Search Results (566)

Chronic hepatitis B (CHB) remains a major global health challenge, largely due to the persistence of covalently closed circular DNA (cccDNA) and impaired host immunity. Interferon-α (IFN-α), a key antiviral cytokine, not only directly restricts HBV replication but also orchestrates innate and adaptive immune responses. This review summarizes current advances in IFN-α-mediated immune regulation, highlighting its effects across diverse immune cell populations. Evidence indicates that IFN-α can reprogram immune responses to promote viral clearance, although clinical efficacy is limited by modest response rates and adverse effects. Recent progress in cytokine engineering, subtype research, and rational combination strategies—including nucleo(s/t)ide analogs, RNA interference therapeutics, antisense oligonucleotides, therapeutic vaccines, and beyond—has expanded opportunities to improve treatment outcomes. While challenges remain, these advances lay the foundation for optimizing IFN-α–based interventions and highlight IFN-α as a key driver for innovative therapies aimed at achieving a functional cure 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

Background/Objectives: Adults aged 19–59 with diabetes are recommended by the Advisory Committee on Immunization Practices (ACIP) to receive vaccination against Hepatitis B Virus (HBV) infection because of their increased risk of contracting HBV. This study aimed to examine hepatitis B (HepB) vaccination rates among U.S. adults aged 19–59 years with diabetes and explore sociodemographic factors associated with HepB vaccination. Methods: Data from the 2015–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed to compare HepB vaccination between adults with and without diabetes. Weighted Chi-square analysis was used to test the associations between HepB vaccination status and various categorical variables. Weighted logistic regression was employed to identify factors associated with being fully vaccinated. Results: A total of 5988 adults aged 19–59 were included in the study, of whom 504 (8.4%) had diabetes. The HepB vaccination rate was 32.3% for those with diabetes vs. 43.6% for those without diabetes (p = 0.01). However, after adjusting for other covariates, having diabetes was not associated with being fully vaccinated against HBV (p = 0.583). Adults aged 45–59 years were less likely to be vaccinated against HBV compared to those aged 19–29 (OR: 0.12, p < 0.0001). Having health insurance, being female, and having a higher educational level were all associated with HepB vaccination status (all p < 0.01). Overall, the HBV infection rate was 1.1%. Having HepB vaccination was associated with a lower risk of HBV infection among both groups with and without diabetes. Conclusions: HepB vaccination among U.S. adults with diabetes was suboptimal and lower than among those without diabetes. Age and education were associated with being fully vaccinated against HBV. Future research is needed to identify and better understand barriers to receiving HepB vaccines. Full article

Background/Objectives: Hepatitis B virus (HBV) remains a persistent challenge for transfusion safety. Although testing for hepatitis B surface antigen (HBsAg) and nucleic acid testing (NAT) reduces transmission risk, antibodies to hepatitis B core antigen (anti-HBc) and antibodies to hepatitis B surface antigen (anti-HBs) provide additional insight into past infection and vaccine-induced immunity. We aimed to determine their seroprevalence among blood donors in southern Croatia and assess associations with age, occupation, and time since vaccination. Methods: This cross-sectional study was conducted between February and November 2024 at two regional transfusion centers in southern Croatia. A total of 1008 voluntary blood donors, all HBsAg- and NAT-negative, were tested for anti-HBc and anti-HBs using chemiluminescent microparticle immunoassay. Demographic and vaccination data were collected through verified medical records. Results: Anti-HBc was detected in 0.5% of donors, exclusively among the unvaccinated. Protective anti-HBs levels were found in 38.1% overall and 70.6% of vaccinated donors, with significant declines by age and more than 15 years post-vaccination (p = 0.024). Healthcare workers showed higher seroprotection than non-healthcare donors (67.0% vs. 35.1%; p < 0.001), although one-third still lacked protective levels. Conclusions: HBV exposure was rare, but waning vaccine-induced immunity was evident, with protective anti-HBs levels in 70.6% of vaccinated donors, declining with age and time since vaccination. These findings highlight the need for periodic monitoring of anti-HBs and targeted booster strategies, especially in older and occupationally exposed groups. HBsAg and NAT provide a high level of transfusion safety, while the role of routine anti-HBc testing in this low-endemic context should be carefully evaluated in view of its potential benefits and drawbacks. Donor-based surveillance is a valuable tool for evaluating long-term vaccine effectiveness and guiding public health policy. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4⁺ and CD8⁺ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment. Full article

Hepatitis B virus (HBV) remains a major global health concern, as it is not only one of the most common hepatotropic viruses but also ranks as the seventh leading cause of mortality worldwide. The most significant routes of infection include vertical transmission (from mother to child before, during, or after birth, including transplacental infection) and horizontal transmission in early childhood through close household contact with infected parents. The aim of our study was to assess the prevalence of chronic and occult hepatitis B virus infection among pregnant women in St. Petersburg (Russia), including molecular characterization. We analyzed plasma samples from 1368 local pregnant women. ELISA screening for HBV markers included qualitative detection of HBsAg, anti-HBs IgG, and anti-HBcore IgG. HBV DNA was identified using highly sensitive nested PCR, followed by whole-genome sequencing for HBV DNA-positive cases. Our study evaluated the prevalence of serological and molecular HBV markers and their association with age, vaccination status, and number of pregnancies. Serological markers HBsAg, anti-HBs IgG, and anti-HBcore IgG were detected in 1.9%, 63.8%, and 12.9% of participants, respectively. HBV DNA was found in 4.7% of pregnant women, including 2.8% with occult HBV infection (OBI). We observed a positive correlation between anti-HBcore IgG and age, but an inverse correlation with anti-HBs IgG; an inverse correlation between anti-HBcore IgG and vaccination status, while anti-HBs IgG showed a positive correlation; and a positive correlation between HBsAg, anti-HBcore IgG, and HBV DNA with the number of pregnancies. We also analyzed the prevalence of clinically significant mutations, including drug resistance mutations, escape mutations (affecting diagnostic detection and vaccine efficacy), and mutations associated with disease progression. The detection of HBsAg-negative HBV infection was linked to circulating viral variants carrying escape mutations, which evade HBsAg detection in diagnostic assays and neutralization by vaccine-induced antibodies. The predominance of HBV isolates in pregnant women harboring dual-threat mutations (those causing diagnostic failure via HBsAg negativity, reduced vaccine/immunoglobulin efficacy, viral reactivation, disease progression) poses a significant public health risk and warrants further investigation. Full article

Hepatocellular carcinoma (HCC) is rising in incidence globally. It is the sixth most common cancer and the third leading cause of cancer-related mortality worldwide. Infection with hepatitis B and/or C virus is a significant risk factor for developing HCC. These viruses exert their carcinogenicity in both direct and indirect ways, including induction of immune exhaustion with prolonged antigen exposure. Therefore, the best therapeutic option for HCC is prevention, i.e., Hepatitis B vaccination and treatment of viral hepatitis. However, when HCC develops because of viral hepatitis or other etiologies, long-lasting effects on the immune system remain even after viral suppression, which affect the response to HCC therapy. Recent studies have suggested a “hot” and “cold” model for HCC, in which the two kinds of HCC tumors have very distinct tumor microenvironments. The microenvironment for hot HCC makes these tumors amenable to immunotherapy with checkpoint inhibitors. Therefore, converting cold HCC tumors to hot tumors may make them susceptible to immunotherapy. In this review, we provide an overview of HCC epidemiology and prevention, an overview of tumor microenvironments of hot and cold HCC, the proposed mechanisms for converting cold tumors to hot tumors, and a concise summary of the evidence for combination checkpoint inhibitor therapy for HCC. Full article

Compound T1089—a novel nitrogen mustard based on an indole-3-carboxylic acid derivative (ICAD)—has been synthesized. The ICAD used as the basis for T1089 is a TLR agonist capable of activating an antitumor immune response. This study describes the synthesis method and presents the results of preliminary investigations of this compound. This research included an assessment of acute toxicity in mice, in vivo clastogenic activity evaluated via the bone marrow chromosome aberration (BMCA) test in mice, in vitro cytotoxicity determined by the MTT assay against human lung carcinoma A549 cells, and in vivo antitumor effects (ATEs) in models of conventional chemotherapy (CCT) of solid tumors in mice. The bifunctional alkylating agent cyclophosphamide (CPA) was used as a reference drug. Toxicological studies revealed that T1089 belongs to toxicity class III (moderately toxic), with acute toxicity values (LD₁₆ and LD₅₀) in mice following intraperitoneal (i.p.) administration being 191 and 202 mg/kg, respectively. The alkylating activity and clastogenic potential of T1089 were demonstrated by its effects in the BMCA test, which were comparable to those of CPA. A single i.p. administration of CPA and T1089 at a dose of 0.064 mmol/kg induced similar stimulation of structural mutagenesis associated with DNA strand breaks. The frequency of karyocytes with aberrations increased 20-fold compared to the control, primarily due to a rise in chromatid breaks and fragments, and to a lesser extent, due to an increase in exchange-type aberrations. In vitro cytotoxicity studies indicated differences in the mechanisms of alkylating activity between CPA and T1089. According to the MTT assay, the cytotoxic effects of CPA were observed only at concentrations exceeding 2 mM (IC₅₀ = 4.2 ± 0.3 mM), corresponding to lethal in vivo doses, which is expected since the formation of CPA’s alkylating metabolite requires hepatic microsomal enzymes. In contrast, significant cytotoxic effects of T1089 were observed at much lower concentrations (15–50 μM, IC₅₀ = 33.4 ± 1.3 μM), corresponding to safe in vivo doses. Differences were also observed in the in vivo ATEs of CPA and T1089 in the Ehrlich solid carcinoma (ESC) CCT model. Following seven i.p. administrations at 48 h intervals (33 mg/kg), both compounds exhibited increasing toxicity, manifested as cumulative body weight loss in treated mice. However, despite the aggressive CCT regimen, ESC showed low sensitivity to CPA. The ATE of CPA developed slowly, reaching a significant level only after four injections, and even after seven administrations, tumor inhibition (TI) did not exceed 30%. In contrast, ESC was significantly more sensitive to T1089 under the same CCT conditions. The ATE of T1089 exhibited a cumulative pattern but developed more rapidly and to a greater extent. A significant antitumor effect was observed after just two injections, with maximal efficacy (TI = 53%) achieved after four injections and sustained until the end of the observation period. A high ATE of T1089 was also observed in the B-16 melanoma CCT model. Following six i.p. administrations at 48 h intervals (28 mg/kg), T1089 treatment was associated with minimal toxicity. Despite this mild CCT regimen, melanoma exhibited high sensitivity to T1089. Maximal ATE (TI = 56%) was achieved after two injections, and subsequent administrations maintained a consistently high efficacy (TI = 52–55%) until the end of the study. In summary, preliminary findings demonstrate that T1089 possesses alkylating activity characteristic of bifunctional agents, accompanied by high in vitro cytotoxicity and in vivo ATEs in CCT models (at high doses). Given that the ICAD used as the basis for T1089 is a TLR agonist capable of stimulating antitumor immunity, T1089 can be considered a dual-action alkylating agent with combined antitumor effects. These results justify further investigation of T1089 in conventional and metronomic chemotherapy regimens, particularly in combination with immune checkpoint inhibitors and antitumor vaccines. Full article

Antigenicity and immunogenicity define a potent immunogen in vaccinology. Nowadays, there are simplified platforms to produce nanocarriers for small-peptide antigen delivery, derived from various infectious agents for the treatment of a variety of diseases, based on virus-like particles (VLPs). They have good cell-penetrating properties and protective action for target molecules from degradation. Human papillomavirus (HPV) causes anogenital warts and six types of cancer in infected women, men, or children, posing a challenge to global public health. The HPV capsid is composed of viral type-specific L1 and evolutionarily conserved L2 proteins. Produced in heterologous systems, the L1 protein can self-assemble into VLPs, nanoparticles sized around 50–60 nm, used as prophylactic vaccines. Devoid of the viral genome, they are safe for users, offering no risk of infection because VLPs do not replicate. The immune response induced by HPV VLPs is promoted by conformational viral epitopes, generating effective T- and B-cell responses. Produced in different cell systems, HPV16 L1 VLPs can be obtained on a large scale for use in mass immunization programs, which are well established nowadays. The expression of heterologous proteins was evaluated at various transfection times by transfecting cells with vectors encoding codon-optimized HPV16L1 and HPV16L2 genes. Immunological response induced by chimeric HPV16 L1/L2 VLP was evaluated through preclinical assays by antibody production, suggesting the potential of broad-spectrum protection against HPV as a prophylactic nanovaccine. These platforms can also offer promising therapeutic strategies, covering the various possibilities for complementary studies to develop potential preventive and therapeutic vaccines with broad-spectrum protection, using in silico new epitope selection and innovative nanotechnologies to obtain more effective immunobiologicals in combating HPV-associated cancers, influenza, hepatitis B and C, tuberculosis, human immunodeficiency virus (HIV), and many other illnesses. Full article

Hepatitis B virus (HBV) infection remains a global public health concern, with perinatal transmission as the primary route in endemic populations. Ayacucho is a priority region due to its high incidence (second nationally between 2019 and 2024) and the significant decline in vaccination coverage (~15%). This study aims to synthesize existing epidemiological evidence on HBV seroprevalence in Ayacucho, Peru, emphasizing temporal changes observed before and after the implementation of vaccination programs to inform control strategies. This review was conducted, integrating data from diverse population groups, including children, pregnant women, blood donors, high-risk individuals (military personnel, female sex workers, prisoners), and household contacts, to identify transmission patterns and evaluate the impact of immunization efforts. Historically, Ayacucho was hyperendemic, with an HBsAg prevalence of 20% in Huanta (1985–1986) and a high mortality from liver diseases. The introduction of a vaccination in the 1990s led to a drastic reduction in infection rates among children, from 24.4–30.4% (1994) to 2.3–5.1% (1997), and improved overall Expanded Program on Immunization (EPI) coverage. However, recent data (2000–2024) reveal a concerning increase in HBV cases since 2012, with peaks in 2016 and 2023, correlating with a decline in vaccination rates post-2021. HBV prevalence remains elevated among high-risk populations—including military personnel, female sex workers, and prisoners—as well as among blood donors (HBsAg: 3.73–5.0%; anti-HBc: 21–33%). In addition, significant knowledge gaps and low adherence to EPI strategies were observed. Despite initial vaccination success, Ayacucho faces a resurgence of HBV infection, exacerbated by declining vaccine coverage and vulnerabilities in high-risk populations. Reinforcing immunization programs and screening strategies is urgent to control and eventually eliminate HBV cases in the region. Full article

Background: A number of viruses are oncogenic. These include the human papilloma virus (HPV), Epstein–Barr virus (EBV), Kaposi sarcoma human herpes virus 2/human herpes virus 8 (KSHHV/HHV8), hepatitis B virus, (HBV), hepatitis C virus (HCV), Merkel cell polyoma virus (McPyV), and the human T-cell leukemia virus type 1 (HTLV-1). These viruses cause malignancies ranging from carcinomas, sarcomas, lymphomas, to leukemias. This review aims to study the effects and efficacy of vaccines against these viruses and the cancers they cause in their prevention and treatment. Methods: The literature in the past 30 years was searched employing Scopus and Google Scholar using the keywords “oncogenic viruses, HPV, EBV, KSHHV, HHV8, Polyoma virus, HTLV-1, COVID-19, carcinoma, sarcoma, lymphoma, leukemia, anti-virus vaccines”. Results: Prophylactic vaccines against the HPV and HBV are highly effective in preventing and reducing the incidence of uterine cervical and hepatocellular carcinomas. Prophylactic vaccines against other oncogenic viruses have been less successful, though efficacious in some experimental animals. Therapeutic vaccines are still mostly under evaluation and development. Conclusions: Identification of oncogenic viruses has rendered anti-viral vaccines conspicuous tools for preventing and treating cancers they cause. Many endeavors for the development of such vaccines have been met with limited success, apart from the very effective anti-HPV and anti-HBV vaccines in universal vaccination programs. With the development of new vaccine technologies, it is hoped that effective vaccines against other oncogenic viruses will be developed in the future. Full article

Background/Objectives: Equitable access to childhood vaccines remains a challenge in many low- and middle-income countries. This study assessed coverage of WHO-recommended childhood vaccines in Cambodia and the Philippines, focusing on urban–rural and wealth disparities, and examined maternal demographic and socioeconomic factors influencing vaccination coverage. Methods: Cross-sectional data from Demographic and Health Surveys from Cambodia (2000–2021/22) and the Philippines (2003–2022) were used. Descriptive analyses were performed to elucidate vaccination coverage trends (BCG, hepatitis B birth dose, DTP, OPV, PCV, and measles). Urban–rural and wealth-related disparities were assessed by calculating absolute differences and Slope Index of Inequality. Logistic regression was used to analyze the impact of maternal demographics and socioeconomic status on vaccination coverage. Results: Cambodia showed significant increases in BCG, DTP, and OPV coverage over the past two decades, whereas those coverage in the Philippines declined slightly since 2017. In 2022, 75.2% of Filipino children received the BCG and hepatitis B (birth dose) vaccines, and around two-thirds completed DTP, OPV, and PCV vaccinations on schedule, lower than the rates in Cambodia. Only half of the children completed measles vaccination in both countries. Urban–rural disparities declined over time in both countries, but wealth inequalities persisted and widened in the Philippines between 2017 and 2022. Women with higher education attainment, from a wealthy household and having fewer children, was associated with increased likelihood of completing childhood vaccinations in both countries. Conclusions: Persistent socioeconomic disparities in childhood vaccination in low- and middle-income countries highlight the need for targeted pro-poor and community-based strategies to ensure equitable access. Full article

Background: Sirolimus is an effective treatment for kaposiform hemangioendothelioma (KHE), a rare vascular tumor in children. However, its immunosuppressive properties raise concerns regarding the safety and efficacy of vaccinations during treatment. This study aims to evaluate the safety and immunogenicity of inactivated and live-attenuated vaccines administered to pediatric KHE patients undergoing sirolimus therapy. Methods: We conducted a prospective study involving 56 KHE children receiving sirolimus who were vaccinated during treatment. Data on vaccine-related adverse events were collected to assess safety. Immunogenicity was evaluated by measuring seroconversion or protective antibody titers against vaccines, including Hepatitis B, DTaP, and MMR. Results: Among 56 catch-up vaccinated children, no serious adverse events related to vaccination were observed. Mild local or systemic reactions occurred in a minority of patients. Serological analysis demonstrated that children with kaposiform hemangioendothelioma (KHE) receiving sirolimus therapy were able to generate and sustain robust protective antibody responses following vaccination. High seroconversion rates and antibody titers were observed for both inactivated vaccines (e.g., hepatitis B and DTaP) and live-attenuated vaccines (e.g., MMR). Protective antibody levels were maintained both within 3 months and beyond 6 months post-vaccination, indicating durable immunogenicity under sirolimus treatment. Conclusions: Vaccination during sirolimus therapy appears to be safe and immunogenic in children with KHE. These findings support the administration of both inactivated and live-attenuated vaccines under appropriate clinical monitoring in this rare patient population. Full article

Background: Children with inflammatory bowel disease (IBD) are at heightened risk for vaccine-preventable infections because of underlying immune dysregulation and long-term immunosuppressive therapy. Despite published guidelines affirming vaccine safety, real-world coverage remains suboptimal. It is a pilot, single-country survey designed to explore baseline knowledge and practices regarding vaccination in paediatric IBD within a specific local healthcare context. Objective: The objective of this study is to evaluate the knowledge, attitudes, and practices of paediatric gastroenterologists (PGs) regarding the immunisation of children with IBD. Methods: We conducted an exploratory pilot, cross-sectional survey of paediatric gastroenterologists in Russia, focusing on immunisation knowledge and practical barriers in routine care. A cross-sectional, anonymous online survey was distributed to PGs nationwide between January 2022 and April 2022. The online questionnaire explored demographic characteristics, awareness of international recommendations, perceptions of vaccine safety at various disease and treatment stages, and routine vaccination practices. Responses were analysed with non-parametric statistics (α = 0.05). In a parallel prospective cohort, the vaccination certificates of 98 paediatric IBD patients (January 2022–April 2023) were audited to quantify real-world coverage. Results: Fifty-one PGs completed the survey. Forty-one per cent agreed that vaccines do not provoke IBD flares, while 17.6% considered live vaccines acceptable during immunosuppressive remission. Nearly one-third (32%) did not personally oversee immunisation, and 18% occasionally discouraged vaccination during therapy. Only 35.3% deemed baseline serology essential before starting immunosuppression; 46.5% supported antibody checks immediately prior to vaccination. The certificate audit revealed a full schedule completion rate of 66.3% for measles–mumps–rubella and 74.2% for hepatitis B, contrasting with parental reports of 82.3% complete coverage. Conclusions: Knowledge gaps, limited guideline awareness, and parental concerns contribute to suboptimal vaccination of paediatric IBD patients. Targeted educational initiatives, clearer shared-care pathways, and routine certificate audits are needed to close the coverage gap and reduce infection-related morbidity. Findings are hypothesis-generating and reflect local practice; as a pilot study, results should be interpreted with caution and may not generalise beyond similar settings. Full article

Chronic hepatitis delta (CHD) represents the most severe form of viral hepatitis due to rapid disease progression towards liver cancer, leading to high morbidity and mortality. Hepatitis delta virus (HDV) can only infect individuals who are infected with hepatitis B. So far, there is no cure or vaccine for HDV. Existing treatment options, including pegylated interferon-α and hepatocyte entry inhibitors, offer limited efficacy. Emerging therapeutic strategies are focused on targeting various steps of the HDV life cycle or enhancing the host immune response to promote viral elimination. A defective antiviral immune response is increasingly recognized as a culprit for HDV persistence; however, the precise immunological mechanism associated with disease progression and pathogenesis has not been well defined. This review provides an update on the current understanding of host immune response in CHD, highlighting its role in both disease pathogenesis and viral clearance. A deeper understanding of these immune correlates may lead the way to novel treatment strategies, including immunotherapies targeting host immune response that can be used in combination with other antiviral therapies to achieve more effective and durable treatment outcomes. Full article