Impact of Hepatitis B Surface and Core Antibody Levels on Hepatitis B Virus Reactivation.

Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody (HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90-3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.

Comparison of the effectiveness four years after Homo/Hetero prime-boost with 10 µg HP and 20 µg CHO recombinant hepatitis B vaccine at 1 and 6 months in maternal HBsAg-negative children.

Introduction: Limited data were available on the effectivenessfour years after Homo or Hetero prime-boost with 10 µg Hansenulapolymorpha recombinant hepatitis B vaccine (HepB-HP) and 20 µgChinese hamster ovary cell HepB (HepB-CHO). Methods: A crosssectional study was performed in maternalhepatitis B surface antigen (HBsAg)-negative children whoreceived one dose of 10 µg HepB-HP at birth, Homo or Heteroprime-boost with 10 µg HepB-HP and 20 µg HepB-CHO at 1 and 6months. HBsAg and hepatitis B surface antibody (anti-HBs) fouryears after immunization were quantitatively detected by achemiluminescent microparticle immunoassay (CMIA). Results: A total of 359 children were included; 119 childrenreceived two doses of 10 µg HepB-HP and 120 children receivedtwo doses of 20 µg HepB-CHO, called Homo prime-boost; 120children received Hetero prime-boost with 10 µg HepB-HP and 20µg HepB-CHO. All children were HBsAg negative. The geometricmean concentration (GMC) and overall seropositivity rate (SPR) ofanti-HBs were 59.47 (95%CI: 49.00 - 72.16) mIU/ml and 85.51%(307/359). Nearly 15% of the study subjects had an anti-HBsconcentration < 10 mIU/ml and 5.01% had an anti-HBsconcentration ≤ 2.5 mIU/ml. The GMC of the 20 µg CHO Homoprime-boost group [76.05 (95%CI: 54.97 - 105.19) mIU/ml] washigher than that of the 10 µg HP Homo group [45.86 (95%CI:31.94 - 65.84) mIU/ml] (p = 0.035). The GMCs of the Heteroprime-boost groups (10 µg HP-20 µg CHO and 20 µg CHO-10 µgHP) were 75.86 (95% CI: 48.98 - 107.15) mIU/ml and 43.65(95%CI: 27.54 - 69.18) mIU/ml, respectively (p = 0.041). Aftercontrolling for sex influence, the SPR of the 20 µg CHO Homoprime-boost group was 2.087 times than that of the 10 µg HPHomo group. Discussion: The HepB booster was not necessary in the generalchildren, Homo/Hetero prime-boost with 20 µg HepB-CHO wouldincrease the anti-HBs concentration four years after immunization,timely testing and improved knowledge about the self-pay vaccinewould be good for controlling hepatitis B.

The lack of HBsAg secretion does neither facilitate induction of antiviral T cell responses nor Hepatitis B Virus clearance in mice.

Immune tolerance to the hepatitis B virus (HBV) is crucial for developing chronic hepatitis B, and the HBV surface antigen (HBsAg) produced and secreted in high amounts is regarded as a key contributor. HBsAg is expressed in HBV-infected hepatocytes and those carrying an HBV integration. Whether either HBsAg secretion or the high antigen amount expressed in the liver determines its immunomodulatory properties, however, remains unclear. We, therefore, developed a novel HBV animal model that allowed us to study the role of secreted HBsAg. We introduced a previously described HBs mutation, C65S, abolishing HBsAg secretion into a replication-competent 1.3-overlength HBV genome and used adeno-associated virus vectors to deliver it to the mouse liver. The AAV-HBV established a carrier state of wildtype and C65S mutant HBV, respectively. We investigated antiviral B- and T-cell immunity in the HBV-carrier mice after therapeutic vaccination. Moreover, we compared the effect of a lacking HBsAg secretion with that of an antiviral siRNA. While missing HBsAg secretion allowed for higher levels of detectable anti-HBs antibodies after therapeutic vaccination, it did neither affect antiviral T-cell responses nor intrahepatic HBV gene expression, irrespective of the starting level. A treatment with HBV siRNA restricting viral antigen expression within hepatocytes, however, improved the antiviral efficacy of therapeutic vaccination, irrespective of the ability of HBV to secrete HBsAg. Our data indicate that clearing HBsAg from blood cannot significantly impact HBV persistence or T-cell immunity. This indicates that a restriction of hepatic viral antigen expression will be required to break HBV immunotolerance.

Current and future use of antibody-based passive immunity to prevent or control HBV/HDV infections.

With the increasing momentum and success of monoclonal antibody therapy in conventional medical practices, there is a revived emphasis on the development of monoclonal antibodies targeting the hepatitis B surface antigen (anti-HBs) for the treatment of chronic hepatitis B (HBV) and hepatitis D (HDV). Combination therapies of anti-HBs monoclonal antibodies, and novel anti-HBV compounds and immunomodulatory drugs presenting a promising avenue to enhanced therapeutic outcomes in HBV/HDV cure regimens. In this review, we will cover the role of antibodies in the protection and clearance of HBV infection, the association of anti-HBV surface antigen antibodies (anti-HBs) in protection against HBV and how antibody effector functions, beyond neutralization, are likely necessary. Lastly, we will review clinical data from previous and ongoing clinical trials of passive antibody therapy to provide a state-of-the-are perspective on passive antibody therapies in combinations with additional novel agents.

Hepatitis B and C infections among Japanese dental health workers: Insights from vaccination rates and screening results in the Oita prefecture.

OBJECTIVE: This study examined the hepatitis B virus (HBV) and hepatitis C virus (HCV) infection rates and vaccination rates for hepatitis B (HB) among dental healthcare workers (DHCWs) in the Oita prefecture, Japan. METHODS: Hepatitis virus testing was conducted on 1920 participants (486 dentists and 1434 dental staff). Anonymous data on age, gender, occupation, hepatitis B surface antigen (HBsAg), antibodies to hepatitis B surface antigen (anti-HBs), antibodies to HCV (anti-HCV), history of HB vaccination, and antiviral treatment for individuals with positive anti-HCV were collected. RESULTS: The positivity rates for HBsAg, anti-HBs, and anti-HCV were 0.5%, 39.7%, and 0.6%, respectively. Dentists had significantly higher rates of anti-HBs positivity (53.9% vs. 34.9%; p < .0001) and anti-HCV positivity (1.4% vs. 0.3%; p = .0080) compared to dental staff. The vaccination and non-vaccination rates among 1395 with a known HB vaccination history were 59.1% and 40.9%, respectively. Dentists had a significantly higher HB vaccine vaccination rate than the dental staff (73.6% vs. 54.0%; p < .0001). Those in the vaccination group were younger (p < .0001), had a higher proportion of males (p = .0022) and dentists (p < .0001), a lower HBsAg positivity rate (p < .0097), and a higher anti-HBs positivity rate (p < .0001) compared to those in the non-vaccination group. The positivity rate of HBsAg and anti-HBs in the unvaccinated group increased with age, with HBsAg positivity reaching 3.8% in the 70s and anti-HBs positivity reaching 40.4% in the 70s and 66.7% in the 80s. CONCLUSIONS: This study highlights the need to raise awareness about hepatitis prevention vaccination, particularly among dental staff, due to differences in HB vaccination rates across occupations. In particular, they indicated that elderly DHCWs may be more vulnerable to HBV infection. Regular monitoring of the vaccination rate and infection risk is crucial.

Seroprevalence Study of Anti-HBs Antibodies in the General Population of Vojvodina, Serbia.

Background and Objectives: Hepatitis B (HB) is a major global health problem and a potentially life-threatening disease caused by the hepatitis B virus (HBV). Also, it is an important cause of morbidity and mortality worldwide. Thanks to serological surveys, testing hepatitis B surface antibodies (anti-HBs) allows for serological assessments of their prevalence. The presence of anti-HBs, which protects against HBV infection, can be attributed to HB vaccination or natural HBV infection. The aim of our study was to evaluate the prevalence of HB surface antibodies (anti-HBs) as an indicator of collective immunity against HBV in the general population of the Autonomous Province of Vojvodina, Serbia. In addition, to distinguish whether anti-HBs were induced by the vaccine or by infection, the presence of antibodies against the hepatitis B core antigen (anti-HBc) was tested among those who were anti-HBs-positive. Materials and Methods: A total of 3467 residual sera samples, collected according to the specifications of the European Sero-Epidemiology Network 2 (ESEN2) study, from April 2015 to March 2016, were screened for the presence of anti-HBs using a chemiluminescence immunoassay. The difference between categorical variables was tested using the chi-square test. Results: Overall, 1870 (53.9%, 95% CI: 52.3-55.6) participants tested positive for anti-HBs. The median age of the study participants was 17 years (IQR 9-35). The anti-HB seroprevalence decreased with age, ranging from 80.7% (95% CI: 78.9-82.4) in the 1-19-year-old group to 16.4% (95% CI: 12.0-20.9) in the ≥60 years' age group. A total of 71 (3.8%, 95% CI: 2.9-4.7) serum samples were also anti-HBc-positive. Higher prevalence, but not statistically significant, was noticed in women (4.1%, 95% CI: 2.8-5.4) compared with men (3.5, 95% CI: 2.4-4.8) (p = 0.542). Also, there was a significant difference across the age groups, where those ≥60 years old had a prevalence of 65.9% (95% CI: 51.9-79.9) and the age category of 1-19-year-olds had just 0.2% (95% CI: 0.0-0.4) (p < 0.001). Conclusions: This study provides a comprehensive assessment of the anti-HBs seroprevalence of the general population in Vojvodina and provides an opportunity to better shape the national preventive strategy related to HBV.

Was antiviral prophylaxis necessary after kidney transplantation utilizing HBcAb+ donors? A systematic review and meta-analysis.

BACKGROUND: Current guidelines lack consensus on whether antiviral prophylaxes should be administered after kidney transplantation from HBcAb+ donors. This systematic review and meta-analysis aimed to evaluate the incidence and risk factors of de novo HBV (DNH) infection, as well as graft and patient survival. METHODS: We searched PubMed, Embase, and the Cochrane Library up to December 31, 2023. We included relevant studies that assessed clinical outcomes following transplantation utilizing HBcAb+ kidneys. Summary measures of effect and 95% confidence intervals (CI) for prevalence, risk factors, as well as graft and patient survival were estimated using random-effects meta-analysis. RESULTS: Thirteen studies were included for the final analysis. The DNH incidence was at 0.36% (9/2516) with low heterogeneity (I2 = 6%). HBsAb+ recipients (OR: 0.78, 95%CI: 0.25-2.38), HBcAb+ recipients (OR: 3.11, 95%CI: 0.91-10.66, P = 0.071), and recipients not receiving any antiviral prophylaxis (OR: 1.26, 95%CI: 0.15-10.58) were not associated with higher DNH risk. Specifically, HBsAb-/HBcAb+ recipients had the highest DNH incidence (4.65%), followed by HBsAb-/HBcAb- (0.49%), HBsAb+/HBcAb- recipients (0.45%), and HBsAb+/HBcAb+ (0%). Furthermore, recipients receiving HBcAb+ kidneys had comparable graft survival (HR: 1.06, 95%CI: 0.94-1.19, P = 0.55) and patient survival (HR:1.16, 95%CI: 0.98-1.38, P = 0.090) compared with recipients receiving HBcAb- kidneys. CONCLUSION: Kidney transplantation utilizing HBcAb+ kidneys contributed to comparable graft and patient survival with an extremely low risk of HBV transmission. Antiviral prophylaxes may only be administered in HBsAb-/HBcAb+ recipients.

Early application of IFNγ mediated the persistence of HBV in an HBV mouse model.

The antiviral activity of interferon gamma (IFNγ) against hepatitis B virus (HBV) was demonstrated both in vivo and in vitro in a previous study. IFNγ can suppress HBV replication by accelerating the decay of replication-competent nucleocapsids of HBV. However, in this study, we found that the direct application of the mouse IFNγ (mIFNγ) expression plasmid to the liver of an HBV hydrodynamic injection (HI) mouse model led to the persistence of HBV, as indicated by sustained HBsAg and HBeAg levels in the serum as well as an increased percentage of the HBsAg positive mice, whereas the level of HBV DNA in the serum and the expression of HBcAg in the liver were inhibited at the early stage after HI. Meanwhile, we found that the productions of both HBcAb and HBsAb were suppressed after the application of mIFNγ. In addition, we found that HBV could be effectively inhibited in mice immunized with HBsAg expression plasmid before the application of mIFNγ. Furthermore, mIFNγ showed antiviral effect and promoted the production of HBsAb when the mice subjected to the core-null HBV plasmid. These results indicate that the application of mIFNγ in the HBV HI mouse model, the mice showed defective HBcAg-specific immunity that impeded the production of HBcAb and HBsAb, finally allowing the persistence of the virus. Moreover, IFNγ-induced negative immune regulatory factors also play an important role in virus persistence.

Occult HBV Infection in Patients Infected by HIV or HCV: Comparison between HBV-DNA and Two Assays for HBsAg.

We investigated the frequency and serological correlates of occult hepatitis B virus infection (OBI) and the potential impact of a highly sensitive assay for HBsAg in subjects infected by human immunodeficiency virus (HIV) or hepatitis C virus (HCV), who are also at risk for hepatitis B virus (HBV) infection, often in an occult form. Samples from 499 patients with HIV, all HBsAg negative and anti-HBc positive, and 137 patients with HCV were tested for HBV-DNA, anti-HBc, anti-HBs, and HBsAg by a conventional and highly sensitive assay. HBV biomarkers were detected in 71.5% of HCV-RNA-positive, with a higher prevalence of cases positive only for anti-HBc in patients with HCV than in those with HIV. HBV-DNA was detectable in 0.6% of HIV-positive and 7.3% of HCV-RNA-positive patients. Among patients with HCV, four were positive for HBsAg and negative for HBV-DNA, bringing the rate of HBV-active infection in this group to 10.2%. Active HBV infection was not related to gender or specific patterns of HBV biomarkers but was higher in HCV patients coinfected by HIV compared to those infected only by HCV. Monitoring patients at high risk for HBV infection and reactivation may require testing for both HBV-DNA and HBsAg.

Overt and occult hepatitis B virus infection detected among chronic kidney disease patients on haemodialysis at a Tertiary Hospital in Ghana.

Hepatitis B virus (HBV) infection is endemic in Ghana and chronic kidney disease patients on haemodialysis are a high-risk group for HBV infection. We determined the prevalence of overt and occult HBV infection among haemodialysis patients at the Korle Bu Teaching Hospital in Ghana. 104 consenting End Stage Renal Disease patients on long-term haemodialysis were recruited for the study and their socio-demographic, clinical and laboratory information were obtained using structured questionnaire. All the participants were tested for the hepatitis B surface antigen (HBsAg). The HBsAg-negative participants were re-tested for hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb) and HBV DNA using chemiluminescence and Roche COBAS Ampli-Prep/TaqMan analyser and real-time polymerase chain reaction. Eight (7.7%) of the total participants were positive for HBsAg. Among the 96 HBsAg-negative participants, 12.5% (12) were HBcAb-positive, 7.3% (7) had detectable HBV DNA (mean = 98.7±53.5 IU/mL) and 40.6% (39) were positive for HBsAb. Five out of the 7 HBV DNA-positive participants were males and only one participant was negative for HBcAb. Seventy-three out of the 96 HBsAg-negative participants were vaccinated and 37 of these vaccinated individuals had significant HBsAb titres (mean = 423.21± 380.72 IU/mL). Our data demonstrated that the prevalence of overt and occult HBV infection among the haemodialysis (HD) patients was 7.7% and 7.3%, respectively, and only 50.7% of those who showed proof of vaccination were protected from HBV infection.

Hepatitis B virus infection on Kwajalein Atoll, Marshall Islands: a seroprevalence, knowledge and attitudes study.

Objective: A study was conducted to determine the seroprevalence of chronic hepatitis B virus (HBV) infection among children and their mothers on Kwajalein Atoll in the Marshall Islands two decades after routine vaccination was introduced in the 1990s. Mothers' knowledge and attitudes towards HBV disease and vaccination were also assessed. Methods: Results of a national seroprevalence survey conducted in 2016-2017 and antenatal records were used to determine the prevalence of HBV seropositivity in children aged 6-8 years and their biological mothers. The associations between demographic, social and vaccination-related factors and seropositivity were explored using Fisher's exact tests. Results: HBV seroprevalence was 0.3% in children and 6.8% in their mothers (during pregnancy). Coverage of timely HBV vaccination was 90.3% for the birth dose and was significantly associated with factors related to place of residence (P < 0.001), place of birth (P < 0.001) and number of antenatal visits (P < 0.001). Maternal attitudes towards infant vaccination and antenatal screening were largely positive (95.8% and 96.7%, respectively) despite low vaccination rates (20.9%) among mothers. Knowledge levels were low for disease complications, treatment and transmission. Discussion: Prevalence of HBV in children and mothers residing on Kwajalein Atoll in 2016-2017 was lower than the national average for the Marshall Islands. Timely birth dose administration appears to have been effective in preventing mother-to-child transmission of HBV in this setting and should be promoted in remote settings where antiviral therapy is not available. Provision of out-of-cold-chain HBV vaccines should be considered to improve access in remote settings.

Analysis of Serum Anti-HBs Levels and HBsAg/HBeAg Markers in Children and Adolescents: A Cross-Sectional Study.

Hepatitis B virus (HBV) is a global public health concern, and China continues to face a high burden of HBV cases. Vaccination plays a critical role in controlling and eradicating HBV. However, studies have shown that some individuals may experience waning immunity over time, highlighting the importance of enhanced immunization strategies. This study aimed to investigate the relationship between age, gender, and anti-HBs antibody levels, as well as the prevalence of serum hepatitis B surface antigen (HBsAg)/HBV e antigen (HBeAg) positivity. This retrospective study included 43,609 pediatric patients who visited the outpatient department between January 2013 and December 2022. Serum biomarkers (HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc) were measured using Roche Cobas 8000. There is a significant difference in anti-HBs titer between genders and across different age groups (p < 0.05). The serological markers HBsAg/HBeAg exhibited the highest positivity rate in the age group of 15-18 years. The findings demonstrate a gradual decrease in anti-HBs levels following HBV vaccination. The prevalence of serum markers HBsAg/HBeAg is higher among adolescents aged 15-18 years, which should be a matter of concern and attention.

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

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

Prevalence of vaccine-derived hepatitis B surface antibodies in children and adolescents in Germany: results from a population-based survey, 2014-2017.

INTRODUCTION: Childhood vaccination against hepatitis B has been recommended in Germany since 1995. WHO defines a primary vaccination series as successful if the initial hepatitis B surface antibody (anti-HBs) level is ≥ 10 IU/L directly after vaccination. Anti-HBs levels vary depending on the number of doses, type of vaccine, and time interval between the last two doses. In 2021, Germany began to recommend three instead of four doses of polyvalent hepatitis-B-containing vaccines. Our aim was to estimate the proportion of vaccinated children in Germany with anti-HBs levels < 10 IU/L, 10-99 IU/L, and ≥ 100 IU/L by number and type of vaccine, and assess if number of doses and compliance with recommended time interval between the last two doses are associated with an anti-HBs level ≥ 10 IU/L when considering type of vaccine and time since last dose. METHODS: We used data from a national cross-sectional study (2014-2017) of children (3-17 years). We excluded participants with unknown vaccination dates, unreadable or incomplete vaccination cards, and hepatitis B virus (HBV)-positive participants. We defined a recommended schedule as a vaccination series with at least six months between the two last doses and having three doses or more. We calculated weighted anti-HBs sero-prevalence for three anti-HBs levels: < 10 IU/L, 10-99 IU/L and ≥ 100 IU/L. We fitted two logistic regression models to examine the relationship between number of doses and recommended schedule on anti-HBs levels (≥ 10 IU/L and ≥ 100 IU/L) considering time since last dose and type of vaccine (Infanrix, Hexavac, Monovalent). RESULTS: We included 2,489 participants. The weighted proportion of vaccinated children per anti-HBs level was < 10 IU/L: 36.3% [95%CI 34.0-38.7%], 10-99 IU/L: 35.7% [33.2-38.2%] and ≥ 100 IU/L: 28.0% [25.9-30.2%]. We did not find an association between a recommended schedule of three versus four doses and anti-HBs ≥ 10 IU/L or ≥ 100 IU/L. CONCLUSIONS: Anti-HBs levels in later childhood were about equal, whether children received three or four doses. This implies that the change in the recommendations does not affect the anti-HBs level among children in Germany. Future studies are needed on the association of anti-HBs levels and adequate sustained protection against HBV.

Prevalence of hepatitis B virus infection among general population of Armenia in 2021 and factors associated with it: a cross-sectional study.

OBJECTIVES: This study sought to determine the prevalence and associated factors of hepatitis B virus (HBV) infection ever in life and chronic HBV infection in Armenia. DESIGN: A population-based cross-sectional seroprevalence study combined with a phone survey of tested individuals. SETTING: All administrative units of Armenia including 10 provinces and capital city Yerevan. PARTICIPANTS: The study frame was the general adult population of Armenia aged ≥18 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The participants were tested for anti-HBV core antibodies (anti-HBc) and HBV surface antigen (HBsAg) using third-generation enzyme immunoassays. In case of HBsAg positivity, HBV DNA and hepatitis D virus (HDV) RNA PCR tests were performed. Risk factors of HBV infection ever in life (anti-HBc positivity) and chronic HBV infection (HBsAg positivity) were identified through fitting logistic regression models. RESULTS: The seroprevalence study included 3838 individuals 18 years and older. Of them, 90.7% (3476 individuals) responded to the phone survey. The prevalence of anti-HBc positivity was 14.1% (95% CI 13.1% to 15.2%) and HBsAg positivity 0.8% (95% CI 0.5% to 1.1%). The viral load was over 10 000 IU/mL for 7.9% of HBsAg-positive individuals. None of the participants was positive for HDV. Risk factors for HBsAg positivity included less than secondary education (aOR=6.44; 95% CI 2.2 to 19.1), current smoking (aOR=2.56; 95% CI 1.2 to 5.6), and chronic liver disease (aOR=8.44; 95% CI 3.0 to 23.7). In addition to these, risk factors for anti-HBc positivity included age (aOR=1.04; 95% CI 1.04 to 1.05), imprisonment ever in life (aOR=2.53; 95% CI 1.41 to 4.56), and poor knowledge on infectious diseases (aOR=1.32; 95% CI 1.05 to 1.67), while living in Yerevan (vs provinces) was protective (aOR=0.74; 95% CI 0.59 to 0.93). CONCLUSION: This study provided robust estimates of HBV markers among general population of Armenia. Its findings delineated the need to revise HBV testing and treatment strategies considering higher risk population groups, and improve population knowledge on HBV prevention.

De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long-term prophylaxis.

Liver transplantation (LT) with hepatitis B core antibody (anti-HBc) positive grafts to hepatitis B surface-antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti-HBs) positivity may safely inform prophylaxis discontinuation post-LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti-HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti-HBs antibodies 1 year or later post-LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow-up of 37 months. The patients without de novo HBV had higher anti-HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti-HBs at the time of transplant or negative anti-HBc at any time point. These results suggest that quantitative anti-HBs titer thresholds rather than qualitative anti-HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.

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

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

A case-control study of risk factors for incident hepatitis B virus infection in South African blood donors.

OBJECTIVES: Hepatitis B virus (HBV) infection remains a global health problem. Risk factors for HBV infection are usually assessed in prevalent rather than incident infections. To identify demographic and behavioral risks associated with incident HBV among South African blood donors. METHODS: A case-control study was performed between November 2014 and January 2018. Cases were blood donors testing positive for HBV DNA with or without hepatitis B surface antigen but negative for antibody to hepatitis B core antigen. Participants completed an audio computer-assisted structured interview on exposures during the previous 6 months. Sex-specific multivariable logistic regression yielded independent associations between risks and HBV infection. RESULTS: 56 females and 37 males with incident HBV were compared to 438 female and 439 male controls, respectively. For females, risk factors were accepting money or goods for sex, using agents to prepare one's anus prior to anal sex, penetrating injury, non-Black race, and lower educational status. Men reporting homosexual or bisexual orientation or sex with other men, previous injury, referral for HBV testing, or lack of medical insurance were at increased risk. For both sexes, having more than two male sexual partners increased risk. CONCLUSIONS: Sexual behaviors predominated over parenteral exposures as risks for incident HBV in both female and male blood donors.

Prevalence of Hepatitis B Virus Markers among the Women with Breast Cancer.

INTRODUCTION: Breast cancer represents a formidable peril to the female populace on a worldwide level. The association between breast cancer and various factors, including viral infections, has been extensively investigated. Recently, the link between HBV infection and breast cancer patients has garnered attention. The present research aims to assess the prevalence of HBV markers among women diagnosed with breast cancer in Ahvaz city, Iran. MATERIALS AND METHODS: Serum specimens were procured from 90 patients who had been clinically diagnosed with breast cancer. The age of the patients ranged from 29 to 80 years, with a mean age of 49.42±10.7. Histological examination of biopsy specimens revealed that 75 (83.33%) were ductal, 11 (8.88%) lobular, 2 (2.22%) mucinous, 1 (1.11%) medullary, and 1 (1.11%) was metastatic. The serum samples were subjected to initial HBsAg and anti-HBc testing via ELISA. Samples that tested seropositive (HBsAg + anti-HBc) were subsequently analyzed for the S region of HBV through nested PCR and DNA sequencing. Finally, a phylogenetic tree was constructed for positive HBV DNA tests. RESULTS: Among the 5/90 (5.55%) cancer patients, it was found that 3 (3.33%) cases of ductal carcinoma and one (1.11%) lobular carcinoma displayed positivity for HBV markers (HBsAg, anti-HBc, HBV PCR). Notably, one (1.11%) patient with ductal carcinoma solely demonstrated anti-HBc positivity. The phylogenetic tree analysis of the S region revealed that all HBV strains identified were categorized as genotype D. CONCLUSION: The statistical analysis did not reveal any significant findings (p= 0.315) in the distribution of cancer types across different age groups. Among patients diagnosed with breast cancer, a notable prevalence of 5.5% was observed in HBV markers. The dominant HBV genotype among breast cancer patients was identified as genotype D.