This study aimed to investigate the potential causal association between chronic hepatitis B (CHB) infection and the risk of pre-eclampsia/eclampsia using a Mendelian randomisation (MR) design.

We conducted a two-sample MR analysis using genome-wide association study (GWAS) summary statistics from three large-scale datasets. For CHB infection, we used data from 351,885 individuals UK Biobank. For pre‑eclampsia/eclampsia, we analysed two FinnGen datasets with sample sizes of 118,291 and 126,760 individuals, respectively. Genetic variants strongly associated with CHB infection (p < 5 × 10-8) were selected as instrumental variables. The inverse-variance weighted (IVW) method was employed as the primary analysis. Sensitivity analyses included MR-Egger regression, weighted median, weighted mode and MR-PRESSO. Cochran's Q test and MR-Egger intercept tests were performed to assess heterogeneity and horizontal pleiotropy, respectively.

MR analysis revealed significant positive genetic associations between CHB infection and increased risk of pre-eclampsia (OR = 1.154, 95%CI = 1.014-1.313, p = .029) and eclampsia (OR = 1.561, 95%CI = 1.030-2.366, p = .035). Findings were robust across sensitivity analyses for both outcomes.

Our study provides genetic evidence that CHB infection increases the risk of both pre-eclampsia and eclampsia. These findings suggest that considering CHB status as a risk factor and implementing targeted HBV screening programmes may be beneficial for pregnant women.

B-cell may participate in the cellular immune process of hepatitis B antigen clearance. However, the function and specific mechanism of B-cell during interferon-pegylated interferon α-2a (Peg-IFN-α) treatment in chronic hepatitis B (CHB) patients have not yet been described.

A total of 150 CHB patients enrolled in this study, who received 48 weeks of Peg-IFN α treatment. The differentiation clusters CD19, CD24, CD27, CD38, CD40, and CD80 of B cell surface markers in CHB patients were detected by flow cytometry. Spearman correlation and Logistic regression analysis were performed for the analysis.

The clearance rate of HBsAg increased significantly with the duration of Peg-IFN-α treatment, reaching 32.2% by 48 weeks. During the Peg-IFN-α therapy, the frequency of B-cell and its subsets increased significantly. However, we did not observe any significant difference in the frequency of the B-cell and its subsets in patients with or without HBsAg clearance after 48 weeks Peg-IFN-α treatment. The change in HBsAg value was negatively related to the change in plasmablasts (CD19+CD38+) level before and after 48 weeks treatment (r = -0.326, p = 0.006). Moreover, the results showed that HBsAg <288.70 IU/mL at baseline and HBsAg <58.05 IU/mL at 12 weeks were strong predictors of HBsAg clearance in patients with 48 weeks Peg-IFN-α treatment.

The remodeling of B cell subsets, especially plasmablasts (CD19+CD38+), during Peg-IFN-α treatment was closed associated with the clearance of hepatitis B antigen.

To investigate the predictive value of serum hepatitis B virus (HBV) RNA on HBeAg seroconversion in treated chronic hepatitis B (CHB) patients.

Sixty-four HBeAg-positive CHB patients were selected. They were divided into HBeAg seroconversion group including 11 cases and HBeAg non-seroconversion group including 53 cases. HBV RNA levels and other laboratory results were measured at baseline and week 12, 24, 48, 72 during treatment in both groups. The predictive value of HBV RNA level for the seroconversion of HBeAg in patients treated for hepatitis B was analyzed.

Significant differences existed in serum HBV DNA and HBV RNA levels between the two groups at baseline while there was no significant difference in HBsAg. The correlation between HBV RNA and HBV DNA was significantly high ( r  = 0.707, P  < 0.05), while the correlation between HBV DNA and HBsAg ( r  = 0.474, P  < 0.05) or HBV RNA and HBsAg was poor ( r  = 0.372, P  < 0.05). Patients with younger age and higher HBV RNA levels at baseline and week 24 were less likely to have HBeAg seroconversion. HBV RNA was better than HBV DNA and HBsAg in predicting HBeAg seroconversion whether at baseline or week 12 and week 24. The area under the curve of HBV RNA level at 24th week was the highest, which was 0.942, and the cutoff value was 4.145 log 10 copies/ml.

HBV RNA level may be a suitable serum marker to predict whether HBeAg seroconversion can occur. CHB patients with serum HBV RNA level lower than 4.145 log 10 copies/ml at week 24 were more likely to achieve HBeAg seroconversion.

HBV integration is considered as the main contributor to hepatocellular carcinoma (HCC). However, whether HBV integrated sequences determine genotype pathogenicity and how to block their function during HCC progression remains unclear.

An in vitro HBV-infected PHH model and liver cancer cell lines were established to confirm the pathogenic potential of HBV-SITEs. The roles of HBV-SITE-1 in HCC development were analyzed using cellular phenotypic assays and molecular biology techniques, including the combined analysis of RNA-seq and ChIP-seq. Animal models were also used to evaluate the therapeutic effect of HBV-miR-2 inhibitors.

We identified nine fragments of HBV Sequences Integrated To Enhancer, termed as "HBV-SITEs". Particularly, a single nucleotide variation (T > G) was embedded at seed sequence of HBV-miR-2 in the highest integrated HBV-SITE-1 between genotypes B and H. Unexpectedly, B-HBV-SITE-1, not H-HBV-SITE-1, could abnormally activate oncogenic genes including TERT and accelerate HCC cell proliferation and migration. Meanwhile, HBV-miR-2 was gradually increased in HBV-infected cells and patient plasma with different HCC stages. Importantly, 227 genes upregulated by HBV, were also activated by HBV-miR-2 through triggering HBV-SITE-1 enhancer. Conversely, enhancer activities were particularly decreased by HBV-miR-2 inhibitors, and further downregulated activated oncogenic genes. Finally, HCC growth was dramatically restrained and HBV-induced transcripts were systematically reduced via injection of HBV-miR-2 inhibitors in animal models.

HBV-SITEs were identified as novel oncogenic elements for HCC, which provides an insightful perspective for the other cancers caused by oncogenic DNA viruses. We demonstrated that the integrated HBV sequence itself acted as oncogenic enhancers and nucleotide variations of HBV genotypes account for particular pathogenic progression, supporting that the viral nucleotide sequences are vital pathogenic substances beyond viral proteins. And modulation of their enhancer activities could be clinically achievable strategy for blocking DNA viruses-related cancer progression in the future.

Hepatocellular carcinoma (HCC), primarily caused by chronic hepatitis B virus (HBV) infection, remains a leading cause of liver cancer worldwide. Despite advances in antiviral therapies, persistent HBV replication, mediated by covalently closed circular DNA (cccDNA), contributes to poor prognoses and frequent recurrence of HCC. This study investigates for the first time the role of circular RNA circBRWD1 in HBV-related HCC, aiming to elucidate its function and regulatory mechanism in HBV replication and hepatocarcinogenesis. Results showed that circBRWD1 was significantly overexpressed in HBV-positive HCC tissues and cell lines compared to HBV-negative controls and promoted HBV replication by increasing cccDNA accumulation. Silencing circBRWD1 markedly reduced the levels of HBV DNA, HBV surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV core antigen (HBcAg), indicating its critical role in HBV replication. Functionally, circBRWD1 knockdown led to reduced cell proliferation, colony formation, and migration while increasing apoptosis in HCC cells. Mechanistic studies revealed that circBRWD1 acts as a sponge for miR-513a-5p, thereby upregulating TNPO1, a key player in promoting HCC malignancy. Rescue experiments confirmed that TNPO1 overexpression reversed the effects of circBRWD1 depletion, restoring cell proliferation, migration, and HBV replication. Additionally, circBRWD1 depletion significantly reduced tumor growth with reduced expression of TNPO1 and increased miR-513a-5p levels in a mouse xenograft model. Collectively, this study identifies circBRWD1 as a key oncogenic circRNA that facilitates HBV replication and HCC progression via the miR-513a-5p/TNPO1 axis. Targeting circBRWD1 may offer a novel therapeutic strategy for HBV-related HCC, potentially addressing the challenge of HBV persistence and improving patient outcomes.

The year 2024 marks the 60th anniversary of the discovery of the Epstein-Barr virus (EBV), the first virus confirmed to cause human cancer. Viral infections significantly contribute to the global cancer burden, with seven known Group 1 oncogenic viruses, including hepatitis B virus (HBV), human papillomavirus (HPV), EBV, Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), and human immunodeficiency virus (HIV). These oncogenic viruses induce cellular transformation and cancer development by altering various biological processes within host cells, particularly under immunosuppression or co-carcinogenic exposures. These viruses are primarily associated with hepatocellular carcinoma, gastric cancer, cervical cancer, nasopharyngeal carcinoma, Kaposi sarcoma, lymphoma, and adult T-cell leukemia/lymphoma. Understanding the mechanisms of viral oncogenesis is crucial for identifying and characterizing the early biological processes of virus-related cancers, providing new targets and strategies for treatment or prevention. This review first outlines the global epidemiology of virus-related tumors, milestone events in research, and the process by which oncogenic viruses infect target cells. It then focuses on the molecular mechanisms by which these viruses induce tumors directly or indirectly, including the regulation of oncogenes or tumor suppressor genes, induction of genomic instability, disruption of regular life cycle of cells, immune suppression, chronic inflammation, and inducing angiogenesis. Finally, current therapeutic strategies for virus-related tumors and recent advances in preclinical and clinical research are discussed.

The covalently closed circular DNA (cccDNA) of the Hepatitis B virus (HBV) serves as a template for producing progeny viruses in virally infected hepatocytes. Promising cccDNA-targeting antiviral agents remain unavailable and unpredictable in the research and development pipelines, making sterile HBV elimination challenging at the current stage. The major challenge of discriminating trace amounts of cccDNA from the abundant HBV relaxed circular DNA (rcDNA), which is nearly identical to cccDNA in sequence, substantially discourages efforts to discover and directly screen cccDNA-targeting drugs. Therefore, an easy cccDNA cell culture system is required for high-throughput drug screening. In this study, we designed an HBV cccDNA self-generating stable cell culture system using a functional complementary concept and successfully generated an HBV cccDNA Gaussia luciferase reporter cell line in HepG2 and Huh7 cells. This design ensures that the Gluc signal is exclusively expressed upon cccDNA formation, allowing for the accurate and easy measurement of cccDNA levels via luminescent signals. Using this system, in conjunction with a firefly luciferase reporter to monitor cell activity, we screened 2074 drugs in the HepG2-HBV-cccDNA/Firefly cell line. Four compounds were selected for further experimentation and their anti-HBV effects were confirmed. Thus, this virus-free hepatitis B cccDNA cell culture system provides a valuable and convenient platform for the high-throughput screening of anti-HBV drugs.

The delivery of nucleic acid into cells using polyethylenimine (PEI) as non-viral carrier is a potential candidate technique for the treatment of hepatitis B virus (HBV) infection.

In the present study, PEI was used as cationic polymers and transfected with unmodified oligodeoxynucleotides in cell cultures and the BALB/c mouse model to investigate its efficiency in blocking HBV surface antigen (HBsAg) secretion.

PEI/oligonucleotide complexes selectively inhibited HBsAg secretion in the culture supernatant, while there were no evident alterations in HBeAg and HBV DNA levels, thereby suggesting its potential inhibitory activity against the production of HBsAg. The complexes formed by PEI with double-stranded decoy oligonucleotides also suppressed HBsAg secretion but showed no expected interference with the intermediate levels of HBV transcription or replication. Furthermore, PEI/plasmid-DNA complexes demonstrated no influence on the expression levels of HBsAg, thus highlighting the specific effects of PEI/oligonucleotides exerted on HBsAg release. PEI-oligonucleotides transfection prior to the viral inoculation impaired HBV infection in HepG2-NCTP cells. Importantly, the PEI/oligonucleotide complex also induced the decline of HBsAg in hydrodynamically injected BALB/c mice. These findings demonstrate that transfection of PEI/oligonucleotide complexes can help effectively reduce HBsAg level and may offer a new potential avenue for the development of anti-HBV treatment.

Nucleos(t)ide analogues (NUC) treatment can reduce the extent of HBV DNA integration in chronic hepatitis B (CHB) patients. However, the mechanism by which NUC reduces HBV integration is unclear. This study investigated the effects of entecavir (ETV), one of the commonly used NUC, on cells with HBV integration. Full genome-length HBV DNA was inserted into HepG2 cell genome using the sleeping beauty transposon system. The resulting cells, named HepG2/SB/HBV, was subjected to ETV treatment. In ETV-treated HepG2/SB/HBV, intracellular HBV DNA was reduced by 2-fold. When treated with ETV, HepG2/SB/HBV had an impaired cell survival (25% reduction in cell proliferation rate when compared with untreated cells; p = 0.043). The median integration frequency in untreated HepG2/SB/HBV was 16 integration sites per 105 cells, which was reduced to 14.8 integration sites per 105 cells when treated with ETV. Analysis of the expression of apoptosis and mitosis markers showed that ETV-treated HepG2/SB/HBV had a reduced expression of mitosis markers phospho-cell division control-2 (p-cdc-2) and phospho-histone H3 (p-histone H3), but that of the apoptotic markers [Poly-ADP-ribose-polymerase] (PARP) and caspase-3 were not affected. In conclusion, ETV suppressed cell proliferation of hepatoma cells with HBV integration via interference of mitosis and reduced expression of p-histone H3, thereby reducing the number of HBV-integrated hepatocytes. This may be the mechanism by which HBV integration is reduced in CHB patients who received ETV therapy.

Chronic hepatitis B virus (HBV) infection poses a significant global public health challenge and is found closely related to extrahepatic cancers, including head and neck cancer. Oral squamous cell carcinoma (OSCC) is the major category of head and neck cancer. This retrospective study was conducted to explore the clinical correlation and survival analysis of OSCC patients with HBV.

The study involved 1,373 patients with OSCC treated at the Hospital of Stomatology, Sun Yat-sen University from 2012 to 2022. Propensity score matching was used to analyze the clinical correlations and survival outcomes, specifically overall survival (OS) and disease-free survival (DFS), in patients with or without hepatitis B surface antigen (HBsAg) seropositivity. Subgroup analyses were conducted for both the early and advanced stages of OSCC. The benefits of neck dissection in OSCC patients with HBV infection were further investigated.

The prevalence of HBV infection in our cohort was 12.0%. The HBsAg (+) group had a higher percentage of individuals under 60 (73.3% versus 63.7%, p = 0.016). Post-matching for age, sex, pathological T category, pathological N category, and neck dissection, the OSCC patients with HBsAg (+) had lower 5-year OS and DFS rates rather than HBsAg (-) patients, especially those with advanced stage and cervical lymph node metastasis. HBsAg (-) was confirmed as an independent protective prognostic indicator for both OS (hazard ratio [HR] = 0.52; 95% confidence interval [CI] = 0.34-0.79; p = 0.002) and DFS (HR = 0.69, 95% CI = 0.50-0.96; p = 0.027). Notably, elective neck dissection was recognized as an independent protective factor influencing 5-year OS and DFS. While DOI and pathological N category were both confirmed as the risk factors for prognosis.

HBsAg is a potential prognostic marker for OSCC. It is essential to screen for HBV infection prior to initiating tumor treatment. Additionally, serological testing, antiviral prophylaxis and therapy play crucial roles in preventing HBV reactivation during the course of tumor treatment. In cases of early OSCC associated with HBV infection, elective neck dissection has been shown to reduce the rates of recurrence and metastasis significantly.

Chronic hepatitis B virus (HBV) infection affects approximately 254 million individuals globally, contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis, which result in millions of fatalities each year. Although approved antiviral nucleos(t)ide analogues can effectively suppress HBV replication, their ability to reduce hepatitis B surface antigen (HBsAg) levels in plasma remains limited. The clinical application of the immunomodulator interferon-alpha is restricted by concerns regarding its safety and the severity of associated adverse reactions, rendering long-term administration challenging. Therefore, current drug development efforts for chronic hepatitis B aim to achieve a functional cure, which is defined as HBsAg serological clearance and sustained suppression of HBV DNA. This review discusses recent advancements in novel direct-acting therapeutic strategies for the treatment of chronic hepatitis B by focusing on the progresses in HBV entry inhibitors, monoclonal antibodies, RNA interferences, and other agents that directly target the virus. Furthermore, we discuss the development of immunomodulatory therapies, including TLR-7/8 agonists, immune checkpoint inhibitors, and therapeutic vaccines. In the end, we conclude by highlighting the importance of the rational combination-strategy design to improve the functional cure rate of HBV.

Hepatitis B infection can lead to liver fibrosis and hepatocellular carcinoma (HCC). Despite antiviral therapies, some patients still develop HCC. This study investigates hepatitis B virus (HBV)-induced hepatocyte-hepatic stellate cell (HSC) crosstalk and its role in liver fibrosis and HCC. Using MYC-driven liver cancer stem cell organoids, HCC-patient-derived xenograft (PDX) models, and HBV replication models, this study reveals that HBV transcription affected hepatocyte development, activated the DNA repair pathway, and promoted glycolysis. HBV activated nicotinamide phosphoribosyltransferase (NAMPT) through DNA damage receptor ATR. NAMPT-insulin receptor (INSR)-mediated hepatocyte-HSC crosstalk caused HSCs to develop a myofibroblast phenotype and activated telomere maintenance mechanisms via PARP1 multisite lactylation. Inhibition of the ATR-NAMPT-INSR-PARP1 pathway effectively blocks HBV-induced liver fibrosis and HCC progression. Targeting this pathway could be a promising strategy for chronic HBV infection management.

Chronic hepatitis B virus (HBV) infection is an incurable pathogen responsible for causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent minichromosome consisting of the viral covalently closed circular DNA (cccDNA) genome and host histones. The viral X gene must be expressed immediately upon infection to induce degradation of the host silencing factor, the Smc5/6 complex. However, the relationship between cccDNA chromatinization and X gene transcription remains poorly understood. By establishing a reconstituted viral minichromosome platform, we found that nucleosome occupancy in cccDNA regulates X transcription. We corroborated these findings in situ and further showed that the chromatin-destabilizing molecule CBL137 inhibits full-length X transcription and HBV infection in primary human hepatocytes. Our results shed light on a long-standing paradox and represent a potential therapeutic approach for the treatment of chronic HBV infection.

Hepatitis B virus (HBV) infection is an important health concern worldwide. HBV infection can lead to acute hepatitis, cirrhosis, hepatocellular carcinoma, liver failure, and death. Nucleos(t)ide analogs (NAs) form the core of the HBV treatment. The safety and efficacy of NAs in long-term follow-up are still critical issues. We enrolled 225 consecutive patients with at least 12 months of longitudinal follow-up using tenofovir alafenamide (TAF), including 39 antiviral naïve and 186 antiviral experienced patients. In the treatment-experienced group, the main reasons for switching from other NAs to TAF were renal dysfunction and osteoporosis. Renal outcome, lipid profile, virological response, and ALT normalization under the TAF treatment were evaluated. Age > 60 years, liver transplant recipients, and patients with decompensated cirrhosis were evaluated separately, as well as the total cohort. Phosphorus levels increased especially in hypophosphatemic individuals, eGFR levels also increased slightly but statistically significantly, and the remarkable improvement in eGFR stages was observed in the eGFR < 60 mL/min/1.73 m2 group. A minimal increase in LDL-c levels occurred after TAF treatment, which did not reach statistical significance. Total cholesterol and HDL-c levels increased significantly, while triglyceride levels remained unchanged. In the total cohort, HBV-DNA was strongly suppressed in either treatment-naïve or experienced patients. ALT and AST levels decreased with the TAF treatment, but ALT normalization rate did not change significantly. No serious adverse events associated with TAF occurred, and discontinuation was not required in the total cohort. Our findings support that TAF treatment is well-tolerated and effective in patients with chronic HBV infection.

Background/Objectives: Hepatitis B virus (HBV) is a virus that can cause chronic hepatitis B (CHB) in humans, leading to cirrhosis and hepatocellular carcinoma (HCC). In this study, we aimed to investigate the relationships between early ALT normalization (at 12 months), the virologic response in CHB patients, and the risk of HCC development. Methods: Data from a retrospective cohort study involving 616 chronic hepatitis B patients were used. The effects of ALT normalization and virologic response on the risk of developing HCC at 12 months of treatment were analyzed. Results: During a median treatment duration of 70.9 months, 36 (5.8%) HCC cases were detected in the total patient population. ALT normalization was detected in 68.83% of patients at 12 months of treatment. The rate of HCC in the group with early ALT normalization was lower than that in the group without ALT normalization, but this difference was not statistically significant (5% vs. 7.8%, p = 0.161). At the end of 12 months of treatment, virologic response was detected in 80.68% of the patients. The rate of patients developing HCC was significantly lower in the virologic response group (4.8% vs. 10.1%, p = 0.028). However, the risk of developing HCC was also significantly higher in the virologically unresponsive group, according to the virologic response at 12 months (p = 0.034). Conclusions: According to the results of this study, achieving virologic response at the end of 12 months in genotype D CHB patients treated with nucleos(t)ide analogs (NAs) reduces the risk of developing HCC.

The liver is an active metabolic site that generates high levels of reactive oxygen species (ROS). Oxidative stress has been implicated in the chronicity of hepatitis and hepatitis B virus (HBV) infection. This study aimed to determine the involvement of oxidative stress in HBV-infected cells and the efficacy of natural Nrf2 activators. The intracellular HBV pregenomic RNA copy number relative to total RNA was measured by RT-PCR, and various protein expressions associated with oxidative stress were analyzed by a Western blot analysis. The results showed that the Nrf2, HO-1, Akt, and Bcl-xL proteins were decreased by the continuous infection, indicating that HBV-positive cells were exposed to oxidative stress. The present study evaluated the anti-HBV infection effects of the Nrf2 activator fucoxanthin (Fx), a marine carotenoid from edible biological resources, including the comparative natural Nrf2 activator pteryxin (Ptx). These Nrf2 activators suppressed the HBV pregenomic RNA production in the HBV-infected cells, thus increasing the expression of the proteins of Nrf2 and HO-1. In the persistently infected cells transfected with the HBV genome, the Bcl-xL and Keap1 proteins, which contribute to suppressing the HBx protein involved in the HBV replication, were overexpressed. In particular, the activity of these protein expressions was marked at low concentrations of Fx. This suggests that natural Nrf2 activators may play a significant role in the HBV infection and could be a valuable source for further development through the functional utilization of food resources.

The effectiveness of immunoprophylaxis for preterm infants delivered by hepatitis B virus(HBV)-infected mothers remains unclear. This study aimed to investigate the effectiveness of immunoprophylaxis in preterm infants.

Infants delivered by HBV-infected mothers between January 1, 2016 and December 31, 2018 were enrolled, Preterm infants received hepatitis B vaccine immediately after birth and at one, two and seven months while full-term infants received vaccine immediately after birth and at one and six months. All infants were followed utill 24 months. Effectiveness of immunoprophylaxis in preterm infants was analyzed by comparing the dynamics of HBV markers and responsible factors were investigated using multivariate regression analysis.

During the study period (2016-2018), 2238 infants were enrolled, including 175 preterm infants and 2063 full-term infants. The differences in the HBsAb concentration between groups were not statistically significant at 7-12 and 24 months of age (P > 0.05), but the concentration in the preterm group were lower relative to the full-term group. Apgar score at 1 min was a predictor of medium-to-high response of HBsAb at 7-12 month (OR 2.687, P = 0.027).

HBsAb concentration in preterm infants delivered by HBV-infected mothers who were vaccinated following the "0-1-2-7″ protocol were similar to those in full-term infants, thereby indicating good outcomes. One-minute Apgar score could be used to predict HBsAb levels in preterm infants at 7-12 months of age after completion of the immunoprophylaxis.

Chronic hepatitis B virus (HBV) infection is a global health issue with limited therapeutic options given the persistence of viral episomal DNA (cccDNA). Previously, we investigated the effects of adeno-associated virus 2 (AAV2) vector-mediated delivery of three guide (g)RNAs/Cas9 selected from 16 gRNAs. AAV2/WJ11-Cas9 effectively suppressed HBV replication in vitro and in humanized chimeric mouse livers. In the present study, we examined the effect of AAV2/WJ11-Cas9 on the acute phase of HBV genotype F infection in an immunocompetent northern tree shrew (Tupaia belangeri; hereafter, "tupaia") model. AAV2/WJ11-Cas9 treatment significantly reduced the HBV viral load in serum at 1, 7, 10, and 14 days post-infection (dpi). HBV-F infection caused enlargement of hepatocytes and mild lymphocytic infiltration in the interlobular connective tissue. Thus, the virus damages hepatocytes and drives infection progression and HBV core antigen (HBcAg) accumulation, which were not observed in AAV2/WJ11-Cas9 treated and normal liver tissues. AAV2/WJ11-Cas9 treatment reduced HBV DNA and cccDNA in liver tissues, as well as serum levels of HBV surface antigen and HBV core-related antigen (HBcrAg), including HBcAg and HBeAg at 14 dpi. Anti-HBc, anti-HBs, and anti-AAV Abs production was also detected. AAV2/WJ11-Cas9 treatment suppressed inflammatory cytokines and TLR1, TLR2, TLR3, TLR4, TLR6, TLR7, and TLR9 mRNA levels. Thus, WJ11/Cas9 delivered by AAV2 vectors may provide a new therapeutic approach for inhibiting HBV infection in immunocompetent animal models, which could be developed for use in humans through further translational research.

HBsAg can be derived from intrahepatic cccDNA and integrated HBV DNA (iDNA). We examined the iDNA from liver tissues of 24 HBeAg(+) and 32 HBeAg(-) treatment-naive CHB participants.

Liver tissues were obtained from the North American Hepatitis B Research Network (HBRN). For cccDNA analysis, DNA was heat-denatured and digested by plasmid-safe ATP-dependent DNase to remove rcDNA and iDNA prior to qPCR. For iDNA detection, total DNA was subjected to HBV hybridization-targeted next generation sequencing (HBV-NGS) assay. The HBV-host junction sequences were identified by ChimericSeq. Comparison of HBV cccDNA and iDNA with serum and intrahepatic virological parameters were assessed.

Intrahepatic cccDNA, serum HBV DNA, HBV RNA, HBcrAg and qHBsAg were higher among the HBeAg(+) participants. Among the HBeAg(+) samples, 87% had positive intrahepatic HBcAg staining compared to 13% of HBeAg(-) samples (p<0.0001). HBsAg staining, in contrast, was present in over 85% of both HBeAg(+) and (-) livers. 23 (95.8%) HBeAg(+) participants had ≤50% iDNA of total HBV DNA whereas 25 (78.1%) HBeAg(-) participants had >50% iDNA in their livers. The iDNA junction-breakpoint distributions for the HBeAg(+) group were random with 15.9% localized to the DR2-DR1 region. In contrast, 52.4% of the iDNA were clustered at DR2-DR1 region among the HBeAg(-) participants. Microhomology-mediated end joining (MMEJ) patterns of dslDNA HBV integration was more frequent in HBeAg (+) livers.

Serum RNA and HBcrAg reflect the intrahepatic cccDNA concentrations. HBeAg(-) CHB participants had high levels of intrahepatic iDNA and HBsAg despite lower cccDNA levels suggesting that iDNA is the primary source of HBsAg in HBeAg(-) CHB.

Hepatitis viruses pose a significant global health challenge, necessitating accurate and efficient diagnostic methods. The CRISPR-Cas system, renowned for gene editing, shows potential tool in virus detection. This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of CRISPR-Cas-based tests for hepatitis viruses, aiming to provide evidence for their effectiveness in clinical settings.

Studies from Web of Science, PubMed, and CNKI were analyzed. A bivariate random-effects model was employed to compute pooled estimates for sensitivity, specificity, and the area under the summary receiver operating characteristic (SROC) curve. Additionally, the methodological quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool.

Following a rigorous screening process, 14 studies meeting our inclusion criteria were selected from an initial pool of 657 studies. The pooled sensitivity and specificity of the CRISPR-Cas system in hepatitis virus detection showed high sensitivity (0.99, 95% CI: 0.95-1.00) and specificity (0.99, 95% CI: 0.93-1.00) with SROC area 1.00 (95% CI: 0.99-1.00). However, considering the notable heterogeneity among the included studies, subgroup analyses and meta-regression were conducted. These analyses revealed that the type of hepatitis virus detected and the format of the final result presentation could be potential sources of this heterogeneity.

This systematic review and meta-analysis demonstrates the high diagnostic accuracy of CRISPR-Cas system in detecting hepatitis viruses. However, conclusions are limited by study number and quality. Therefore, more high-quality data are still needed to support this conclusion.

The onset of decompensation in advanced chronic liver disease (ACLD) is a hallmark in natural history, with a poor prognosis and a significantly increased liver-related mortality. Etiological treatments for viral hepatitis or abstinence in cirrhosis due to alcohol abuse have demonstrated that some patients experience partial to complete clinical and analytical improvement, a stage termed "recompensation." Although recompensation is primarily defined clinically based on treatable etiologies, it is still evolving for conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). Despite the need for specific biomarkers in hepatic recompensation, no biomarkers have been thoroughly studied in this context. Biomarkers identified in compensated ACLD (cACLD) following etiological treatment might be explored for recompensation. Although the pathophysiology mechanisms underlying the hepatic recompensation remain unclear, understanding the mechanism involved in cirrhosis decompensation could help identify potential targets for recompensation. This review provides an update on the hepatic recompensation concept, examines the existing data on invasive and non-invasive biomarkers, mainly in cACLD after cure, that could be raised in recompensation, and explores future therapeutic targets for the hepatic recompensation process.

HBsAg serves as an important immune-modulatory factor in chronic hepatitis B. One aspect of such modulation may act through monocytes, which are the major Ag-presenting cells taking up HBsAg. There is evidence for the encapsulation of hepatocellular microRNAs (miRNAs) by HBsAg particles, while its pathobiological significance is unclear. Here, we characterized the miRNA profile in patients with chronic hepatitis B and probed their association with liver inflammation.

We collected plasma from patients that are treatment-naive with chronic hepatitis B (n = 110) and quantified total/HBsAg-enveloped miRNAs by qRT-PCR and plasma cytokines by ELISA. The biological effects of HBsAg-delivered miRNAs in monocytes were evaluated using multiple approaches. The clinical significance of candidate miRNAs and cytokines was corroborated in patients with HBV-associated advanced liver diseases. The plasma miRNA profile showed 2 major clusters, one significantly associated with HBsAg titer and the other correlated with liver inflammation. Among HBsAg-carried miRNAs, miR-939 displayed the most significant correlation with IL-8. Mechanistically, miR-939 in subviral particles enters monocytes and significantly augments IL-8 production through the mitogen-activated protein kinase (MAPK) p38 signaling pathway. Finally, the findings that miR-939 positively correlated with IL-8 level and inflammation/fibrosis stage in the cohort of HBV-associated advanced liver diseases support its causative role in the progression of liver diseases.

HBsAg particles carry hepatocellular miRNAs, including miR-939, which enter monocytes and alter their functional status, such as IL-8 secretion. Our findings demonstrate that the HBsAg-miR-939-IL-8 axis may play a crucial role in HBV-induced hepatic necro-inflammation and the progression of advanced liver diseases.

N6-methyladenosine (m6A) is a common RNA modification, which plays a critical role in RNA fate and regulating such aspects as splicing, stability, nuclear export, and translation efficiency. The introduction, removal, and recognition of m6A modifications in RNA are regulated by a number of factors, known as writer, eraser, and reader proteins. It is known that the m6A modification can play an important role in the life cycle of viruses, including hepatitis B virus. The m6A methylation system has a significant impact on the hepatitis B viral cycle (HBV), particularly, on stability of mRNA transcripts, encapsidation efficiency, and reverse transcription of HBV pgRNA. In this study, we assessed the effect of knockout and activation of expression of several factors of the m6A methylation system on the HBV viral cycle, including pregenomic RNA (pgRNA) and circular covalently closed DNA (cccDNA). The study was carried out using the StCas9 nuclease system for knockout and the dCas9-p300 system for activation of gene expression. The levels of pgRNA and cccDNA were estimated by real-time PCR. The data obtained show the restriction of the viral cycle at the basal level by the factors METTL3, METTL14, METTL16, FTO, JMJD6, and hnRNPA2B1, as well as suppression of the viral cycle with overexpression of all of the above factors, except for hnRNPA2B1.

Chronic hepatitis B (CHB) remains a serious global health problem. In our previous investigation, HBV was found to activate a mild ER stress, which facilitated the establishment of persistent HBV infection. However, the role of ER stress manipulation in HBV replication and its underlying mechanisms remain still unclear. Our data showed that mild ER stress inhibited HBV transcription and replication, while severe ER stress enhanced them. Mechanistically, in contrary to the effect on HBV replication, mild ER stress activated whereas severe ER stress inhibited mTOR signaling in HBV-infected cells. Further, mTOR signaling was revealed to be critical for mild ER stress-mediated HBV inhibition. Furthermore, ATF6 but not PERK or IRE1α was found to be involved in mild ER stress-mediated mTOR and the following HBV inhibition. Moreover, ATF6, per se, could inhibit HBV transcription and replication via activating mTOR signaling. Together, ATF6-mediated mild ER stress inhibited HBV transcription and replication through mTOR activation, which might present as an important therapeutic target for CHB patients.

As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.

Hepatitis B virus surface antigen (HBsAg), IgM and IgG antibodies to hepatitis B virus core antigen (anti-HBcIgM and anti-HBcIgG) comprise serological markers of hepatitis B virus (HBV) infection of great importance in the epidemiological surveillance of hepatitis B, since they have been routinely considered for classifying the acute and chronic clinical forms of HBV infection. This classification is established according to the expression and dynamics of these markers in the infected person's bloodstream, which serves as the basis for the differential diagnosis between the two clinical entities. However, in certain circumstances, both acute and chronic infection, the detection of these markers may not occur in the bloodstream, favoring the occurrence of atypical serological profiles of infection, and compromising the correct infection clinical classification. In addition, the complex and varied nature of hepatitis B serological profiles may compromise the health professional's ability to analyze the case and, thus, correctly classify the infection's clinical form. Since the expression of these markers in the bloodstream occurs dynamically, with consequent changes in the patient's serological profile as he progresses towards recovery or chronicity, the diagnosis of acute or chronic infection may also be compromised, if it is established based on the collection of a single sample and without knowing the patient's clinical history and their epidemiological antecedents. This manuscript addresses the sensitivity and specificity of HBsAg, anti-HBcIgM, and anti-HBcIgG serological markers detection in the clinical classification of HBV infection and in the epidemiological surveillance of hepatitis B. This review is covering the clinical and epidemiological interpretations of the markers in and of themselves, not in reference to any specific assays.

Chronic hepatitis B virus (HBV) infection is still a widespread global health issue. HuaganJiedu Decoction (HGJDD) is a common prescription for treating HBV in China, which has the effect of enhancing antiviral efficacy and improving clinical efficacy. However, its precise mechanism of action remains unclear, warranting further investigation to elucidate its therapeutic potential and integration into standard medical practices.

This study aims to explore the therapeutic mechanism of HuaganJiedu Decoction (HGJDD) in HBV.

We investigated the therapeutic potential of HGJDD, and LC-MS analysis characterized the chemical profile of HGJDD. In vitro, we utilized HepG2.2.15 cell line to assess cytotoxicity and treatment efficacy of HGJDD compared to Entecavir controls. In vivo, assessments included monitoring HBV-related biomarkers and viral load. Network pharmacology and RNA-seq analyses identified molecular pathways and targets influenced by HGJDD treatment. Immunofluorescence and Western blotting provided further insights into the therapeutic mechanisms underlying HGJDD for HBV.

HGJDD showed no toxicity on HepG2.2.15 cells at 10%, 20%, 40%, and 80% serum concentrations. In vitro, HGJDD reduced HBsAg, HBeAg, and HBV DNA levels by dose-dependently and time-dependently. HGJDD can decrease the levels of HBsAg, HBeAg, and HBV DNA in serum and liver levels, meanwhile the therapeutic effect of high-dose HGJDD approach to EVT's in HBV Tg mice. According to intersection of network pharmacology and transcriptome, FOXO signal pathway was highlighted as potential targets and Immunofluorescence find that FOXO4D protein expression lever was increased in three HGJDD group, especially in high-dose HGJDD group. Western blotting confirmed increased level of FOXO4, ERK, and p-ERK and decreased levels of HNF4α, which reflected that the therapeutic effect was closely to FOXO4/ERK/HNF4α signal pathway.

Traditional Chinese medicine (TCM) offers diverse herbal treatments for HBV, with HGJDD showing efficacy in reducing HBsAg, HBeAg, and HBV DNA levels at cellular and animal levels. This study identified that FOXO4/ERK/HNF4α signal pathway played an important role in HGJDD's therapeutic effects. These findings support HGJDD's potential in HBV treatment, providing a scientific basis for clinical use.

The liver is a vital organ responsible for numerous metabolic processes in the human body, including the metabolism of drugs and nutrients. After liver damage, the organ can rapidly return to its original size if the causative factor is promptly eliminated. However, when the harmful stimulus persists, the liver's regenerative capacity becomes compromised. Substantial theoretical feasibility has been demonstrated at the levels of gene expression, molecular interactions, and intercellular dynamics, complemented by numerous successful animal studies. However, a robust model and carrier that closely resemble human physiology are still lacking for translating these theories into practice. The potential for liver regeneration has been a central focus of ongoing research. Over the past decade, the advent of organoid technology has provided improved models and materials for advancing research efforts. Liver organoid technology represents a novel in vitro culture system. After several years of refinement, human liver organoids can now accurately replicate the liver's morphological structure, nutrient and drug metabolism, gene expression, and secretory functions, providing a robust model for liver disease research. Regenerative medicine aims to replicate human organ or tissue functions to repair or replace damaged tissues, restore their structure or function, or stimulate the regeneration of tissues or organs within the body. Liver organoids possess the same structure and function as liver tissue, offering the potential to serve as a viable replacement for the liver, aligning with the goals of regenerative medicine. This review examines the role of liver organoids in regenerative medicine.

The intricate link between cholesterol metabolism and host immune responses is well recognized, but the specific mechanisms by which cholesterol biosynthesis influences hepatitis B virus (HBV) replication remain unclear. In this study, we show that SREBP2, a key regulator of cholesterol metabolism, inhibits HBV replication by interacting directly with the HBx protein, thereby preventing its nuclear translocation. We also found that inhibiting the ER-to-Golgi transport of the SCAP-SREBP2 complex or blocking SREBP2 maturation significantly enhances HBV suppression. Notably, we demonstrate that the C-terminal domain (CTD) of SREBP2, rather than its N-terminal domain (NTD), mediates this inhibition by interacting with HBx and promoting its extracellular secretion, thus reducing nuclear HBx accumulation. These findings reveal a novel regulatory pathway that links cholesterol metabolism to HBV replication via SREBP2-mediated control of HBx localization. This insight provides a potential basis for new therapeutic strategies against HBV infection, addressing an important global health issue.

Hepatitis B virus (HBV) infections remain a significant global health challenge, especially in low- and middle-income countries where access to healthcare services is often limited. This study aimed to assess the prevalence of hepatitis B virus (HBV), hepatitis delta virus (HDV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) co-infections in a cohort of 426,528 patients tested for HBsAg in Romania between 2018 and 2023. Of the 17,082 HBsAg-positive individuals (4.0% prevalence), the highest HBV positivity rates were observed in the 30-39 and over 60 age groups. Chronic HBV infection was identified in 13.2% of the cohort, with 3.6% testing positive for HBeAg, indicating active viral replication. Co-infection rates were 11.3% for HDV, 1.4% for HCV, and 0.45% for HIV. The incidence of HDV co-infection increased significantly from 2018 to 2023, particularly in older populations. HCV co-infection was more prevalent in individuals aged 50-59 and over 60, with a declining trend from 2020 onward. The study also revealed a weak correlation between liver enzyme levels (ALT and AST) and HBV viral load, suggesting that liver function tests may not fully reflect the severity of HBV infection. HIV co-infection was notably rare compared to other regions, likely due to regional healthcare interventions. The findings from our study highlight the need for targeted interventions, particularly for high-risk groups such as older adults and middle-aged individuals, to reduce the burden of chronic HBV and its complications.

Lactams are a crucial class of compounds with broad therapeutic applications, including in the treatment of cancer, diabetes, and infectious diseases. Functionalised lactams are essential core structures in numerous alkaloids and pharmaceuticals. The introduction of fluorine-containing groups, such as a trifluoromethyl (CF3) group, into organic molecules significantly alters their physical and chemical properties. This review highlights the primary biological targets, as well as the most important synthetic pathways, associated with trifluoromethylated β-lactams (four-atom rings), γ-lactams (five-atom rings), δ-lactams (six-atom rings), and ε-lactams (seven atom rings). Furthermore, we analyze the most common lactam scaffolds, evaluating their potential for future chemical synthesis and emphasizing those that merit attention despite having limited reported analogues. This article aims to provide a comprehensive overview of the importance of trifluoromethylated lactams in drug discovery and design.

This study aims to construct and validate noninvasive diagnosis models for evaluating significant liver fibrosis in patients with chronic hepatitis B (CHB). A cohort of 259 CHB patients were selected as research subjects. Through random grouping, 182 cases were included in the training set and 77 cases in the validation set. The nomogram was developed based on univariate analysis and multivariate regression analysis. Various machine learning models were employed to construct prediction models for significant liver fibrosis. The area under the ROC curve (AUC), sensitivity, specificity, NPV, PPV, and F1 score were used to evaluate the diagnostic performance. The new nomogram had excellent diagnostic efficiency (AUC 0.806, 95% CI: 0.740-0.872). Compared with other traditional noninvasive diagnostic models, the nomogram demonstrated higher AUC values and better prediction performance. Among six machine learning models, the random forest (RF) model achieved the highest AUC (AUC 0.819, 95% CI: 0.720-0.906). Finally, the importance of all variables in the RF model was ordered to illustrate the contribution of different variables, providing the clinical factors associated with the risk of significant liver fibrosis. This new nomogram may more reliably than other traditional models and the RF model demonstrated superior accuracy among six machine learning models.

Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV. However, hepatocytes expressing NTCP exhibit varying susceptibilities to HBV infection. This study aimed to investigate whether other host factors modulate the process of HBV infection.

Liver biopsy samples obtained from children with hepatitis B were used for single-cell sequencing and susceptibility analysis. Primary human hepatocytes, HepG2-NTCP cells, and human liver chimeric mice were used to analyze the effect of candidate host factors on HBV infection.

Single-cell sequencing and susceptibility analysis revealed a positive correlation between neuropilin-1 (NRP1) expression and HBV infection. In the HBV-infected cell model, NRP1 overexpression before HBV inoculation significantly enhanced viral attachment and internalization, and promoted viral infection in the presence of NTCP. Mechanistic studies indicated that NRP1 formed a complex with LHBs (large hepatitis B surface proteins) and NTCP. The NRP1 b domain mediated its interaction with conserved arginine residues at positions 88 and 92 in the preS1 domain of LHBs. This NRP1-preS1 interaction subsequently promoted the binding of preS1 to NTCP, facilitating viral infection. Moreover, disruption of the NRP1-preS1 interaction by the NRP1 antagonist EG00229 significantly attenuated the binding affinity between NTCP and preS1, thereby inhibiting HBV infection both in vitro and in vivo.

Our findings indicate that NRP1 is a novel host factor for HBV infection, which interacts with preS1 and NTCP to modulate HBV entry into hepatocytes.

HBV infection is a global public health problem, but the understanding of the early infection process of HBV remains limited. Through single-cell sequencing, we identified a novel host factor, NRP1, which modulates HBV entry by interacting with HBV preS1 and NTCP. Moreover, antagonists targeting NRP1 can inhibit HBV infection both in vitro and in vivo. This study could further advance our comprehension of the early infection process of HBV.

HBV genotype A has two major subtypes, A1 (commonly in Africa) and A2 (commonly in Europe) with only 4% nucleotide differences. Individuals infected with these two subtypes appear to have different clinical manifestations and virologic features. Whether such a difference results from the virus or host has not been established. Using HBV generated from molecule clones of subtypes A1 and A2 in cell culture (HBVcc), we demonstrate that HBVcc of subtypes A1 and A2 can be passaged in vitro and in vivo and respond equally well to human IFN-α treatment. HBVcc passaged in human liver chimeric mice (HBVmp) infected human hepatocytes more efficiently than that of the original HBVcc. Subtype A2 showed a much higher viral replication level than that of subtype A1. Mechanistic investigations using constructs with chimeric A1/A2 sequences and specific mutations indicated that subtype A2 has an inherently higher replication phenotype due to specific polymorphisms in the HBx gene resulting in amino acid variations. Studies of HBx expression demonstrated that A1 HBx is expressed at a much lower level than that of A2 HBx. Mutagenesis studies identified two HBx amino acid variations responsible for the observed phenotypic difference. Using AlphaFold2, we generated structural models of HBx proteins of A1 and A2. Superposition of the two models reveal that the overall structural motifs are similarly aligned, except for the C-terminal peptides diverging between the A1 and A2 models, possibly explaining their functional difference. In conclusion, using various in vitro and in vivo models, here we show that subtype A2 has an inherently higher replication phenotype due to polymorphisms in HBx that result in possible differences in structure and expression level of the two subtype HBx proteins. This genotypic difference potentially explains the reported clinical differences between the two subtypes as well as providing a previously unrecognized association between viral sequence variations and clinical manifestations of HBV infection in humans.

CD8+T cells are crucially associated with the fight against hepatitis B virus (HBV) infection. CD161 has been shown to express remarkably on HCV-specific CD8+T cells. However, the accurate function of CD161+CD8+T cells in HBV immunity or pathogenesis remains undetermined.

Blood samples were collected from 25 chronic hepatitis B (CHB) patients. Peripheral blood levels of CD161+CD8+T cells and their correlation with serum ALT levels were analyzed in CHB patients. To analyze the in vivo CD161+CD8+T cell's number, function, and intrahepatic recruitment characteristics, HBV replication mouse models were established. The expression of CD161 on HBV-specific CD8+T cells was also detected by analyzing CD161+CD8+T cell functions during infection.

Patients with CHB infection had a markedly lower peripheral blood frequency of CD161+CD8+T cells than did healthy controls and negatively correlated with serum ALT level. Furthermore, compared to the control mice, the frequency of CD161+CD8+T cells was significantly decreased in the blood of acute and chronic HBV-replicating mice. Moreover, CHB-replicating mice had significantly increased hepatic levels of CD161+CD8+T cells, which was not observed in the acute group of mice. Additionally, the CD161+CD8+T cells were categorized into CD161hi and CD161intCD8+T cells and it was revealed that in the liver of CHB-replicating mice the primary recruited cells were CD161hiCD8+T. Intrahepatic CD161hiCD8+T cells demonstrated increased CXCR6 expression, enhanced production of cytokine IL-17 and TNF-ɑ, and reduced IFN-γ secretion. Accordingly, the CXCL16 mRNA expression in the liver tissue of CHB-replication mice was markedly higher than in acute HBV-replicating and control mice. The study also revealed that HBV-specific CD8+T cells were mainly CD161-CD8+T cells.

During HBV infection, the intrahepatic recruitment of CD161+CD8+T cells was mainly CD161hiCD8+T cell subpopulation, which has a weak antiviral response, but increased pro-inflammatory effect, suggesting that CD161 may serve as a potential marker of liver-damaging T cells.

Tea is obtained from the young leaves and shoots of the evergreen perennial plant Camellia sinensis (L.) Kuntze, the most popular and frequently consumed product using a natural beverage worldwide. Some kinds of tea products, such as green tea, black tea, and oolong tea, have assorted flavors depending on the manufacturing techniques. Green tea has been studied for many years for its important beneficial effects, including anticancer, antiobesity, anti-diabetes, anti-inflammatory, neuroprotective, and cardiovascular effects. These effects are primarily associated with tea polyphenols, and regular consumption has been reported to decrease the incidence of some chronic diseases. Current studies support that green tea catechins play an important role in healing and improving the pathology of many diseases. Epigallocatechin-3-gallate (EGCG) is the most a highly found polyphenol in the leaves and is of great interest for its protective role in the prevention of diseases. Therefore, this review presents the efficacy and possible mechanisms of EGCG against sexually transmitted viruses. Moreover, EGCG and its derivatives are recognized as safe bioactive phytochemicals for external and internal use in preventing and treating viral STIs and other concurrent infections. Multidisciplinary studies are essential to discover cheaper, safer, and more effective treatments using EGCG and its derivatives to improve the toxicity and formulations of viral STI medications.