Search Results (1,152)

Chronic hepatitis B virus (HBV) infection is a major health problem that leads to approximately one million deaths every year worldwide. Mother-to-child transmission (MTCT) is the major cause of chronic HBV infection. HBV e antigen (HBeAg) is a secretory viral protein and modulates the immunological landscape of the newborn to promote HBV persistence. HBeAg actively reprograms innate and adaptive immunity. Mechanistically, HBeAg regulates macrophage polarization, suppresses dendritic cell and natural killer (NK) cell activities, impairs T cell and B cell functions, and promotes the expansion of myeloid-derived suppressor cells (MDSCs). These multifaceted effects contribute to immune tolerance and persistent HBV infection in the offspring of carrier mothers. Clinically, HBeAg status is a critical determinant for MTCT risk stratification and intervention, particularly in resource-limited settings. Despite advances in neonatal immunoprophylaxis and maternal antiviral therapy, residual transmission of HBV persists. Emerging approaches targeting HBeAg directly or restoring antiviral immunity offer promising avenues for breaking immune tolerance and achieving HBV elimination. This review summarizes current understanding of HBeAg-mediated immune modulation and highlights strategies that are being used to disrupt MTCT and treat HBV patients. Full article

Chronic hepatitis B virus (HBV) and Occult HBV infection (OBI) remain a health burden in sub-Saharan Africa. This study investigated HBV prevalence, circulating genotypes, and associated risk factors with HBV exposure among HIV-positive adults on antiretroviral therapy and pregnant women in southwestern Cameroon. A total of 233 HIV patients and 190 third-trimester pregnant women were screened for HBV DNA, viral load, serological markers (HBsAg, anti-HBc, and anti-HBs), and HBV genotypes were determined by partial sequencing of the S gene. HBV DNA was detected in 10% of HIV-positive patients and 4% of pregnant women, with an overall prevalence of 7%. OBI accounted for 9% and 3%, respectively. Anti-HBc seroprevalence was high (75% in HIV, 46% in pregnant women), while self-reported vaccination coverage was low (1% and 11%). Genotypes A, B, D, and E were identified, with genotype B reported for the first time in Cameroon. Immune escape mutations and the adefovir resistance mutation rtA181V were detected. Self-reported alcohol use was associated with HBV exposure in HIV patients (aOR = 2.08; p = 0.028) and inversely associated with tertiary education in pregnant women (aOR = 0.18; p = 0.038). This study highlights a significant burden of HBV and OBI among vulnerable populations in Cameroon. Full article

Background: Breast cancer patients with hepatitis B virus (HBV) infection or past HBV infection face heightened risks of chemotherapy-induced hepatotoxicity and HBV reactivation (HBVr). This study aims to evaluate the impact of different HBV serological statuses on the safety of chemotherapy regimens based on paclitaxel throughout the treatment cycle. Methods: This retrospective cohort study analyzed 4562 female breast cancer patients, categorized into three groups: 366 with HBV infection (HBsAg+), 2529 with past HBV infection (HBsAg−/HBcAb+), and 1667 without HBV infection (control group). The Primary events included liver injury, HBVr, treatment interruption, and laboratory indicator evaluation. Demographic characteristics and periodic laboratory parameters were recorded for within-subject longitudinal analysis. Results: Before chemotherapy, the incidence of liver injury was highest in the HBV-infected group (18.2%), intermediate in the past-infection group (13.2%), and lowest in the control group (12.0%). Throughout chemotherapy, the cumulative incidence of liver injury remained highest in the HBV-infected group (83.2%), compared to the past-infection (71.2%) and control (70.9%) groups. Chemotherapy interruption rates followed a similar gradient: 12.4% in the HBV-infected group, 6.9% in the past-infection group, and 5.5% in the control group. HBV-infected patients had a significantly higher risk of hepatotoxicity than controls during cycle 4 (relative risk 1.56, 95% CI 1.06 to 2.29) and cycle 5 (1.28, 1.09 to 1.75). HBVr occurred in 13 patients with HBV-infected. Conclusions: HBV serological status significantly impacts chemotherapy safety and treatment interruption. Prophylactic antiviral therapy and intensified monitoring during high-risk cycles (cycle 4 and cycle 5) are critical. These findings underscore the necessity of stratified management for HBV-affected breast cancer patients during chemotherapy. Full article

Background/Objectives: Fatality of cirrhotic patients greatly increases when they progress to the decompensated state. Only a few studies to date have applied machine learning (ML) methods to predict decompensation in cirrhosis patients. In the present study, we attempted to apply self-developed ML models for validating their capability of predicting different complications in hepatitis B virus (HBV)-related cirrhosis patients. Methods: Data were extracted from electronic health records of 50,047 patients who were tested and diagnosed with HBV in a tertiary hospital. Four different algorithms (Support Vector Machine (SVM), Logistic Regression (LR), Decision Tree (DT), Random Forest (RF)) were utilized, and a total of 32 ML models were trained and tested to predict variceal bleeding, ascites, jaundice, and multiple complications (≥2 complications) in HBV-related cirrhosis patients. The use of two antiviral drugs were considered: entecavir (ETV) and lamivudine (LAM). Performance of the models was assessed using area under receiver operating characteristic curve (AUROC) and accuracy score. Results: SVM and RF classifications produced the best overall predictions for decompensation in HBV-related cirrhosis patients, with AUROCs ranging from 0.85 to 0.93 and accuracy scores between 0.77 to 0.88 for ascites, jaundice, and multiple complications. The SVM and LR algorithms generated the best performance in differentiating ascites among ETV users, with AUROC of 0.93 and 0.92 and accuracy of 0.88 and 0.86, respectively. Antiviral treatment (type, length of use, adherence), and other routinely collected clinical information may serve as informative markers in differentiating decompensated cirrhosis. Conclusions: ML-based prediction of decompensation using electronic health records may assist clinicians in decision making. Findings of this study also underline the impact of antiviral therapy as a key predictor for decompensation. Full article

In this multicenter, retrospective study involving 62 patients, we investigated whether switching from entecavir (ETV) or tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) represents a superior treatment strategy for patients with chronic hepatitis B (CHB) experiencing low-level viremia (LLV). The study determined that TAF significantly improved both virological and biochemical outcomes. At 48 weeks, the complete virological response (CVR) rate was 77.8% for those who switched from ETV and 81.8% for those who switched from TDF, with Hepatitis B virus deoxyribonucleic acid (HBV DNA) negativity reaching 81% by month 12. Additionally, significant normalization of liver enzymes, albumin, and platelet counts was observed across the cohort. While the switch from TDF was associated with a significant increase in triglycerides and high-density lipoprotein (HDL) and a decrease in estimated glomerular filtration rate (eGFR), no such changes were detected in the ETV group. This evidence suggests that TAF provides robust virological control in LLV patients and is associated with favorable biochemical improvements. However, due to the study’s limitations, the strong assertion that TAF promotes the regression of liver fibrosis and reduces the risk of hepatocellular carcinoma (HCC) must be interpreted with caution. Full article

Hepatitis B virus (HBV) infection is a global health concern with an estimated 254 million people with chronic HBV infection. The utilization of immunosuppressive therapies (ISTs) is increasing and expanding continuously with new agents being implemented across multiple medical disciplines. The occurrence of HBV reactivation (HBVr) during or after IST varies from 15% to 50% in HBsAg-positive individuals and can be higher than 75% after stem cell transplantation. HBVr is gaining increasing significance in contemporary clinical practice. The American Gastroenterological Association (AGA) in 2025, the European Association for the Study of the Liver (EASL) in 2025, and the Asian Pacific Association for the Study of the Liver (APASL) in 2021, published their most recent clinical guidelines as major societies in the area, which enables us to better predict and manage HBVr. This narrative review focuses on comparing these three current guidelines, highlighting key similarities and differences to provide valuable guidance for practitioners navigating the complex, sometimes conflicting recommendations, thereby aiding clinicians in their decision-making. The risk of HBVr during IST has been stratified into three categories in all three guidelines: high (>10%), moderate (1–10%), and low (<1%). The effectiveness of prophylaxis scales with baseline risk for HBV reactivation. Prophylaxis is clearly cost-effective for high-risk patients, potentially beneficial for those at moderate risk, and generally may not be justified for low-risk individuals. Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are all highly effective in preventing HBV reactivation during immunosuppression and all are considered to be economically viable options for HBVr high risk patients. When selecting among these agents, safety considerations—particularly renal and bone toxicity—and insurance coverage remain the primary factors directing clinical decision-making. Full article

Hepatocellular carcinoma (HCC), the most common primary liver malignancy worldwide, is strongly associated with chronic Hepatitis B Virus (HBV) infection, a significant risk factor. The ubiquitin–proteasome system, central to protein degradation, cellular homeostasis, and cell cycle regulation, has been implicated in the pathogenesis of several cancers, including HCC. Despite this, the specific expression patterns of proteasomal subunits during HBV infection and HBV-induced HCC, as well as the association between mRNA expression of proteasomal subunits and proteasomal activity, remain poorly defined. To address this critical knowledge gap, we analyzed mRNA expression profiles of proteasomal subunits in HBV-infected humanized mouse models to uncover HBV-specific molecular alterations. Our findings revealed that the chymotrypsin-like activity (β5) subunit of the proteasome (PSMB5) is consistently overexpressed following HBV infection. Functional studies demonstrated that β5 deficiency decreases MHC I levels on the cell surface and leads to the accumulation of ubiquitinated proteins, establishing a direct link between β5 overexpression and increased proteasomal activity. Concordantly, HBV-infected patient livers—regardless of HCC status—displayed elevated β5 mRNA/protein levels and enhanced chymotrypsin-like activity. Additionally, analysis of Protein Atlas data revealed that elevated β5 mRNA expression correlates with poor clinical prognosis in HCC patients. In summary, this study highlights how HBV infection induces significant alterations in proteasome function by elevating β5 expression and activity in human and mouse livers. These findings underscore the critical role of proteasomal dysregulation in HBV-associated liver pathology and provide new insights into its involvement in HCC development. Understanding the interplay between HBV infection and proteasome dynamics offers a valuable avenue for the identification of novel therapeutic targets and biomarkers in HCC. Full article

Hepatitis B virus (HBV) represents a significant global health challenge, affecting over 254 million individuals and contributing to 1.1 million deaths from liver-related complications in 2022. The World Health Organization has set ambitious targets to reduce HBV infections and mortality by 2030. However, only a small proportion (13%) of infected individuals receives timely diagnosis and treatment. HBV elimination efforts necessitate substantial improvements in HBV diagnosis, particularly in identifying early-stage infections, occult HBV infections (OBI), and breakthrough cases. The hepatitis B surface antigen (HBsAg) is a key biomarker in HBV diagnosis, serving as a reliable indicator of infection status and treatment response. Conventional HBsAg assays, with a lower limit of detection (LoD) between 0.03 and 250 IU/mL, often fail to detect OBI and HBV reactivation. In contrast, ultrasensitive HBsAg assays, with an LoD as low as 0.005 IU/mL, can improve the identification of low concentration levels of HBsAg, facilitating earlier diagnosis, monitoring of therapeutic response, and assessment for functional cure. Research confirms the superiority of ultrasensitive assays in detecting HBV in cases missed by conventional assays, detecting NAT-yield samples, and enabling earlier detection of HBV reactivation. This review examines the challenges in HBV diagnostics and the clinical utility of ultrasensitive HBsAg assays in improving progress toward global HBV elimination. Full article

This study evaluated the characteristics of patients receiving prophylactic antiviral therapy against hepatitis B virus (HBV) infection due to immunosuppressive treatment and assessed the occurrence of HBV reactivation. Between January 2015 and January 2025, 199 adult patients followed in the Infectious Diseases and Clinical Microbiology outpatient clinic who had received prophylactic oral antiviral therapy were retrospectively analyzed. Demographic characteristics, underlying diseases, immunosuppressive treatment history, HBV serological results, biochemical and virological findings, and prophylactic antiviral regimens were recorded. Patients were stratified into low-, moderate-, and high-risk groups according to the American Gastroenterological Association (AGA) 2025 classification. The mean age was 60.4 years; 50.3% of patients were male. Serologically, 26.6% were HBsAg- and anti-HBc-positive, 33.2% showed isolated anti-HBc positivity, and 40.2% had dual anti-HBc/anti-HBs positivity. The risk of HBV reactivation was low in 41.2%, moderate in 22.1%, and high in 36.7% of patients. Prophylaxis consisted of entecavir in 76.4%, tenofovir alafenamide in 13.1%, and tenofovir disoproxil fumarate in 10.5%. HBV reactivation occurred in only one patient, who had discontinued treatment. These findings emphasize the importance of HBV screening and timely prophylactic antiviral therapy in patients undergoing immunosuppression to effectively prevent HBV reactivation. Full article

The recent resurgence of COVID-19 in a Hepatitis B virus some endemic countries could lead to adverse outcomes. In this article, we formulate and analyse a mathematical model to explains the co-infection dynamics of Hepatitis B virus and COVID-19. Our aim is to investigate the effect of Hepatitis B virus prevention, COVID-19 prevention, COVID-19 vaccination, and environmental factors on transmission dynamics, and formulate conditions for extinction and persistence of the diseases. First, we derive the basic reproduction number for HBV only, COVID-19 only, and co-infection stochastic models using the next-generation matrix method. Next, we establish the conditions for stability in the stochastic sense for HBV only, COVID-19 only sub-models, and the co-infection model using suitable Lyapunov functions. Furthermore, we devote our attention to finding sufficient conditions for extinction and persistence. Finally, motivated by Ghana data, we applied the Euler–Murayama scheme to illustrate the dynamics of the co-infection, COVID-19, HBV, and the effect of some parameters on disease transmission dynamics by means of numerical simulations. Full article

Hepatitis B Virus (HBV) continues to pose a significant global health challenge, with over 254 million chronic infections and current therapies being non-curative, necessitating lifelong treatment. The HBV ribonuclease H (RNase H) is essential during HBV reverse transcription by cleaving the viral pregenomic RNA after it has been copied into the (−) polarity DNA strand, enabling the viral polymerase to synthesize the (+) DNA strand. Although RNase H inhibition terminates viral replication and thus viral infectiveness, its targeting as an HBV treatment is unexploited. Its catalytic site contains four carboxylates that bind to two Mg²⁺ ions essential for RNA hydrolysis. As part of our ongoing research on RNase H inhibitors, we developed 23 novel N-hydroxypyridinedione (HPD) analogues. Specifically, 17 HPD imines, 4 HPD oximes, 1 2,6-diamino-4-((substituted)oxy)pyrimidine 1-oxide derivative, and 1 barbituric acid analogue were designed, synthesized, and tested for their anti-HBV activity. The HPD derivatives could be docked in the RNase H active site to coordinate the two Mg²⁺ ions and effectively inhibited viral replication in cellular assays. The 50% effective concentration (EC₅₀) values of these HPD compounds ranged from 0.5 to 73 μM, while the 50% cytotoxic concentration (CC₅₀) values ranged from 15 to 100 μM, resulting in selectivity indexes (SIs) up to 112. Furthermore, the novel HPD derivatives exhibited favourable pharmacokinetic-relevant characteristics, including high cellular permeability, good aqueous solubility, and overall drug-like properties. These findings indicate that HPD imines and oximes possess substantial antiviral potency and selectivity against HBV, underscoring the potential of the HPD scaffold as a promising framework for the development of next-generation anti-HBV agents. Full article

Hepatitis B virus (HBV) particles containing HBV RNA are secreted into the blood; these RNA-containing particles are non-infectious byproducts of the replication cycle and are distinct from mature, DNA-containing virions. The proportion of these particles increases during nucleoside/nucleotide analog therapy, but the clinical significance of serum HBV RNA remains unclear. We evaluated longitudinal changes in serum HBV RNA and their association with the antiviral efficacy of nucleoside/nucleotide analog therapy. Eighty-six patients with chronic HBV infection (baseline HBV DNA ≥ 5.0 Log IU/mL and ALT < 500 U/L) treated with entecavir (ETV, N = 80) or tenofovir alafenamide (TAF, N = 6) were included. Serum HBV RNA was quantified using Cobas HBV RNA (RUO) at baseline, week 12, and week 48. Associations with clinical variables and treatment response were analyzed. Baseline HBV RNA correlated with HBsAg, HBV DNA, and hepatitis B core-related antigen. Both HBV DNA and RNA tended to decrease with advanced liver fibrosis. HBV DNA and RNA declines did not differ between HBeAg-positive and -negative patients, but the HBV RNA/DNA ratio at week 48 was significantly higher in HBeAg-positive cases (p < 0.001). Patients with baseline ALT ≥ 100 U/L showed significantly lower RNA levels at weeks 12 and 48 (p = 0.004, p < 0.001). While HBV DNA decline was similar between ETV and TAF (p = 0.076), RNA decline was significantly greater with TAF at week 12 (p = 0.027). Serum HBV RNA reflects intrahepatic viral replication and may not be influenced by fibrosis progression. HBV RNA decline during nucleoside/nucleotide analog therapy differed between ETV and TAF, suggesting drug-specific effects on viral RNA dynamics. Full article

Fluorescence anisotropy (FA) has been widely used for analyzing biomolecules due to its high throughput, homogeneous detection, and strong resistance to photobleaching. However, the traditional FA method suffers from low sensitivity when the target molecules are small and rotate rapidly, often producing insignificant changes in the FA value. In this study, by combining double signal amplification through the trans-cleavage of CRISPR-Cas12a and DNA tetrahedron assemblies with a large molecular size, a new, fast, simple and highly sensitive FA method was constructed to achieve the quantitative detection of hepatitis B virus DNA (HBV-DNA). The experimental results showed that the linear range of this method was 0.5–9 nmol/L, and the detection limit (LOD = 3σ/k) was 48 pmol/L. In addition, the method demonstrated excellent selectivity and anti-interference, and it was successfully applied to detect HBV-DNA in human serum, indicating that this method has the potential for clinical diagnosis. Full article

Chronic hepatitis B poses a serious threat to human health and life, and early diagnosis is essential to improving patient cure rates. Hepatitis B virus (HBV) and Alpha-fetoprotein (AFP) are two key biomarkers for diagnosing chronic hepatitis B. In this study, we propose a silicon nanowire array field effect transistor (SiNW-array FET) biosensor that enables highly sensitive, real-time, and low-cost joint detection of both HBV and AFP. The SiNW-array FET is fabricated using traditional micro-nano fabrication techniques such as self-limiting oxidation and anisotropic etching, and its morphology and electrical properties were tested. The results show that the diameters of the fabricated silicon nanowires (SiNWs) are uniform and the SiNW-array FET exhibits a strong output signal and high signal-to-noise ratio. Through specific chemical modification on the surface of SiNWs, the SiNW-array FET is highly sensitive and specific to HBV-DNA fragments and AFP, with ultralow detection limits of 0.1 fM (HBV-DNA) and 0.1 fg/mL (AFP). The detection curve of the SiNW-array FET exhibits good linearity within the HBV-DNA concentration range of 0.1 fM to 100 pM and AFP concentration range of 0.1 fg/mL to 1000 pg/mL. More importantly, the device could also detect HBV-DNA successfully in serum samples, laying a solid foundation for the highly sensitive clinical detection of chronic hepatitis B. Full article

Background: Since the introduction of the hepatitis B virus (HBV) vaccination program in Oman in 1990, the HBV prevalence has markedly decreased. However, hepatitis D virus (HDV) infection, which is associated with progressive liver disease in patients with chronic HBV, remains understudied in the Omani population. This study aimed to estimate HDV’s seroprevalence, characterize its virological and clinical features, and identify factors associated with anti-HDV positivity among adult Omani patients with chronic HBV infection. Methods: We conducted a multicenter cross-sectional study in 2024 at two referral hospitals and two polyclinics in Oman. Adult Omani patients with chronic HBV (HBsAg-positive for >6 months) were enrolled. Demographic, clinical, laboratory, imaging, and elastography data were collected. The total anti-HDV antibodies were tested using an ELISA; HDV RNA was tested for anti-HDV-positive or equivocal results. Liver Fibrosis was assessed non-invasively through liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE); FibroScan^® and clinical evaluation. Ridge (penalized) logistic regression identified predictors independently associated with anti-HDV positivity. Results: Among 639 patients (59.3% male; mean age of 46.6 ± 8.8 years), 36 patients were anti-HDV-positive, resulting in an HDV seroprevalence of 5.6% (95% CI: Exact 3.98–7.71; Wilson 4.10–7.70). Only one anti-HDV-positive patient had detectable HDV RNA, which became undetectable on follow-up without HDV treatment. The anti-HDV-positive patients were more frequently female and had a higher frequency of prior blood transfusions. In a penalized multivariable analysis, blood transfusions were independently associated with anti-HDV positivity (OR of 19.94), whereas male sex was associated with lower odds of being anti-HDV-positive (OR of 0.15). All the anti-HDV-positive patients had mild fibrosis (F0–F1). Conclusions: Our study demonstrated an anti-HDV prevalence of 5.63% among adult Omani patients with chronic HBV infection, while active viremia appeared to be rare. Blood transfusions were the main identified risk factor. Given the very low HDV viremia, targeted screening of higher-risk groups may be efficient. Full article