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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 -
Journal of Infection in Developing... May 2024Human immunodeficiency virus (HIV) / hepatitis B virus (HBV) causes higher rates of liver disease compared to infection with just one virus. Co-infection can accelerate...
INTRODUCTION
Human immunodeficiency virus (HIV) / hepatitis B virus (HBV) causes higher rates of liver disease compared to infection with just one virus. Co-infection can accelerate the progression to liver fibrosis or hepatocellular carcinoma and disturb the treatment response. APOBEC3G is a host defense factor which interferes with HIV-1 and HBV. We aimed to determine the prevalence of hepatitis B surface antigen (HBsAg) among HIV-infected patients and seronegative controls, and screen the HIV/HBV population for APOBEC3G variants rs8177832, rs35228531 and rs2294367, previously associated with HIV-1 infection susceptibility in Morocco.
METHODOLOGY
A case control study was conducted on 404 individuals (204 HIV-infected and 200 eligible blood donors) from April to November 2021. HBsAg was measured on the Roche Cobas e411 automatic analyzer (Roche Diagnostics, Basel, Switzerland) and APOBEC3G polymorphisms were identified using the TaqMan genotyping allelic discrimination method. Fisher Exact test, odds ratio (OR) with 95% confidence interval (CI), and haplotype frequencies were calculated.
RESULTS
Of the 204 HIV-1 seropositive patients and 200 controls, 4.9% (95%CI: 2.38-8.83) and 2.50% (95% CI: 0.82-5.74) were HBsAg-positive respectively. There was a significant association between increasing age (> 40 years) and HBV infection among controls (p = 0.04). The distribution of genotypes and alleles frequencies of APOBEC3G variants was heterogenous and five different haplotypes with frequencies ≥ 5% were obtained, of which ACC (rs8177832, rs35228531, rs2294367) was the most prevalent.
CONCLUSIONS
HBV co-infection is common among HIV-1 infected individuals in Morocco. Efforts should be made to prevent, treat and control HBV transmission in this population.
Topics: Humans; Morocco; Male; HIV Infections; Female; Adult; Coinfection; APOBEC-3G Deaminase; Case-Control Studies; Hepatitis B Surface Antigens; Middle Aged; Prevalence; Hepatitis B; HIV-1; Young Adult; Hepatitis B virus
PubMed: 38865405
DOI: 10.3855/jidc.18781 -
Frontiers in Immunology 2024This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)...
Machine learning-based model for predicting tumor recurrence after interventional therapy in HBV-related hepatocellular carcinoma patients with low preoperative platelet-albumin-bilirubin score.
INTRODUCTION
This study aimed to develop a prognostic nomogram for predicting the recurrence-free survival (RFS) of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with low preoperative platelet-albumin-bilirubin (PALBI) scores after transarterial chemoembolization (TACE) combined with local ablation treatment.
METHODS
We gathered clinical data from 632 HBV-related HCC patients who received the combination treatment at Beijing You'an Hospital, affiliated with Capital Medical University, from January 2014 to January 2020. The patients were divided into two groups based on their PALBI scores: low PALBI group (n=247) and high PALBI group (n=385). The low PALBI group was then divided into two cohorts: training cohort (n=172) and validation cohort (n=75). We utilized eXtreme Gradient Boosting (XGBoost), random survival forest (RSF), and multivariate Cox analysis to pinpoint the risk factors for RFS. Then, we developed a nomogram based on the screened factors and assessed its risk stratification capabilities and predictive performance.
RESULTS
The study finally identified age, aspartate aminotransferase (AST), and prothrombin time activity (PTA) as key predictors. The three variables were included to develop the nomogram for predicting the 1-, 3-, and 5-year RFS of HCC patients. We confirmed the nomogram's ability to effectively discern high and low risk patients, as evidenced by Kaplan-Meier curves. We further corroborated the excellent discrimination, consistency, and clinical utility of the nomogram through assessments using the C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA).
CONCLUSION
Our study successfully constructed a robust nomogram, effectively predicting 1-, 3-, and 5-year RFS for HBV-related HCC patients with low preoperative PALBI scores after TACE combined with local ablation therapy.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; Middle Aged; Machine Learning; Bilirubin; Neoplasm Recurrence, Local; Nomograms; Hepatitis B virus; Chemoembolization, Therapeutic; Prognosis; Blood Platelets; Hepatitis B; Adult; Serum Albumin; Retrospective Studies; Platelet Count
PubMed: 38863693
DOI: 10.3389/fimmu.2024.1409443 -
Scientific Reports Jun 2024Hepatitis B virus (HBV) infection is highly prevalent in Guangzhou, China. This study aimed to examine the long-term trend of HB incidence from 2008 to 2022 and the...
Hepatitis B virus (HBV) infection is highly prevalent in Guangzhou, China. This study aimed to examine the long-term trend of HB incidence from 2008 to 2022 and the independent impacts of age, period, and cohort on the trends. HBV data were collected from the China Information System for Disease Control and Prevention. Joinpoint regression was utilized to examine temporal trends, and an age-period-cohort model was employed to estimate the effects of age, period, and cohort. A total of 327,585 HBV cases were included in this study. The incidence of chronic and acute HB showed a decreasing trend in Guangzhou over the past 15 years, with an average annual percent change of - 4.31% and - 16.87%, respectively. Age, period, and cohort all exerted significant effects. The incidence of HB was higher in males than in females and non-central areas compared to central areas. Age groups of 0-4 years and 15-24 years were identified as high-risk groups. The period relative risks for chronic HB incidence decreased initially and then stabilized. Cohorts born later had lower risks. Chronic HB incidences remain high in Guangzhou, especially among males, younger individuals, and residents of non-central areas. More efforts are still needed to achieve hepatitis elimination targets.
Topics: Humans; China; Female; Male; Incidence; Adolescent; Adult; Middle Aged; Infant; Child; Child, Preschool; Young Adult; Hepatitis B; Infant, Newborn; Aged; Age Factors; Cohort Effect; Hepatitis B virus; Risk Factors
PubMed: 38862511
DOI: 10.1038/s41598-024-63796-0 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... May 2024To investigate the prognostic value of M2 macrophage-related genes (MRG) in hepatitis B virus (HBV)- related hepatocellular carcinoma (HCC).
OBJECTIVE
To investigate the prognostic value of M2 macrophage-related genes (MRG) in hepatitis B virus (HBV)- related hepatocellular carcinoma (HCC).
METHODS
The transcriptome data of 73 patients with HBV-related HCC were obtained from TCGA database, and the MRG modules were identified by WGCNA. The MRG-based risk scoring model was constructed by LASSO regression analysis and validated using an external dataset. The correlation of the risk score with immune cell infiltration and drug sensitivity of HCC were analyzed with CIBERSORT and R. pRRophetic. The signaling pathways of the differential genes between the high- and low-risk groups were investigated using GSVA and GSEA enrichment analyses, and MRG expressions at the single cell level were validated using R.Seurat. The cell interaction intensity was analyzed by R.Cellchat to identify important cell types related to HCC progression. MRG expression levels were detected by RT-qPCR in THP-1 cells with HCC-conditioned medium-induced M2 polarization and in HBV-positive HCC cells.
RESULTS
A high M2 macrophage infiltration level was significantly correlated with a poor prognosis of HCC, and 5 hub MRG (VTN, GCLC, PARVB, TRIM27, and GMPR) were identified. The overall survival of HCC patients was significantly lower in the high-risk than in the low-risk group. The high- and the low-risk groups showed significant enrichment of M2 macrophages and na?ve B cells, respectively, and were sensitive to BI. 2536 and to AG. 014699, AKT. inhibitor. Ⅷ, AZD. 0530, AZD7762, and BMS. 708163, respectively. The proliferation-related and metabolism-related pathways were enriched in the high-risk group, where monocytes showed the most active cell interactions during HCC progression. VTN was significantly upregulated in HCC cell lines, while GCLC, PARVB, TRIM27, and GMPR were upregulated in M2 THP-1 cells.
CONCLUSION
The MRG-based risk scoring model can accurately predict the prognosis of HBV-related HCC and reveal the differences in tumor microenvironment to guide precision treatment of the patients.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis; Macrophages; Hepatitis B virus; Transcriptome; Hepatitis B; Gene Expression Regulation, Neoplastic; Tumor Microenvironment
PubMed: 38862440
DOI: 10.12122/j.issn.1673-4254.2024.05.04 -
PloS One 2024All-trans retinoic acid (ATRA), recognized as the principal and most biologically potent metabolite of vitamin A, has been identified for its inhibitory effects on...
All-trans retinoic acid (ATRA), recognized as the principal and most biologically potent metabolite of vitamin A, has been identified for its inhibitory effects on hepatitis B virus (HBV) replication. Nevertheless, the underlying mechanism remains elusive. The present study reveals that ATRA induces E6-associated protein (E6AP)-mediated proteasomal degradation of HBx to suppress HBV replication in human hepatoma cells in a p53-dependent pathway. For this effect, ATRA induced promoter hypomethylation of E6AP in the presence of HBx, which resulted in the upregulation of E6AP levels in HepG2 but not in Hep3B cells, emphasizing the p53-dependent nature of this effect. As a consequence, ATRA augmented the interaction between E6AP and HBx, resulting in substantial ubiquitination of HBx and consequent reduction in HBx protein levels in both the HBx overexpression system and the in vitro HBV replication model. Additionally, the knockdown of E6AP under ATRA treatment reduced the interaction between HBx and E6AP and decreased the ubiquitin-dependent proteasomal degradation of HBx, which prompted a recovery of HBV replication in the presence of ATRA, as confirmed by increased levels of intracellular HBV proteins and secreted HBV levels. This study not only contributes to the understanding of the complex interactions between ATRA, p53, E6AP, and HBx but also provides an academic basis for the clinical employment of ATRA in the treatment of HBV infection.
Topics: Humans; Viral Regulatory and Accessory Proteins; Trans-Activators; Proteasome Endopeptidase Complex; Virus Replication; Hepatitis B virus; Tretinoin; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases; Hep G2 Cells; Down-Regulation; Ubiquitination; Proteolysis; Promoter Regions, Genetic; DNA Methylation; Cell Line, Tumor
PubMed: 38861553
DOI: 10.1371/journal.pone.0305350 -
Infection, Genetics and Evolution :... Aug 2024Hepatitis B virus (HBV) belongs to the family Hepadnaviridae and is the smallest human DNA virus, with a genome that is only 3200 nucleotides long. The absence of... (Review)
Review
Hepatitis B virus (HBV) belongs to the family Hepadnaviridae and is the smallest human DNA virus, with a genome that is only 3200 nucleotides long. The absence of proofreading function in HBV reverse transcriptase provides a wide range of genetic variants for targeted outgrowth at different stages of infection. A number of sub genotypes and ten HBV genotypes (A through J) have been identified through analyses of the divergence of HBV genomic sequences. Numerous clinical outcomes, including the emergence of chronicity, the course of the disease, the effectiveness of treatment, and the response to vaccination, have been related to differences in genotype between HBV isolates. There are just seven studies that have been done in Ethiopia that examine the molecular epidemiology of HBV. Moreover, these studies haven't been compiled and reviewed yet. In this review, we looked at the genetic diversity and molecular epidemiology of HBV, the relationship between HBV genotypes and clinical outcomes, the immunopathogenesis of HBV, and finally the molecular epidemiology of HBV in Ethiopia. PubMed, Embase, and Google Scholar search engines were used to find relevant articles for the review. By using HBV genotyping, clinicians can better tailor vaccination decisions and antiviral therapy for patients with chronic hepatitis B who are more likely to experience the disease's progression.
Topics: Hepatitis B virus; Humans; Ethiopia; Molecular Epidemiology; Genotype; Hepatitis B; Genetic Variation; Phylogeny
PubMed: 38857639
DOI: 10.1016/j.meegid.2024.105618 -
Archives of Iranian Medicine Jun 2024Occult hepatitis B infection (OBI) refers to the presence of hepatitis B virus (HBV) DNA in the serum or liver of individuals who tested negative for HBV surface antigen... (Review)
Review
BACKGROUND
Occult hepatitis B infection (OBI) refers to the presence of hepatitis B virus (HBV) DNA in the serum or liver of individuals who tested negative for HBV surface antigen (HBsAg). This study aimed to determine seropositivity for antibodies against HBV core antigen (anti-HBc) and the frequency of OBI among the HBsAg non-reactive blood donors in Mashhad, northeastern Iran.
METHODS
In this cross-sectional study, serum samples of HBsAg-negative blood donors were examined for anti-HBc during June and August 2018. Anti-HBc-positive samples were tested for antibodies against HBsAg (anti-HBs), and those with negative results were classified as isolated anti-HBc cases. The presence of HBV DNA in the C, S, and X gene regions was assessed by a qualitative real-time polymerase chain reaction method in all HBsAg-negative samples. OBI subjects were detected by the presence of at least one HBV genomic region.
RESULTS
Of 540 HBsAg-negative donors, 29 (5.4%; 95% confidence interval: 3.6-7.6%) showed seroreactivity for anti-HBc, of whom 18 individuals were also seropositive for anti-HBs. All donors showed negative results for all three HBV genes regardless of their serum anti-HBc status.
CONCLUSION
Based on our findings, we suggest routine screening of Iranian blood donation volunteers for serum anti-HBc and anti-HBs but not HBV DNA.
Topics: Humans; Cross-Sectional Studies; Iran; Blood Donors; DNA, Viral; Adult; Male; Hepatitis B Antibodies; Hepatitis B; Female; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B Core Antigens; Middle Aged; Young Adult; Prevalence; Adolescent
PubMed: 38855800
DOI: 10.34172/aim.28579 -
PloS One 2024As adoptive cellular therapies become more commonplace in cancer care, there is a growing need to monitor site-specific localization of engineered cells-such as chimeric...
As adoptive cellular therapies become more commonplace in cancer care, there is a growing need to monitor site-specific localization of engineered cells-such as chimeric antigen receptor T (CAR-T) cells and T-cell receptor T (TCR-T) cells-in patients' tissues to understand treatment effectiveness as well as associated adverse events. Manufacturing CAR-T and TCR-T cells involves transduction with viral vectors commonly containing the WPRE gene sequence to enhance gene expression, providing a viable assay target unique to these engineered cells. Quantitative PCR (qPCR) is currently used clinically in fresh patient tissue samples and blood with target sequences specific to each immunotherapy product. Herein, we developed a WPRE-targeted qPCR assay that is broadly applicable for detection of engineered cell products in both fresh and archival formalin-fixed paraffin embedded (FFPE) tissues. Using both traditional PCR and SYBR Green PCR protocols, we demonstrate the use of this WPRE-targeted assay to successfully detect two CAR-T cell and two TCR-T cell products in FFPE tissue. Standard curve analysis reported a reproducible limit of detection at 100 WPRE copies per 20μL PCR reaction. This novel and inexpensive technique could provide better understanding of tissue abundance of engineered therapeutic T cells in both tumor and second-site toxicity tissues and provide quantitative assessment of immune effector cell trafficking in archival tissue.
Topics: Humans; Formaldehyde; Hepatitis B Virus, Woodchuck; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen; T-Lymphocytes; Tissue Fixation; Immunotherapy, Adoptive; Real-Time Polymerase Chain Reaction
PubMed: 38843256
DOI: 10.1371/journal.pone.0303057