAb respectively. OBI prevalence among HBsAg-/HBcAb+ participants was 16.7% (n = 5, 95% CI: 6.5-23.7) with a median HBV DNA level of 139.2 IU/ml (IQR, 96.7-142.0). The prevalence of OBI among HIV-positive participants in the Cape Coast Metropolis highlights the need to consider screening for HBV among HIV patients using nucleic acid amplification tests. This can inform medical management and reduce the risk of liver complications, including HCC.
Topics: Humans; Ghana; HIV Infections; Female; Male; Adult; Hepatitis B; Prevalence; Middle Aged; Cross-Sectional Studies; Hepatitis B virus; Hepatitis B Surface Antigens; Coinfection; DNA, Viral; Young Adult
PubMed: 38924017
DOI: 10.1371/journal.pone.0305862 -
Journal of Zhejiang University.... Jun 2024Artificial vascular graft (AVG) fistula is widely used for hemodialysis treatment in patients with renal failure. However, it has poor elasticity and compliance, leading...
Artificial vascular graft (AVG) fistula is widely used for hemodialysis treatment in patients with renal failure. However, it has poor elasticity and compliance, leading to stenosis and thrombosis. The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery, which is primarily maintained by collagen in the extracellular matrix (ECM) of arterial cells. Studies have revealed that in hepatitis B virus (HBV)-induced liver fibrosis, hepatic stellate cells (HSCs) become hyperactive and produce excessive ECM fibers. Furthermore, mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure. Based on the above factors, we transfected HSCs with the hepatitis B viral X () gene for simulating the process of HBV infection. Subsequently, these -HSCs were implanted into a polycaprolactone-polyurethane (PCL-PU) bilayer scaffold in which the inner layer is dense and the outer layer consists of pores, which was mechanically stimulated to promote the secretion of collagen nanofiber from the -HSCs and to facilitate crosslinking with the scaffold. We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization. Then, the vessel scaffold was implanted into a rabbit's neck arteriovenous fistula model. It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit's body. Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels, providing a novel approach for creating clinical vascular access for dialysis.
Topics: Rabbits; Animals; Hepatic Stellate Cells; Renal Dialysis; Polyesters; Viral Regulatory and Accessory Proteins; Tissue Scaffolds; Transfection; Bionics; Polyurethanes; Blood Vessel Prosthesis; Extracellular Matrix; Humans; Hepatitis B virus; Collagen; Tissue Engineering; Trans-Activators
PubMed: 38910495
DOI: 10.1631/jzus.B2300479 -
BMC Infectious Diseases Jun 2024Currently, several studies have observed that chronic hepatitis B virus infection is associated with the pathogenesis of kidney disease. However, the extent of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Currently, several studies have observed that chronic hepatitis B virus infection is associated with the pathogenesis of kidney disease. However, the extent of the correlation between hepatitis B virus infection and the chronic kidney disease risk remains controversial.
METHODS
In the present study, we searched all eligible literature in seven databases in English and Chinese. The random effects model was used to conduct a meta-analysis. Quality of included studies was assessed using the Newcastle-Ottawa Quality Scale.
RESULTS
In this analysis, a total of 31 studies reporting the association between hepatitis B virus infection and chronic kidney disease risk were included. The results showed a significant positive association between hepatitis B virus infection and the risk of chronic kidney disease (pooled OR, 1.20; 95% CI, 1.12-1.29), which means that hepatitis B virus increases the risk of developing chronic kidney disease.
CONCLUSION
This study found that hepatitis B virus infection was associated with a significantly increased risk of chronic kidney disease. However, the current study still cannot directly determine this causal relationship. Thus, more comprehensive prospective longitudinal studies are needed in the future to provide further exploration and explanation of the association between hepatitis B virus and the risk of developing chronic kidney disease.
Topics: Humans; Renal Insufficiency, Chronic; Risk Factors; Hepatitis B, Chronic; Hepatitis B; Hepatitis B virus
PubMed: 38909191
DOI: 10.1186/s12879-024-09546-z -
BMC Infectious Diseases Jun 2024Toll-Like receptors (TLRs) play an important role in the immune response during hepatitis B virus (HBV) infection. In this study, we evaluated the association between...
BACKGROUND
Toll-Like receptors (TLRs) play an important role in the immune response during hepatitis B virus (HBV) infection. In this study, we evaluated the association between two SNP variants (TLR3 rs3775290 and TLR4 rs4986790) and susceptibility to chronic HBV infection in Mauritania.
SUBJECTS AND METHODS
A total of 188 subjects were recruited for this study: 102 chronically infected patients and 86 individuals with spontaneously resolved HBV infection who were considered controls. Targeted PCR products were sequenced using Sanger sequencing.
RESULTS
We found that TLR3 rs3775290 was significantly more frequent in patients with chronic HBV than in the control population (p = 0.03). However, no association was found between the TLR4 rs3775290 polymorphism and chronic infection.
CONCLUSION
Our results suggest that the TLR3 rs3775290 polymorphism may be a risk factor for susceptibility to chronic HBV infection in the Mauritanian population.
Topics: Humans; Toll-Like Receptor 3; Male; Female; Case-Control Studies; Polymorphism, Single Nucleotide; Adult; Hepatitis B, Chronic; Genetic Predisposition to Disease; Middle Aged; Mauritania; Young Adult; Hepatitis B virus
PubMed: 38907187
DOI: 10.1186/s12879-024-09503-w -
Polish Journal of Microbiology Jun 2024Interferon-alpha (IFN-α) is a first-line drug for treating chronic hepatitis B (CHB). Guanylate-binding protein 1 (GBP1) is one of the interferon-stimulating factors,...
Interferon-alpha (IFN-α) is a first-line drug for treating chronic hepatitis B (CHB). Guanylate-binding protein 1 (GBP1) is one of the interferon-stimulating factors, which participates in the innate immunity of the host and plays an antiviral and antibacterial role. In this study, we explored how GBP1 is involved in IFN-α antiviral activity against HBV. Before being gathered, HepG2-NTCP and HepG2 2.15 cells were transfected with the wild-type hGBP1 plasmid or si-GBP1, respectively, and followed by stimulation with Peg-IFNα-2b. We systematically explored the role of GBP1 in regulating HBV infection in cell models. Additionally, we also examined GBP1 levels in CHB patients. GBP1 activity increased, and its half-life was prolonged after HBV infection. Overexpression of GBP1 inhibited the production of HBsAg and HBeAg, as well as HBs protein and HBV total RNA levels, whereas silencing of GBP1 inhibited its ability to block viral infections. Interestingly, overexpressing GBP1 co-treatment with Peg-IFNα-2b further increased the antiviral effect of IFN-α, while GBP1 silencing co-treatment with Peg-IFNα-2b partly restored its inhibitory effect on HBV. Mechanistically, GBP1 mediates the anti-HBV response of Peg-IFNα-2b by targeting HBs. Analysis of clinical samples revealed that GBP1 was elevated in CHB patients and increased with Peg-IFNα-2b treatment, while GBP1 showed good stability in the interferon response group. Our study demonstrates that GBP1 inhibits HBV replication and promotes HBsAg clearance. It is possible to achieve antiviral effects through the regulation of IFN-α induced immune responses in response to HBV.
Topics: Humans; Interferon-alpha; Hepatitis B virus; Antiviral Agents; GTP-Binding Proteins; Hep G2 Cells; Hepatitis B, Chronic; Male; Hepatitis B Surface Antigens; Female; Adult; Virus Replication; Hepatitis B
PubMed: 38905278
DOI: 10.33073/pjm-2024-021 -
European Journal of Medical Research Jun 2024As a hepatotropic virus, hepatitis B virus (HBV) can establish a persistent chronic infection in the liver, termed, chronic hepatitis B (CHB), which causes a series of... (Review)
Review
As a hepatotropic virus, hepatitis B virus (HBV) can establish a persistent chronic infection in the liver, termed, chronic hepatitis B (CHB), which causes a series of liver-related complications, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCC with HBV infection has a significantly increased morbidity and mortality, whereas it could be preventable. The current goal of antiviral therapy for HBV infection is to decrease CHB-related morbidity and mortality, and achieve sustained suppression of virus replication, which is known as a functional or immunological cure. The natural history of chronic HBV infection includes four immune phases: the immune-tolerant phase, immune-active phase, inactive phase, and reactivation phase. However, many CHB patients do not fit into any of these defined phases and are regarded as indeterminate. A large proportion of indeterminate patients are only treated with dynamic monitoring rather than recommended antiviral therapy, mainly due to the lack of definite guidelines. However, many of these patients may gradually have significant liver histopathological changes during disease progression. Recent studies have focused on the prevalence, progression, and carcinogenicity of indeterminate CHB, and more attention has been given to the prevention, detection, and treatment for these patients. Herein, we discuss the latest understanding of the epidemiology, clinical characteristics, and therapeutic strategies of indeterminate CHB, to provide avenues for the management of these patients.
Topics: Humans; Hepatitis B, Chronic; Antiviral Agents; Hepatitis B virus; Liver Neoplasms; Carcinoma, Hepatocellular; Liver Cirrhosis; Disease Progression
PubMed: 38902822
DOI: 10.1186/s40001-024-01942-0 -
Signal Transduction and Targeted Therapy Jun 2024This study aimed to develop a pan-genotypic and multifunctional small interfering RNA (siRNA) against hepatitis B virus (HBV) with an efficient delivery system for...
This study aimed to develop a pan-genotypic and multifunctional small interfering RNA (siRNA) against hepatitis B virus (HBV) with an efficient delivery system for treating chronic hepatitis B (CHB), and explore combined RNA interference (RNAi) and immune modulatory modalities for better viral control. Twenty synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and evaluated. The lipid nanoparticle (LNP) formulation was optimized by adopting HO-PEG-DMG lipid and modifying the molar ratio of traditional polyethylene glycol (PEG) lipid in LNP prescriptions. The efficacy and safety of this formulation in delivering siHBV (tLNP/siHBV) along with the mouse IL-2 (mIL-2) mRNA (tLNP/siHBVIL2) were evaluated in the rAAV-HBV1.3 mouse model. A siRNA combination (terms "siHBV") with a genotypic coverage of 98.55% was selected, chemically modified, and encapsulated within an optimized LNP (tLNP) of high efficacy and security to fabricate a therapeutic formulation for CHB. The results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA (up to 3log reduction; vs PBS) in dose- and time-dependent manners at single-dose or multi-dose frequencies, with satisfactory safety profiles. Further studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus, via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4 and CD8 T cell responses by expressed mIL-2 protein. By adopting tLNP as nucleic acid nanocarriers, the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV, thus offering a promising translational therapeutic strategy for treating CHB.
Topics: Animals; Mice; Hepatitis B virus; Interleukin-2; Humans; RNA, Small Interfering; Nanoparticles; RNA, Messenger; Hepatitis B, Chronic; RNA Interference; Hepatitis B; RNAi Therapeutics; Liposomes
PubMed: 38902241
DOI: 10.1038/s41392-024-01871-8 -
World Journal of Gastroenterology Jun 2024In this editorial, we offer a summary of the risk associated with hepatitis B reactivation (HBVr) in the setting of both solid and hematologic malignancies treated with...
In this editorial, we offer a summary of the risk associated with hepatitis B reactivation (HBVr) in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase (BTK) inhibitors, with insights derived from current studies. Furthermore, we emphasize the critical need for a framework regarding robust risk evaluation in patients undergoing such treatments. This framework is essential for identifying those at increased risk of HBVr, enabling healthcare providers to implement proactive measures to prevent reactivation and ensure the safe administration of BTK inhibitor therapy.
Topics: Humans; Agammaglobulinaemia Tyrosine Kinase; Virus Activation; Hepatitis B virus; Protein Kinase Inhibitors; Antiviral Agents; Hepatitis B; Risk Assessment; Hepatitis B, Chronic; Hematologic Neoplasms; Tyrosine Kinase Inhibitors
PubMed: 38899330
DOI: 10.3748/wjg.v30.i21.2748 -
Journal of Cellular and Molecular... Jun 2024Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs)....
Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMP%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMP% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMP% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.
Topics: Humans; Hepatitis B, Chronic; Male; Female; Hepatitis B virus; Adult; Mitochondria; Middle Aged; Leukocyte Count; Leukocytes; DNA, Viral; Membrane Potential, Mitochondrial; Monocytes; Neutrophils
PubMed: 38890792
DOI: 10.1111/jcmm.18440