Doses Of Hepatitis B Virus Vaccine Research Articles

Decentralised same day test and treatment of hepatitis C levering existing peer support networks among men who inject drugs: feasibility and effectiveness

BackgroundPrevalence of hepatitis C virus (HCV) infection among people who inject drugs in the state of Manipur, India, is 43%; however, access to care is poor. We piloted a Community-led and comprehensive hepatitis care model that included same-day HCV treatment at drug treatment centres.MethodsScreening was conducted through venipuncture samples collected by community peer PWID, using HCV antibody (HCV Ab) rapid screening and hepatitis B virus (HBV) surface antigen (HBsAg) rapid diagnostic tests. Reactive HCV Ab samples were tested for HCV RNA using near point-of-care Truenat® HCV on Truelab® Quattro. Eligible HCV RNA-positive participants were treated on the same day using direct-acting antivirals and followed for sustained virologic response (SVR). HBsAg-negative participants received rapid HBV vaccination regimen while those positive for HBsAg were tested for DNA and referred for treatment.ResultsBetween November 2021 and August 2022, 643 individuals were approached and 503 consented and were screened. All screened were males with history of injection drug use, and a median age of 27 years (IQR 23–32). Of the 241 (47.9%) HCV Ab reactive all underwent RNA testing and 156 (64.7%) were RNA detectable. Of those with viraemia, 155 (99.4%) were initiated on treatment with 153 (98.1%) on same day, with 2 (1.2%) HBsAg positive and waiting for HBV DNA results. Among those 153, median time from HCV Ab screening to treatment was 6 h 38 min (IQR 5 h 42 min–8 h 23 min). In total 155 (100%) completed HCV treatment, of those 148 (95.5%) completed SVR testing and 130 (87.8%) achieved SVR12. 27 (5%) participants were HBsAg-positive, 3 (11.1%) were also living with HCV viraemia; 443 (97.6%) were eligible for vaccination and 436 (98.4%) received all 3 vaccine doses.ConclusionCommunity-led hepatitis care incorporating same day “test and treat” for HCV was feasible and effective. HBV screening identified a large proportion who were unvaccinated. Peer support extended resulted in ensuring compliance to care and treatment cascade and completing all the three doses of HBV vaccination. As the screening, diagnostics infrastructure and vaccine are available in most countries with national viral hepatitis programs also in place, our model can be adapted or replicated to progress towards global elimination targets.

2511. Screening for Hepatitis B Virus (HBV) and Tuberculosis (TB) Infection among Non-U.S.-Born Adults from High HBV and TB Burden Countries

Abstract Background Hepatitis B virus (HBV) infection and tuberculosis (TB) infection both disproportionately affect non-U.S.–born persons from countries with hepatitis B surface antigen (HBsAg) seroprevalence ≥2% or TB incidence rates ≥20/100,000 population. Early identification and treatment of chronic HBV and TB infection are critical to reduce morbidity and mortality, but little is known about HBV and TB screening among non-U.S.–born persons in the United States. Methods In a cross-sectional study using electronic health record data, we assessed HBV and TB infection screening practices among Kaiser Permanente Northern California eligible members aged ≥18 years born in countries with intermediate to high burdens of both HBV and TB infection. HBV screening was defined as testing for HBV surface antigen and HBV core antibody. TB infection screening was defined as testing with interferon gamma release assay or tuberculin skin test. We calculated the proportion of individuals from intermediate and high HBV-TB burden countries who had HBV or TB infection screening and the proportion of patients positive for HBV or TB infection. Results Of 498,339 non-U.S.–born adults, 275,708 (55.3%) were born in intermediate or high HBV-TB burden countries. Most patients were aged ≥50 years (65.3%) and 23.5% had diabetes. Among persons born in intermediate or high HBV-TB burden countries, 67.1% were screened for HBV infection, 29.4% were screened for TB infection, and only 23.7% were screened for both HBV and TB infection. Among all persons born in intermediate or high HBV-TB burden countries (both screened and unscreened), 3.7% had HBV infection and 10.1% had TB infection. Among 231,431 persons born in intermediate or high HBV-TB burden countries without current or prior HBV infection, 72.9% had received at least one HBV vaccine dose. Conclusion Among non-U.S.–born adults from intermediate or high HBV-TB burden countries, we found low screening proportions, intermediate prevalence of chronic HBV infection and high prevalence of TB infection. Given the large population of persons from intermediate or high HBV-TB burden countries in Kaiser Permanente Northern California, screening for both infections at the same time could improve early diagnosis and treatment for both conditions. Disclosures Jacek Skarbinski, MD, Genentech: Grant/Research Support|Gilead Sciences: Grant/Research Support Robert J. Wong, MD, MS, Gilead Sciences: Grant/Research Support

Delays in Hepatitis B Immunization Series Completion in People With Human Immunodeficiency Virus.

Studies have demonstrated low hepatitis B virus (HBV) vaccine series completion among persons with human immunodeficiency virus (HIV). We conducted a retrospective record review of persons entering HIV care at 2 clinics in Houston, Texas, between 2010 and 2018. Kaplan-Meier curves summarized time to receipt of HBV vaccines for those eligible for vaccination. We estimated the proportions of patients who had received 1, 2, or 3 HBV vaccine doses at 12 and 24 months after entry to care. A Prentice Williams and Peterson total time model was used to evaluate associations between patient characteristics and time to vaccination. Of the 5357 patients who entered care, 2718 were eligible for HBV vaccination. After 2 years of follow-up, 51.2% of those eligible had received 1 HBV vaccine, 43.2% had received 2, and 28.4% received 3 vaccines. With adjustment for significant cofactors, patients whose CD4 cell count was ≥200/μL (adjusted hazard ratio [aHR], 1.43 [95% confidence interval (CI), 1.29-1.59]) and transgender patients (1.49 [1.08-2.04]) received any given vaccine dose sooner than those with CD4 cell counts <200/μL or cisgender patients, respectively. Compared with non-Hispanic whites, Hispanic patients were vaccinated sooner (aHR, 1.28 [95% CI, 1.07-1.53]). Those with an active substance use history had a significantly longer time to vaccination than those with no substance use history (aHR, 0.73 [95% CI, .62-.85]). Strategies are needed to increase HBV vaccine completion rates in our study population, particularly among those with CD4 cell counts <200/μL or with a substance use disorder.

Antenatal hepatitis B virus sero-prevalence, risk factors, pregnancy outcomes and vertical transmission rate within 24 months after birth in a high HIV prevalence setting

BackgroundDespite the availability of an effective vaccine, chronic hepatitis B virus (HBV) infections remain a major cause of liver cirrhosis and hepatocellular carcinoma. HBV burden in pregnancy, risk factors and the timing of mother to child transmission remain poorly described especially during this era of lifelong use of Tenofovir/Lamivudine/Efavirenz as firstline for HIV treatment. We aimed to determine the burden of HBV in pregnancy and infants receiving their first dose of HBV vaccine 6 weeks after birth in a high HIV-prevalence setting.MethodsPregnant women ≥ 20 weeks’ gestational age were enrolled and followed up as mother-infant dyads from delivery, 6, 24 and 96 weeks after birth. HBV surface antigen (HBsAg) was tested (fresh plasma, immunochromatography) in pregnancy. Women testing HBsAg-seropositive were further evaluated for other four HBV-biomarkers. Maternally HBV exposed babies were tested for HBsAg from birth and HBs-antibodies from 6 months of age. Maternal-infant factors were tested in univariable and multivariable analyses for predictors of HBsAg-seropositivity.Results Six hundred HIV-uninfected and 608 HIV-infected women on Tenofovir/Lamivudine/Efavirenz-regimen with median (interquartile range) 350: (87–1477) days of therapy use were enrolled. The overall HBsAg-seroprevalence was 32/1208: 2.65%, 95% confidence interval (CI) [1.74, 3.55]; being 7/600: 1.17%, 95% CI [0.37, 1.97] and 25/608: 4.11%, 95% CI [2.52, 5.68] in HBsAg-monoinfected and HBsAg/HIV-coinfected respectively, disproportionately detected in 31/32: 96.9%, 95% CI [90.8, 100] women presumably HBV-unvaccinated in infancy.HBV exposed babies tended to be born prematurely (< 37 weeks); 15.2% versus 9.9% in the HBV-unexposed, p = 0.009.In multivariate logistic regression-models with variable elimination, HIV-infection and reported tooth extractions predicted antenatal HBsAg-seropositivity; odds ratios (CI): 3.85 (1.61–10.7) and 2.46 (1.07–5.34), respectively.None of the exposed infants were HBsAg-seropositive neither before nor after 6 weeks of age. No HBs-antibodies were detected in 23.3% of HBsAg-exposed infants at two years despite having successfully completed the HBV vaccination schedule.ConclusionLow and moderate HBV endemics were observed in HIV-uninfected and HIV-infected pregnant women, respectively. This underscores the need to routinely screen for HBV in pregnancy, especially the HIV-infected attending antenatal-care. Being HIV-infected and reported tooth extractions were independent risk factors for maternal HBsAg-seropositivity. Vertical and child horizontal transmissions were both absent, probably due to ~ the 50% frequency of antenatal anti-HBe-antibodies observed. Of concern was the absence of anti-HBs-antibodies in 23.3% of fully vaccinated/maternally HBV-exposed infants by two years. Absence of molecular diagnosis may have underestimated HBV burden.Trial registrationwww.clinicaltrials.gov, trial registration number: NCT04087239.

Strategies for Hepatitis B Virus Prevention in People Living with HIV.

Coinfection with HIV and hepatitis B virus (HBV) is common owing to shared routes of transmission, and persons with HIV-HBV coinfection experience an accelerated progression of liver disease. Despite the widespread availability of HBV vaccination, rates of seroprotection in people living with HIV (PLWH) have historically been low. In this article, we review strategies in HBV prevention among PLWH, focusing specifically on updates in HBV vaccination and chemoprophylaxis. Vaccination remains the hallmark of HBV prevention, and recent studies suggest that a double dose of HBV vaccine and Heplisav-B can improve rates of seroprotection among PLWH. The use of tenofovir-containing antiretroviral therapy (ART) has similarly been shown to provide some HBV protection in PLWH; however, this protection can be lost when switching to newer tenofovir-sparing regimens, including long-acting injectables. All HBV-susceptible persons with HIV should be vaccinated against HBV, regardless of ART regimen and CD4 count.

Hepatitis B virus infection status and associated factors among health care workers in selected hospitals in Kisumu County, Kenya: A cross-sectional study.

Poorly managed medical waste produced at the health facilities are potential source of infections including occupational exposure to Hepatitis B Virus (HBV). This study evaluated the prevalence of HBV infection among healthcare workers (HCWs) in Kisumu County. We determined prevalence of HBV infections among 192 HCWs from nine purposively selected high-patient volume public hospitals in Kisumu County. A structured questionnaire was administered, and 4.0 ml of venous blood sample collected for Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and total hepatitis B core antibody (anti-HBc) testing using enzyme immunoassay (EIA). Of 192 HCWs sampled, 52.1% were males and the median participants age was 34.4 years with interquartile range (IQR) of 11 (28-39) years. Most participants (44%) had worked for between 1-5 years. There was low HBV vaccine uptake with 35.9% completing the required 3 doses, while 40.6% had never been vaccinated. HBV prevalence was 18.8% (36/192), prevalence of past resolved infection was 25.5% (49/192), while 37.5% (72/192) of HCW had evidence of vaccine-derived immunity and 17.7% (34/192) were susceptible. HBV prevalence among HCW who had worked for less than one year and those who had never been vaccinated was 37.5% and 35.9% respectively. Significant risk of HBV lifetime exposure was noted among HCWs with one vaccine dose, those with no known exposure, while highest in those with knowledge on HBV transmission (aOR, 7.97; 95% CI, 2.10-153.3, p-value = 0.008). HCWs who had received ≥2 doses of HBV vaccine (aOR, 0.03; 95% CI, 0.01-0.10, p-value = <0.0001) had significant HBV protection. Duration of service was not associated with HBV among HCWs. HBV prevalence was high among HCWs from nine high patient volume public hospitals in Kisumu County. Efforts to strengthen HBV vaccination uptake and dose completion are needed to reduce HBV infections among HCWs.

ABO blood types, but not Secretor or Lewis blood types, influence strength of antibody response to Hepatitis B vaccine in Black South African children.

Subunit vaccines for the Hepatitis B virus (HBV) have greatly reduced the prevalence of infection and morbidity through HBV-related liver cirrhosis and cancer. However, strength of immune response to vaccination varies considerably. While it is known that ABO blood types may influence HBV infection risk, the role of ABO and related blood types in strength of immune response to HBV vaccine has not been investigated. We examined 16 polymorphisms in the ABO, FUT2, and FUT3 genes and their related phenotypes for associations with strength of antibody response to HBV vaccine in Black South African infants. Anti-HBc and anti-HBs antibody levels were measured by CMIA assay 1-3months after the last dose of HBV vaccine. Prior infection occurred in 8/207 individuals (3.86%) who were removed from further study. Of the remaining 199 individuals, 83.4% individuals were strong responders (anti-HBs≥100 mIU/ml, median 973 mIU/ml), another 15.6% were weak responders (anti-HBs<100 mIU/ml, median 50 mIU/ml) and 1% were non-responders (anti-HBs<10 mIU/ml). The frequency of weak responders to HBV vaccine was not significantly affected by sex, birthweight, use of an additional booster dose of vaccine or cohort of origin. We characterised patterns of genetic variation present at the ABO, FUT2 and FUT3 loci by use of MassArray genotyping and used these data to predict ABO, Secretor and Lewis phenotypes. We observed significant association of ABO blood type with strength of antibody response to HBV vaccine in a Black South African cohort (p=0.002). In particular, presence of rs8176747G and expression of B antigen (whether in B blood type or AB blood type) was associated with decreased antibody response to HBV vaccine. Secretor and Lewis blood types were not associated with antibody response to HBV vaccine. This work increases our understanding of the impact that host genetic variation may have on vaccine immunogenicity.

Efficacy of Hepatitis B Vaccination Procedures in Infants and Children Born from HBsAg-positive Mothers in Iran: A Case Study of Khorasan Razavi Province, Iran

Background: Viral infections have been a major public health concern in recent years. Viral hepatitis B virus (HBV) is one of the serious healthcare system issues in Iran. Family transmission of HBV in pregnant women is a major cause of the high prevalence of HBV infection in neonates and related persons. The expanded program on immunization (EPI) was the main way to prevent this infection. Objectives: This study aimed to estimate the effectiveness of the hepatitis B vaccine in infants born to HBsAg-positive mothers in Khorasan Razavi province. Materials and Methods: This cross-sectional descriptive study was conducted on 53 HBsAg-positive women between March 2017 and April 2019 in Khorasan Razavi province, Iran. The enzyme-linked immunosorbent assay (ELISA) was employed to conduct screenings for HBsAg in children. Risk factors for HBV infection were investigated using medical records and structured questionnaires. Results: The prevalence of HBsAg positivity was 1.2% (1/83) among children aged 1-3 years old. All children received three doses of HBV vaccine according to the HBV immunization program. The positive hepatitis B surface antibody (HBsAb) test among children under study was 80.7% (n=67). Conclusion: The results indicated a low prevalence of hepatitis B infection among infants and children born to HBsAg-positive mothers (1.2); however, protective anti-HBs levels were reported in 80.7% (&lt;95%) of the children. It appears that the efficiency level of the hepatitis B vaccination procedure was not sufficient in this study. Overall, revaccination is recommended for children who are anti-HBs-negative or not protected.

Lowering costs: the golden rule for achieving WHO goals

The WHO Global Health Sector Strategy on Viral Hepatitis 2016–21 has established specific objectives aimed at eliminating viral hepatitis as a major public health concern by 2030. 1 Global health sector strategy on viral hepatitis 2016–2021. https://www.who.int/publications/i/item/978-92-4-155058-1Date: 2016 Date accessed: April 4, 2023 Google Scholar To achieve this goal, all WHO regions are striving for a 90% reduction in new cases of chronic hepatitis B virus (HBV) infection by 2030, which is equivalent to a prevalence of HBsAg of less than 0·1% among children aged 5 years. As most HBV-related illnesses stem from infections contracted during infancy through perinatal or early childhood exposure to the virus, the global targets for 2030 aim to ensure that 90% of infants receive a timely birth dose of HBV vaccine and that 90% of the neonate population receive two to three additional doses of the HBV vaccine. 1 Global health sector strategy on viral hepatitis 2016–2021. https://www.who.int/publications/i/item/978-92-4-155058-1Date: 2016 Date accessed: April 4, 2023 Google Scholar Impact and cost-effectiveness of hepatitis B virus prophylaxis in pregnancy: a dynamic simulation modelling studyPAP 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. Full-Text PDF Open Access

The association between internet use to obtain health information and receiving three doses of the Hepatitis B vaccine in a multi-ethnic population in Ohio

While most cancer incidence and mortality rates are decreasing, liver cancer rates are increasing. The Hepatitis B Virus (HBV) vaccine prevents liver cancer, although not everyone receives all three doses of the vaccine. This study examined the association between using the internet as the primary source of health information and receiving three HBV vaccine doses among a multi-ethnic population in Ohio. From May 2017 through February 2018, participants in the Community Initiative Towards Improving Equity and Health Status (CITIES) study reported their primary health information source and if they received three HBV vaccine doses. A multivariable logistic regression model was fit using backwards selection. Overall, 26.6% received three HBV vaccine doses. After adjusting for race/ethnicity and education, the association between internet use and receiving three HBV vaccine doses was not significant (p-value = 0.73). In the process of model-building, race/ethnicity and educational attainment were identified as factors associated with completing the HBV vaccine; Hispanics (OR = 0.35; 95% CI = 0.17, 0.69) and African Americans (OR = 0.53; 95% CI = 0.35, 0.81) had lower odds of receiving three doses compared to whites; compared to college graduates, those with a high school diploma or less also had lower odds (OR = 0.33; 95% CI = 0.21, 0.52). This study suggests no association between internet use and complete HBV vaccination; however, associations between both race/ethnicity and educational attainment and HBV vaccine completion were identified. Future research should consider factors that stem from racial/ethnic and educational disparities that may influence adherence to HBV vaccination (i.e., healthcare system mistrust, access to accurate health information).

Seroconversion following Heplisav-B, hepatitis B vaccine (recombinant), adjuvanted, in patients with end-stage renal disease at an urban safety net hospital.

Heplisav-B is a novel recombinant adjuvanted vaccine for hepatitis B virus (HBV) that has been approved as a 2-dose regimen and shown to have similar seroconversion rates in healthy adults as single-antigen HBV vaccines. More data are needed to determine whether similarly high rates of seroconversion and immunity are observed in immunocompromised patient populations such as in patients with end-stage renal disease (ESRD) on hemodialysis. Patients with ESRD who presented for emergency-only hemodialysis and either were HBV vaccine naive or had a hepatitis B surface antibody (anti-HBs) titer of less than 10 IU/mL received 3 standard 20-μg doses of Heplisav-B at week 0, week 4 (±2 weeks), and week 24 (±2 weeks), with anti-HBs titer measured at week 28 (±2 weeks). Thirty-two patients received at least one dose in the study timeframe, with 24 patients completing the vaccine series and measurement of anti-HBs titer. The mean age of the patients was 46 years, and 58% of patients were male. Of the 24 patients who completed the vaccine series, 20 (83%) seroconverted after the third dose. Three of the 4 patients who did not seroconvert after 3 doses were revaccinated with an additional 20-μg dose, and 2 of the 3 patients had an anti-HBs titer of greater than 10 IU/mL 4 weeks after this dose. Patients with ESRD who received three 20-μg doses of recombinant HBV vaccine had a seroconversion rate of 83%, representing a similar seroconversion rate and fewer doses of vaccine as compared to the standard HBV vaccine regimen for patients with ESRD.

Serologic status and vaccine response against hepatitis B virus after allogeneic hematopoietic cell transplantation in pediatric patients.

Although vaccination against hepatitis B virus (HBV) is recommended for hematopoietic cell transplantation (HCT) recipients, previous studies evaluating serologic status and immunologic response to HBV vaccination in pediatric allogeneic HCT recipients are not enough. This study aimed to evaluate serologic status against HBV and immunologic responses to HBV vaccination in children and adolescents receiving allogeneic HCTs. Medical records of the enrolled 61 pediatric patients < 19 years of age who received their first allogeneic HCTs were retrospectively reviewed. Twenty-two (36.1%) of the enrolled patients were positive for hepatitis B surface antibody (HBsAb) after HCT. Chronic graft-versus-host disease was significantly associated with negative HBsAb status after HCT (p = 0.01). With one dose of HBV vaccination after HCT, 40.5% of the vaccinated patients became positive for HBsAb. No clinical factor was associated with the positive conversion of HBsAb after vaccination. Considering the unsatisfactory seropositive rate and vaccine response against HBV and the lack of significant clinical and laboratory factors predicting serostatus in HCT recipients, universal three doses of HBV vaccination should be necessary after allogeneic HCT.

HUMORAL IMMUNITY RESPONSES AFTER VACCINATION FOR HEPATITIS B VIRUS IN AUTOGRAFTED PATIENTS: A SINGLE CENTER EXPERIENCE

The effectiveness of vaccinations post hematopoietic stem cell transplantation (HSCT), is a reliable marker for immune system's functionality assessment. In autologous HSCT (AHSCT) setting, the general aspect is that the immune system recovers quite soon and patients (pts) are considered to be immunocompetent in a period of approximately 3-6 months post AHSCT. We evaluated the hepatitis B virus (HBV) vaccination responses in autografted pts who were in remission and off chemotherapy post AHSCT. 27 autografted pts aged 51,6 (22-67) ys, who had antiHbs titers <10 IU/ml before AHSCT and at the time of vaccination, were studied. After a successful engraftment the median absolute lymphocytes count at +3 months was 1740(450-4090)/mm 3 . In 4,3(0,6–8,5) ys post AHSCT, 3 doses of recombinant HBV vaccine were given monthly. The response rates for pts who completed 3 vaccine doses, compared with an internal group of healthy individuals, vaccinated in the same period with the same product. After the 1 st , 2 nd and 3 rd dose the response rates in the study group were 11%, 81% and 88% respectively. No factor statistically significantly influenced the achievement of protective antiHbs titers. The responses were lower as compared to product's efficacy profile (19%, 86% and 100% after the 1 st , 2 nd and 3 rd dose respectively), while in the comparative analysis with the internal control group, a trend for inferior responses in autografted pts was also noticed (88% vs 100%, p=0,07). This study, in a relatively homogenous group of pts, to our knowledge, is the only one that directly compares the HBV vaccine responses in autografted pts with healthy individuals. Although vaccination was offered late post AHSCT, the responses were lower compared to healthy individuals, indicating a possible long lasting immune impairment post AHSCT highlighting the necessity of prolonged surveillance and intensified vaccination programs for autografted pts.

Factors associated with receipt of a timely infant birth dose of hepatitis B vaccine at a tertiary hospital in North-Central Nigeria.

The World Health Organization recommends universal vaccination of medically stable infants with Hepatitis B vaccine within 24 hours of birth to prevent mother-to-child transmission of Hepatitis B virus (HBV) infection. However, the proportion of infants who receive a timely birth dose is extremely low in Nigeria. We reviewed the implementation of an infant HBV vaccine schedule at a single center and identified factors affecting the receipt of a timely birth dose of HBV vaccine. We conducted a retrospective cohort study utilizing data from the INFANT study, a 2013-2017 prospective cohort study of pregnant women with and without HIV and their infants We utilized bivariate and multivariable logistic regression to assess if maternal characteristics, or the day of the week on which the infant was born were significantly associated with timely receipt of a birth dose of HBV vaccine. Receipt of HBV vaccine on the day of birth or the following calendar day were considered a timely birth dose. Among 409 infants in our cohort, 133 infants (33%) received a timely birth dose of HBV vaccine. Only the day of the week on which infants were born was significant (p<0.0001): when compared to Friday, infants born Monday through Thursday had significantly higher odds of receiving a timely birth dose, while infants born on a Saturday or Sunday had similar (low) odds. We found no association between maternal age, education, marital status, HIV status, parity and mode of delivery, and infant receipt of a timely birth dose of HBV vaccine. National immunization programs could improve timely HBV birth dose rates by providing access to vaccine immediately following birth at all infant delivery venues on all days of the week. Where not possible, there should be rapid linkage to the nearest facility where HBV vaccination is immediately available.

Insights into induction of the immune response by the hepatitis B vaccine.

After more than four decades of hepatitis B virus (HBV) vaccine implementation, its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved. Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth. All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications. However, there are still many drawbacks to overcome. The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization. Additionally, the current most widely used second-generation vaccines do not induce protective immunity in 5% to 10% of the population, particularly in people over 40-years-old, obese (body mass index > 25 kg/m2), heavy smokers, and patients undergoing dialysis or infection with human immunodeficiency virus. Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance, particularly in difficult settings. These advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.

Adverse Events of Vaccination against Hepatitis B Virus in Post-Marketing Surveillance from 2005 to 2017 in Guangdong Province, China.

The present study focused on the adverse events following the vaccination against hepatitis B virus (HBV) in the Guangdong Province of China between 2005 and 2017. In total, more than 88 million doses of HBV vaccine were administered in the Guangdong Province during the study period. A total of 3115 adverse events following immunization (AEFI) related to HBV vaccination occurred, with an overall incidence of 35.39 per million doses. Of these, 1801 cases were male, and 1314 were female; 74.01% (2376/3115) of the cases occurred in children aged less than 2 years; 56.05% (1746/3115) of the cases were classified as common vaccine reactions; and 30.37% (946/3115) of the cases were grouped into rare vaccine reactions. Additionally, 27.74% (864/3115) of the cases were classified as allergic reactions, 0.10% (3/3115) were temporary neurological events, and 1.28% (36/3115) were diagnosed as severe adverse events. This study suggested that the HBV vaccine posed a reasonable profile because most adverse events remained relatively mild, and the neurological events were relatively rare. This study concluded that the incidence of severe vaccine reactions related to HBV vaccination are extremely low.

Improving Hepatitis B Vaccination Rates among At-risk Children and Adolescents with Inflammatory Bowel Disease.

Introduction:Patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor alpha inhibitors (TNFai) may be at higher risk for hepatitis B virus (HBV) infection. We conducted a quality improvement (QI) initiative to improve HBV vaccination rates in seronegative children with IBD.Methods:This QI initiative implemented an HBV vaccination strategy from September 2018 to March 2020 in patients with newly diagnosed IBD with hepatitis B surface antibody (HBsAb) <10 mIU/mL. The project aimed to (1) increase HBV vaccination rates in seronegative patients and (2) document immunogenicity after completing a three-dose vaccine series. Outcome measures included the percentage of seronegative patients who received HBV vaccines (dose 1 and three-dose series). Interventions included applying a standardized vaccination protocol, and creating a vaccine workflow in two clinical areas, previsit planning and stakeholder engagement.Results:One hundred seventy-four children and adolescents with IBD were evaluated during the study period, and 132 (76%) were HBsAb negative. After plan-do-study-act (PDSA) 1, the proportion of eligible patients who received HBV vaccine dose 1 increased from a baseline of 7% to 100% and was sustained for over 12 months. During PDSA 2, the proportion of patients completing the three-dose vaccine series improved from a baseline of 0% to 82% (n = 100); among 93 children in this subgroup who had repeat serology performed, 86 (92%) demonstrated serologic evidence of HBV protection.Conclusions:A multidisciplinary approach applying QI methodology allowed for improved and sustained HBV vaccination rates in at-risk seronegative children and adolescents with IBD. A three-dose HBV vaccine series proved immunogenic in 92% of eligible patients.

Hepatitis B Virus Vaccination after Allogeneic Hematopoietic Cell Transplantation Prevents Post-Transplantation Hepatitis B Virus Reactivation

Hepatitis B virus (HBV) reactivation in allogeneic hematopoietic cell transplantation (HCT) recipients with evidence of pretransplantation resolved HBV infection is an important cause of morbidity, usually occurring 1 year or later after HCT. We retrospectively studied a cohort of allogeneic HCT recipients with resolved HBV infection, some of whom were vaccinated for HBV following transplantation, to understand whether post-HCT HBV vaccination influenced the risk of HBV reactivation. The study included all patients with resolved HBV who underwent allogeneic HCT at our institution between January 1, 2000, and December 31, 2015, where HBV vaccination starting at 1 year after HCT became standard in 2012 and antiviral prophylaxis is not used. Resolved HBV infection was defined as positive HBV-core IgG (HBcAb), negative HBV-surface antigen (HBsAg), and undetectable HBV DNA before HCT. HBV reactivation was defined as the development of detectable HBsAg and HBV DNA after HCT. Follow-up for outcomes concluded on January 1, 2018. Among 136 patients with resolved HBV infection before HCT, 19 developed reactivation during follow-up (cumulative incidence, 14%). The median time to HBV reactivation was 21 months (range, 2 to 47 months). When accounting for competing risks, the cumulative incidence of HBV reactivation among HCT recipients who survived for 1 year or longer after transplantation without early HBV reactivation and were HBV vaccinated versus those who were unvaccinated was 2.9% versus 10.0% at 2 years post-HCT and 6.6% versus 26.5% at 4 years post-HCT (P=0.03, Gray's test). In a time-dependent Cox model, the adjusted hazard ratio (aHR) of HBV reactivation in patients with a pretransplantation HBsAb level >10 IU/L was 0.34 (95% confidence interval [CI], 0.13 -0.90). The aHR of HBV reactivation in patients who were vaccinated with 2 or more doses of recombinant HBV vaccine after HCT was 0.18 (95% CI, 0.04-0.80) compared with those who received 1 or no post-HCT vaccine doses. HBV reactivation is a late complication of allogeneic HCT in at-risk recipients, particularly in those with low pre-HCT HBsAb. HBV vaccination starting at 1 year after HCT may be protective.

A real world comparison of HepB (Engerix-B®) and HepB-CpG (Heplisav-B®) vaccine seroprotection in patients receiving maintenance dialysis.

Vaccination against hepatitis B virus (HBV) is recommended for dialysis patients. Two reports comparing seroprotection (SP) rates following HepB and HepB-CpG in vaccine-naïve patients with chronic kidney disease enrolled few dialysis patients (n = 122 combined). SP rates in a subset of dialysis patients were not reported or not powered to detect statistically significant differences. SP rates in those requiring additional vaccine series or booster doses are not known. A retrospective cohort analysis including dialysis patients completing HepB or HepB-CpG vaccination between January 2019 and December 2020. Vaccine-naïve patients received a series of HepB or HepB-CpG (Series 1). A repeat series was given to nonresponders (Series 2). A booster regimen consists of one dose of either vaccine. Primary outcome was achieving SP (anti-HBs >10 mIU/mL) at least 60 days after the last HBV vaccine dose for Series 1 and Series 2, and achieving SP at least 3 weeks post-booster. For Series 1 (n = 3509), SP after HepB vaccination was significantly higher (62.9% versus 50.1% for HepB-CpG; P<0.0001). Series 2 (n = 1040) and booster (n = 2028) SP rates were similar between vaccines. Patients that received up to four HepB-CpG doses had higher SP rates compared with four doses of HepB (82.0% versus 62.9%, respectively; P<0.0001). SP rates in hepatitis B vaccine-naïve dialysis patients administered a recommended four doses of HepB were higher than those recommended two doses of HepB-CpG. SP rates were higher and achieved sooner if HepB-CpG was utilized initially and, if needed, for Series 2. Optimal HepB-CpG dosing deserves further study.

Chronic Hepatitis B Infection in Children

Source: Ling SC, Lin HHS, Murray KF, et al. Chronic hepatitis is common and often untreated among children with hepatitis B infection in the United States and Canada. J Pediatr. 2021;237:24-33.e12; doi:10.1016/j.jpeds.2021.05.035Investigators from multiple institutions conducted a prospective cohort study of children in North America with chronic hepatitis B to assess outcomes over time. The study was conducted by the Hepatitis B Research Network at 6 clinical sites in the US and 1 in Canada. Study participants were children >6 months and <18 years old at baseline with hepatitis B surface antigen (HBsAg) positivity and were enrolled between 2010 and 2017. After a baseline visit, study participants had follow-up visits at 24 and 48 weeks, and annually thereafter. Data collected included demographics and clinical information, and blood specimens were obtained for measurement of alanine aminotransferase (ALT), platelet count, HBsAg, Hepatitis B e antigen (HBeAg), and hepatitis B virus (HBV) DNA on a regular basis. Treatment with anti-HBV therapy was documented, as was meeting criteria for this treatment based on guidelines from the American Association for the Study of Liver Diseases (AASLD). ALT was classified as normal or elevated when levels were greater than the upper limits of normal (ULN). Study outcomes included clinical events such as death, development of cirrhosis, liver transplantation, development of hepatocellular cancer, ALT flares (ALT levels ≥400 U/L in male patients and ≥350 U/L in female patients), hepatitis B serologic and virologic outcomes, anti-HBV treatment, and decreases in platelet counts (as an indicator of liver fibrosis progression).Data were analyzed on 362 children. Overall, 79% of study participants were Asian, 74% were born outside of the US or Canada, and 98% acquired HBV through vertical transmission. At baseline, 81% of study patients had elevated ALT values, with 66% having values >1–3 times >ULN; 75% were HBeAg positive. Median duration of follow-up in participants was 4.2 years (range 0.8–7.9 years). One study child died from a cause not related to liver disease, and 1 participant developed cirrhosis at age 14 years. Over the course of the study, 13 children had ALT flares, and there was an association between acute fall in platelet counts and occurrence of an ALT flare. At the last follow-up, ALT levels were elevated in 72% of patients. There were 40 patients treated with anti-HBV drugs. However, of 129 children who met AASLD criteria for anti-HBV treatment, only 25 (19%) received it. During the follow-up period, 2.4% of study patients became HBsAg negative, 15% of those who had detectable HBV DNA at baseline had unquantifiable levels measured at least once, and 20.8% of those who were HBeAg positive at baseline became HBeAg negative.The authors conclude that, among children in the US and Canada with chronic hepatitis B, many remained at risk for chronic liver disease.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.HBV is efficiently transmitted from infected pregnant women to their newborn infants via blood exposures during labor and delivery.1 These infants are at increased risk of chronic HBV infection and its late complications of end-stage liver disease and liver cancer.2 The best strategies to prevent chronic HBV infection are to test pregnant women for HBsAg, refer women with positive HBsAg for potential treatment, immunize all infants with HBV vaccine at birth, and for those infants born to mothers with positive HBsAg, provide both HBV vaccine and hepatitis B immune globulin (HBIG), preferably within 12 hours of delivery.1 These strategies may not be available to infants born outside the US and Canada, and therefore screening for HBV infection should be included in the initial testing of immigrant and internationally adopted children, especially those from Asia.3Children who are positive for HBsAg need follow-up testing to see if the antigen clears. Those who have persistent positive HBsAg for at least 6 months are defined as chronically infected.1 Diet and exercise should be optimized to minimize their development of nonalcoholic fatty liver disease, which can contribute to additional liver injury.4 Referral to a hepatologist facilitates additional investigations and early appropriate initiation of anti-HBV therapies.5Another group of children and adolescents who need screening for chronic HBV infection is those with inflammatory bowel disease and rheumatologic conditions who are candidates for tumor necrosis factor alpha (TNF-α) inhibitor therapies.6 Because TNF-α is a mediator of the immune response against HBV infection, TNF-α inhibitors may promote viral reactivation and potentially fatal liver failure.Chronic HBV infection can lead to liver cancer and liver failure. The major prevention strategy is receipt of the birth dose of HBV vaccine.