CEP290 is Associated With Chromatin Accessibility of Hepatitis B virus cccDNA.

Hepatitis D Infection: a puzzle still unsolved?

Hepatitis B virus (HBV) has been implicated in hepatocellular carcinoma (HCC) progression, partly through regulation of the tumor suppressor phosphatase and tensin homolog (PTEN). Although transcriptional regulation of PTEN by HBV is well characterized, its post-transcriptional regulation remains poorly understood. Because RNA 5-methylcytosine (m5C) modification influences post-transcriptional gene control and cancer development, we investigated whether HBV modulates PTEN through m5C. Methylated RNA immunoprecipitation (MeRIP)-quantitative polymerase chain reaction showed a marked reduction in m5C on PTEN mRNA in HBV-producing cells. MeRIP sequencing further identified decreased m5C within the PTEN coding sequence region (chr10:89717747-89717771) in HBV-producing HepAD38/tetracycline-off cells, with chr10:89717756 emerging as a critical site where HBV suppresses m5C enrichment and PTEN expression. Mechanistically, the m5C "writer" NOP2/Sun RNA methyltransferase 2 (NSUN2) and the "reader" Y-box binding protein 1 (YBX1) stabilized PTEN mRNA in an m5C-dependent manner. HBV disrupted this pathway, decreasing PTEN mRNA stability via NSUN2- and YBX1-mediated m5C. Overexpression of NSUN2 or YBX1 attenuated HBV-driven proliferation, migration, and invasion, and these effects were partially reversed by the PTEN inhibitor VO-Ohpic. The small hepatitis B surface antigen and hepatitis B X protein downregulated NSUN2 and YBX1, linking viral proteins to PTEN suppression. Further, HBV is associated with reduced NSUN2 expression in HBV transgenic (HBV-Tg) mice, HBV-infected primary human hepatocytes as well as HBV-positive clinical HCC specimens, supporting the physiological and clinical relevance of this finding. Together, these findings identify the NSUN2/YBX1/PTEN axis as a potential therapeutic target in HBV-associated HCC.

In hepatitis B surface antigen (HBsAg)-negative recipients with antibody to hepatitis B core antigen (anti-HBc)-positive liver grafts, hepatitis B virus (HBV) can be reactivated under post-transplant immunosuppression. We recently reported a median intrahepatic covalently closed circular DNA (cccDNA) level of 238 copies/μg in HBsAg-positive patients. Meanwhile, the potential levels of intrahepatic cccDNA in anti-HBc-positive grafts have never been focused on as a factor for HBV recurrence. Among 168 patients who underwent living donor liver transplantation (LDLT) between 2018 and 2022, 4 HBsAg-negative recipients with anti-HBc-positive grafts were consecutively enrolled in this prospective study. Intrahepatic cccDNA levels in donor grafts were measured based on an intraoperative liver biopsy and digital droplet polymerase chain reaction. In all four donor grafts, intrahepatic cccDNA levels ranged from 5.2 to 408 copies/μg, and all were negative for the high-sensitivity hepatitis B core-related antigen. Three of four recipients experienced HBV reactivation 14-24 months after LDLT. Two patients developed hepatitis with high HBV DNA and HBsAg levels, escape mutations (G145R ± K141R) with genotype B or C were detected. Entecavir therapy achieved serological and virological clearance within 2-9 months. The fourth patient remained recurrence-free during 36 months of follow-up. Even among patients with resolved HBV infection, there are cases possessing intrahepatic cccDNA levels as high as or even higher than those in HBsAg-positive patients. To resolve this critical pitfall in immunosuppressed patients, the development of serum markers that precisely reflect intrahepatic cccDNA levels will be essential for improving HBV prophylaxis strategies.

The seroconversion rate after hepatitis B virus (HBV) vaccination in people living with human immunodeficiency virus (HIV) is reportedly lower than that in non-HIV controls. Follicular helper T (Tfh) cells play a central role in humoral immunity, and IL-21 secreted by Tfh cells is essential for B cells to differentiate into plasma cells. This study investigated the frequency and function of circulating Tfh (cTfh) cells isolated from people living with HIV (PWH) who are negative for hepatitis B virus (HBV) surface antigen (HBsAb-) in a small cohort of PWH who received HBV vaccination. The frequency of cTfh cells in HBsAb- PWH (HBsAb levels less than 10 mIU/mL) was the same as that in non-HIV controls and HBsAb positive (HBsAb+) PWH, who maintained HBsAb at 10 mIU/mL for at least 1 year after receiving three doses of the HBV vaccine. However, after immune stimulation with anti-CD3/CD28 antibodies, the frequency of cTfh cells in the non-HIV controls and HBsAb+ PWH increased, whereas the frequency of cTfh cells in the HBsAb- PWH tended to be more gradual. cTfh17-like and cTfh2-like cells, subsets of cTfh cells, are involved in humoral immunity, and PD-1 regulates the function of these cells in the germinal center. The frequencies of PD-1+ cTfh17-like and cTfh2-like cells at baseline did not differ significantly among the three groups. However, HBsAb- PWH had a lower frequency of PD-1+ cTfh17-like cells after immune stimulation than non-HIV controls did. The frequencies of PD-1+ cTfh17-like cells and cTfh2-like cells with high PD-1 expression were significantly lower in HBsAb- PWH than in non-HIV controls. Furthermore, the production of IL-21, which is essential for plasma cell differentiation, tended to be lower in HBsAb- PWH than in non-HIV controls or HBsAb+ PWH. cTfh cells isolated from HBsAb- PWH may be unable to produce sufficient IL-21 after immune stimulation. This study is the first to suggest that cTfh cells may not function adequately in some PWH. This study highlights the need for large-scale validation of cTfh cell frequency and function in PWH. Not applicable.

Although New York City (NYC) is a hotspot for hepatitis delta virus (HDV) in the United States (US), the epidemiology of HDV remains poorly understood. We aimed to determine HDV testing and positivity rates, calculate prevalence of liver disease progression by HDV status, and assess the association between HDV and community resources. We utilized the INSIGHT database, which contains data from the five major NYC health systems, to identify adults with laboratory and/or diagnosis code evidence of hepatitis B virus (HBV) from 2010-2023. HDV positivity included HDV RNA ≥ 20 IU/mL and/or positive results for HDV Ab, RNA, and Ag. Prevalence of liver-related complications was calculated. Community deprivation index was used to evaluate socioeconomic disparities by HDV testing and positivity status. Here we show that among 106,210 patients with HBV, 5,388 (5.1%) have received HDV testing; 294 (5.5%) are HDV + . HDV-tested individuals are more likely to be older and Asian, receive comprehensive HBV care, and have more community resources. HDV+ individuals are more likely to be female, White, and have higher prevalence of liver disease progression. HDV is undertested and under-detected, even in a high-prevalence US region. Early linkage to treatment is essential given high rates of liver disease progression.

Situated between two of the world's largest opium-producing regions, South Asia faces significant public health threats associated with drug trafficking and injecting drug use. People who inject drugs (PWID) in South Asia experience disproportionately high rates of bloodborne viruses (BBVs), including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). These high rates are driven by factors such as drug trafficking routes, socioeconomic marginalization, poor surveillance, and inadequate harm reduction services. Pakistan has the highest reported prevalence rates, with HIV and HCV rates exceeding 30% and 50%, respectively, while India, Bangladesh, and Afghanistan report localized epidemics in urban and border areas. Co-infections, particularly HIV/HCV, further complicate clinical management and public health responses. Despite the implementation of needle-syringe programs and opioid substitution therapy in several countries, service coverage remains below recommended levels due to legal, financial, and structural barriers. Marginalized subgroups, including women and incarcerated individuals, remain underserved and often overlooked. In this review, we discuss the burden of these infections among PWID in South Asia, current control strategies, and the precarious future given the recent instability to the USAID, PEPFAR, WHO, and the Global Fund by the Trump administration.

Objective: Chronic hepatitis B virus (HBV) infection poses a risk of viral reactivation in patients receiving immunosuppressive therapies, including anti-tumor necrosis factor (TNF) agents. This study aimed to evaluate HBV screening practices, antiviral prophylaxis, and reactivation outcomes in patients with inflammatory bowel disease (IBD) undergoing biologic therapy at a tertiary referral center in Turkey. Methods: Patients diagnosed with IBD who initiated biologic therapy between 2009 and 2025 were retrospectively reviewed. Demographic and clinical characteristics, HBV serologic status, antiviral prophylaxis, vaccination history, and HBV reactivation events were recorded. Chronic HBV infection was defined as persistent hepatitis B surface antigen (HBsAg) positivity for more than 6 months. Occult HBV infection was defined as HBsAg negativity with anti–HBc positivity and detectable HBV DNA. HBV reactivation was defined as the reappearance of HBV DNA or HBsAg in patients with previously undetectable levels, or a greater than 10-fold increase in HBV DNA, in accordance with EASL 2025 criteria. Results: A total of 437 patients were included (59% male; mean age 33.2±12.8 years), of whom 72% had Crohn’s disease. Anti-HBc positivity was detected in 70 patients (16%). Five patients (1.1%) were HBsAg positive, and 1 patient had occult HBV infection; all 6 received antiviral therapy. Overall, 12 patients (2.7%) received antiviral prophylaxis. During a mean biologic exposure of 33.5±28.6 months, no HBV reactivation occurred in patients receiving or not receiving antiviral therapy. HBV vaccination was documented in 25.8% of patients, with loss of vaccine-acquired immunity observed in 18.5%. Among patients with natural immunity, 15.1% experienced anti-HBs seroreversion. Conclusion: Real-life data from this tertiary IBD center demonstrate appropriate HBV screening and antiviral prophylaxis in high-risk patients. The absence of HBV reactivation supports close monitoring rather than routine prophylaxis in intermediate-risk groups. Periodic reassessment of HBV serology is recommended due to antibody loss during immunosuppressive therapy. Cite this article as: Eşkazan T, Sonsuz A. Hepatitis B virus screening, prophylaxis, and reactivation in inflammatory bowel disease patients undergoing biologic therapy: real-life data from a tertiary center in Türkiye. Cerrahpaşa Med J. 2026, 50, 0013, doi: 10.5152/cjm.2026.26013.

Abstract Background Hepatitis B virus (HBV) infection is a primary global public health concern since it is commonly recognized as the primary risk factor for cirrhosis and liver cancer globally. This study aims to evaluate the level of knowledge and the prevailing attitudes of Jordanian nursing students toward hepatitis B, with a particular focus on identifying knowledge gaps and factors influencing their understanding and perceptions. Materials and methods A descriptive design was employed to collect data from December 1, 2023, to April 1, 2024. A self-administered questionnaire was used to conduct convenience sampling among senior Jordanian nurses. Result A total of 455 participants were analyzed, revealing a young cohort with a mean age of 22.5 years. The participants demonstrated moderate knowledge of hepatitis B, with specific misconceptions identified. Besides, participants demonstrated a moderately positive attitude toward hepatitis B. However, demographic characteristics showed significant differences in knowledge by sex, whereas certain factors did not. Still, attitudes significantly differed based on those infected with hepatitis B and family members infected with hepatitis B. Conclusion This study focused on training and awareness programs to enhance knowledge and foster a positive attitude towards hepatitis B amongst nursing students. Moreover, combining these training and awareness activities would help improve hospital safety protocols in Jordan and ensure that a hepatitis B virus outbreak is averted.

Canadian Blood Services implemented a re-entry programme in 2014. Donors deferred because of false-reactive or indeterminate screening tests can provide a specimen for re-entry testing 6 months after their initial test, and resume donating if they test negative for all infectious markers. We evaluated the impact of the programme on donor return and retention, and assessed factors associated with reactive results upon re-entry testing. Using extracted data from our donor database, we followed up donors who tested false-reactive for hepatitis B virus (HBV), human immunodeficiency virus (HIV) and hepatitis C virus (HCV), from the implementation of the programme on 3 February 2014 until 30 June 2025 (n = 8094). We characterized the donors reaching each step of the programme by sex, age, donation status and infection marker. We employed logistic regression to identify important predictors of obtaining reactive results upon re-entry testing. Overall, 17.3% of donors eligible for re-entry testing successfully returned and donated. Re-entry testing participation rates were 35.5%, with repeat and older donors more likely to participate. Among re-entry tested donors, 59.2% tested negative. Most donors continued to donate for multiple years upon re-entry. Upon return, 13.1% tested false reactive on a subsequent donation. False-reactives upon re-entry testing were more likely for first-time donors and less likely when a different assay was employed than for the initially false-reactive. The implementation of a donor re-entry programme has resulted in donor retention and increases in the blood supply. Sending reminder notifications to eligible donors could increase participation.

Hepatitis B virus (HBV) contributes substantially to liver cancer, related mortality, and liver transplantation worldwide. The small hepatitis B surface antigen (HBsAg), particularly its major hydrophilic region (MHR) and the "a" determinant, is the primary target of serological diagnostics. However, escape mutant amino acid variants (EMAVs) within this region may reduce diagnostic specificity and sensitivity. In this study, publicly available HBsAg sequences were analyzed to determine the prevalence of EMAVs circulating in Ethiopia. We computationally designed three region-specific recombinant antigens (MeRPYS1, MeRPYS2, and MeRPYS3) by incorporating both wild-type and prevalent EMAV sequences. Linear and conformational B-cell epitopes, as well as T helper cell epitopes, were predicted for each antigen. Homology analyses were also performed to assess similarity to host proteins. Secondary and tertiary structures of the antigens were predicted to generate theoretical molecular models. Molecular docking analyses were performed to explore putative interaction patterns between each designed antigen and an anti-HBsAg-specific antibody. The predicted antigen-antibody complexes were further examined using molecular dynamics (MD) simulations to assess their theoretical stability and behavior over time. The resulting simulations provide predictive computational insights into possible antigenic features and interaction tendencies of the designed constructs. These findings are intended to generate testable hypotheses and should be interpreted cautiously, as the study is limited to in silico analyses and requires experimental validation.

Hepatitis B virus (HBV) infections are associated with an increased risk of B-cell lymphomas, including follicular lymphoma (FL). Chronic HBV infection and shifts in infection status following treatment can influence lymphomagenesis and immune reprogramming, potentially affecting clinical outcomes. Using the CosMx Spatial Molecular Imaging, after integrated with dynamic HBV infection states and duration of overt infection, this refines four recurrent patterns, especially memory B cell-like malignant cells (MBLM) subtype (PTPRCAP + ) that is traced with atypical features and latent indolence, and virus protein transport-related follicular dendritic cell (FDC) which shows interplay with MBLM. Except for virus-induced immune exhaustion, distinct contributions to POD24 occurrence from malignant cells and immunosuppressive cell communities under distinct HBV infection states are discerned such as through CCL21/CCR7 signaling pathway. Taken together, our spatial multicellular dynamics reveal an increased prevalence of MBLM and variable FDC phenotypes which is associated with POD24 occurrence in HBV-related FL tumors.

Discovery of therapeutic targets for hepatocellular carcinoma (HCC) is urgently needed. As an important hepatitis B virus (HBV) oncoprotein, pre-S2 mutant activates multiple signalling pathways to induce HCC development. This study investigated the effect of pre-S2 mutant on regulating microRNA (miRNA) expression and the role of miRNAs in mediating pre-S2 mutant's oncogenic functions. The results showed that 9 miRNAs were downregulated in both tumour tissues of pre-S2 mutant-positive HCC patients and pre-S2 mutant-expressed human HCC cell lines, contributing to pre-S2 mutant-promoted cell proliferation, anchorage-independent cell growth, cell cycle progression, and tumour growth and malignancy. Moreover, pre-S2 mutant downregulated miRNA expression at the epigenetic levels through suppression of lysine acetyltransferase 3B (KAT3B)- and KAT5-mediated histone H3 lysine 9 acetylation (H3K9ac) and H4K5ac modifications. The decreased levels of pre-S2 mutant-dysregulated miRNAs could also be detected in blood exosomes of patients. Collectively, this study provided new mechanistic insights and therapeutic perspectives for pre-S2 mutant-associated HCC tumorigenesis.

Hepatitis B virus (HBV) and human T-lymphotropic virus type 1 (HTLV-1) are blood-borne pathogens with overlapping transmission routes, resulting in an increased prevalence of HBV among individuals infected with HTLV-1. Notwithstanding the widespread application of mathematical modeling to the study of each virus in isolation, the within-host dynamics of HBV–HTLV-1 co-infection remain insufficiently characterized. This study introduces a novel within-host co-infection model that characterizes the interactions between HBV and HTLV-1, where HTLV-1 infects CD4+ T cells and HBV targets hepatocytes. A comprehensive qualitative analysis yields four threshold parameters (Ri,i=1,2,3,4) governing the existence and stability of equilibrium points, with global stability established using Lyapunov functions. Numerical simulations validate the analytical results, and sensitivity analysis identifies parameters that most strongly influence the basic reproduction numbers for HBV (R1) and HTLV-1 (R2) mono-infections. Our results corroborate that, in patients with HBV, the presence of HTLV-1 contributes to an elevated HBV viral load and CD4+ T cells play a crucial role in controlling HBV infection.

ABSTRACT Hepatitis B virus (HBV) infection remains a major concern in Nigeria. Nationally, increasing infection rates continue to pose a significant challenge, which may be due to inadequate diagnosis. Known markers, such as Hepatitis B Surface Antigen (HBsAg) and Hepatitis B e antigen (HBeAg), are good at indicating exposure rates, but generally poor at reflecting active viral replication. The hepatitis B core-related antigen (HBcrAg) may provide a clearer picture of the viral activity and treatment response. We conducted a cross-sectional study involving 450 participants aged 16–65 years from hospitals in Osun and Plateau States. HBsAg screening was performed using rapid diagnostic tests, confirmed by enzyme-linked immunosorbent assay (ELISA), and further evaluated for HBeAg and HBcrAg levels. Correlation analysis was used to test the relationships between these markers. Of the 450 participants screened, 188 (41.7%) were confirmed positive for HBV. HBcrAg was observed in adults aged 17–45 years, suggesting replication activity in symptom-free individuals. Atypical serological profiles, such as HBsAg and HBsAb co-positivity, were also identified. Incorporation of HBcrAg in HBV screening, especially in endemic countries, may be useful in assessing HBV replication stage, reactivation, and staging of chronic infection, especially in resource-limited settings.

RNA interference (RNAi) therapeutics targeting hepatitis B virus (HBV) RNAs and monoclonal antibodies (mAbs) targeting HBV surface antigen (HBsAg) represent potential strategies for enabling functional cure in chronic HBV patients. Tobevibart (VIR-3434) is an investigational, Fc-engineered human mAb that targets HBsAg with pan-genotypic neutralizing activity. Elebsiran (VIR-2218) is an investigational small interfering RNA targeting a conserved region of the HBV genome. The in vitro antiviral activity of elebsiran was assessed in HBV-infected primary human hepatocytes and hepatoma cells and showed potent inhibition of viral markers HBeAg (EC50 of 2.5 nM and 53.7 pM, respectively) and HBsAg (EC50 of 1.4 nM and 66.5 pM, respectively). Tobevibart and elebsiran activity in vivo was determined using two well-established HBV mouse models: AAV-HBV transduced C57BL/6 mice and human liver-chimeric mice. Mice were treated with a monotherapy or a combination of muHBC34 (the murinized parental mAb of tobevibart) and elebsiran at different doses. In both models, the mouse surrogate of tobevibart or elebsiran monotherapy was effective in reducing blood HBsAg levels. Combined treatment improved suppression of HBsAg (maximum mean reductions of 2.81 log in the AAV-HBV model and 2.51 log in human liver-chimeric mice) and HBV DNA over monotherapy. Tobevibart and elebsiran have been tested in clinical trials for the treatment of chronic hepatitis B and chronic hepatitis Delta.

Real-world evidence regarding biologic therapy in geriatric psoriasis is limited, particularly concerning systemic inflammatory burden and infection-related safety. This study evaluates the clinical efficacy of biologic therapy and its impact on systemic inflammatory indices while emphasizing safety related to hepatitis B virus (HBV) serology and tuberculosis screening. We conducted a retrospective analysis of eighty biologic-naïve patients aged 65 years and older with plaque psoriasis undergoing biologic therapy. Patients were categorized by biologic class: tumor necrosis factor-α (TNF-α) inhibitors, interleukin-17 inhibitors, an interleukin-12/23 inhibitor, and interleukin-23 inhibitors.The primary outcomes included changes in Psoriasis Area and Severity Index (PASI) scores and blood count-derived inflammatory indices over time (baseline and 6 months). Secondary outcomes encompassed changes in HBV serologic status and QuantiFERON-TB (QFT) results. Data analysis utilized longitudinal mixed-effects models for repeated measures. Blood count-derived inflammatory indices, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), were assessed at baseline and 6 months, alongside HBV serology and QFT results.PASI scores demonstrated significant improvement over time (p<0.001), with no notable differences among biologic classes after adjusting for baseline covariates. Significant time effects were observed for all inflammatory indices (all p< 0.001), with significant group × time interactions noted for SII and NLR (both p< 0.05). Variability in HBV serologic markers and QFT results was observed during follow-up; however, no cases of active tuberculosis or clinically overt hepatitis were identified. In conclusion, biologic therapy led to substantial clinical improvement in geriatric psoriasis, accompanied by reductions in systemic inflammatory indices over a 6-month period, without evidence of clinically overt hepatitis or active tuberculosis during follow-up.

Innate immunity constrains the hepatitis B virus (HBV) by sensing pathogen-associated molecular patterns (PAMPs) and inducing type I/III interferons and interferon-stimulated genes. This review synthesizes molecular mechanisms by which HBV nucleic acids and proteins are detected by pattern recognition receptors (PRRs) and how the virus evades such surveillance. At the DNA level, covalently closed circular DNA (cccDNA) persists as a chromatin-like episome with low immunogenicity; cGAS–STING signaling is functionally dampened, whereas nuclear interferon-inducible protein 16(IFI16) and cytoplasmic/nuclear ABCF1 bind cccDNA to repress transcription, and APOBEC3A-mediated deamination requires robust interferon signaling. At the RNA level, TLR3/7/8 and retinoic acid-inducible Gene I(RIG-I) sense circulating HBV RNA and 5′-triphosphate pregenomic RNA, respectively. HBV counteracts RIG-I-like receptor (RLR) pathways through ADAR1 editing, TIAR-dependent translational control, and a metabolic checkpoint involving lactate-MAVS/hexokinase, whereas spliced viral RNAs (svRNAs) have emerged as immunologically relevant species. At the protein level, Hepatitis B Surface Antigen (HBsAg) impairs interferons (IFN) induction by blocking the TAK1–TAB2–NF-κB/IRF axis; Hepatitis B Virus X Protein (HBx) sustains cccDNA transcription via DDB1-directed Smc5/6 degradation and broadly suppresses PRR/IFN signaling, with TRIM25 acting as a host restriction factor. These insights nominate combinatorial strategies—PRR agonists (TLR/STING), MAVS sensitization, metabolic disinhibition, pharmacological disruption of the HBx–DDB1 axis, and reinforcement of IFI16/ABCF1—to achieve functional control of cccDNA and advance curative hepatitis B virus (HBV) therapy.

It is known that between 5-10% of individuals vaccinated against hepatitis B virus (HBV) do not develop protective antibody levels. Several factors negatively influence the immune response. The aim of this paper was to evaluate the immunological response to HBV vaccination in at-risk populations and analyze its variation according to the type of vaccination schedule (primary vaccination or booster dose), age, sex, and risk group. A longitudinal descriptive study was conducted on patients between 04/11/2021-15/06/2023 at the Preventive Medicine vaccination clinic at Hospital Infanta Leonor (Madrid, Spain). Patients from risk groups who had completed a full vaccination schedule (high-dose or adjuvant vaccine) or received a booster dose were included. Criteria for exclusion were incomplete vaccination schedules and absence of post-vaccination serology. A non-probabilistic convenience sampling was used, including all available patients who met the inclusion criteria. The sample size was 77 patients. Variables considered were: age, sex, risk pathology, and HBsAbs levels at 1 to 2 months post-vaccination. The immune response (HBsAbs ≥10 mUI/ml) was analyzed according to the collected variables using chi-square and logistic regression. Out of 572 patients that were assessed, 97 had received vaccination. Serology data was available for 77 patients: primary vaccination (n=51), booster dose (n=24), and revaccination (n=2). Mean age was 43.7 (15.7) years, 76.6% were men. Distribution by risk group was: 59.7% HIV, 28.6% immunosuppression, 11.7% chronic kidney disease. Among the 77 patients included in the study, 87% (95% CI: 77.4-93.6) responded to vaccination, with differences in response evident in the age ranges: 96.8% (95% CI: 83.3-99.9) of those under fourty years of age responded adequately compared to 50% (95% CI: 18.7-81.3) of those over fifty-five years (p=0.002). In the primary vaccinated group, those patients that were over fifty-five years of age had a 96% lower probability of mounting an adequate immune response compared to those under fourty years, adjusted for other variables (OR=0.04, 95%CI: 0.002; 0.70) (p=0.028). Most individuals vaccinated against HBV show an adequate immune response, although older age is associated with a reduction in response to the vaccination. Maintaining complete and updated vaccination schedules is essential, especially in older patients, to ensure effective protection.

Hepatitis B virus (HBV) infection is a significant risk factor for hepatocellular carcinoma (HCC). During the infection, HBV DNA integrates into the host genome, promoting hepatocarcinogenesis through both gene-dependent and gene-independent mechanisms. It can activate oncogenic gene transcription or produce chimeric and novel proteins that contribute to tumorigenesis. On the other hand, it also compromises genomic stability on a large scale. Furthermore, HBV integration can alter the liver microenvironment, fostering conditions conducive to tumor development. HCC remains one of the most challenging cancers to treat, primarily due to the incomplete understanding of HCC, inadequate diagnostic and prognostic strategies, and limited effective therapeutic options. Liquid biopsy represents a significant advancement in oncology, offering a non-invasive tool for cancer detection and management. HBV integration detection through liquid biopsy serves as a promising strategy for managing HBV-associated HCC. Importantly, it exhibits preferential patterns that differentiate HCC from chronic hepatitis or cirrhosis patients, making it a potential biomarker for HCC diagnosis. Moreover, the quantification of HBV-host chimeric reads in the bloodstream can indicate the presence of residual tumor cells post-surgery, serving as a promising biomarker for the screening of HCC recurrence. HBV integration additionally contributes to the production of HBV surface antigen (HBsAg), which is crucial for achieving a functional cure for HBV infection and influences the efficacy of antiviral treatments. Overall, HBV integration plays a pivotal role in hepatocarcinogenesis, and its detection via liquid biopsy will greatly enhance the clinical management of HBV-associated HCC.