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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 -
Scientific Reports Jun 2024Occult hepatitis B virus infection (OBI) is characterized by the presence of HBV DNA in the absence of detectable HBsAg. OBI is an important risk factor for cirrhosis...
Occult hepatitis B virus infection (OBI) is characterized by the presence of HBV DNA in the absence of detectable HBsAg. OBI is an important risk factor for cirrhosis and hepatocellular carcinoma, but its pathogenesis has not been fully elucidated. Mutations in the HBV preS/S genes can lead to impaired secretion of either HBsAg or S-protein resulting in the accumulation of defective viruses or S protein in cells. In our previous work, the M133S mutation was present in the HBV S gene of maintenance hemodialysis (MHD) patients with OBI. In this study, we investigated the potential role of amino acid substitutions in S proteins in S protein production and secretion through the construction of mutant S gene plasmids, structural prediction, transcriptome sequencing analysis, and in vitro functional studies. Protein structure prediction showed that the S protein M133S mutant exhibited hydrophilic modifications, with greater aggregation and accumulation of the entire structure within the membrane phospholipid bilayer. Differential gene enrichment analysis of transcriptome sequencing data showed that differentially expressed genes were mainly concentrated in protein processing in the endoplasmic reticulum (ER). The expression of heat shock family proteins and ER chaperone molecules was significantly increased in the wild-type and mutant groups, whereas the expression of mitochondria-associated proteins was decreased. Immunofluorescence staining and protein blotting showed that the endoplasmic reticulum-associated protein PDI, the autophagy marker LC3, and the lysosome-associated protein LAMP2 co-localized with the S proteins in the wild-type and mutant strains, and their expression was increased. The mitochondria-associated TOMM20 protein was also co-expressed with the S protein, but expression was significantly reduced in the mutant. The M133S mutation in the S gene is expressed as a defective and misfolded protein that accumulates in the endoplasmic reticulum causing secretion-impaired endoplasmic reticulum stress, which in turn triggers mitochondrial autophagy and recruits lysosomes to fuse with the autophagosome, leading to mitochondrial clearance. This study preliminarily demonstrated that the mutation of M133S in the S gene can cause OBI and is associated with disease progression, providing a theoretical basis for the diagnosis and treatment of OBI.
Topics: Humans; Mitophagy; Renal Dialysis; Hepatitis B; Hepatitis B virus; Endoplasmic Reticulum Stress; Hepatitis B Surface Antigens; Male; Mutation; Female; Middle Aged; Viral Envelope Proteins; Mitochondria; Amino Acid Substitution; Adult
PubMed: 38886481
DOI: 10.1038/s41598-024-64943-3 -
Mathematical Biosciences and... Mar 2024Hepatitis B is one of the global health issues caused by the hepatitis B virus (HBV), producing 1.1 million deaths yearly. The acute and chronic phases of HBV are...
Hepatitis B is one of the global health issues caused by the hepatitis B virus (HBV), producing 1.1 million deaths yearly. The acute and chronic phases of HBV are significant because worldwide, approximately 250 million people are infected by chronic hepatitis B. The chronic stage is a long-term, persistent infection that can cause liver damage and increase the risk of liver cancer. In the case of multiple phases of infection, a generalized saturated incidence rate model is more reasonable than a simply saturated incidence because it captures the complex dynamics of the different infection phases. In contrast, a simple saturated incidence rate model assumes a fixed shape for the incidence rate curve, which may not accurately reflect the dynamics of multiple infection phases. Considering HBV and its various phases, we constructed a model to present the dynamics and control strategies using the generalized saturated incidence. First, we proved that the model is well-posed. We then found the reproduction quantity and model equilibria to discuss the time dynamics of the model and investigate the conditions for stabilities. We also examined a control mechanism by introducing various controls to the model with the aim to increase the population of those recovered and minimize the infected people. We performed numerical experiments to check the biological significance and control implementation.
Topics: Humans; Incidence; Hepatitis B virus; Hepatitis B; Computer Simulation; Hepatitis B, Chronic; Basic Reproduction Number; Liver Neoplasms; Models, Biological; Algorithms
PubMed: 38872533
DOI: 10.3934/mbe.2024230 -
Journal of Infection in Developing... May 2024Hepatitis B virus infection is a global public health concern and has a high degree of associated morbidity and mortality. In Ethiopia, Hepatitis B virus infection has a...
INTRODUCTION
Hepatitis B virus infection is a global public health concern and has a high degree of associated morbidity and mortality. In Ethiopia, Hepatitis B virus infection has a variable seroprevalence among different regions with an estimated overall prevalence of around 6%. However, there is a scarcity of data specific to cancer patients.
METHODOLOGY
A hospital-based cross-sectional study was conducted among 384 cancer patients who came for follow-up at the oncology unit of Hawassa University Comprehensive Specialized Hospital from January 1/2020 to October 11/2021. A systematic sampling technique was employed to select the participants. Data was collected using structured and interviewer-administered questionnaires and blood samples were drawn from the patients to test hepatitis B virus sero-status. Data was entered to Epi- Data version 4.6 then exported and analysis was done using SPSS version 25. Descriptive statistics were used to describe the study participants. Finally, bivariable and multivariable binary logistic regression was used to identify significantly associated factors.
RESULTS
The seroprevalence of hepatitis B virus infection among cancer patients was 7.6% [95% CI: (4.54 - 9.79)]. Having multiple sexual partners (AOR = 6.24, 95% CI (3.35-16.80)), a history of dental procedures (AOR = 3.34; 95% CI (1.007‑7.66)), and being a hepatocellular carcinoma patient (AOR = 6.13; 95% CI (3.66-18.77)) were factors associated with seropositive status for Hepatitis B virus.
CONCLUSIONS
The seroprevalence of Hepatitis B virus infection among cancer patients was high. It is better to consider HBV screening in cancer patients and doing cancer surveillance in HBV-infected patients.
Topics: Humans; Ethiopia; Seroepidemiologic Studies; Male; Female; Cross-Sectional Studies; Adult; Middle Aged; Hepatitis B; Neoplasms; Young Adult; Risk Factors; Hospitals, University; Aged; Adolescent; Hepatitis B virus; Prevalence; Hospitals, Special
PubMed: 38865407
DOI: 10.3855/jidc.18479