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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 -
Journal of Cellular and Molecular... Jun 2024As an important protein encoded by hepatitis B virus (HBV), HBV X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). It has been...
As an important protein encoded by hepatitis B virus (HBV), HBV X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). It has been shown that seven in absentia homologue 1 (SIAH1) could regulates the degradation of HBx through the ubiquitin-proteasome pathway. However, as a member of SIAH family, the regulatory effects of SIAH2 on HBx remain unclear. In this study, we first confirmed that SIAH2 could reduce the protein levels of HBx depending on its E3 ligase activity. Moreover, SIAH2 interacted with HBx and induced its K48-linked polyubiquitination and proteasomal degradation. Furthermore, we provided evidence that SIAH2 inhibits HBx-associated HCC cells proliferation by regulating HBx. In conclusion, our study identified a novel role for SIAH2 in promoting HBx degradation and SIAH2 exerts an inhibitory effect in the proliferation of HBx-associated HCC through inducing the degradation of HBx. Our study provides a new idea for the targeted degradation of HBx and may have great huge significance into providing novel evidence for the targeted therapy of HBV-infected HCC.
Topics: Humans; Viral Regulatory and Accessory Proteins; Carcinoma, Hepatocellular; Trans-Activators; Ubiquitination; Liver Neoplasms; Ubiquitin-Protein Ligases; Cell Proliferation; Nuclear Proteins; Proteolysis; Hepatitis B virus; Cell Line, Tumor; Signal Transduction; Hep G2 Cells
PubMed: 38842124
DOI: 10.1111/jcmm.18484 -
Journal of Nanobiotechnology Jun 2024Chronic hepatitis B poses a significant global burden, modulating immune cells, leading to chronic inflammation and long-term damage. Due to its hepatotropism, the... (Review)
Review
Chronic hepatitis B poses a significant global burden, modulating immune cells, leading to chronic inflammation and long-term damage. Due to its hepatotropism, the hepatitis B virus (HBV) cannot infect other cells. The mechanisms underlying the intercellular communication among different liver cells in HBV-infected individuals and the immune microenvironment imbalance remain elusive. Exosomes, as important intercellular communication and cargo transportation tools between HBV-infected hepatocytes and immune cells, have been shown to assist in HBV cargo transportation and regulate the immune microenvironment. However, the role of exosomes in hepatitis B has only gradually received attention in recent years. Minimal literature has systematically elaborated on the role of exosomes in reshaping the immune microenvironment of the liver. This review unfolds sequentially based on the biological processes of exosomes: exosomes' biogenesis, release, transport, uptake by recipient cells, and their impact on recipient cells. We delineate how HBV influences the biogenesis of exosomes, utilizing exosomal covert transmission, and reshapes the hepatic immune microenvironment. And based on the characteristics and functions of exosomes, potential applications of exosomes in hepatitis B are summarized and predicted.
Topics: Exosomes; Humans; Hepatitis B virus; Liver; Animals; Hepatitis B, Chronic; Hepatocytes; Cell Communication; Cellular Microenvironment; Hepatitis B
PubMed: 38840207
DOI: 10.1186/s12951-024-02544-y -
Virology Journal Jun 2024The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored...
BACKGROUND
The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA.
METHODS
Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log IU/mL ≤ HBV DNA < 7 log IU/mL), moderate (7 log IU/mL ≤ HBV DNA < 8 log IU/mL), and high (HBV DNA ≥ 8 log IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis.
RESULTS
The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis.
CONCLUSION
Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.
Topics: Humans; Hepatitis B, Chronic; Male; Female; Adult; Liver Cirrhosis; DNA, Viral; Alanine Transaminase; Hepatitis B e Antigens; Hepatitis B virus; Middle Aged; Viral Load; Young Adult; Liver; Biopsy
PubMed: 38835029
DOI: 10.1186/s12985-024-02368-0 -
International Journal of Gynaecology... Jul 2024To explore the relationships between gestational hepatitis B virus (HBV) infection, antiviral therapy, and pregnancy outcomes.
OBJECTIVE
To explore the relationships between gestational hepatitis B virus (HBV) infection, antiviral therapy, and pregnancy outcomes.
METHODS
We retrospectively selected hepatitis B surface antigen (HBsAg)-positive pregnant women hospitalized for delivery at Fujian Medical University Affiliated Hospital from October 1, 2016 to October 1, 2020. The control group included randomly selected healthy pregnant women hospitalized for delivery during the same time.
RESULTS
Overall, 1115 participants were enrolled and grouped into control (n = 380) and HBsAg-positive groups (n = 735), which were further divided into groups I (n = 407; low viral load), II (n = 207; high viral load without antiviral therapy), and III (n = 121; high viral load with antiviral therapy). Pregnant women with HBV were positively correlated with the incidence of intrahepatic cholestasis of pregnancy (ICP) (adjusted odds ratio [aOR] 5.1, 95% confidence interval [CI] 2.62-9.92, P < 0.001), neonatal jaundice (aOR 10.56, 95% CI 4.49-24.83, P < 0.001), and neonatal asphyxia (aOR 5.03, 95% CI 1.46-17.27, P = 0.01). Aspartate aminotransferase (AST) greater than the upper limit of normal (ULN) was an independent risk factor for increased ICP incidence (aOR 3.49, 95% CI 1.26-9.67, P = 0.019). Antiviral therapy considerably reduced HBV DNA and improved liver function. High viral load and antiviral therapy did not correlate significantly with adverse pregnancy outcomes (P < 0.05).
CONCLUSION
Pregnant women with HBV have significantly elevated incidence of ICP, neonatal jaundice, and neonatal asphyxia not significantly correlated with viral load. AST greater than ULN independently increases the risk of ICP. Antiviral therapy effectively reduces viral replication and improves liver function without increasing the risk of adverse outcomes.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Antiviral Agents; Pregnancy Complications, Infectious; Adult; Pregnancy Outcome; Hepatitis B; Viral Load; Cholestasis, Intrahepatic; China; Hepatitis B Surface Antigens; Hepatitis B virus; Infant, Newborn; Case-Control Studies; Jaundice, Neonatal; Pregnancy Complications
PubMed: 38831742
DOI: 10.1002/ijgo.15716 -
Proceedings of the National Academy of... Jun 2024Epitranscriptomic RNA modifications have emerged as important regulators of the fate and function of viral RNAs. One prominent modification, the cytidine methylation...
Epitranscriptomic RNA modifications have emerged as important regulators of the fate and function of viral RNAs. One prominent modification, the cytidine methylation 5-methylcytidine (mC), is found on the RNA of HIV-1, where mC enhances the translation of HIV-1 RNA. However, whether mC functionally enhances the RNA of other pathogenic viruses remains elusive. Here, we surveyed a panel of commonly found RNA modifications on the RNA of hepatitis B virus (HBV) and found that HBV RNA is enriched with mC as well as ten other modifications, at stoichiometries much higher than host messenger RNA (mRNA). Intriguingly, mC is mostly found on the epsilon hairpin, an RNA element required for viral RNA encapsidation and reverse transcription, with these mC mainly deposited by the cellular methyltransferase NSUN2. Loss of mC from HBV RNA due to NSUN2 depletion resulted in a partial decrease in viral core protein (HBc) production, accompanied by a near-complete loss of the reverse transcribed viral DNA. Similarly, mutations introduced to remove the methylated cytidines resulted in a loss of HBc production and reverse transcription. Furthermore, pharmacological disruption of mC deposition led to a significant decrease in HBV replication. Thus, our data indicate mC methylations as a critical mediator of the epsilon elements' function in HBV virion production and reverse transcription, suggesting the therapeutic potential of targeting the mC methyltransfer process on HBV epsilon as an antiviral strategy.
Topics: Hepatitis B virus; RNA, Viral; Cytidine; Humans; Reverse Transcription; Methylation; Virus Replication; Epigenesis, Genetic; Virion; Transcriptome
PubMed: 38830096
DOI: 10.1073/pnas.2400378121 -
Terapevticheskii Arkhiv Jun 2024Patients with rheumatic diseases infected with hepatitis B virus (HBV) are difficult to manage not only due to the presence of risk factors for the development and rapid... (Review)
Review
Patients with rheumatic diseases infected with hepatitis B virus (HBV) are difficult to manage not only due to the presence of risk factors for the development and rapid progression of liver cirrhosis, but also due to the likelihood of reactivation of this infection. Despite the successes achieved in the fight against HBV, the virus cannot be completely defeated due to the presence of hidden forms of the disease, escaping the field of vision of a rheumatologist and an infectionist. Based on the results of the analysis of current publications, the paper presents the rationale for a complete immunological screening of patients with rheumatic diseases when prescribing antirheumatic therapy. The issues of the role of COVID-19 in the exacerbation of chronic viral hepatitis B, antiviral prevention and monitoring are discussed, the classification of antirheumatic drugs according to the risk of HBV reactivation is presented.
Topics: Humans; Rheumatic Diseases; Hepatitis B, Chronic; COVID-19; Virus Activation; Antirheumatic Agents; Hepatitis B virus; Mass Screening; Antiviral Agents; SARS-CoV-2; Risk Factors
PubMed: 38829815
DOI: 10.26442/00403660.2024.05.202707 -
Journal of Medical Virology Jun 2024Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine... (Observational Study)
Observational Study
Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. This study provides novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Patients having CHB with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 using propensity score matching. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. A mouse model of carbon tetrachloride-induced liver injury was established to validate the effect of key differential metabolites on liver injury. Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with PnALT levels were matched as controls. Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl- l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.
Topics: Humans; Hepatitis B, Chronic; Male; Female; Alanine Transaminase; Antiviral Agents; Adult; Prospective Studies; Middle Aged; Biomarkers; Animals; Mice; Hepatitis B virus; Sustained Virologic Response; DNA, Viral; Disease Models, Animal; Liver; Viral Load
PubMed: 38828911
DOI: 10.1002/jmv.29723 -
Molecular Phylogenetics and Evolution Aug 2024Chronic infection of hepatitis B virus (HBV) and hepatitis D virus (HDV) causes the most severe form of viral hepatitis. Due to the dependence on HBV, HDV was deemed to...
Chronic infection of hepatitis B virus (HBV) and hepatitis D virus (HDV) causes the most severe form of viral hepatitis. Due to the dependence on HBV, HDV was deemed to co-evolve and co-migrate with HBV. However, we previously found that the naturally occurred HDV/HBV combinations do not always reflect the most efficient virological adaptation (Wang et al., 2021). Moreover, regions with heavy HBV burden do not always correlate with high HDV prevalence (e.g., East Asia), and vice versa (e.g., Central Asia). Herein, we systematically elucidated the spatiotemporal evolutionary landscape of HDV to understand the unique epidemic features of HDV. We found that the MRCA of HDV was from South America around the late 13th century, was globally dispersed mainly via Central Asia, and evolved into eight genotypes from the 19th to 20th century. In contrast, the MRCA of HBV was from Europe ∼23.7 thousand years ago (Kya), globally dispersed mainly via Africa and East Asia, and evolved into eight genotypes ∼1100 years ago. When HDV stepped in, all present-day HBV genotypes had already formed and its global genotypic distribution had stayed stable geographically. Nevertheless, regionalized HDV adapted to local HBV genotypes and human lineages, contributing to the global geographical separation of HDV genotypes. Additionally, a sharp increase in HDV infections was observed after the 20th century. In conclusion, HDV exhibited a distinct spatiotemporal distribution path compared with HBV. This unique evolutionary relationship largely fostered the unique epidemic features we observe nowadays. Moreover, HDV infections may continue to ramp up globally, thus more efforts are urgently needed to combat this disease.
Topics: Hepatitis Delta Virus; Hepatitis B virus; Humans; Hepatitis D; Phylogeny; Evolution, Molecular; Genotype; Epidemics; Spatio-Temporal Analysis; Coinfection
PubMed: 38825156
DOI: 10.1016/j.ympev.2024.108114