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Molecular Genetics and Genomics : MGG Jun 2024Sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter, plays a crucial role in regulating bile acid levels and influencing the risk of HBV...
Sodium taurocholate co-transporting polypeptide (NTCP), a bile acid transporter, plays a crucial role in regulating bile acid levels and influencing the risk of HBV infection. Genetic variations in the SLC10A1 gene, which encodes NTCP, affect these functions. However, the impact of SLC10A1 gene variants on the metabolic and biochemical traits remained unclear. We aimed to investigate the association of SLC10A1 gene variants with the clinical and biochemical parameters, and the risk of different HBV infection statuses and gallstone disease in the Taiwanese population. Genotyping data from 117,679 Taiwan Biobank participants were analyzed using the Axiom genome-wide CHB arrays. Regional-plot association analysis demonstrated genome-wide significant association between the SLC10A1 rs2296651 genotypes and lipid profile, gamma glutamyl transferase (γGT) level and anti-HBc-positivity. Genotype-phenotype association analyses revealed significantly lower total cholesterol, low-density lipoprotein (LDL) cholesterol and uric acid levels, a higher γGT level and a higher gallstone incidence in rare rs2296651-A allele carrier. Participants with the rs2296651 AA-genotype exhibited significantly lower rates of anti-HBc-positivity and HBsAg-positivity. Compared to those with the GG-genotype, individuals with non-GG-genotypes had reduced risks for various HBV infection statuses: the AA-genotype showed substantially lower risks, while the GA-genotype demonstrated modestly lower risks. Predictive tools also suggested that the rs2296651 variant potentially induced protein damage and pathogenic effects. In conclusion, our data revealed pleiotropic effects of the SLC10A1 rs2296651 genotypes on the levels of biochemical traits and the risk of HBV infection and gallstone disease. This confirms SLC10A1's versatility and implicates its genotypes in predicting both biochemical traits and disease susceptibility.
Topics: Humans; Organic Anion Transporters, Sodium-Dependent; Gallstones; Female; Genetic Predisposition to Disease; Symporters; Male; Polymorphism, Single Nucleotide; Hepatitis B; Hepatitis B virus; Middle Aged; Taiwan; Adult; Genotype; Genome-Wide Association Study; Genetic Association Studies; Risk Factors
PubMed: 38869622
DOI: 10.1007/s00438-024-02153-2 -
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 -
Zhonghua Gan Zang Bing Za Zhi =... May 2024Chronic hepatitis B virus (HBV) infection is one of the major public health issues of ongoing global concern. Due to inadequate understanding of the HBV life cycle,... (Review)
Review
Chronic hepatitis B virus (HBV) infection is one of the major public health issues of ongoing global concern. Due to inadequate understanding of the HBV life cycle, there is a lack of effective drugs to cure chronic hepatitis B. During HBV replication, covalently closed circular DNA (cccDNA) serves as the template for viral replication and can be transcribed to produce five viral RNAs of 3.5, 2.4, 2.1 kb and 0.7 kb in length, which are translated to produce HBeAg, core protein, polymerase (P) protein, HBsAg and HBx proteins, respectively. Among them, the 3.5 kb pregenomic RNA (pgRNA) is also the template for viral reverse transcription. Polymerase protein recognizes and binds to the capsid assembly signal on the pgRNA to initiate capsid assembly and reverse transcription. Recent studies have revealed that the processes of splicing, nuclear export, stability, translation, and pgRNA encapsidation of HBV RNAs are regulated by a post-transcriptional regulatory network within the host cell and depend on unique post-transcriptional regulatory elements in the HBV RNA structure. The aim of this review is to overview the post-transcriptional regulatory mechanisms of HBV RNA and their applications in the study of HBV antiviral therapeutics, with the aim of providing new ideas for the development of new drugs targeting HBV RNA.
Topics: Hepatitis B virus; RNA, Viral; Humans; Virus Replication; Antiviral Agents; Gene Expression Regulation, Viral; Hepatitis B, Chronic; RNA Processing, Post-Transcriptional
PubMed: 38858198
DOI: 10.3760/cma.j.cn501113-20240410-00191 -
Zhonghua Gan Zang Bing Za Zhi =... May 2024To analyze hepatitis B serologic tests and the current prevalence of hepatitis B virus (HBV) infection among pregnant and postpartum women in China from 2021 to 2023....
To analyze hepatitis B serologic tests and the current prevalence of hepatitis B virus (HBV) infection among pregnant and postpartum women in China from 2021 to 2023. Data on managing the prevention of mother-to-child transmission of HIV, syphilis, and hepatitis were retrieved from the National Information System. A positive serum HBsAg test was used to define HBV infection. The (2) test was used to compare the coverage rate of the hepatitis B serologic test across different years, in early-stage pregnancy, and the current HBV infection in pregnant and postpartum women. A two-sided value of <0.05 was considered a statistically significant difference. The coverage rate for hepatitis B serological detection in pregnant (including intrapartum) and postpartum women and early-stage pregnancy rose from 99.68% (10 463 059/10 496 883) and 82.96% (8 707 765/10 496 883) to 99.94% (8 678 777/8 684 387, < 0.001) and 88.87% (7 717 857/8 684 387, < 0.001) in China between 2021 and 2023. The current prevalence rate of HBV infection decreased from 4.98% (521 479/10 463 059) in 2021 to 4.56% (396 148/8 678 777) in 2023 among pregnant and postpartum women ( < 0.001). The current prevalence rate of HBV infection ranged from 1.53% to 10.39% among pregnant and postpartum women in various provinces of China in 2023. The coverage rate for hepatitis B serologic tests in China increased significantly between 2021 and 2023 in pregnant and postpartum women. Therefore, the current prevalence rate of HBV infection has decreased significantly in pregnant and postpartum women, but a regional difference still exists.
Topics: Humans; Female; Pregnancy; China; Hepatitis B; Prevalence; Postpartum Period; Pregnancy Complications, Infectious; Hepatitis B virus; Adult; Hepatitis B Surface Antigens; Infectious Disease Transmission, Vertical
PubMed: 38858194
DOI: 10.3760/cma.j.cn501113-20240422-00219 -
Zhonghua Gan Zang Bing Za Zhi =... May 2024Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic...
Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.
Topics: Humans; Hepatitis B, Chronic; China; Antiviral Agents; Interferon-alpha; Hepatitis B virus; Polyethylene Glycols
PubMed: 38858191
DOI: 10.3760/cma.j.cn501113-20240325-00156