Peg-IFNα combined with hepatitis B vaccination contributes to HBsAg seroconversion and improved immune function.

PURPOSE: The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. METHODS: We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. RESULTS: The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). CONCLUSIONS: After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

Outcome of Infants Born to Women with Chronic Hepatitis B: A Local Risk-Based Strategy in a Low Prevalence Country.

BACKGROUND: Chronic hepatitis-B virus (HBV) infection due to mother-to-child transmission (MTCT) during the perinatal period is an important global health concern. Chile is a low-prevalence country with an increasing migratory inflow from Latin- American countries, with intermediate to high endemic rates of HBV infection, and until 2021, there is no universal maternal screening. This study aimed to evaluate infant outcomes using a risk-based strategy of maternal screening to prevent MTCT of hepatitis B virus (HBV) in a low-prevalence country. METHODS: This prospective study included infants born to HBsAg-positive women detected using a local risk-based strategy. The exposed infants received immunoprophylaxis (IP) and follow-up to evaluate their clinical outcomes and immune responses through post-serological vaccine testing (PSVT) after completing the three- dose schedule of the HBV vaccine. RESULTS: A total of 99 HBsAg-positive mothers were detected. Seventy-six (82%) infants completed the follow-up and had PSVT between 9 and 12 months of age. 55.2% female, the median gestational age was 39 weeks (25-41) and the median birth weight was 3,130g (816-4,400 g). All patients received IP with recombinant HBV vaccine plus hepatitis-B virus immunoglobulin (HBIG) and three doses of the HBV vaccine. There were no cases of HBV infection, and 96% (72) responded to immunization with HBsAg antibodies (anti-HBsAg) >10 UI/ml, with a median level of 799 IU/ml. CONCLUSIONS: A high-risk strategy can be implemented in countries with non-universal screening for VHB. Timely IP plus high-uptake VHB vaccination in infants born to HBsAg-positive mothers was associated with a high immunogenic response and absence of MTCT.

Therapeutic vaccine-induced plasma cell differentiation is defective in the presence of persistently high HBsAg levels.

BACKGROUND & AIMS: Mechanisms behind the impaired response of antigen-specific B cells to therapeutic vaccination in chronic hepatitis B virus (HBV) infection remain unclear. The development of vaccines or strategies to overcome this obstacle is vital for advancing the management of chronic hepatitis B. METHODS: A mouse model, denominated as E6F6-B, was engineered to feature a knock-in of a B-cell receptor (BCR) that specifically recognizes HBsAg. This model served as a valuable tool for investigating the temporal and spatial dynamics of humoral responses following therapeutic vaccination under continuous antigen exposure. Using a suite of immunological techniques, we elucidated the differentiation trajectory of HBsAg-specific B cells post-therapeutic vaccination in HBV carrier mice. RESULTS: Utilizing the E6F6-B transfer model, we observed a marked decline in antibody-secreting cells 2 weeks after vaccination. A dysfunctional and atypical pre-plasma cell population (BLIMP-1+ IRF4+ CD40- CD138- BCMA-) emerged, manifested by sustained BCR signaling. By deploying an antibody to purge persistent HBsAg, we effectively prompted the therapeutic vaccine to provoke conventional plasma cell differentiation. This resulted in an enhanced anti-HBs antibody response and facilitated HBsAg clearance. CONCLUSIONS: Sustained high levels of HBsAg limit the ability of therapeutic hepatitis B vaccines to induce the canonical plasma cell differentiation necessary for anti-HBs antibody production. Employing a strategy combining antibodies with vaccines can surmount this altered humoral response associated with atypical pre-plasma cells, leading to improved therapeutic efficacy in HBV carrier mice. IMPACT AND IMPLICATIONS: Therapeutic vaccines aimed at combatting HBV encounter suboptimal humoral responses in clinical settings, and the mechanisms impeding their effectiveness have remained obscure. Our research, utilizing the innovative E6F6-B mouse transfer model, reveals that the persistence of HBsAg can lead to the emergence of an atypical pre-plasma cell population, which proves to be relevant to the potency of therapeutic HBV vaccines. Targeting the aberrant differentiation process of these atypical pre-plasma cells stands out as a critical strategy to amplify the humoral response elicited by HBV therapeutic vaccines in carrier mouse models. This discovery suggests a compelling avenue for further study in the context of human chronic hepatitis B. Encouragingly, our findings indicate that synergistic therapy combining HBV-specific antibodies with vaccines offers a promising approach that could significantly advance the pursuit of a functional cure for HBV.

Silk Fibroin-Coated Nano-MOFs Enhance the Thermal Stability and Immunogenicity of HBsAg.

Vaccines are widely regarded as one of the most effective weapons in the fight against infectious diseases. Currently, vaccines must be stored and transported at low temperatures as high temperatures can lead to a loss of vaccine conformation and reduced therapeutic efficacy. Metal-organic frameworks (MOFs), such as zeolitic imidazole framework-8 (ZIF-8), are a new class of hybrid materials with large specific surface areas, high loading rates, and good biocompatibility and are successful systems for vaccine delivery and protection. Silk fibroin (SF) has a good biocompatibility and thermal stability. In this study, the hepatitis B surface antigen (HBsAg) was successfully encapsulated in ZIF-8 to form HBsAg@ZIF-8 (HZ) using a one-step shake and one-pot shake method. Subsequently, the SF coating modifies HZ through hydrophobic interactions to form HBsAg/SF@ZIF-8 (HSZ), which enhanced the thermal stability and immunogenicity of HBsAg. Compared to free HBsAg, HZ and HSZ improved the thermostability of HBsAg, promoted the antigen uptake and lysosomal escape, stimulated dendritic cell maturation and cytokine secretion, formed an antigen reservoir to promote antibody production, and activated CD4+ T and CD8+ T cells to enhance memory T-cell production. Importantly, HSZ induced a strong immune response even after 14 days of storage at 25 °C. Furthermore, the nanoparticles prepared by the one-step shake method exhibited superior properties compared to those prepared by the one-pot shake method. This study highlights the importance of SF-coated ZIF-8, which holds promise for investigating thermostable vaccines and breaking the vaccine cold chain.

Eliminating mother-to-child transmission of hepatitis B virus: practice and progress in Baoan, a national pilot district of China.

BACKGROUND: While mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a significant challenge in China, research investigating the effectiveness of the September 2017 pilot program to eliminate MTCT of HIV, syphilis, and HBV is limited. Baoan district, which has a higher-than-average rate of hepatitis B infection among pregnant women and strong support from the government, was one of six national pilot districts selected for the program. Therefore, this study aims to assess the progress and implementation of the elimination of MTCT of HBV in Baoan district over a period of 5 years. METHODS: Data was collected from the national information system for the prevention of MTCT, registration forms, and follow-up forms of pregnant women and their live births from 2018 to 2022. Joinpoint models were used to analyze changing trends over time, calculating annual percentage change (APC) and the corresponding 95% confidence interval (95%CI). Multivariate logistic regression models were used to analyze risk factors for HBV MTCT. RESULTS: From 2018 to 2022, the coverage of HBV screening during pregnancy increased from 98.29 to 99.55% (APC = 0.30, P = 0.012). The coverage of HBV early screening within 13 gestational weeks increased from 40.76 to 86.42% (APC = 18.88, P = 0.033). The prevalence of maternal HBV infection declined by an APC of - 3.50 (95% CI -6.28 ~ - 0.63). The coverage of antiviral therapy among high-risk pregnant women increased from 63.59 to 90.04% (APC = 11.90, P = 0.031). Coverage for timely administration of hepatitis B immunoglobulin, hepatitis B birth dose vaccine, and three-dose hepatitis B vaccination remained consistently above 97.50%. The coverage of post-vaccination serological testing (PVST) in high-risk infants was 56.15% (1352/2408), and the MTCT rate of HBV was 0.18%. Mothers with high-school education or below (OR = 3.76, 95% CI 1.04 ~ 13.60, P = 0.04) and hepatitis B e antigen (HBeAg) positivity (OR = 18.89, 95% CI 1.98 ~ 18.50, P = 0.01) had increased MTCT risk. CONCLUSIONS: The implementation of comprehensive prevention strategies in Baoan district, including screening, treatment, and immunoprophylaxis, has proven effective in maintaining the MTCT of HBV at an extremely low level. However, it remains crucial to raise public awareness, specifically on the importance of improving the coverage of PVST for infants exposed to HBV.

Using the AS04C-adjuvanted hepatitis B vaccine in patients classified as non-responders.

BACKGROUND: Chronic hepatitis B (HB) remains a significant global health concern, despite the widespread availability of the HB vaccine. While the standard vaccine demonstrates an impressive serological response rate exceeding 90%, a subset of individuals exhibit suboptimal immunity. This study aims to elucidate the efficacy of the AS04C-adjuvanted HB vaccine in addressing non-responsiveness. METHODS: Conducted at the Preventive Medicine Service of the University Albacete Hospital in Spain from 2017 to 2021, this single-center observational study enrolled 195 patients. Among them, 126 (65%) were classified as non-responders following one or two complete standard vaccination courses. RESULTS: After the administration of a complete four-dose regimen of the AS04C-adjuvanted vaccine, 73.81% of non-responder patients exhibited antibody titers indicative of robust immunity (anti-HBs >10). CONCLUSIONS: These findings underscore the pivotal role of the AS04C-adjuvanted HB vaccine in addressing non-responsiveness, emphasizing its potential as a crucial tool in augmenting immunization strategies for various populations. This includes non-responders to standard vaccination, individuals with chronic kidney disease, those requiring seroprotection due to factors like immunosuppression or occupational hazards, as well as patients for whom conventional revaccination strategies have proven futile. Additional research is needed to expand on the promising results obtained through our protocol.

Therapeutic vaccination with lentiviral vector in HBV-persistent mice and two inactive HBsAg carriers.

BACKGROUND & AIMS: Immunotherapy for chronic hepatitis B virus (HBV) infection has not yet demonstrated sufficient efficacy. We developed a non-integrative lentiviral-vectored therapeutic vaccine for chronic hepatitis B and tested its antiviral effects in HBV-persistent mice and two inactive HBsAg carriers. METHODS: Lentiviral vectors (LVs) encoding the core, preS1, or large HBsAg (LHBs) proteins of HBV were evaluated for immunogenicity in HBV-naïve mice and therapeutic efficacy in a murine model of chronic HBV infection. In addition, two inactive HBsAg carriers each received two doses of 5×107 transduction units (TU) or 1×108 TU of lentiviral-vectored LHBs (LV-LHBs), respectively. The endpoints were safety, LHBs-specific T-cell responses, and serum HBsAg levels during a 24-week follow-up. RESULTS: In the mouse models, LV-LHBs was the most promising in eliciting robust antigen-specific T cells and in reducing the levels of serum HBsAg and viral load. By the end of the 34-week observation period, six out of ten (60%) HBV-persistent mice vaccinated with LV-LHBs achieved serum HBsAg loss and significant depletion of HBV-positive hepatocytes in the liver. In the two inactive HBsAg carriers, vaccination with LV-LHBs induced a considerable increase in the number of peripheral LHBs-specific T cells in one patient, and a weak but detectable response in the other, accompanied by a sustained reduction of HBsAg (-0.31 log10 IU/ml and -0.46 log10 IU/ml, respectively) from baseline to nadir. CONCLUSIONS: A lentiviral-vectored therapeutic vaccine for chronic HBV infection demonstrated the potential to improve HBV-specific T-cell responses and deplete HBV-positive hepatocytes, leading to a sustained loss or reduction of serum HBsAg. IMPACT AND IMPLICATIONS: Chronic HBV infection is characterized by an extremely low number and profound hypo-responsiveness of HBV-specific T cells. Therapeutic vaccines are designed to improve HBV-specific T-cell responses. We show that immunization with a lentiviral-vectored therapeutic HBV vaccine was able to expand HBV-specific T cells in vivo, leading to reductions of HBV-positive hepatocytes and serum HBsAg.

Society for Maternal-Fetal Medicine Consult Series #69: Hepatitis B in pregnancy: updated guidelines.

More than 290 million people worldwide, and almost 2 million people in the United States, are infected with hepatitis B virus, which can lead to chronic hepatitis B, a vaccine-preventable communicable disease. The prevalence of chronic hepatitis B infection in pregnancy is estimated to be 0.7% to 0.9% in the United States, with >25,000 infants born annually at risk for chronic infection due to perinatal transmission. Given the burden of disease associated with chronic hepatitis B infection, recent national guidance has expanded both the indications for screening for hepatitis B infection and immunity and the indications for vaccination. The purpose of this document is to aid clinicians caring for pregnant patients in screening for hepatitis B infection and immunity status, discuss the perinatal risks of hepatitis B infection in pregnancy, determine whether treatment is indicated for maternal or perinatal indications, and recommend hepatitis B vaccination among susceptible patients. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend triple-panel testing (hepatitis B surface antigen screening, antibody to hepatitis B surface antigen, and total antibody to hepatitis B core antigen) at the initial prenatal visit if not previously documented or known to have been performed (GRADE 1C); (2) we recommend universal hepatitis B surface antigen screening alone at the initial prenatal care visit for all pregnancies where there has been a previously documented negative triple-panel test (GRADE 1B); (3) we recommend that individuals with unknown hepatitis B surface antigen screening status be tested on any presentation for care in pregnancy; we also recommend that those with clinical hepatitis or those with risk factors for acute hepatitis B infection be tested at the time of admission to a birthing facility when delivery is anticipated (GRADE 1B); (4) we do not recommend altering routine intrapartum care in individuals chronically infected with hepatitis B; administration of neonatal immunoprophylaxis is standard of care in these situations (GRADE 1B); (5) we do not recommend cesarean delivery for the sole indication of reducing perinatal hepatitis B virus transmission (GRADE 1B); (6) we recommend that individuals with HBV infection can breastfeed as long as the infant has received immunoprophylaxis at birth (GRADE 1C); (7) we suggest individuals with hepatitis B infection who desire invasive testing may have the procedure performed after an informed discussion on risks and benefits in the context of shared decision-making and in the context of how testing will affect clinical care (GRADE 2C); (8) in individuals with hepatitis viral loads >200,000 IU/mL (>5.3 log 10 IU/mL), we recommend antiretroviral therapy with tenofovir (tenofovir alafenamide at 25 mg daily or tenofovir disoproxil fumarate at 300 mg daily) in the third trimester (initiated at 28-32 weeks of gestation) as an adjunctive strategy to immunoprophylaxis to reduce perinatal transmission (GRADE 1B); (9) we recommend administering hepatitis B vaccine and hepatitis B immunoglobin within 12 hours of birth to all newborns of hepatitis B surface antigen-positive pregnant patients or those with unknown or undocumented hepatitis B surface antigen status, regardless of whether antiviral therapy has been given during the pregnancy to the pregnant patient (GRADE 1B); and (10) we recommend hepatitis B vaccination in pregnancy for all individuals without serologic evidence of immunity or documented history of vaccination (GRADE 1C).

Hepatitis B in Healthcare Personnel: An Update on the Global Landscape.

Despite the outstanding progress that has been made in the prevention, detection, and management of hepatitis B during the past decades, hepatitis B remains a problem among healthcare personnel (HCP) in many countries. We reviewed studies on all aspects of hepatitis B in HCP published from 2017 through April 2023. They revealed wide variations on the prevalence of infection among HCP, ranging from 0.6% in Europe to >8.7% in Africa, almost always in association with very low vaccination rates. Many studies found a significant association between HCP's knowledge about hepatitis B and hepatitis B vaccines, their vaccination status, and practices. This research also discloses global inequities regarding vaccination policies against hepatitis B, free-of-charge vaccinations, and access to post-exposure prophylaxis (PEP). Strategies to prevent and manage accidental exposures are needed in order to reduce the burden of hepatitis B on HCP, while written policies for all aspects of infection prevention, protective equipment, and PEP should be available. Lastly, HCP should be accordingly educated. These are all imperative given the decline of routine vaccinations in the COVID-19 era, particularly in countries with fragile vaccination programs, and the disruptions of interventions for hepatitis B that are expected to provide a pool of virus transmission to future generations.

Bad Liver and a Broken Heart: Hepatitis B in the Newborn.

Hepatitis B viral infection is a significant source of morbidity and mortality worldwide. The United States has experienced a precipitous drop in acute hepatitis B infection after the introduction and widespread adoption of recombinant vaccines. Neonates experience significant risk from both vertical and horizontal hepatitis B exposure during a period of immaturity of the innate and adaptive immune systems. Acquisition of hepatitis B virus at or near birth confers the highest lifetime risk of chronic infection and subsequent complications including liver cirrhosis and hepatocellular carcinoma. Pregnant women should be screened for the presence of hepatitis B surface antigen, indicating acute or chronic infection, and, if positive, hepatitis B viral deoxyribonucleic acid, allowing for quantification of viral load. The development of highly effective and safe recombinant vaccines allows partial protection of late preterm and term neonates immediately after birth. Additionally, administration of hepatitis B immune globulin in the setting of suspected or confirmed exposure supplements the immune response and decreases the risk of chronic infection. The optimal timing of vaccination is later in low-birth-weight neonates due to the aforementioned immune system immaturity. Health care providers serving neonates must familiarize themselves with national guidelines regarding hepatitis B vaccination and hepatitis B immune globulin therapy. Understanding the risks of infection and the evidence basis supporting vaccination and immunotherapy will allow providers to educate families and support decision-making, with the potential to eradicate this vaccine-preventable illness in our lifetime.

Potentiating humoral and cellular immunity using a novel hybrid polymer-lipid nanoparticle adjuvant for HBsAg-VLP vaccine.

Aluminium adjuvants are commonly used in vaccines to stimulate the immune system, but they have limited ability to promote cellular immunity which is necessary for clearing viral infections like hepatitis B. Current adjuvants that do promote cellular immunity often have undesired side effects due to the immunostimulants they contain. In this study, a hybrid polymer lipid nanoparticle (HPLNP) was developed as an efficient adjuvant for the hepatitis B surface antigen (HBsAg) virus-like particle (VLP) vaccine to potentiate both humoral and cellular immunity. The HPLNP is composed of FDA approved polyethylene glycol-b-poly (L-lactic acid) (PEG-PLLA) polymer and cationic lipid 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP), and can be easily prepared by a one-step method. The cationic optimised vaccine formulation HBsAg/HPLNP (w/w = 1/600) can maximise the cell uptake of the antigen due to the electrostatic adsorption between the vaccine nanoparticle and the cell membrane of antigen-presenting cells. The HPLNP prolonged the retention of the antigen at the injection site and enhanced the lymph node drainage of antigen, resulting in a higher concentration of serum anti-HBsAg IgG compared to the HBsAg group or the HBsAg/Al group after the boost immunisation in mice. The HPLNP also promoted a strong Th1-driven immune response, as demonstrated by the significantly improved IgG2a/IgG1 ratio, increased production of IFN-γ, and activation of CD4 + and CD8 + T cells in the spleen and lymph nodes. Importantly, the HPLNP demonstrated no systemic toxicity during immunisation. The advantages of the HPLNP, including good biocompatibility, easy preparation, low cost, and its ability to enhance both humoral and cellular immune responses, suggest its suitability as an efficient adjuvant for protein-based vaccines such as HBsAg-VLP. These findings highlight the promising potential of the HPLNP as an HBV vaccine adjuvant, offering an alternative to aluminium adjuvants currently used in vaccines.

Uptake of hepatitis B vaccination and associated factors among health sciences students, Mogadishu, Somalia.

Background: Hepatitis B is a potentially fatal liver infection caused by the hepatitis B virus (HBV). It is a serious issue for global health. It considerably raises the risk of cirrhosis and liver cancer-related death and can result in chronic infection. The risk of infection is high among health sciences students due to the risk of occupational contact with fluids of infected patients and the risk of needle stick injury. The most effective way of preventing HBV infection is the vaccination of students prior to their posting to healthcare settings. There is no data available about HBV vaccination uptake among Health Sciences students in Somalia. Therefore, this study aimed to determine HBV vaccination uptake and associated factors toward HBV among health science students in Somalia. Methods: A cross-sectional study was undertaken among health sciences students from August to October 2022. Data were gathered using Kobo Toolbox using a standardized questionnaire with questions on characteristics, knowledge attitude, and HBV prevention practices. A total of 569 students were involved in the study. Stata version 15 was utilized for the analysis. Bivariate and multivariate logistic regression analysis, as well as descriptive statistics, were performed. In order to assess the existence and significance of the relationship between the outcome and risk factors, an adjusted odds ratio with a 95% confidence interval (CI) was used. Statistical significance was considered as a p-value ≤0.05. Results: Of the 569 study participants, 33.4% (95%CI: 29.6-37.4) received a full dose of the HBV vaccine in this study. Participants had good HBV prevention knowledge, attitudes, and practices at 69.6, 37.96, and 50.6%, respectively. The lack of access and the high cost of the vaccine were the reasons for not taking the vaccine. Second-year [AOR: 0.22 (0.12-0.43)]. Positive attitude [AOR: 0.54 (0.31-0.93)], and good practice [AOR: 6.99 (3.62-13.5)]. Discussion: The study indicated that 33.4% of health sciences students had received the required HBV vaccination doses, academic year, attitude, and practice were significantly associated with full-dose vaccination status. The unavailability of the vaccine and the high cost of vaccination were the most common reasons for not taking the vaccine. It is recommended that students receive vaccinations before beginning clinical rotations, and give instruction on infection prevention strategies and general precautions, particularly regarding HBV infection.

Reduced protective efficacy of hepatitis B vaccine among fully vaccinated children in Ethiopia.

BACKGROUND: Hepatitis B vaccination is recommended for all children at birth within 24 hours or during childhood. OBJECTIVE: This study was aimed to evaluate protective efficacy of hepatitis B vaccine and estimate the sero-prevalence of hepatitis B virus infection among vaccinated children. MATERIALS AND METHODS: A community-based cross-sectional study was conducted from March, 2021 to October, 2021 in Debre Markos town. A simple random sampling technique was used to select 165 fully vaccinated children aged 5-12 years old. A serum sample was used to determine hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (anti-HBc), anti-hepatitis B surface antibody titer (anti-HBs) using ELISA. RESULTS: The seroprevalence of HBsAg and anti-HBc anti-body was found to be 4.2% and 4.8% respectively. Of 165 fully vaccinated children, 129 (78.2%) had anti-HBs titer ≥ 10 mIU/ml. Among 129 sero-protected children, 76 (58.9%) were hypo-responders whereas the rest 53 (41.1%) were good responders. Those children within the age group of 5-7 years were 2.9 times (AOR: 2.873, 95% CI: 1.156, 7.141) (P<0.023) more likely to respond to HBV vaccine. Multivariate logistic regression revealed that children who were born from HBV positive mothers (AOR 3.917, 95% CI: 1.456, 5.365, P<0.027) and those who had history of injectable medications (AOR 9.232, 95% CI: 1.503, 11.697, P<0.016) were more likely to be HBsAg positive. Children who had history of hospital admission (AOR 6.973, 95% CI: 1.495, 8.530, P<0.013) were more likely to be anti-HBcAb positive. CONCLUSIONS: There was an intermediate prevalence of childhood HBV infection despite being vaccinated suggesting low protective efficacy of hepatitis B vaccine in the study area.

Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study.

BACKGROUND: The 2016 World Health Assembly endorsed the elimination of hepatitis B virus (HBV) infection as a public health threat by 2030; existing therapies and prophylaxis measures make such elimination feasible, even in the absence of a virological cure. We aimed to estimate the national, regional, and global prevalence of HBV in the general population and among children aged 5 years and younger, as well as the rates of diagnosis, treatment, prophylaxis, and the future burden globally. METHODS: In this modelling study, we used a Delphi process with data from literature reviews and interviews with country experts to quantify the prevalence, diagnosis, treatment, and prevention measures for HBV infection. The PRoGReSs Model, a dynamic Markov model, was used to estimate the country, regional, and global prevalence of HBV infection in 2022, and the effects of treatment and prevention on disease burden. The future incidence of morbidity and mortality in the absence of additional interventions was also estimated at the global level. FINDINGS: We developed models for 170 countries which resulted in an estimated global prevalence of HBV infection in 2022 of 3·2% (95% uncertainty interval 2·7-4·0), corresponding to 257·5 million (216·6-316·4) individuals positive for HBsAg. Of these individuals, 36·0 million were diagnosed, and only 6·8 million of the estimated 83·3 million eligible for treatment were on treatment. The prevalence among children aged 5 years or younger was estimated to be 0·7% (0·6-1·0), corresponding to 5·6 million (4·5-7·8) children with HBV infection. Based on the most recent data, 85% of infants received three-dose HBV vaccination before 1 year of age, 46% had received a timely birth dose of vaccine, and 14% received hepatitis B immunoglobulin along with the full vaccination regimen. 3% of mothers with a high HBV viral load received antiviral treatment to reduce mother-to-child transmission. INTERPRETATION: As 2030 approaches, the elimination targets remain out of reach for many countries under the current frameworks. Although prevention measures have had the most success, there is a need to increase these efforts and to increase diagnosis and treatment to work towards the elimination goals. FUNDING: John C Martin Foundation, Gilead Sciences, and EndHep2030.

The impacts of the COVID-19 pandemic on patients with viral hepatitis B infection: follow-up, compliance with antiviral treatment, and vaccine preferences.

OBJECTIVE: Elimination programs and interventions for patients with viral hepatitis B (HBV) have been disrupted during the COVID-19 pandemic. This study aimed to evaluate the effects of the COVID-19 pandemic on patients with HBV infection in terms of COVID-19 vaccine preferences, follow-up visits, and antiviral treatment compliance. PATIENTS AND METHODS: In this retrospective single-center cross-sectional study, 129 patients with viral hepatitis B infection were evaluated. The patients were surveyed at the time of admission. A special form was created for patients with viral hepatitis B infection, and the form contained information about the patients at admission to collect the study data. RESULTS: A total of 129 participants were included in the study. Of the participants, 49.6% were males and the median age was 50 years. In total, 73 (56.6%) patients had their follow-up visits disrupted because of the COVID-19 pandemic. No newly diagnosed case of HBV infection was detected. Among the 129 patients, 46 had inactive hepatitis B, and 83 had chronic hepatitis B infection and were receiving antiviral treatment. None of the patients had trouble reaching antiviral treatments during the COVID-19 pandemic. A liver biopsy was recommended for 8 patients. Half of these 8 patients did not have follow-up visits during the COVID-19 pandemic. Most of the patients (123/129, 95.3%) received the COVID-19 vaccine and the most frequent vaccine that was used was the Pfizer-BioNTech (n: 92, 71.3%) vaccine. Serious side effects of the COVID-19 vaccines were not detected. Mild side effects were found in 41.9% (13/31) of the patients. The COVID antibody level was found to be statistically and significantly higher in the patients who received the Pfizer-BioNTech vaccine than in those that received the CoronoVac vaccine. CONCLUSIONS: It was reported that elimination programs and interventions for HBV infection decreased or stopped because of the COVID-19 pandemic. In the present study, no newly diagnosed case of HBV infection was detected. Most of the patients had their follow-up visits disrupted. There were no patients who could not receive antiviral treatment, the vaccination rate of the patients was high, and the vaccines were well tolerated.

Cured HCV patients with suboptimal hepatitis B vaccine response exhibit high self-reactive immune signatures.

BACKGROUND AND RATIONALE: Chronic HCV infection induces lasting effects on the immune system despite viral clearance. It is unclear whether certain immune alterations are associated with vaccine responses in cured HCV patients. APPROACH: Thirteen cured HCV patients received the standard 3-dose hepatitis B vaccine and were followed up at the 0, 1st, 6th, and 7th months (M0, M1, M6, and M7) after the first dose of vaccination. Thirty-three-color and 26-color spectral flow cytometry panels were used for high-dimensional immunophenotyping of the T-cell and B-cell subsets, respectively. RESULTS: Compared to the healthy controls (HC), 17 of 43 (39.5%) immune cell subsets showed abnormal frequencies in cured HCV patients. Patients with cured HCV were further divided into high responders (HR, n = 6) and nonresponders (NR1, n = 7) based on the levels of hepatitis B surface antibodies at M1. Alterations in cell populations were more significant in NR1. Moreover, we found that high levels of self-reactive immune signatures, including Tregs, TD/CD8, IgD-only memory B, and autoantibodies, were associated with suboptimal hepatitis B vaccine responses. CONCLUSIONS: Our data suggest that cured HCV patients exhibit persistent perturbations in the adaptive immune system, among which highly self-reactive immune signatures may contribute to a suboptimal hepatitis B vaccine response.

Impact and cost-effectiveness of hepatitis B virus prophylaxis in pregnancy: a dynamic simulation modelling study.

BACKGROUND: In 2020, WHO recommended the addition of peripartum antiviral prophylaxis (PAP) to hepatitis B birth dose vaccination (HepB-BD) and hepatitis B infant vaccination (HepB3) to reduce mother-to-child transmission of hepatitis B virus (HBV) infection in pregnant women who have a marker of high infectivity (ie, HBV DNA ≥200 000 international units per mL or HBeAg-positive). We aimed to evaluate the impact and cost-effectiveness of this recommendation and of a theoretical simplified strategy whereby PAP is given to all pregnant women who are HBsAg-positive without risk stratification. METHODS: This modelling study used a dynamic simulation model of the HBV epidemic in 110 countries in all WHO regions, structured by age, sex, and country. We assessed three strategies of scaling up PAP for pregnant women: PAP for those with high viral load (PAP-VL); PAP for those who are HBeAg-positive (PAP-HBeAg); and PAP for all pregnant women who are HBsAg-positive (PAP-universal), in comparison with neonatal vaccination alone (HepB-BD). We investigated how different diagnostic and antiviral drug costs affected the cost-effectiveness of the strategies evaluated. Using a health-care provider perspective, we calculated incremental cost-effectiveness ratios in cost (US$) per disability-adjusted life-year (DALY) averted in each country's population and compared these with country-specific cost-effectiveness thresholds. We also calculated new neonatal infections averted for each of the strategies. FINDINGS: Adding PAP-VL to HepB-BD could avert around 1·1 million (95% uncertainty interval 1·0 million-1·2 million) new neonatal infections by 2030 and around 3·2 million (95% uncertainty interval 3·0 million-3·4 million) new neonatal infections and approximately 8·8 million (7·8 million-9·7 million) DALYs by 2100 across all the countries modelled. This strategy would probably be cost-effective up to 2100 in 28 (26%) of 106 countries analysed (which included some of the countries that have the greatest HBV burden) if costs are as currently expected to be, and in 74 (70%) countries if diagnostic and monitoring costs were lowered (by about 60-75%). The relative cost-effectiveness of PAP-VL and PAP-HBeAg was finely balanced and depended on the respective diagnostic and monitoring costs. The PAP-universal strategy could be more cost-effective than either of these strategies in most countries, but the use of antiviral treatment could be five times as high than with PAP-VL. INTERPRETATION: PAP can provide substantial health benefits, and, although the current approach might already be cost-effective in some high-burden settings, decreased diagnostic costs would probably be needed for PAP to be cost-effective in most countries. Therefore, careful consideration needs to be given about how such a strategy is implemented, and securing reduced costs for diagnostics should be a priority. The theoretical strategy of offering PAP to all women who are HBsAg-positive (eg, if diagnostic tests to identify mothers at risk of transmission are not available) could be a cost-effective alternative, depending on prevailing costs of diagnostics and antiviral therapy. FUNDING: UK Medical Research Council, UK National Institute for Health and Care Research, and the Vaccine Impact Modelling Consortium.

The effectiveness of hepatitis B vaccine in toddlers based on the five-year period national basic health research (Riskesdas 2007, 2013 and 2018) in Indonesia.

Background: Hepatitis B is a viral infection that has a high prevalence in Indonesia. The Ministry of Health of Indonesia has conducted a national vaccination program for hepatitis B. In order to evaluate the success of the hepatitis B vaccination in Indonesia, a community study based on basic health research (Riskesdas) was performed nationwide since 2007 for five year period in 2007, 2013, and 2018. Methods: Further statistical analysis was performed specifically for the children under 59 months old (toddlers) immunized in both urban and rural areas in 2007, 2013, and 2018 based on certain characteristics by examining antibodies against HBsAg (anti-HBs), IgG antibodies against the core antigen (HBcAb), surface antigen (HBsAg) of hepatitis B virus (HBV). The data obtained from the data management laboratory of Ministry of Health, Indonesia, was analyzed with Bivariate analysis with continuity correction chi-square or Pearson chi-square using Stata software version 16. Results: This study showed an increase in hepatitis B coverage of complete immunization (30% in 2007, 60.3% in 2013, and 57% in 2018), which was also influenced by mothers' level of education (Pearson chi-square , p ¡ 0.05) and access to health service points within 30 minutes (OR = 1.3-2.8, p ¡ 0.05). The trend of the percentage of immune status (anti-HBs) was increased (41.8% in 2007; 56.1% in 2013; and 79.1% in 2018). The higher anti-HBs was found in complete hepatitis B immunization status (OR = 1.5-2, p ¡ 0.05) and in good nutritional status (p ¡ 0.05). However, the anti-HBs was found decreased with increasing age (p ¡ 0.05). The trend of positive HBcAb (exposure to HBV infection) showed a decrease gradually of almost ten times from 2007 (8.6%-13.5%) compared to 2013 (2.6%-11.1%) and 2018 (1.1%-2%). Urban areas were at higher risk of hepatitis B exposure (OR = 1.4-2.2) than rural areas (OR = 0.37-0.80). The HBsAg data were only available in 2013 and 2018. Riskesdas data analysis showed the prevalence of hepatitis B (HBsAg) was lower in complete immunization status than that in incomplete one (p ¡ 0.05), but with an increase from 3.9% (2013) to 9.3% (2018), possibly due to inappropriate implementation of birth dose immunization or a vaccine-escape mutant from the HBV variants. Conclusions: The effectiveness of hepatitis B vaccine obtained from the three Riskesdas periods in Indonesia showed an improvement, with an increase in immune status, reduced exposure to HBV and a lower prevalence of hepatitis B in children with complete vaccination. However, there is still an increase in hepatitis B infection, especially in urban areas. Therefore, a long-term evaluation of immunization coverage especially ensuring that the initial dose of immunization was given within the first 24 h of birth, HBsAg and HBcAb, nutritional status, genomic surveillance of HBV, and other aspects of program quality evaluation are needed to ensure that elimination efforts have been implemented properly.

Spermidine enhances the efficacy of adjuvant in HBV vaccination in mice.

Background: Various vaccine adjuvants have been developed to eliminate HBV from patients with chronic HBV infection. In addition, spermidine (SPD), a type of polyamine, has been reported to enhance the activity of immune cells. In the present study, we investigated whether the combination of SPD and vaccine adjuvant enhances the HBV antigen-specific immune response to HBV vaccination. Methods: Wild-type and HBV-transgenic (HBV-Tg) mice were vaccinated 2 or 3 times. SPD was orally administered in drinking water. Cyclic guanosine monophosphate-AMP (cGAMP) and nanoparticulate CpG-ODN (K3-SPG) were used as the HBV vaccine adjuvants. The HBV antigen-specific immune response was evaluated by measuring the HBsAb titer in blood collected over time and the number of interferon-γ producing cells by enzyme-linked immunospot assay. Results: The administration of HBsAg + cGAMP + SPD or HBsAg + K3-SPG + SPD significantly enhanced HBsAg-specific interferon-γ production by CD8 T cells from wild-type and HBV-Tg mice. The administration of HBsAg, cGAMP, and SPD increased serum HBsAb levels in wild-type and HBV-Tg mice. In HBV-Tg mice, the administration of SPD + cGAMP or SPD + K3-SPG with HBV vaccination significantly reduced HBsAg levels in the liver and serum. CONCLUSIONS: These results indicate that the combination of HBV vaccine adjuvant and SPD induces a stronger humoral and cellular immune response through T-cell activation. These treatments may support the development of a strategy to completely eliminate HBV.

Universal Adult Hepatitis B Screening and Vaccination as the Path to Elimination.

This Viewpoint describes new recommendations from the CDC regarding universal screening of adults for hepatitis B virus infection.