Universal Hepatitis B Virus Vaccination Research Articles

Good Practices and Initiatives for the Control and Elimination of Hepatitis B in the World: A Scoping Review.

Hepatitis B virus (HBV) infection remains a significant global public health challenge, leading to considerable morbidity and mortality. Implementationof effective strategies and novel initiatives is necessary to control and eliminate HBV. To identify the key approaches and actions used worldwide for HBV control and elimination, we conducted a comprehensive scoping review. We searched various sources, including PubMed, Scopus, Web of Science, Google Scholar, the official websites of the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), and relevant articles and reports published in the past decade. Our inclusion criteria focused on studies that reported on strategies for HBV control and elimination, provided evidence of their effectiveness, and assessed their impact on public health outcomes. We included 16 articles in our review, which highlighted a range of strategies, such as universal HBV vaccination, prevention of mother-to-child transmission, mass screening programs, and treatment of chronically infected individuals. These strategies have shown promising results in reducing HBV transmission rate, improving health outcomes, and making progress towardHBV elimination. Moreover, several challenges, including limited access to care, low awareness, stigma, and funding constraints, hinder the effectiveness of elimination programs. The findings underscore the importance of sustained efforts and investment in comprehensive strategies for HBV control and elimination. It is crucial to address barriers to care and enhance public awareness to achieve the goal of eliminating HBV as a public health threat by 2030.

Survey of hepatitis B virus infection status after 35 years of universal vaccination implementation in Taiwan.

Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'ɑ' determinant variants were evaluated if indicated. After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.

Impact of the Universal Implementation of Adolescent Hepatitis B Vaccination in Spain.

The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991-1993 and in 1994-1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 (p < 0.001). The incidence in 2014-2021 was lower for regions that started adolescent vaccination in 1991-1993 rather than in 1994-1996 (IRR 0.76; 95% CI 0.72-0.83; p < 0.001). In the 20-29 age group, incidence in regions that started adolescent vaccination in 1991-1993 was also lower (IRR 0.87; 95% CI 0.77-0.98; p = 0.02 in 2005-2013 and IRR 0.71; 95% CI 0.56-0·90; p < 0.001 in 2014-2021). Anti-HBc prevalence in the 35-39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant (p = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030.

Prospects for Controlling Hepatitis B Globally.

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission.

HBV Vaccines: Advances and Development.

Hepatitis B virus (HBV) infection is a global public health problem that is closely related to liver cirrhosis and hepatocellular carcinoma (HCC). The prevalence of acute and chronic HBV infection, liver cirrhosis, and HCC has significantly decreased as a result of the introduction of universal HBV vaccination programs. The first hepatitis B vaccine approved was developed by purifying the hepatitis B surface antigen (HBsAg) from the plasma of asymptomatic HBsAg carriers. Subsequently, recombinant DNA technology led to the development of the recombinant hepatitis B vaccine. Although there are already several licensed vaccines available for HBV infection, continuous research is essential to develop even more effective vaccines. Prophylactic hepatitis B vaccination has been important in the prevention of hepatitis B because it has effectively produced protective immunity against hepatitis B viral infection. Prophylactic vaccines only need to provoke neutralizing antibodies directed against the HBV envelop proteins, whereas therapeutic vaccines are most likely needed to induce a comprehensive T cell response and thus, should include other HBV antigens, such as HBV core and polymerase. The existing vaccines have proven to be highly effective in preventing HBV infection, but ongoing research aims to improve their efficacy, duration of protection, and accessibility. The routine administration of the HBV vaccine is safe and well-tolerated worldwide. The purpose of this type of immunization is to trigger an immunological response in the host, which will halt HBV replication. The clinical efficacy and safety of the HBV vaccine are affected by a number of immunological and clinical factors. However, this success is now in jeopardy due to the breakthrough infections caused by HBV variants with mutations in the S gene, high viral loads, and virus-induced immunosuppression. In this review, we describe various types of available HBV vaccines, along with the recent progress in the ongoing battle to develop new vaccines against HBV.

Hybrid large hepatitis B surface protein composed of two viral genotypes C and D induces strongly cross-neutralizing antibodies

Hepatitis B virus (HBV) vaccination is known to effectively decrease the risk of HBV infection. However, several issues need to be addressed in order to develop an improved HBV vaccine. Although the HBV vaccine has been shown to be effective, this vaccine needs to be more efficacious in defined groups, including non-responders (i.e., individuals who do not develop a protective response even after vaccination) and in health care workers and travelers who require rapid protection. Furthermore, it has been reported that universal HBV vaccination has accelerated the appearance of vaccine-escape mutants resulting from the accumulation of mutations altering the “a” determinant of the hepatitis B surface (HBs) protein. To address these problems, we have been focusing on the large HBs (LHBs) protein, which consists of three domains: pre-S1, pre-S2, and S (in N- to C-terminal order). To enhance the immunogenicity of LHBs, we developed a yeast-derived hybrid LHBs (hy-LHBs) antigen composed of the LHBs proteins from two distinct genotypes (Genotypes C and D). The levels of antibodies induced by hy-LHBs immunization were high not only against S, but also against the pre-S1 and pre-S2 domains. Additionally, hy-LHBs immunization induced significantly more strongly cross-reactive neutralizing antibodies than did small HBs (SHBs) or LHBs of any genotype alone. These findings suggested that hy-LHBs might serve as a candidate antigen for use in an improved prophylactic HBV vaccine.

Susceptibility to hepatitis B virus infection in adults living inSpain.

A protective hepatitis B virus (HBV) vaccine has been available for four decades. Universal HBV vaccination of infants is recommended by the WHO since the 1990s. Furthermore, HBV immunization is advised for all adults with high-risk behaviours and no seroprotection. However, HBV vaccine coverage remains globally suboptimal. The advent of new more efficacious trivalent HBV vaccines has renewed the interest in HBV vaccination. At present, the extent of current HBV susceptibility in adults remains unknown in Spain. HBV serological markers were assessed on a large and representative sample of adults in Spain, including blood donors and individuals belonging to high-risk groups. Serum HBsAg, anti-HBc and anti-HBs were tested in specimens collected during the last couple of years. From 13 859 consecutive adults tested at seven cities across the Spanish geography, overall 166 (1.2%) had positive HBsAg. Past HBV infection was recognized in 14% and prior vaccine immunization in 24%. Unexpectedly, 37% of blood donors and 63% of persons belonging to high-risk groups had no serum HBV markers and therefore were potentially HBV susceptible. Roughly 60% of adults living in Spain seem to be HBV susceptible. Waning immunity might be more common than expected. Hence, HBV serological testing should be performed at least once in all adults regardless of risk exposures. HBV vaccine full courses or boosters should be administered to all adults lacking serological evidence of HBV protection.

Trends of hepatitis B virus genotype distribution in chronic hepatitis B patients in Japan.

Hepatitis B virus (HBV) is one of the most prevalent chronic viral infections that causes chronic hepatitis B (CHB). In Japan, genotypes B and C account for most of acute and chronic cases of hepatitis. However, previous studies showed that the prevalence of genotype A in CHB gradually increased every 5years. Therefore, we have conducted a nationwide survey to comprehensively investigate the trends of HBV genotype distribution in CHB patients in Japan. 4421 CHB patients were recruited between 2015 and 2016. Clinical characteristics and distribution of CHB patients among different age groups and genotypes in 2015-2016 was compared with those in 2000-2001, 2005-2006, and 2010-2011. The percentages of genotype A, B, C, and D were 4.0, 16.2, 79.1, and 0.7%, respectively. While the overall percentage of CHB patients with genotype A did not change in the past 5years, CHB with genotype A increased in young adults. On the other hand, the peak distribution of CHB with genotypes B and C, two genotypes with the largest patient population, has shifted to an older age group. In Japan, the peak distribution for CHB with genotypes B and C advanced to an older age group while CHB with genotype A expanded in a younger age group. Given the universal HBV vaccination launch in Japan in 2016, these pre-vaccination survey data provide important baseline information for comparative studies of the impact of universal vaccination on HBV genotypes.

Low prevalence of hepatitis B virus infection in HIV-uninfected pregnant women in Cape Town, South Africa: implications for oral pre-exposure prophylaxis roll out

BackgroundOral daily preexposure prophylaxis (PrEP) using emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is recommended as standard of care for prevention in individuals at high risk for HIV infection, including pregnant and postpartum cisgender women. FTC/TDF is also active against hepatitis B virus (HBV); however, concern has been raised that providing PrEP to individuals infected with HBV could lead to hepatitis flares and liver injury, especially in the setting of suboptimal PrEP use.MethodsWe conducted a cross-sectional analysis of baseline data from the PrEP in pregnant and postpartum women (PrEP-PP) cohort study from February 2020–March 2022 in one antenatal care clinic in Cape Town, South Africa (SA) to evaluate: (1) the field performance of a point of care test (POCT) (Determine II, Abbott Inc., Japan) for diagnosis of hepatitis B surface antigen (HBsAg) in a maternity setting, (2) the prevalence of HBV in a cohort of pregnant women not living with HIV.ResultsWe enrolled 1194 HIV sero-negative pregnant women at their first antenatal visit. Median age was 26 years (IQR = 22–31 years); 52% were born before 1995 (before universal HBV vaccination had started in South Africa). Median gestational age was 22 weeks (IQR = 16–30 weeks). There were 8 POCT and laboratory confirmed HBV cases among 1194 women. The overall prevalence of 0.67% (95% CI = 0.34–1.32%). In women born before 1995, 8 of 622 women were diagnosed with HBsAg; the prevalence was 1.29% (95% CI = 0.65–2.52%), and in women born in 1995 or after (n = 572); the prevalence was 0% (95% CI = 0.0–0.67%). We confirmed the test results in 99.8% of the rapid HBsAg (Determine II). Sensitivity was 100% (95% CI = 68–100%). Specificity was 100% (95% CI = 99.67–100%).ConclusionThe prevalence of HBV was very low in pregnant women not living with HIV and was only in women born before the HBV vaccine was included in the Expanded Program of Immunization. The Determine II POCT HBsAg showed excellent performance against the laboratory assay. HBV screening should not be a barrier to starting PrEP in the context of high HIV risk communities.

Universal HBV vaccination dramatically reduces the prevalence of HBV infection and incidence of hepatocellular carcinoma.

Universal vaccination of newborns with hepatitis B virus (HBV) vaccine is the most important strategy to prevent chronic HBV infection and its complications of which hepatocellular carcinoma (HCC) as the deadliest. To evaluate the impact of universal HBV vaccination on the prevalence of chronic HBV infection, and the incidences of HCC and hepatic events in young adults born before and after the introduction of the universal HBV vaccination programme in 1988 in Hong Kong METHODS: This was a territory-wide retrospective observational cohort study of consecutive adult subjects born in 1970-2002 with hepatitis B surface antigen (HBsAg) checked. Subjects born during the vaccination era (1988-2002) were included in the vaccinated cohort; subjects born between 1970 and 1987 were included in theunvaccinated cohort. We included 695,925 subjects for HBV prevalence analysis. Chronic HBV infection dropped from 14.3% in subjects born in 1970, to 6.7% in subjects born in 1988. In total, 53,960 vaccinated and 318,290 unvaccinated subjects who had available clinical data were included for event analysis. HCC and hepatic events occurred in 44 (0.1%) and 75 (0.1%) of the vaccinated subjects and in 1305 (0.4%) and 1806 (0.6%) of the unvaccinated subjects, respectively. All incidence rates remained numerically lower in vaccinated subjects after adjustment for age, gender and antiviral treatment, but failed to reach statistical significance due to very low incidence rates. Universal HBV vaccination markedly reduces the prevalence of chronic HBV infection and may contribute to the decreased incidences of HCC and hepatic events.

Accelerating Decreases in the Incidences of Hepatocellular Carcinoma at a Younger Age in Shanghai Are Associated With Hepatitis B Virus Vaccination

BackgroundRoutine vaccination of infants for protecting against hepatitis B virus (HBV) infection and its serious consequences, including hepatocellular cancer (HCC), has been carried out in Shanghai, China, since 1986. We therefore have examined the trend of HBV infection and HCC incidences before and after HBV vaccination over decades to assess the potential influences of the Shanghai HBV vaccination program.MethodsData on incidences of HBV infection and HCC were collected from the Shanghai Cancer Registry and the Shanghai HBV vaccination follow-up study. Joint-point regression and the Bayesian age-period-cohort statistical analysis methods were used.ResultsThe incidences of HBV infection dramatically declined from 23.09 and 1.13 per 100,000 for males and females in 2000 to 3.24 (-85.97%) and 0.22 (-80.53%) per 100,000 in 2014, respectively. Sero-epidemiological data from the sampling surveys during 20 years of follow-up showed that less than 1% of people undergoing HBV vaccination have a positive serum HBsAg. Consistently, the annual adjusted standardization rates (ASR) of HCC steadily fell from 33.38 and 11.65 per 100,000 for males and females in 1973 to 17.34 (-49.2%) and 5.60 (-51.9%) per 100,000 in 2014, respectively. The annual percentage change in overall HCC incidences is about -2%. HCC incidences in males at younger age groups (age <50 years old), particularly in those with age <34 groups, showed an accelerating decrease over time, whereas HCC incidences significantly declined in the female population across all age groups except for those under 19 years of age. The results supported that the universal HBV vaccination in newborns is easy to implement with high coverages and is effective for preventing both HBV infection and HCC in populations.

Universal Hepatitis B Antibody Screening and Vaccination in Pregnancy: A Cost-Effectiveness Analysis.

To evaluate the cost effectiveness of universal screening for hepatitis B immunity and vaccination among pregnant women in the United States. We designed a decision-analytic model to evaluate the outcomes, costs, and cost effectiveness associated with universal hepatitis B virus (HBV) immunity screening in pregnancy with vaccination of susceptible individuals compared with no screening. A theoretical cohort of 3.6 million women, the approximate number of annual live births in the United States, was used. Outcomes included cases of HBV, hepatocellular carcinoma, decompensated cirrhosis, liver transplant and death, in addition to cost and quality-adjusted life-years (QALYs). Model inputs were derived from the literature, and the willingness-to-pay threshold was $50,000 per QALY. Univariate sensitivity analyses and Monte Carlo simulation models were performed to evaluate the robustness of the results. In a theoretical cohort of 3.6 million women, universal HBV immunity screening and vaccination resulted in 1,702 fewer cases of HBV, seven fewer cases of decompensated cirrhosis, four fewer liver transplants, and 11 fewer deaths over the life expectancy of a woman after pregnancy. Universal screening and vaccination were found to be cost effective, with an incremental cost-effectiveness ratio of $1,890 per QALY. Sensitivity analyses demonstrated the model was robust even when the prevalence of HBV immunity was high and the annual risk of HBV acquisition low. Among pregnant women in the United States, universal HBV immunity screening and vaccination of susceptible persons is cost effective compared with not routinely screening and vaccinating.

Hepatitis B virus/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic.

Hepatitis D virus (HDV) is a defective liver-tropic virus that needs the helper function of hepatitis B virus (HBV) to infect humans and replicate. HDV is transmitted sexually or by a parenteral route, in co-infection with HBV or by super-infection in HBV chronic carriers. HDV infection causes acute hepatitis that may progress to a fulminant form (7%-14% by super-infection and 2%-3% by HBV/HDV co-infection) or to chronic hepatitis (90% by HDV super-infection and 2%-5% by HBV/HDV co-infection), frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma (HCC). Peg-interferon alfa the only recommended therapy, clears HDV in only 10%-20% of cases and, consequently, new treatment strategies are being explored. HDV endemicity progressively decreased over the 50 years from the identification of the virus, due to improved population lifestyles and economic levels, to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination programs. Further changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic, unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments, lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.

Immunosurveillance and molecular detection of hepatitis B virus infection amongst vaccinated children in the West Gonja District in Savanna Region of Ghana.

Hepatitis B vaccination is the most effective preventive measure in reducing the incidence of chronic hepatitis B virus (HBV) infection and its consequences such as cirrhosis, hepatocellular carcinoma, liver failure and death. Ghana introduced the universal HBV vaccination in the national Expanded Programme on Immunization in 2002. The current study sought to determine the sero-protection rate and the prevalence of HBV infection among fully vaccinated children in the West Gonja District in the Savanna Region of Ghana. This cross-sectional study recruited three hundred and fifty (350) fully vaccinated children who visited West Gonja Catholic Hospital from September to December 2019 for healthcare. Structured questionnaires were administered to obtain information on the demographics. The clinical history of the participants was obtained from the hospital records. Sera were separated from 2-5ml of blood sample collected from each participant after informed consent had been sought from their parents/guardians. Sera were tested for HBsAg, anti-HBs and anti-HBc using ELISA. Samples positive for HBsAg or anti-HBc were tested for HBV DNA by Real-Time Polymerase Chain Reaction. The overall sero-protection rate (anti-HBs titers ≥ 10 mIU/mL) among the studied participants was 56% with anti-HBs geometric mean titer (GMT) of 95.7 mIU/mL (± 6.0; 95% CI) compared with GMT of 2.8 mIU/mL (± 0.2; 95% CI) among non-seroprotected participants. There was no statistically significant difference in sero-protection rate between males and females (p-value = 0.93) and in relation to age (p-value = 0.20). The prevalence of HBV infection among studied participants as determined by the HBV DNA/HBsAg positivity was 1.4% while anti-HBc sero-positivity was 2%. Even though the sero-protection rate and HBV infection rate reported in the current study compares with that of other international studies further studies need to be conducted to understand the factors related to sero-protection and HBV infection rate in the Savanna Region of Ghana.

Hepatitis B virus prevalence in first-time blood donors in Flanders, Belgium: Impact of universal vaccination and migration.

Transfusion-transmissible infections such as hepatitis B virus (HBV) remain a major concern for the safety of blood transfusion. This cross-sectional study aimed to assess the trend of HBV prevalence and associated risk factors among a first-time donor population in a low endemic country. Between 2010 and 2018, blood samples were collected from first-time donors presented at donor collection sites of Belgian Red Cross-Flanders. They were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), and HBV DNA, HIV and hepatitis virus C (HCV) antibodies and RNA, and syphilis antibodies. A total of 211,331 first-time blood donors (43.7% males, median age 25 years) were analyzed. HBsAg prevalence decreased from 0.06% in 2010 to 0.05% in 2018 (p= .004) and this declining trend was accompanied by an increased number of donors in the HBV vaccinated birth cohort (p< .001). HBsAg prevalence was 0.33% in foreign-born donors and 0.02% in Belgian natives (p< .001). Multivariate risk profiling showed that anti-HBc positivity was significantly associated with mainly foreign-born donors (odds ratio [OR]=9.24) but also with older age (OR=1.06), male gender (OR=1.32), year of blood donation (OR=0.94), and co-infections with HCV (OR=4.31) or syphilis (OR=4.91). The decreasing trend in HBV prevalence could mainly be explained by the introduction of the universal HBV vaccination. Being born in endemic areas was the most important predictor for HBV infection while the co-infections with syphilis suggest unreported sexual risk contacts.

Evaluating the cost-effectiveness of universal hepatitis B virus vaccination in Iran: a Markov model analysis

ABSTRACT Vaccination is an essential way to prevent the transmission of hepatitis B virus (HBV). Various studies have been published on the cost-effectiveness of HBV vaccination, but since the results vary according to the target population and related health outcomes, this study examined the cost-effectiveness of the universal HBV vaccination in Iran. In this economic evaluation study, a decision tree with the Markov model was used to compare the universal HBV vaccination with a strategy of non-vaccination. Health states used in the model included healthy, chronic hepatitis B, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death. Analyses were performed from a payer’s perspective. Incremental cost-effectiveness ratio (ICER) per life-year gained, and quality-adjusted life-years (QALYs) gained were calculated at a 5% annual discount rate. The sensitivity analysis was conducted using Monte Carlo simulation. Analyses were performed using Microsoft Excel and TreeAge Pro 2011 software. In 2017, the estimated cost per dose for any HBV vaccine was $3.20 USD. The universal HBV vaccination was economically advantageous compared to non-vaccination, and the estimated cost of this program per life-year and QALY gained were $6,319 and negative (-) $1,183.85 USD, respectively. Given the uncertainty of all parameters, the model remained robust and reliable. In Iran, the universal HBV vaccination strategy for both health outcomes of QALY and life-years gained was cost-effective and advantageous. The vaccination strategy saved money, increased life years and improved quality of life. Therefore, it is recommended that this program continues to be provided.

The impact of universal hepatitis B vaccine on the trend of liver cancer from the Global Burden of Disease Study 2017.

This study aims to assess the trend of hepatitis B virus (HBV)-attributable liver cancer as well as the impact of HBV vaccine on it. We retrieved data from Global Burden Disease study to estimate trends of HBV-attributable liver cancer by region and age from 1990 to 2017 and HBV vaccine data from World Health Organization to assess its impact on these trends for children (0-14years), adolescents and young adults (15-29years). Change of cancer cases, age-standardized incidence rate (ASR) and estimated annual percentage change (EAPC) were used to quantify the trends of HBV-attributable liver cancer. In this study, reduction in HBV-attributable cancer incident cases was found among children (from 2080 to 1430), adolescents and young adults (from 10890 to 9090). In terms of ASR, overall reduction was observed globally by an average of -0.45% (95% CI: -0.62 to -0.29) per year in the same period. The highest reduction in ASR was found in adolescents and young adults with EAPC of -3.02 (95% CI: -3.57 to -2.46). Although the ASR has decreased from all the five regions with universal HBV immunization programme, it has increased in the region without universal vaccination and the highest increase was found among children with EAPC of 1.97 (95% CI: 1.71-2.23). Significant reduction in HBV-attributable liver cancer among children was mainly because of the universal HBV vaccination. However, the increasing trend of HBV-attributable liver cancer in region without universal HBV vaccination suggested the necessity of introducing universal immunization.

Hepatocellular carcinoma in transfusion dependent thalassemia patients: a review from a clinical perspective

Survival in patients with transfusion-dependent thalassemias (TDT) has increased, and complications such as hepatocellular carcinoma (HCC) are emerging. Risk factors include viral infection, mainly hepatitis C virus (HCV), iron overload, the presence of cirrhosis, and immune dysregulation. Median survival after HCC occurrence has been estimated at 12 months, while data regarding the incidence of HCC in this population are minimal. Implementing effective hepatitis B virus (HBV)/HCV antiviral treatment and universal HBV vaccination programs is expected to decrease the risk for hepatocarcinogenesis substantially. Significant hemosiderosis and hepatic fibrosis are common in patients with TDT despite chelation therapy and have been correlated with HCC development. Thus, iron overload should be monitored with liver iron concentration and ferritin levels, and effective chelation therapy should be applied. In addition, all TDT patients, particularly those with cirrhosis, should be under surveillance every six months with abdominal ultrasound ± alpha-fetoprotein levels, as this combination seems to provide better sensitivity for early HCC detection.

1054. A Randomized Controlled Trial of Hepatitis B virus (HBV) Revaccination among Men Who Have Sex with Men and Were Born in the Era of Universal Neonatal HBV Immunization

BackgroundPeople who have lost anti-HBs antibody decades after neonatal vaccination but are at high risk of acquiring HBV are recommended to undergo HBV revaccination. The optimal revaccination strategy remains unknown, however. We aimed to compare the efficacy of revaccination with standard- (20-μg) vs double-dose (40-μg) of HBV vaccine among men who have sex with men (MSM).MethodsMSM aged ≥ 20 years who had undergone HBV vaccination at birth and tested negative for HBsAg and anti-HBc with anti-HBs titer < 10 mIU/ml were randomized to receive standard- or double-dose HBV vaccine (1:1 ratio with a block size of 4) at weeks 0, 4, and 24. Plasma HIV RNA < 50 copies/ml for ≥ 6 months was required for HIV-positive MSM. The primary endpoint was the proportion of participants achieving anti-HBs ≥ 10 mIU/ml at week 28. The secondary endpoints were high-titer response (≥ 100 mIU/ml) at weeks 28 and 48, serological response at week 48, and adverse events (AE).ResultsFrom Sep 2017 to Jun 2020, 161 HIV-positive and 77 HIV-negative MSM were enrolled. The serological response at week 28 was 86.2% for the standard-dose group and 94.9% for the double-dose group (p=0.070). The proportion of high-titer response was higher for the double-dose group than the standard-dose group at 28 weeks (84.6% vs 70.1%, p=0.041). The respective serological response and high-titer response at week 48 were 81.3% and 58.7% for the standard-dose group vs 94.2% and 78.3% for the double-dose group (p=0.023 and p=0.013, respectively). In generalized estimating equations model, double-dose HBV revaccination (aOR, 1.7; 95% CI, 1.1-2.8) and baseline anti-HBs ≥ 2.5 mIU/ml (aOR, 7.5; 95% CI, 4.3-13.5) were associated with high-titer responses. HIV infection was not associated with serological response (aOR, -1.2; 95%CI, -2.47-1.60) and high-titer response (aOR, -1.1; 95%CI, -1.95-1.49). The double-dose group had a higher rate of local AEs (27.2% vs 38.7%, p=0.118). One (0.8%) severe AE occurred in the double-dose group, which resolved without sequelae.Table 1. Baseline characteristic of participants Table 2. Serological response after revaccination Table 3. GEE model of vaccine efficacy and associated factors ConclusionDouble-dose HBV revaccination results in sustained serological and high-titer responses among MSM who were born in the era of universal neonatal HBV vaccination. Anti-HBs titer ≥ 2.5 mIU/ml at baseline is associated with high-titer response.Disclosures All Authors: No reported disclosures

Hepatitis B Virus Seropositivity Is a Poor Prognostic Factor of Pediatric Hepatocellular Carcinoma: a Population-Based Study in Hong Kong and Singapore.

BackgroundHepatocellular carcinoma (HCC) is a rare hepatic malignancy in children. Hepatitis B virus (HBV) infection is a key predisposing factor in endemic regions but its impact on outcome has not been studied. We aim to evaluate the prognostic implication of HBV seropositivity and role of cancer surveillance in children with HCC from East Asian populations with national HBV vaccination.MethodsReview of population-based databases for patients (< 18 years old) diagnosed with HCC from 1993 to 2017 in two Southeast Asian regions with universal HBV vaccination (instituted since 1988 and 1987 in Hong Kong and Singapore, respectively).ResultsThirty-nine patients were identified (Hong Kong, 28; Singapore, 11). Thirty were male; median age at diagnosis was 10.8 years (range, 0.98–16.6). Abdominal pain was the commonest presentation while five patients were diagnosed through surveillance for underlying condition. Alpha-fetoprotein was raised in 36 patients (mean, 500,598 ng/ml). Nineteen had bilobar involvement, among the patients in whom pretreatment extent of disease (PRETEXT) staging could retrospectively be assigned, 3 had stage I, 13 had stage II, 4 had stage III, and 11 had stage IV disease. Seventeen had distant metastasis. HBsAg was positive in 19 of 38 patients. Two patients had fibrolamellar HCC. Upfront management involved tumor resection in 16 (liver transplantation, 2), systemic chemotherapy in 21, interventional procedures in 6 [transarterial chemoembolization (TACE), 5, radiofrequency ablation (RFA), 1], and radiotherapy in 4 (selective internal radiation, 3, external beam radiation, 1). Five-year event-free survival (EFS) and overall survival (OS) were 15.4 ± 6.0 and 26.1 ± 7.2%, respectively. Patient’s HBsAg positivity, metastatic disease and inability to undergo definitive resection represent poor prognostic factors in univariate and multivariable analyses. Patients diagnosed by surveillance had significantly better outcome.ConclusionPediatric HCC has poor outcome. HBV status remains relevant in the era of universal HBV vaccination. HBV carrier has inferior outcome and use of surveillance may mitigate disease course.