Incidences of new hepatitis B infection and anti-hepatitis B core-negative occult hepatitis B infection among Japanese blood donors in relation to anti-hepatitis B surface antigen levels.

A transfusion-transmitted hepatitis B virus (HBV) infection caused by blood only positive for anti-hepatitis B surface antigen (anti-HBs) was reported. Occult HBV infection (OBI) with sole anti-HBs among blood donors is an issue. The incidence of HBV infection among repeat blood donors was investigated with a detailed HBV infection phase, focusing on the influence of anti-HBs level. This study followed 3 435 653 donors for HBV DNA conversion over 4 years and 9 months. Infection phase was determined based on marker changes over DNA conversion. This study identified 115 hepatitis B surface antigen (HBsAg) conversions, 72 DNA-only conversions, and 15 DNA plus anti-hepatitis B core (anti-HBc) conversions among donors all negative for HBV DNA, HBsAg, and anti-HBc. Total incidence was 2.38/100 000 person-years (PY). None of these 202 new HBV infections arose in the group with anti-HBs titer ≥ 10 mIU/mL. In total, 30 anti-HBc-negative OBIs were identified (incidence; 0.35/100 000 PY); 7 showed typical secondary anti-HBs response, and 23 showed stable anti-HBc and anti-HBs levels at DNA conversion. The HBV infection-protective ability of anti-HBs ≥ 10 mIU/mL was reinforced. In addition to new infections, the blood donor population includes anti-HBc-positive- and negative OBI with immune reactions or abortive HBV infection.

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.

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.

Potent broadly neutralizing antibody VIR-3434 controls hepatitis B and D virus infection and reduces HBsAg in humanized mice.

BACKGROUND & AIMS: Chronic hepatitis B is a global public health problem, and coinfection with hepatitis delta virus (HDV) worsens disease outcome. Here, we describe a hepatitis B virus (HBV) surface antigen (HBsAg)-targeting monoclonal antibody (mAb) with the potential to treat chronic hepatitis B and chronic hepatitis D. METHODS: HBsAg-specific mAbs were isolated from memory B cells of HBV vaccinated individuals. In vitro neutralization was determined against HBV and HDV enveloped with HBsAg representing eight HBV genotypes. Human liver-chimeric mice were treated twice weekly with a candidate mAb starting 3 weeks post HBV inoculation (spreading phase) or during stable HBV or HBV/HDV coinfection (chronic phase). RESULTS: From a panel of human anti-HBs mAbs, VIR-3434 was selected and engineered for pre-clinical development. VIR-3434 targets a conserved, conformational epitope within the antigenic loop of HBsAg and neutralized HBV and HDV infection with higher potency than hepatitis B immunoglobulins in vitro. Neutralization was pan-genotypic against strains representative of HBV genotypes A-H. In the spreading phase of HBV infection in human liver-chimeric mice, a parental mAb of VIR-3434 (HBC34) prevented HBV dissemination and the increase in intrahepatic HBV RNA and covalently closed circular DNA. In the chronic phase of HBV infection or co-infection with HDV, HBC34 treatment decreased circulating HBsAg by >1 log and HDV RNA by >2 logs. CONCLUSIONS: The potently neutralizing anti-HBs mAb VIR-3434 reduces circulating HBsAg and HBV/HDV viremia in human liver-chimeric mice. VIR-3434 is currently in clinical development for treatment of patients with chronic hepatitis B or D. IMPACT AND IMPLICATIONS: Chronic infection with hepatitis B virus and co-infection with hepatitis D virus place approximately 290 million individuals worldwide at risk of severe liver disease and cancer. Available treatments result in low rates of functional cure or require lifelong therapy that does not eliminate the risk of liver disease. We isolated and characterized a potent human antibody that neutralizes hepatitis B and D viruses and reduces infection in a mouse model. This antibody could provide a new treatment for patients with chronic hepatitis B and D.

Stratified management based on surface antibody for the prevention of hepatitis B virus reactivation in lymphoma patients.

This study aimed to investigate a stratified approach based on hepatitis B virus (HBV) surface antibody (anti-HBs) for managing HBV reactivation (HBVr) in lymphoma patients with serological protection against HBV. A retrospective analysis was conducted on 209 lymphoma patients with a baseline anti-HBs titre of ≥10 iu/L, who were either positive or negative for HBV core antibody (anti-HBc). The results revealed that 15.7% of patients lost serological protection following 6-month anti-lymphoma therapy. With a median follow-up of 28.1 months, the cumulative rates of HBVr at 6 months, 2 years and 4 years were 2.9%, 4.7% and 6.3% respectively. Without intervention, the overall rate of reactivation was 2.0% for patients with isolated anti-HBs and 10.5% for those with positive anti-HBs and anti-HBc. To identify patients at high risk of losing seroprotection and susceptible to HBVr, a predictive model was developed. The high-risk group had significantly higher rates of serological protection loss (27.8% vs. 2.2%) and cumulative incidence of HBVr (22.0% vs. 0%) compared to the low-risk group. Overall, this study highlights the risk of HBVr in lymphoma patients with positive anti-HBs, with or without positive anti-HBc, and recommends periodic monitoring for low-risk patients and early intervention for high-risk patients.

Transfusion-transmitted HBV infection with isolated anti-HBs-positive blood.

BACKGROUND: Hepatitis B virus (HBV)-positive individuals with isolated anti-HBs are found among HBV vaccine recipients and healthy blood donors with no vaccination history. HBV infectivity from blood transfusions derived from such individuals remains unclear. CASE PRESENTATION: A male patient who received transfusion with blood negative for individual donation-NAT, HBsAg and anti-HBc but weakly positive for anti-HBs developed typical transfusion-transmitted (TT)-HBV with anti-HBc response. The responsible blood donor was a frequent repeat donor showing a marked increase in anti-HBs titer without anti-HBc response 84 days after index donation. Test results for his past donations showed transient viremia with very low viral load and fluctuating low-level anti-HBs. The HBV vaccination history of this donor was unknown. DISCUSSION: Anti-HBs and anti-HBc kinetics of the donor suggest a second antibody response to new HBV challenge, representing a vaccine breakthrough case. On the other hand, transient low-level viremia and fluctuating anti-HBs in the test results of past donations suggested chronic occult HBV infection with isolated anti-HBs. CONCLUSION: Whatever the basic infection state, blood donors with isolated weak anti-HBs may include a small population with a risk of causing TT-HBV. Identifying individuals harboring such TT-HBV risk among individuals positive only for anti-HBs is difficult under current screening strategies. Active surveillance for the occurrence of TT-HBV with blood positive only for anti-HBs is necessary.

Size Matters! Anti-HBs Titer and HBV Reactivation During Anti-TNF Therapy.

BACKGROUND AND AIMS: We and others have previously described that hepatitis B surface antibody (anti-HBs) seems to protect against clinically significant HBV reactivation in cohort studies of patients undergoing anti-tumor necrosis factor (TNF) therapy. However, there were too few cases of HBV reactivation within cohort studies to assess the role of anti-HBs titer on reactivation. The purpose of this study was to systematically review the correlation between anti-HBs titer and the degree of clinically relevant HBV reactivation in patients undergoing anti-TNF therapy. METHODS AND RESULTS: We systemically reviewed all studies discussing anti-TNF therapy in patients with resolved HBV infection, defined as hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive. We identified a total of 48 cases of reactivation from 5 cohort studies and 10 case reports or case series; 21 were anti-HBs negative, 7 were only reported as anti-HBs positive, 16 were anti-HBs positive with titer below 100, and 4 were anti-HBs positive with titer above 100. HBsAg sero-reversion was dominantly seen in patients with negative, low and/or declining anti-HBs titers. There was a significant trend toward less clinically relevant form of reactivation with increase in baseline anti-HBs titer (p = 0.022). CONCLUSION: Anti-HBs titers greater than 100 iU/L protect against clinically relevant HBV reactivation, while patients with low anti-HBs titers or negative anti-HBs had more clinically relevant HBV reactivation and higher rates of HBsAg sero-reversion. This suggests the importance of baseline quantitative anti-HBs prior to starting anti-TNF therapy and consideration vaccination for boosting anti-HBs titers prior to and/or during therapy.

Anti-HBc-nonreactive occult hepatitis B infections with HBV genotypes B and C in vaccinated immunocompetent adults.

Absence of anti-HBc reactivity with detectable anti-HBs was observed in blood donors with occult hepatitis B virus (HBV) infection (OBI). The prevalence and mechanisms underlying this uncommon condition were investigated over time in Chinese blood donors with OBI. Isolated anti-HBs OBI status was identified from 466,911 donors from Dalian, China, and monitored in follow-up (range: 2.6-84.3 months). HBV vaccination status was documented, and infecting viral strains were characterized. Of 451 confirmed OBIs (1:1035), 43 (9.5%; 1:10,858) had isolated anti-HBs as only serological marker. Isolated anti-HBs OBIs differed from anti-HBc-reactive OBIs by significantly younger age (median 24 years), higher HBV DNA (median: 20 IU/ml) and anti-HBs (median 60.5 IU/L) levels, paucity of mutations in HBV Core and S proteins, and high vaccination rate (72%). Vaccinated isolated anti-HBs OBIs (n = 31) differed from unvaccinated (n = 11) by significantly younger age (22 vs 38 years), higher anti-HBs level at index (48% vs 9% with anti-HBs >100 IU/L) and higher frequency of anti-HBs immune response (44% vs 20%). Of 15 vaccinated and 5 unvaccinated OBIs follow-up, 65% (8 vaccinated and 5 unvaccinated) became HBV DNA negative suggesting aborted recent infection, while 35% (7 vaccinated) had low persistent viraemia 2 to 65 months post index. In conclusion, isolated anti-HBs OBI in Chinese blood donors appears associated with young, vaccinated, adults exposed to HBV who predominantly develop low level aborted infection revealed by transient HBV DNA and immune anti-HBs response. However, a subset of individuals still experienced low but persistent viral replication whose clinical outcome remains uncertain.

Two-year immune effect differences between the 0-1-2-month and 0-1-6-month HBV vaccination schedule in adults.

BACKGROUND: The short-term 0-1-2-month hepatitis B virus (HBV) vaccination schedule was previously implemented in the adult population; however, its long-term immune effect remains unclear. The present study aimed to investigate (1) the 2-month and 2-year immune effects of HBV vaccination and (2) the compliance rate between the 0-1-2-month and 0-1-6-month vaccination schedules in adults. METHOD: A total of 1281 subjects tested for hepatitis B surface antigen HBsAg(-) and hepatitis B surface antibody (anti-HBs)(-) were recruited. Participants from two distant counties were inoculated with the hepatitis B yeast vaccine at 10 µg per dose, with vaccination schedules of 0, 1, and 2 months (n = 606) and 0, 1, and 6 months (n = 675); sequential follow-up was performed at 2 months and 2 years after the 3rd injection. RESULTS: There were no significant differences in the anti-HBs seroconversion rates between the those in the 0-1-2-month and 0-1-6-month vaccination schedule groups at 2 months (91.96% vs. 89.42%, p = 0.229) and 2 years (81.06% vs. 77.14%, p = 0.217). The quantitative anti-HBs level in those in the 0-1-2-month vaccination schedule group was not different from that in those in the 0-1-6-month vaccination schedule group at 2 months (anti-HBs1) (342.12 ± 378.42 mIU/ml vs. 392.38 ± 391.96 mIU/ml, p = 0.062), but it was higher at 2 years (anti-HBs2) (198.37 ± 286.44 mIU/ml vs. 155.65 ± 271.73 mIU/ml, p = 0.048). According to the subgroup analysis, the 0-1-2-month vaccination schedule induced better maintenance (p = 0.041) and longer reinforcement (p = 0.019) than the 0-1-6 vaccination schedule. The 0-1-2-month vaccination schedule group also had a higher 3rd injection completion rate (89.49% vs. 84.49%, p = 0.010). CONCLUSION: The 0-1-2-month vaccination schedule was associated with a similar short-term immune effect and might induce better long-term immune memory and a higher completion rate in the adult population. Trial registration None.

Hepatitis B Virus prevalence and serological profiles in a hospital in Southern Italy.

Viral hepatitis still represents a significant worldwide public health issue, being an important cause of morbidity and mortality. The aim of our study is to evaluate the prevalence of Hepatitis B virus (HBV) markers from serologic analysis of hospitalized patients at University Hospital of Campania "Luigi Vanvitelli" and also to investigate the prevalence of HBV/HCV coinfection. We screened serum Anti-Hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to hepatitis B core antigen (anti-HBc), and antibody to Hepatitis C Virus (Anti-HCV) Anti-HCV from January to December 2020. Analyses of HBV serological profile based on age showed that the 51-60 age group was the most numerous and with the highest cases of HBsAg. The 61-70 age group recorded the highest prevalence of anti-HBc while age groups 0-10 years and 31-40 years the highest cases of anti-HBs. Antibody levels decline with time. In subjects older than 20 years, compared to vaccinated cohort individuals, anti-HBc seropositive prevalence increased linearly. This study underlined, in our geographic region, the decreased incidence of hepatitis B and high immunogenicity in the young population. Therefore, administration of HBV vaccine booster dose should be considered for the population rather than vaccination in the first year of life. In conclusion, our findings reaffirm the importance of health surveillance in hospitalized subjects, stressing the need to improve immunized subjects to increase the general population's health.

Post vaccination antibody titres of hepatitis B surface antigen (anti-HBs) in a mixed cohort of health care workers.

Background: Hepatitis B (HepB) is an important vaccine preventable infection among healthcare workers (HCWs). Vaccination against Hep B virus, remains the foremost preventive approach. This study aims to measure the antibody titres to Hep B surface antigen (anti-HBs) in a mixed cohort of HCWs. It also aims to study the association between time since vaccination and the anti-HBs titres thus evaluating the duration of seroprotection. Methods: A total of 200 HCWs, including nursing students (n = 112), nursing staff (n = 49), laboratory technicians (n = 30) and doctors (n = 9) who had received all three doses of the Hep B vaccine and met the inclusion criteria of having taken all three doses of vaccine were included in this study. Anti-HBs titres were estimated by bioMérieux mini VIDAS® automated immunoassay based on the principle of enzyme-linked fluorescence assay. Results: Two hundred subjects aged 19 to 52 years were included in the study; mean age was 27.29 ± 0.568 years. Duration since vaccination in the study cohort was ≤ 5 years in 149 (74.5.0%), 6-10 years in 20 (10.0%) and >10 years in 31 (15.5%) subjects. Postvaccination antibody titres were > 100 mIU/ml in 85.0%, 10-100 mIU/ml in 11.0% and ≤ 10 mIU/ml in 3.5%. There was a decline noted in antibody titres as duration after vaccination increased. Increasing age was associated with falling protective titres. Conclusion: The study revealed that majority of the HCWs had adequate anti-HBs titres and were protected after vaccination.

Outcome of nucleos(t)ide analog intervention in patients with preventive or on-demand therapy for hepatitis B virus reactivation.

Preventive or on-demand nucleos(t)ide analog (NA) therapy can prevent severe hepatitis related to hepatitis B virus reactivation (HBV-R). However, it is unclear if NA can be safely stopped in such patients after cytotoxic therapies or during immunosuppressive therapies. We retrospectively evaluated 133 patients who initiated NA therapy between 2007 and 2018. A total of 103 patients were positive for HBV surface antigen (HBsAg) at baseline, and NA therapy was started before cytotoxic or immunosuppressive therapy (preventive group). Thirty patients with resolved HBV infection were treated with NA therapy after HBV reactivation (on-demand group). Virological relapse was defined as a serum HBV DNA level >20 IU/ml. NA therapy was stopped in 12 (12%) patients (preventive group), and in 16 (53%) patients (on-demand group). After the cessation of NA therapy, the cumulative rates of relapse were 36% and 39% at 12 and 24 months, respectively. High levels of HBsAg both at baseline and at the cessation of NA therapy were related to the occurrence of relapse. Relapse did not occur in patients with HBsAg levels <20 IU/ml (preventive group). HBV relapse occurred in five (33%) patients in the on-demand group. Relapse occurred only in anti-HBs-negative patients at the cessation of NA therapy. There were no cases of hepatitis flare after the cessation of NA therapy. HBsAg predicted HBV relapse after the cessation of NA therapy in HBsAg-positive patients. Anti-HBs could be a predictive marker for NA therapy cessation in patients with resolved HBV.

Seroreversion of hepatitis B surface antigen among subjects with resolved hepatitis B virus infection: A community-based cohort study.

BACKGROUND AND AIM: Hepatitis B virus (HBV) surface antigen (HBsAg) seroreversion usually occurs during immunosuppressive therapy. The risk and factors of HBsAg seroreversion from resolved HBV infection in the general population remained unclear. METHODS: This retrospective study enrolled subjects with resolved HBV infection and who had received at least two times of screening in a longitudinal community screening program. HBsAg, hepatitis B surface antibody (anti-HBs), and hepatitis C virus antibody (anti-HCV) were tested every time in all subjects. The primary endpoint was HBsAg seroreversion. RESULTS: Of the 7630 subjects enrolled, 5158 (67.6%) subjects had positive anti-HBs at baseline. HBsAg seroreversion occurred in 84 subjects during 42 815-person-year follow-up with an annual incidence of 0.2% and a 10-year cumulative risk of 1.9%. Anti-HBV treatment-experienced subjects had a significantly higher risk of HBsAg seroreversion than anti-HBV treatment-naive subjects (83/310 [26.8%] vs 1/7320 [0.01%], P < 0.001). Lower rates of positive anti-HBs and anti-HCV were observed in anti-HBV treatment-experienced subjects who developed HBsAg seroreversion. Both positive anti-HBs (hazard ratio/95% confidence interval: 0.56/0.348-0.903, P = 0.017) and positive anti-HCV (hazard ratio/95% confidence interval: 0.08/0.030-0.234, P < 0.001) were independent factors of HBsAg seroreversion in anti-HBV treatment-experienced subjects. Less than 5% of the HBsAg seroreverters had clinical hepatitis flare at HBsAg seroreversion. The HBsAg titer was low, and only transient reappeared in most of the HBsAg seroreverters. CONCLUSIONS: Subjects with resolved HBV infection were at a minimal risk of HBsAg seroreversion, unless with prior anti-HBV treatment experience. Fortunately, even with a reappearance of HBsAg, it was transient and clinically non-relevant.

Hepatitis B vaccination in Indian children: Seroprotection and age-related change in antibody titres.

BACKGROUND: Childhood immunization against hepatitis B is one of the most effective strategies for reducing the global burden of chronic hepatitis B infection and its sequelae. There are limited data from India on both the anti-Hep B antibody titres in children after vaccination and the age-related decline in the titres. This study was planned to estimate the proportion of children in the age group of 1-10 years who develop protective levels of anti-hepatitis B antibodies after childhood vaccination and to examine the change in antibody titres with age in these children. METHODS: A hospital-based cross-sectional study was carried out in children admitted to the hospital for various ailments. Basic demographic data, vaccination history and HBsAg status of the mother were recorded. All the enrolled children were evaluated for HBsAg and anti hepatitis B surface antibody (anti-HBS) titres. Institutional ethical clearance was obtained, and informed consent from the parents of the children was taken before drawing samples. RESULTS: We found that 68.86% Confidence Interval ((CI): 59.8-76.8%) of the children showed protective antibody titres after vaccination, while 31.14% (CI: 23.1-40.2%) of the children had titres less than 10 IU/L. Although 100% of children in the age group from birth to three years had titres more than 10 IU/L, this percentage showed a decline across the age groups, and 60% of children aged 9-10 years had titres less than 10 IU/L. CONCLUSION: Childhood vaccination against hepatitis B is effective in 68% children, and the antibody levels showed a steady decline with increasing age.

Prevalence and clinical features of patients with concurrent HBsAg and anti-HBs: Evaluation of the hepatitis B research network cohort.

The prevalence of concurrent HBsAg and anti-HBs in plasma of persons with chronic hepatitis B virus (HBV) infection is variable and its clinical significance enigmatic. We examined the prevalence and clinical and virological features of concurrent HBsAg and anti-HBs in children and adults with chronic HBV infection living in North America. A total of 1462 HBsAg positive participants in the Hepatitis B Research Network paediatric and adult cohorts were included (median age 41 (range 4-80) years, 48% female, 11% white, 13% black, 73% Asians). Only 18 (1.2%) were found to be anti-HBs positive (≥10 mIU/mL) at initial study evaluation. Distributions of sex, race, HBV genotype and ALT were similar between participants with and without concurrent anti-HBs. Those who were anti-HBs positive appeared to be older (median age 50 vs 41 years, P = .06), have lower platelet counts (median 197 vs 222 × 103/mm3 , P = .07) and have higher prevalence of HBeAg (44% vs 26%, P = .10). They also had lower HBsAg levels (median 2.0 vs 3.5 log10 IU/mL, P = .02). Testing of follow-up samples after a median of 4 years (range 1-6) in 12 of the 18 participants with initial concurrent anti-HBs showed anti-HBs became undetectable in 6, decreased to <10 mIU/mL in 1 and remained positive in 5 participants. Two patients lost HBsAg during follow-up. In conclusion, prevalence of concurrent HBsAg and anti-HBs was low at 1.2%, with anti-HBs disappearing in some during follow-up, in this large cohort of racially diverse children and adults with chronic HBV infection living in North America. Presence of concurrent HBsAg and anti-HBs did not identify a specific phenotype of chronic hepatitis B, nor did it appear to affect clinical outcomes.

Hepatitis B reactivation in hematopoietic stem cell transplanted patients: 20 years of experience of a single center from a middle endemic country.

Hematopoietic stem cell transplantation (HSCT) is a risk factor for viral hepatitis reactivations because it affects lymphocyte number and functions. Latent hepatitis B virus (HBV) may stay in dormant form in hepatocytes and may be reactivated in prolonged immunosuppression. This study analyzes the incidence of reactivation of HBV infections in HSCT patients in a middle endemic country like Turkey. Five hundred and sixty-one HSCT patients from 1994 to 2015 were retrospectively evaluated. Sixty-six patients had a serologic feature of HBV infection. Fifteen patients were hepatitis B surface antigen (HBsAg)-positive patients (3 allogeneic and 12 autologous) while 51 of them were anti-hepatitis B core IgG (anti-HBc IgG)-positive patients (22 allogeneic and 29 autologous). Although under lamivudine prophylaxis, reactivation was seen in three of 12 (25%) chronic HBV (HBsAg positive) patients who received autologous HSCT and in two of the three HBsAg-positive patients who received allogeneic HSCT. Rate of reactivation in the whole HBsAg-positive group was 33%. Reactivation occurred on median 270th day (range: 60-730). Reverse seroconversion incidence was 10% on 133th day for HBsAg negative, but anti-HBc IgG-positive patients, which increased to 17% on 360th and to 23% on 1500th day. Cumulative incidence increased to 41% on 2280th day for isolated anti-HBc IgG-positive patients. Hepatitis B surface antibodies (anti-HBs) were found to be protective as reactivation did not exceed 11% on 5050th day when anti-HBs was positive. When anti-HBc IgG-positive cases were analyzed according to their transplantation types, allogeneic HSCT was found to have higher cumulative incidence (45% on 3258th day) for HBV reactivation than autologous HSCT (7% on 5050th day). Besides, HBV reactivation in anti-HBc IgG-positive patients who received allogeneic transplantation was related to mortality. Findings of this study suggest that HBV prophylaxis extending over 1 year should be prescribed for HBsAg-positive patients independent of the transplantation type. Prophylaxis should also be given to anti-HBc IgG-positive patients if an allogeneic HSCT is to be performed.

Assessment of anti-HBs antibody concentration in children with juvenile idiopathic arthritis treated with biological drugs, vaccinated against viral type B hepatitis in infancy.

OBJECTIVES: The introduction of vaccinations against viral hepatitis B in the years 1994-1996 in Poland significantly improved the epidemiological situation of hepatitis B virus (HBV) infections in our country. According to the report of the National Institute of Public Health - National Institute of Hygiene in 2018, 40 cases of acute hepatitis B were noted while still in the 1980s between 10 and 20 thousand new cases were reported annually. The aim of the study was to determine whether in children treated with biological drugs (adalimumab, etanercept, infliximab) due to juvenile idiopathic arthritis (JIA), vaccinated against hepatitis B in infancy, a protective concentration of anti-HBs antibodies persists. In patients, the value ≥ 10 mIU/ml is regarded as a protective concentration of antibodies, determined at least four weeks after administration of the last vaccine dose. Among healthy individuals, presence of anti-HBs antibodies in any concentration means seroprotection. No booster vaccinations are recommended in basically vaccinated healthy individuals. MATERIAL AND METHODS: The concentrations of anti-HBs antibodies were determined in 56 children with JIA (38 girls - 67.9% and 18 boys - 32.1%) aged from 2 years and 4 months to 17.5 years, treated for at least three months with biological drugs. The diagnosis of JIA was made based on the International League of Associations for Rheumatology (ILAR) criteria. All studied patients were at the stable stage of the disease and received a full course of hepatitis B vaccination during infancy (in accordance with 0,1,6 months injection scheme). RESULTS: In the studied children a protective anti-HBs antibody concentration was found in 34 cases (60.7%), and 22 children (39.3%) had anti-HBs antibody concentration < 10 mIU/ml (in these children no seroprotection was found). CONCLUSIONS: The post-vaccination antibody concentration should be determined in children with JIA, treated with biological drugs and, in case of absence of a protective concentration, revaccination should be started.

Circulating interferon-λ3 and post-vaccination antibodies against the surface antigen of hepatitis B virus in hemodialysis patients exposed to hepatitis E virus.

Responsiveness to the hepatitis B virus (HBV) vaccination in hemodialysis (HD) patients who had been exposed to the hepatitis E virus (HEV) and persistently generate antibodies against HEV remains unknown. Interferon (IFN)-λ3 positively correlates with the surface HBV antibodies (anti-HBs) in both healthy and HD subjects. We aimed to show whether HD patients differ in circulating IFN-λ3 and vaccine-induced anti-HBs titers concerning natural HEV immunization. HBV/HCV negative HD patients (31 HEV IgG positive, 45 HEV negative), HBV vaccinated and receiving booster doses as needed, had been tested for anti-HBs titers (CMIA) and IFN-λ3 concentrations (ELISA) in the blood collected before a dialysis session. There were no differences in circulating IFN-λ3 and anti-HBs titers between both groups. In responders to the HBV vaccine, there was a positive correlation between plasma IFN-λ3 levels and anti-HBs titers (r = 0.505, adjusted P = 0.01 in HEV exposed subjects; r = 0.523, adjusted P = 0.001 in controls). HEV past infection does not attenuate post-vaccination anti-HBs generation and does not influence a correlation between circulating IFN-λ3 levels and anti-HBs titers.

Hepatitis B Vaccination and Waning Hepatitis B Immunity in Persons Living with HIV.

PURPOSE OF REVIEW: Persons with HIV are at a higher risk for acquiring HBV (hepatitis B virus) than the general population due to shared modes of transmission and are significantly more likely to develop and die from sequelae of chronic HBV infection. Early vaccination is key to achieving HBV protective immunity, but response rates are still much lower than in the general population, ranging from 35 to 70%. Individuals with HIV also experience more rapidly waning immunity than those without HIV. Strategies to augment initial response and improve long-term immunity in individuals with HIV include alterations in dose, frequency, and the use of immune adjuvants. RECENT FINDINGS: Recent studies have focused on the use of different vaccine formulations, the use of vaccine adjuvants, increased number and strength of vaccine dosages, increased dose frequency, alternative routes of administration, dual vaccinations, and the use of booster vaccines. Although no consensus has been reached on the use of certain vaccination regimens, three and four double-dose vaccine schedules via the intramuscular route have demonstrated higher initial response rates. Early vaccination when CD4 cell counts are greater than 350/mm3 with low viral loads has been shown to improve initial response, along with completion of immunization series. Adjuvants such as TLR4 and TLR9 agonists appear to improve response to HBV vaccination, but further research is needed in individuals with HIV. Persons with HIV have significant lower initial and long-term seroresponse rates after HBV vaccination than immunocompetent individuals. Recent and ongoing studies continue to evaluate multiple strategies to improve these rates within a uniquely susceptible population.

Seroprevalence and factors associated with hepatitis B virus infection among the hill tribe youths, northern Thailand.

BACKGROUND: Hepatitis B virus (HBV) infection is a major viral infection, particularly in people living in the Western Pacific region, including the hill tribe people living in northern Thailand. This study aimed to estimate the prevalence of HBV infection and to detect the factors associated with HBV infection among hill tribe youths in Thailand. METHODS: A cross-sectional study was conducted to estimate the prevalence and determine the factors associated with HBV infection among hill tribe youths living in northern Thailand. A validated questionnaire and 5 mL blood sample were used for data collection. The Wondfo Diagnostic Kit®, the Wondfo One Step HBsAg Serum/Plasma Test®, and the Wondfo One Step HBsAg Serum/Plasma Test® were used for anti-HBsAg, HBsAg, and total anti-HBc detections, respectively. Logistic regression was used to detect associations between variables with an α = 0.05 significance level. RESULTS: A total of 836 participants were included in the study; 62.7% were female, 58.9% were aged 15-17 years, 58.7% were Buddhist, 78.4% graduated high school, and 89.1% had no income. The majority were Akha (30.0%), Yao (16.3%), and Hmong (15.8%); 13.2% smoked, 21.5% used alcohol, 13.3% had tattoos, 3.9% experienced drug injection from illegal practitioners, and 35.7% had no history of HBV immunization. The prevalence of HBsAg was 3.0%; anti-HBs, 10.2%; and total anti-HBc, 8.1%. In the multivariate analysis, four variables were found to be significantly associated with HBV infection among the hill tribe youths: age, tribe, work experience, and number of partners. Those aged 18-20 years and 21-24 years had 2.13 times (95%CI = 1.35-3.29) and 2.39 times (95%CI = 1.05-3.90) greater odds of HBV infection, respectively, than those aged 15-17 years. Akha, Lahu, and Hmong youths had 3.12 times (95%CI = 1.07-9.12), 3.71 times (95%CI = 1.21-11.41), and 3.84 times (95%CI = 1.26-11.69) greater odds of HBV infection, respectively, than Lisu youths. Those who had experience working outside of the village had a 1.77 times (95%CI = 1.18-2.98) greater chance of HBV infection than those who did not have experience working outside of the village, and those who had ≥2 partners had a 2.66 times (95%CI = 1.96-3.87) greater chance of HBV infection than those who had no partner. CONCLUSIONS: Effective HBV prevention programs should be promoted in Akha, Lahu, and Hmong youth populations, particularly to those who have sexual partners, work outside of the village and are aged 18-24 years.