Hepatitis B Virus Core Research Articles

Novel function of SART1 in HNF4α transcriptional regulation contributes to its antiviral role during HBV infection

Our understanding of the interactions between HBV and its host cells is still quite limited. Spliceosome associated factor 1 (SART1) has recently been found to restrict HCV. Thus, we aimed to dissect its role in HBV infection. SART1 was knocked down by RNA interference and over-expressed by lentiviral or adeno-associated virus (AAV) vectors in HBV-infected cell cultures and invivo in HBV-infected mice. Luciferase reporter assays were used to determine viral or host factor promoter activities, and chromatin immunoprecipitation (ChIP) was used to investigate protein-DNA interactions. In HBV-infected cell cultures, downregulation of SART1 did not affect covalently closed circular HBV DNA but resulted in markedly enhanced HBV RNA, antigen expression and progeny virus production. On the other hand, HBV transcription and replication were significantly inhibited by overexpression of SART1. Similar results were observed in AAV-HBV-infected mice persistently replicating HBV. Inhibition of Janus kinases had no effect on SART1-mediated inhibition of HBV replication. HBV promoter assays revealed that SART1 reduced HBV core promoter activity. By screening known HBV transcription factors, we found that SART1 specifically suppressed the expression of hepatocyte nuclear factor 4α (HNF4α). Luciferase reporter and ChIP assays demonstrated a direct downregulation of HNF4α expression by association of SART1 with the HNF4α proximal P1 promoter element. We identify SART1 as a novel host factor suppressing HBV cccDNA transcription. Besides its effect on interferon-stimulated genes, SART1 exerts an anti-HBV activity by suppressing HNF4α expression, which is essential for transcription of HBV cccDNA. Hepatitis B virus (HBV) infects hepatocytes and persists in the form of covalently closed circular DNA (cccDNA), which remains a major obstacle to successful antiviral treatment. In this study, using various HBV models, we demonstrate that the protein SART1 restricts HBV cccDNA transcription by suppressing a key transcription factor, HNF4α.

Cross-sectional hospital-based study on the seroprevalence of hepatitis B virus markers among healthcare workers, NWR, Cameroon

BackgroundHepatitis B virus (HBV) infection is a major public health issue worldwide, with about 257 million people reported to be chronic carriers by the WHO fact sheet updated in 2018....

Silencing hepatitis B virus covalently closed circular DNA: The potential of an epigenetic therapy approach.

Global prophylactic vaccination programmes have helped to curb new hepatitis B virus (HBV) infections. However, it is estimated that nearly 300 million people are chronically infected and have a high risk of developing hepatocellular carcinoma. As such, HBV remains a serious health priority and the development of novel curative therapeutics is urgently needed. Chronic HBV infection has been attributed to the persistence of the covalently closed circular DNA (cccDNA) which establishes itself as a minichromosome in the nucleus of hepatocytes. As the viral transcription intermediate, the cccDNA is responsible for producing new virions and perpetuating infection. HBV is dependent on various host factors for cccDNA formation and the minichromosome is amenable to epigenetic modifications. Two HBV proteins, X (HBx) and core (HBc) promote viral replication by modulating the cccDNA epigenome and regulating host cell responses. This includes viral and host gene expression, chromatin remodeling, DNA methylation, the antiviral immune response, apoptosis, and ubiquitination. Elimination of the cccDNA minichromosome would result in a sterilizing cure; however, this may be difficult to achieve. Epigenetic therapies could permanently silence the cccDNA minichromosome and promote a functional cure. This review explores the cccDNA epigenome, how host and viral factors influence transcription, and the recent epigenetic therapies and epigenome engineering approaches that have been described.

Cango Lyec (Healing the Elephant): Chronic Hepatitis B Virus among post-conflict affected populations living in mid-Northern Uganda.

BackgroundThe legacy of war in Northern Uganda continues to impact people’s health and wellbeing in the Acholi region. Despite increasing attention to Hepatitis B Virus (HBV) in Uganda and globally, concerns remain that unique drivers of infection, and barriers to screening, and treatment, persist among those affected by conflict.MethodsCango Lyec (Healing the Elephant) cohort survey involved conflict-affected adults aged 13–49 in three mid-Northern Uganda districts (Gulu, Amuru and Nwoya). Baseline (2011–2012) samples were tested for HBV surface antigen (HBsAg), HBV e-antigen (HBeAg), antibodies to HBV surface antigen (HBsAb), antibodies to HBV e-antigen (HBeAb), and antibodies to HBV core antigen (HBcAb). All HBsAg positive samples were tested for IgM antibodies to HBV B core antigen (HBc-IgM) and where available, >6-month follow-up samples were tested for HBeAg and HBV DNA. Data were analyzed using STATA 15 software. Logistic regression accounted for variance due to complex two-stage sampling that included stratification, unequal selection probabilities and community clustering. Odds ratios measured effect potential risk factors associated with chronic HBV infection.ResultsAmong 2,421 participants, 45.7% were still susceptible to HBV infection. HBsAg seropositivity was 11.9% (10.9–13.0), chronic HBV was 11.6% (10.4–12.8), acquired immunity resulting from vaccination was 10.9%, and prior natural infection was 31.5%. Older age (OR:0.570; 95%CI:0.368–0.883) and higher education (OR:0.598; 95%CI:0.412–0.868) were associated with reduced odds of chronic HBV infection. Being male (OR:1.639; 95%CI:1.007–2.669) and having been abducted (OR:1.461; 95%CI:1.055–2.023) were associated with increased odds of infection. Among women, having 1 or 2 pregnancies (compared to none or >2) was associated with increased odds of infection (OR:1.764; 95%CI:1.009–3.084).ConclusionChronic HBV is endemic in Gulu, Amuru and Nwoya districts. Recommended strategies to reduce post-conflict prevalence include establishment of Northern Uganda Liver Wellness Centres, integration of screening and treatment into antenatal care, and roll out of birth-dose vaccination.

Ultrasmall Copper (I) Sulfide Nanoparticles Prevent Hepatitis B Virus Infection

AbstractHepatitis B virus (HBV) poses a severe threat to public health and social development. Here, we synthesized 4±0.5 nm copper (I) sulfide (Cu2S) nanoparticles (NPs) with 46 mdeg chiroptical property at 530 nm to selectively cleavage HBV core antigen (HBcAg) and effectively blocked HBV assembly and prevented HBV infection both in vitro and in vivo under light at 808 nm. Experimental analysis showed that the chiral Cu2S NPs specific bound with the functional domain from phenylalanine23 (F23) to leucine30 (L30) from HBcAg primary sequence and the cutting site was between amino acid residues F24 and proline25 (P25). Under excitation at 808 nm, the intracellular HBcAg concentration was reduced by 95 %, and in HBV transgenic mice, the levels of HBV surface antigen (HBsAg) and HBV DNA were decreased by 93 % and 86 %, respectively. Together, these results reveal the potential nanomedicine for HBV control and provide fresh tools for viral infection.

Ultrasmall Copper (I) Sulfide Nanoparticles Prevent Hepatitis B Virus Infection

AbstractHepatitis B virus (HBV) poses a severe threat to public health and social development. Here, we synthesized 4±0.5 nm copper (I) sulfide (Cu2S) nanoparticles (NPs) with 46 mdeg chiroptical property at 530 nm to selectively cleavage HBV core antigen (HBcAg) and effectively blocked HBV assembly and prevented HBV infection both in vitro and in vivo under light at 808 nm. Experimental analysis showed that the chiral Cu2S NPs specific bound with the functional domain from phenylalanine23 (F23) to leucine30 (L30) from HBcAg primary sequence and the cutting site was between amino acid residues F24 and proline25 (P25). Under excitation at 808 nm, the intracellular HBcAg concentration was reduced by 95 %, and in HBV transgenic mice, the levels of HBV surface antigen (HBsAg) and HBV DNA were decreased by 93 % and 86 %, respectively. Together, these results reveal the potential nanomedicine for HBV control and provide fresh tools for viral infection.

A novel therapeutic HBV vaccine candidate induces strong polyfunctional cytotoxic T cell responses in mice

Background & AimsCurrent standard-of-care suppresses HBV replication, but does not lead to a functional cure. Treatment aiming to cure chronic hepatitis B (CHB) is believed to require the induction of strong cellular immune responses, such as by therapeutic vaccination.MethodsWe designed a therapeutic HBV vaccine candidate (YF17D/HBc-C) using yellow fever vaccine YF17D as a live-attenuated vector to express HBV core antigen (HBc). Its ability to induce potent cellular immune responses was assessed in a mouse model that supports flavivirus replication.ResultsFollowing a HBc protein prime, a booster of YF17D/HBc-C was found to induce vigorous cytotoxic T cell responses. In a direct head-to-head comparison, these HBc-specific responses exceeded those elicited by adenovirus-vectored HBc. Target-specific T cells were not only more abundant, but also showed a higher degree of polyfunctionality, with HBc-specific CD8+ T cells producing interferon γ and tumour necrosis factor α in addition to granzyme B. This immune phenotype translated into a superior cytotoxic effector activity toward HBc-positive cells in YF17D/HBc-C vaccinated animals in vivo.ConclusionsThe results presented here show the potential of YF17D/HBc-C as a vaccine candidate to treat CHB, and warrant follow-up studies in preclinical animal models of HBV persistence in which other candidate vaccines have been unable to achieve a sustained virologic response.Lay summaryResolution of CHB requires the induction of strong cellular immune responses. We used the yellow fever vaccine as a vector for HBV antigens and show that it is capable of inducing high levels of HBV-specific T cells that produce multiple cytokines simultaneously and are cytotoxic in vivo.

Prevalence study of different methods for hepatitis B virus diagnosis with blood donor people in Baghdad city

Background: Globally, infecting with hepatitis B virus (HBV) is a big issue today. The present study was aimed to assess the prevalence and year-wise trend of the HBV surfaces antigens (HBs-Ag), antibodies vs. HBV core antigens (anti-HBcs) while HBV-DNA in serum sample patients and replacement blood donors in Baghdad, Iraq. Methods: During the period between 2017 and 2019, a total of 212 blood donors of ages 18–70 years were screened for HBs-Ag, anti-HBs by enzyme-linked immunosorbent assay (ELISA) technique, and anti-HBc antigen–antibody (Ag–Ab) and HBV-DNA using real-time PCR. Results: A total of 110 (51.8%) of 212 blood donors were positive to all tests: HBs-Ag, anti-Hbs, anti-HBc and HBV-DNA. Forty-six (41.8%) were positive for HBV-DNA, HBs-Ag and anti-HBc, whereas 14 (12.7%) were positive for HBs-Ag and anti-HBc. Although nine (8.1%) blood donors were positive in real-time PCR (HBV-DNA loaded) with a negative result in ELISA. Forty one (37.2%) markers indicated a high number of inveterate or resolvable contagion. The total diffusion increment significance in 2017–2018, stabilized thereafter and started decreasing from 2018 to 2019 marginally. There is a high significance variance at (P < 0.01) while comparison among examined groups. Conclusions: Significance and impact of study: the prevalence of HBV infection in 3 years is lower in Baghdad blood donors (51.8%) compared to other regions of Iraq. A high number of infections with no signs of HBs-Ag or viral DNA were recorded. Therefore, the inclusion of anti-HBc seromarker and DNA in the routine screening could isolate potential infectious blood units.

Development of a cellular high-content, immunofluorescent HBV core assay to identify novel capsid assembly modulators that induce the formation of aberrant HBV core structures

Hepatitis B Virus (HBV) core protein has multiple functions in the viral life cycle and is an attractive target for new anti-viral therapies. Capsid assembly modulators (CAMs) target the core protein and induce the formation of either morphologically normal (CAM-N) or aberrant structures (CAM-A), both devoid of genomic material. To date a diverse family of CAM-N chemotypes has been identified, but in contrast, described CAM-As are based on the heteroaryldihydropyrimidine (HAP) scaffold. We used the HBV-inducible HepG2.117 cell line with immunofluorescent labeling of HBV core to develop and validate a cellular high-content image-based assay where aggregated core structures are identified using image analysis spot texture features. Treatment with HAPs led to a dose- and time-dependent formation of aggregated core appearing as dot-like structures in the cytoplasm and nucleus. By combining a biochemical and cellular screening approach, a compound was identified as a novel non-HAP scaffold able to induce dose-dependent formation of aberrant core structures, which was confirmed by electron microscopy and native gel electrophoresis. This compound displayed anti-HBV activity in HepG2.117 cells, providing proof-of-concept for our screening approach. We believe our combined biochemical and cellular high-content screening method will aid in expanding the range of CAM-A chemotypes.

Hepatitis B Virus Infection and Heart Transplantation Outcomes: An Analysis of the ISHLT Registry Data

<h3>Purpose</h3> Hepatitis C Virus is no longer a contraindication to heart transplant (HT) thanks to curative antiviral therapy. Despite the advent of anti-Hepatitis B Virus (HBV) agents, a cure is less likely. While routine antiviral prophylaxis for resolved/inactive HBV infection is not recommended, the risk of reactivation in immunosuppressed HT recipients is unknown. We studied whether new antivirals have resulted in a higher number of recipients with history of HBV infection and examined their outcomes. <h3>Methods</h3> We performed a retrospective analysis of adult HT recipients transplanted in 1996-2018 who had HBV data reported in the ISHLT Registry. Chronic HBV (c-HBV) infection at HT was defined by a positive HBV surface antigen (HBsAg), resolved/inactive infection (r-HBV) by negative HBsAg and positive HBV core antibody, and HBV negative patients by negative serology. We examined 5-year freedom from chronic liver disease (CLD) and survival. <h3>Results</h3> Among 40,774 recipients, there were 580 with c-HBV and 1,509 with r-HBV. The proportion of patients with history of HBV has doubled from ∼3% to ∼6% (p<0.05) following approval of new antivirals in 2002. Freedom from CLD after HT was lower for c-HBV and r-HBV patients (p<0.001), and this difference remained after multivariable adjustment (Figure 1A). r-HBV was associated with slightly higher mortality in univariate and multivariable analyses (Figure 1B). The overall risk of mortality was lower in the 2003-2018 vs 1996-2002 era. The improvement in survival was similar in patients with HBV history compared to HBV negative patients. <h3>Conclusion</h3> Approximately 6% of recent HT recipients have history of HBV infection and these patients have a higher risk of developing CLD after transplant. While survival in these patients is favorable, we identified a small excess in mortality in r-HBV patients. Whether the adverse events seen are a result of the sequelae of HBV infection or are due to HBV reactivation that could be mitigated by antiviral prophylaxis should be further studied.

A novel cell culture model reveals the viral interference during hepatitis B and C virus coinfection

Coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) may result in severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that HBV replication is suppressed by replicating HCV and often rebounds after treatment with drugs against HCV. Thus, a highly efficient cell culture system permissive for HBV/HCV would facilitate investigation on the interaction and pathogenesis after coinfection. Here we reported a robust HBV/HCV coinfection cell culture model by overexpressing human sodium-taurocholate cotransporting polypeptide (NTCP), CD81 and Mir122 into HepG2 cells and investigated interactions between HBV and HCV. In this system, HepG2-NTCP/CD81/Mir122 cells not only supported robust infection and replication of HBV and HCV, but also allowed HBV/HCV coinfection in the single cell level. Our result showed cells with replicating HBV still supported HCV infection. However, HBV replication was suppressed by HCV through the inhibition of HBV core promoter and S promoter II activity, and this inhibition was attenuated by the interferon alpha (IFNα) treatment, suggesting HCV influence on HBV at transcriptional level. Coinfection of HBV/HCV in this system did not block IFN stimulated genes expression. Inhibition of HCV by direct-acting antiviral drugs restored HBV replication and expression of viral genes. Conclusions: HepG2-NTCP/CD81/Mir122 fully supports HBV/HCV coinfection, replication and interaction. This novel cell model offers a platform to advance our understanding of the molecular details of the interaction, pathogenesis and outcomes of HBV/HCV coinfection.

Occult and active hepatitis B virus detection in donated blood in São Paulo, Brazil.

The present study determined the HBV antigen, antibody, and DNA status in blood donations deemed to be HBV positive. Individuals with an occult HBV infection (OBI), defined as being positive for HBV DNA but negative for HBV surface antigen (HBsAg), as well as those with active infection (HBsAg-positive), were identified and characterized. From a total pool if 198,363 blood donations, we evaluated in a cross-sectional study, 1106 samples that were positive in screening tests for antibody to HBV core antigen (HBcAb), HBsAg, and/or HBV DNA by nucleic acid testing (NAT-HBV). The presence of genetic variants in the HBV pol/S gene in individuals with an active HBV infection was also determined. OBIs were detected in six of 976 samples (0.6%) that were positive only for HBcAb. The rate of HBV active infection was 0.024% (48/198,363) and there was a predominance of HBV sub-genotype A1 (62.2%, 28/45), followed by D3 (17.8%, 8/45). Mutations in the S gene were found in 57.8% (26/45) and immune escape mutations in 37.8% (17/45) of active HBV-infected donors. Among them, T123N, G145A, and D144G high-impact immune escape mutations were identified. Highly sensitive molecular tests improve the capacity to detect OBIs. When NAT is performed in pooled samples, HBcAb test has value in the detection of donors with OBI and improves transfusion safety. Mutations in the S gene are frequent in HBsAg-positive blood, including those associated with diagnostic failure and vaccine escape mutations.

Generation of an HBV core phenotyping assay for evaluating HBV capsid compounds

Hepatitis B virus (HBV) capsids are assembled from HBV core protein and assembly is a critical step in the propagation of the virus. Due to its multiple functions in the viral life cycle, core is an attractive target for new antiviral therapies. For HBV capsid assembly modulators (CAMs), several resistance mutants have been identified, both from the clinic and in vitro. However, currently there is no convenient in vitro assay to monitor resistance to CAMs in the clinic. Here, we developed a facile, cassette-based phenotyping assay to assess the antiviral activity of CAMs on a panel of clinical isolates. Using this system, the core genes from 13 patients infected with HBV genotypes A–H were expressed as chimeric virus and tested for sensitivity to CAMs. No substantial differences in antiviral activity were observed across genotypes due to the conservation of the drug binding pocket. In addition, we tested a panel of constructs encoding 13 single amino acid polymorphs in the CAM binding site, including some polymorphs with previously-described resistance to CAMs. Overall, 11 of 13 constructs replicated in vitro, 6 constructs showed reduced susceptibility to CAMs. The 11 polymorphs which could replicate in vitro remained sensitive to the nucleotide analog tenofovir alafenamide (TAF), indicating that there is no cross-resistance.

A 2020 update on the progress of treatment and new drug clinical trials for hepatitis B

Long term antiviral therapy with nucleos(ti)ide analogues could suppress HBV viral load thereby prevent the progression to cirrhosis and hepatocellular carcinoma. Interferon-based therapy could result in sustained virological response in a fair proportion of patients and even HBsAg loss in a small proportion of them. Novel therapies aiming at functional cure (loss of HBsAg) are under active development. Among the categories of many, HBV core protein inhibitors are safe and could suppress the HBV DNA and HBV RNA, but only with modest effect on the level of HBsAg; silencing of HBV mRNA by siRNA or antisense oligonucleotides could produce meaningful and sustainable declining in HBsAg levels; immune modulators with different mode of action showed modest effect on the reduction of HBsAg, but with noticeable adverse event (especially transaminase flares) related to the mode of action. Novel clinical trial design on the combination or sequential use of innovative molecules will ultimately lead to the functional cure of CHB in the near future.

Identification of a new class of HBV capsid assembly modulator

The HBV core protein is a druggable target of interest due to the multiple essential functions in the HBV life cycle to enable chronic HBV infection. The core protein oligomerizes to form the viral capsid, and modulation of the HBV capsid assembly has shown efficacy in clinical trials. Herein is described the identification and hit to lead SAR of a novel series of pyrazolo piperidine HBV capsid assembly modulators.

Seroprevalence of hepatitis B virus infection markers among children in Ukraine, 2017

BackgroundBefore hepatitis B vaccine (HepB) introduction, level of endemicity of hepatitis B virus (HBV) in Ukraine was estimated as intermediate but the prevalence of HBV infection markers has not been measured in population-based serosurveys. Coverage with 3 doses of HepB, introduced in 2002, was 92%-98% during 2004–2007 but declined to 21%-48% during 2010–2016. To obtain data on HBV prevalence among children born after HepB introduction, we tested specimens from a serosurvey conducted in Ukraine in 2017, following circulating vaccine-derived poliovirus outbreak in 2015, among birth cohorts eligible for polio immunization response. MethodsThe serosurvey was conducted in Zakarpattya, Sumy, and Odessa provinces, and Kyiv City, targeting 2006–2015 birth cohorts. One-stage cluster sampling in the provinces and stratified simple random sampling in Kyiv were used for participant selection. All participants were tested for antibodies against HBV core antigen (anti-HBc). Anti-HBc-positive children were tested for HBV surface antigen (HBsAg). We also obtained information on HepB vaccination status for all children. ResultsOf 4,596 children tested, 81 (1.8%) were anti-HBc-positive and eight (0.2%) were HBsAg-positive. HBsAg prevalence was 0.7% (95% confidence interval, 0.3%-1.4%) in Zakarpattya, 0.1% (0.0%-0.4%) in Sumy, 0% (0.0%-03%) in Odessa, and 0.1% (0.0%-0.8%) in Kyiv. Across survey sites, the proportion of recipients of ≥ 3 HepB doses was 53%-80% in the 2006–2009 cohort and 28%-59% in the 2010–2015 cohort. ConclusionHBV prevalence among children in surveyed regions of Ukraine in 2017 was low, including in Zakarpattya—the only site above the 0.5% European Regional target for HBsAg seroprevalence. However, HepB vaccination was suboptimal, particularly among children born after 2009, resulting in large numbers of unvaccinated or incompletely vaccinated children at risk of future HBV infection. HepB coverage should be increased to further reduce HBV transmission among children in Ukraine and achieve regional and global hepatitis B control/elimination targets.

The current status of virus-positive liver transplantation.

The last 2 years have seen significant developments in virus-positive liver transplantation. This review provides an updated account of the transplantation of hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV-positive livers, with a specific focus on studies published in the last 18 months. The advent of highly efficacious direct acting antiviral agents, nucleos(t)ide analogues and a continued organ shortage have led to the well tolerated utilization of HCV, HBV and HIV-positive organs. There has been a significant increase in the transplantation of HCV seropositive and NAT+ organs into HCV-negative recipients, without compromising patient or graft survival. Early reports of HBV core antibody (HBVcAb), HBV surface antigen (HBVsAg) positive and NAT+ donors are growing in the USA with promising results. Similarly, small studies have described the use of HIV-positive to HIV-positive liver transplantation without concerns for superinfection. HCV, HBV and HIV-positive liver transplantations can be accomplished safely and are associated with equivalent outcomes when paired with appropriate recipients. The practice of virus positive liver transplantation should be encouraged to combat the ongoing organ shortage.

HBV Core Protein Is in Flux between Cytoplasmic, Nuclear, and Nucleolar Compartments.

ABSTRACTHepatitis B virus (HBV) core protein (Cp) can be found in the nucleus and cytoplasm of infected hepatocytes; however, it preferentially segregates to a specific compartment correlating with disease status. Regulation of this intracellular partitioning of Cp remains obscure. In this paper, we report that cellular compartments are filled and vacated by Cp in a time- and concentration-dependent manner in both transfections and infections. At early times after transfection, Cp, in a dimeric state, preferentially localizes to the nucleolus. Later, the nucleolar compartment is emptied and Cp progresses to being predominantly nuclear, with a large fraction of the protein in an assembled state. Nuclear localization is followed by cell-wide distribution, and then Cp becomes exclusively cytoplasmic. The same trend in Cp movement is seen during an infection. Putative nucleolar retention signals have been identified and appear to be structure dependent. Export of Cp from the nucleus involves the CRM1 exportin. Time-dependent flux can be recapitulated by modifying Cp concentration, suggesting transitions are regulated by reaching a threshold concentration.

Coverage with Timely Administered Vaccination against Hepatitis B Virus and Its Influence on the Prevalence of HBV Infection in the Regions of Different Endemicity.

Universal hepatitis B vaccination of newborns was implemented in Russia starting from 1998. From 1998 to 2019, the incidence of acute hepatitis B reduced from 43.8 to 0.57 cases per 100,000 population. Here, we assessed the timely coverage of newborns with the birth dose (HepB-BD), second dose (HepB-2nd), and three vaccine doses (HepB3) in two remote regions of Russia with low (Belgorod Oblast) and high (Yakutia) levels of hepatitis B virus (HBV) endemicity. Vaccination data were obtained from the medical records of 1000 children in Yakutia and 2182 children in Belgorod Oblast. Sera of healthy volunteers from Belgorod Oblast (n = 1754) and Yakutia (n = 1072) across all age groups were tested for serological markers of HBV to assess the infection prevalence and herd immunity. Average HepB-BD coverage was 99.2% in Yakutia and 89.4% in Belgorod Oblast (p < 0.0001) and in both regions varied significantly, from 66% to 100%, between medical centers. The principal reason for the absence of HepB-BD was parent refusal, which accounted for 63.5% of cases of non-vaccination (83/123). While timely HepB-2nd coverage was only 55.4%–64.7%: HepB3 coverage by the age of one year exceeded 90% in both study regions. HBV surface antigen (HBsAg) prevalence in the 1998–2019 birth cohort was 0.2% (95% CI: 0.01–1.3%) in Belgorod Oblast and 3.2% (95% CI: 1.9–5.2%) in Yakutia. The proportion of persons testing negative for both antibodies to HBsAg (anti-HBs) and antibodies to HBV core antigen (anti-HBc) in the 1998–2019 birth cohort was 26.2% (125/481) in Belgorod Oblast and 32.3% (162/501) in Yakutia. We also assessed the knowledge of and attitude towards vaccination among 782 students and teachers of both medical and non-medical specialties from Belgorod State University. Only 60% of medical students knew that hepatitis B is a vaccine-preventable disease. Both medical and nonmedical students, 37.8% and 31.3%, respectively, expressed concerns about safety and actual necessity of vaccination. These data indicate the need to introduce a vaccine delivery audit system, improve medical education with respect to vaccination strategies and policies, and reinforce public knowledge on the benefits of vaccination.

1055. Assessing the Impact of the Routine Childhood Hepatitis B Immunization and the Need for Hepatitis B Vaccine Birth Dose in Sierra Leone, 2018

BackgroundAll African countries recommend 3 doses of hepatitis B vaccine (HepB3), most at 6, 10, and 14 weeks of age, but few recommend a HepB birth dose (HepB-BD). To evaluate the role of mother to child transmission (MTCT) of hepatitis B virus (HBV) with the 3 dose HepB schedule, we conducted a serosurvey in Sierra Leone among 4–30 month old children and their mothers, and 5–9 year old children.MethodsWe conducted a multi-stage cluster survey in 3 districts. Enumeration areas (EA) were selected by probability proportional to size, followed by random selection of eligible households to identify 1901 children per age group. We tested all participants for HBV surface antigen (HBsAg) by rapid test and collected children’s HepB vaccination history. Serum from all HBsAg+ mothers and 1 HBsAg- mother per EA was tested for total antibodies to HBV core antigen (anti-HBc), HBsAg, HBV e antigen (HBeAg), and HBV DNA. We assessed the association of HBsAg prevalence with HepB vaccination and maternal HBV markers.ResultsAmong 1889 children aged 4–30 months, 20 (1.3%; 95% CI:0.8%–2.0%) were HBsAg+; HepB3 coverage was 85%. Among 2025 children aged 5–9 years, 32 (1.6%; 95% CI:1.1%–2.3%) were HBsAg+; HepB3 coverage was 77%. Of HBsAg+ children, 70% (14/20) of younger and 56% (18/32) of older children received HepB3. Among 1776 mothers of younger children, 169 (9.8%; 95% CI:8.1%–11.7%) were HBsAg+. HBsAg prevalence for children with HBsAg+ mothers was 5.9% (10/169) and 0.7% (6/1605) for those with HBsAg- mothers (adjusted OR=10.6 [95% CI:2.8–40.8]). Of 139 HBsAg+ mothers, 13 (9%) were HBeAg+ and 126 (91%) had detectable HBV DNA. Maternal HBsAg (p=0.026), HBeAg (p< 0.001), and HBV DNA levels ≥ 200,000 IU/mL (p< 0.001) were associated with HBsAg positivity in younger children (Table 1).Table 1: Association of maternal HBV serological and molecular markers with HBsAg positivity in 4–30-month old children — Sierra Leone hepatitis B serosurvey, 2018 ConclusionHBsAg prevalence was much lower among children than among mothers, for whom HepB would not have been available, indicating that routine infant HepB vaccination has substantially lowered HBV burden. Increasing HepB3 coverage could further reduce HBsAg prevalence among children. As HBsAg positivity in young children was strongly associated with having a mother with active HBV infection and > 50% of HBsAg+ children received HepB3, HepB-BD is needed to prevent MTCT of HBV and chronic HBV infections in children.Disclosures All Authors: No reported disclosures