anti-HBs Titers Research Articles

Multivariate analysis of immune effect of hepatitis B vaccination in post-liver transplantation children aged under 5 years old

Objective To investigate the effect of hepatitis B vaccine immune response after liver transplantation in children under 5 years old and assess the necessity of multiple vaccination. Methods A retrospective collection of children who had liver transplantation from February 2014 to December 2018 in the same liver transplantation group in the Department of General Surgery, Beijing Friendship Hospital, Capital Medical University were analyzed. In accordance with the requirements of the doctor, 170 children under 5 years old injected with over 4 doses were enrolled, including 75 males and 95 females, aged from 4 months to 5 years old. After every dose of vaccination, the blood were collected to detect hepatitis B following regular review in liver transplantation clinic, observe the effect of HBsAb (hepatitis B surface antibody) after postoperative hepatitis B vaccination.Count data were represented by cases and percentage (%), and comparison between groups were analyzed by chi-square test. Results After the first course of treatment, in total children under 5 years old who completed the first course of treatment, 121 cases got successful immune responses(HBsAb≥100 IU/L) and 49 cases got the responses failure (HBsAb 100 IU/L anti-HBs titer had a higher immune response rate after the first course of postoperative vaccination (84.72%), and the immune response rate of children with anti-HBs titers <100 IU/L after the first course of hepatitis B vaccine was slightly lower(60.71%). Conclusions Most post-liver transplantation children can obtain protective antibodies to prevent re-infection of hepatitis B virus by inoculation with hepatitis B vaccine. Multiple inoculation can effectively induce hepatitis B antibody production and improve immune response level economically. The hepatitis B vaccination proved to be indispensable and is one of the current methods promoted and applied to post-liver transplantation. Key words: Liver transplantation; Hepatitis B vaccines; Child, preschool; Immunity

Long-term persistence of anti-HBs after hepatitis B vaccination among adults: 8-year results

ABSTRACT The long-term persistence of hepatitis B surface antibody (anti-HBs) after hepatitis B vaccination among adults was not known clearly. This study aimed to assess the immunogenicity and persistence of antibodies 8 years after hepatitis B immunization with different vaccination schedules among adults who tested negative for hepatitis B surface antigen (HBsAg), anti-HBs, and hepatitis B core antibody (anti-HBc). A total of 771 participants who received the full vaccination course (three doses) and also had a blood sample taken 1 month after the first vaccination were recruited. Of these, 529 were excluded due to the missing data of anti-HBs 8 years after the first vaccination. Vaccinations were carried out at 0–1–3, 0–1–6 and 0–1–12 month vaccination schedules, and 104, 45, and 93 participants were included, respectively. The positive seroprotection rate was 85.9% 1 month after the third vaccination, and 58.3% 8 years later (χ 2 = 54.52, P < .001), while the geometric mean titer (GMT) of anti-HBs was 158.49 mIU/mL [95% confidence interval (CI): 131.83–190.55)] and 15.14 mIU/mL (95% CI: 10.96–20.42) after 1 month and 8 years, respectively. Compared with the standard 0–1–6 month vaccination schedule, the positive seroprotection rate and the GMT of the 0–1–3 month vaccination schedule had no difference. The long-term immune effect of the 0–1–3 month vaccination schedule was better than that of the 0–1–12 month vaccination schedule. No correlation was found between the GMT of anti-HBs 1 month and 8 years later.

Evaluation of the efficacy of accelerated hepatitis B vaccine among students of Assiut Nursing School and College

Introduction Hepatitis B (HB) vaccine prevents infection with hepatitis B virus, thus reducing the incidence of chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, and transmission of infection to susceptible individuals. Vaccine-induced immune response is defined as anti-HBs titer greater than 10 mIU/ml after complete vaccination schedule. Aim The aim was to evaluate the efficacy of accelerated HB vaccine among students of Assiut Nursing School and College. Participants and methods This study included 100 students of Assiut Nursing School and College, and 10% of them had received only a single dose of HB vaccine previously (in the period 6–12 months before the study) but had not completed the vaccination schedule, and their prestudy anti-HBs titer was less than 10 mIU/ml. Prevaccination testing of HBs Ag, Anti-HBs, Anti-HBc IgG, and HCV-Ab was negative. A vaccination schedule of 0, 1, and 2 months was used. Then, anti-HBs were measured one month after the last vaccine dose to detect antibody response by third-generation ELISA. Results Postvaccination anti-HBs titer was significantly higher in comparison with its prevaccination level (4.072.62 before vs 66.44±11.61 after vaccination; P=0.01). The authors found that students receiving a single dose of HB vaccine in the period 6–12 months before the study had high anti-HBs titer either before the study (9.78±2.01) and after the study (179.50±40.11) in comparison with those not receiving a vaccine dose recently. Conclusion Seroprotection rate was 100%, that is, all enrolled participants show postvaccination anti-HBs titer greater than 10 mIU/ml, and students with a higher prevaccination anti-HBs titer had a higher postvaccination anti-HBs antibody titer.

Evaluation of AntiHBs titer in vaccinated hemodialysis Patients and the relating factors in Kowsar hospital of Semnan city

Introduction: The medical literature contains several studies showing that the response of hemodialysis patients after vaccination is inferior to that of the general population.Concerning the specific response to HBV vaccination, several additional factors contribute to an inefficient immune protection. This study was designed to investigate the possible relationship between AntiHBs titers and several factors in our population. Materials & Methods: in this cross-sectional study all of the vaccinated hemodialysis patients in Kowsar hospital of semnan were enrolled as cases. The information required to analyze the data, including age, sex, BMI, underlying disease, smoking, duration of treatment with hemodialysis and the time elapsed since the last dose of vaccination and AntiHBs titers of them through their hospital documentations were entered in checklist. Data were analyzed by the chi- square test, T test and Fishers exact test and Mann-Whitney U test. Results: In this study 79 hemodialysis vaccinated patients were studied. After data analysis it was indicated that there was no statistically significant relation between the variables and AntiHBs titer. On the other hand, the relation between AntiHBs titer and the time elapsed since the last dose of vaccination was significant (p=0.010). Conclusion: our findings indicate that in our hemodialysis center, only the time since last dose of vaccination is effective both on AntiHBs titer and immunity of patients somehow after 12 months of full vaccination there is a significant decrease in AntiHBs levels leading to losing the protective titer.

Seroprevalence of Anti-HBs Titers in Health-care Workers in a Tertiary Care Hospital in Mumbai

Introduction: Hepatitis B is a vaccine preventable disease caused by Hepatitis B virus which is a partially double stranded virus. Sharp injuries are the most common occupational injuries among healthcare workers (HCW). HCW are prone to sharp injuries during work, and infection after exposure. Materials and Methods: Anti-HBs titres were measured in 231 HCW in a tertiary care hospital in Mumbai. Result: Eighty six males and 145 females participated in the study. Out of these 41 were vaccine non compliant; 37 were partially immunized and 4 were not immunized. 32 out of 231 individuals tested had titres below 10 mIU/ml (10 mIU/ml considered to be the minimal protective titre). Among the individuals who had titres <10 mIU/ml, 17 were medical assistants, 10 were nursing officers and 5 were doctors. Out of these there were 04 who had not received any HepB vaccination in the past. The rest had received either complete or partial immunization. All those who had completed primary vaccination series and had titres <10 mIU/ml (n = 14) had completed primary vaccination more than 5 years ago. Conclusions: In our study 82.2% were vaccine compliant and 27.8% were vaccine non compliant. Out of 231 individuals 32 (13.85%) had titres <10 mIU/ml. This study highlights the need for HCW to undergo anti-HBs titres post primary vaccination and after 5 years of primary vaccination to identify susceptible individuals. The HCW with non protective titres should be give Hep B booster and antibody levels should be tested to confirm protective titres.

Sex Disparity in Response to Hepatitis B Vaccine Related to the Age of Vaccination.

Hepatitis B virus (HBV) infection is one of the major infectious hazards for health-care workers (HCWs) because of the frequency of percutaneous exposures to blood or body fluids. For this reason, all HCWs should be vaccinated, including students in medicine and health professional degree programs. The aim of this study was to assess the immune coverage to anti-HBV vaccine and long-lasting protective titres of anti-HBs antibodies in female and male students to evaluate gender-related differences in response to HBV vaccination. Data relative to anti-HBs antibody titre, sex, age, and age at vaccination were collected and analyzed from 5291 Italian students (1812 males and 3479 females) of the graduate courses at the School of Medicine, who underwent the mandatory health surveillance of workers exposed to biological risk. The results indicated that gender affects the immune response to HBV vaccine, particularly evident in the case of females vaccinated after one year of age who exhibited a statistically significant (p = 0.0023) 1.21-fold increase in median antibody titre with respect to males. Our findings could contribute to the optimization of HBV vaccination schedules in health surveillance of HCWs.

Sociodemographic risk factors for hepatitis C virus infection in a prospective cohort study of 257 persons in Canada who inject drugs.

Approximately 60% of incident hepatitis C virus (HCV) infections are due to intravenous drug use; therefore, understanding the socio-demographics of people who inject drugs (PWID) is necessary to achieve HCV elimination. In this prospective cohort study of PWID, we determined patients' baseline HCV antibody, hepatitis B virus (HBV), and HIV serological status. HCV antibody- negative (anti-HCV-negative) cases were followed for seroconversion (median 17 mo with q3m testing) as part of a larger study to develop a vaccine for HCV. An interviewer-administered baseline questionnaire completed with all patients evaluated socio-demographic and clinical characteristics. We tested 257 PWID (median age 40 [range 49-31]y, 81% men, 63% Caucasian, 28% Indigenous). Of these, 28% were positive for HCV antibodies (anti-HCV-positive) (median age 42 [range 49-36]y, 74% men, 69% Caucasian, 29% Indigenous). Compared with anti-HCV-negative PWID, anti-HCV-positive PWID reported injecting more morphine and hydromorphone, using more hydromorphone via non-injection routes, and were more likely to be enrolled in methadone programs. More than 60% reported previous HCV testing, but recent testing (<2y) was more frequent in the anti-HCV-negative group (p = 0.03). All were HBV negative, but more than 50% of the anti-HCV-positive group had anti-HBs titres more than 10 IU/L compared with 35% of the anti-HCV-negative group (p = 0.01), and 3 of 257 were HIV positive (1 co-infected with HCV-HIV). In this prospective study, differences in age, timing of HCV testing and risk behaviours were found between anti-HCV-positive and anti-HCV-negative groups.

High chance to overcome the non-responder status to hepatitis B vaccine after a further full vaccination course: results from the extended study on healthcare students and workers in Florence, Italy

ABSTRACT Healthcare workers (HCWs) are considered high-risk subjects for Hepatitis B Virus (HBV) infection due to occupational exposure to blood and body fluids. Vaccination represents the core strategy for HBV infection prevention. Following our previous publication on this topic, we aimed to assess the effectiveness of booster vaccine doses in eliciting the immunological response in seronegative (<10 mIU/mL) HCWs and students of Careggi Teaching Hospital, Florence (Italy). All subjects received primary vaccination course, and they were tested for serum anti-HBs antibodies. In seronegative subjects, a challenge dose of vaccine was administered and the test was repeated 1 month later. Six hundred and ninety-eight (87.8%) of 795 HCWs and students tested responded to the challenge dose. After this challenge dose, males more often had negative anti-HBs titer compared with females (15.9% vs 10.2%; p < .05). The completion of the second vaccination course was offered to subjects with persistently negative anti-HBs titer. 76.2% (32) of those who accepted the fifth dose, and 3 of the 5 who accepted the sixth dose seroconverted. This report shows the importance to convey a strong message to negative subjects at the initial anti-HBs dosage: accepting all the three additional vaccine doses allows the vast majority of them to obtain protection.

Japanese original delayed hepatitis B vaccination provides adequate immunogenicity against mother-to-child hepatitis B virus infection in preterm infants: A nationwide survey in Japan

ObjectiveWe aimed to evaluate immunogenicity following Japanese original delayed hepatitis B (HB) vaccinations for prevention of mother-to-child HB infection in preterm infants. MethodsA nationwide survey in Japan was conducted at certified neonatology facilities in 2014. Eighty-four preterm infants born from a serum hepatitis B surface (HBs) antigen-positive mother were included. We collected data on the following parameters: gestational age, birth weight (BW), age at HB vaccination, age at examination of serum anti-HBs titer, and serum anti-HBs titer. The delayed HB vaccination schedule was 3 doses of HB vaccines at 2, 3 and 5 months of age. A seropositive immunogenic response to HB vaccination was defined as an anti-HBs titer ≥10 mIU/mL. Seropositive rates were calculated in all participants. Four subgroups based on BW were as follows: <1000 g (n = 13), 1000–1499 g (n = 16), 1500–1999 g (n = 26), and ≥2000 g (n = 29). ResultsAmong 84 preterm infants who completed the delayed vaccination schedule, 82 (98%) achieved seropositive anti-HBs titer at a median age of 6 months. Seropositive rates of infants <1000 g, 1000–1499 g, 1500–1999 g, and ≥2000 g were 92%, 94%, 100%, and 100%, respectively. ConclusionThe Japanese original delayed HB vaccinations achieved sufficient seropositive rates in preterm infants and provide immunogenicity against mother-to-child HB infection.

No Improvement of Hepatitis B Vaccination Response in Patients Dialysed with a Polymethylmethacrylate Membrane Compared to High-Flux Polysulfone: Results of the HEPADIAL Study

Background: An altered immune response and decreased vaccine response are observed in patients with chronic renal failure. A preliminary study of 15 non-immunised patients, despite appropriate previous hepatitis B vaccination, showed a 60% seroconversion rate after 3 months of dialysis with a polymethylmethacrylate (PMMA) membrane. This response was associated with circulating soluble CD40 (CD40s) decrease, a natural inhibitor of the humoral immune response. The aim of the study is to confirm these results in a randomised study. Methods: We conducted a multicentre randomised intention-to-treat superiority clinical trial comparing polysulfone and a PMMA membrane in 2 parallel patient groups. The primary end point was the vaccine response rate, as defined by an anti-HBs antibodies titre of >10 IU/L, 1 month after the last vaccination with a double dose of Engerix B20®, performed at weeks 12, 16, 20, and 36. Results: Twenty-five patients were randomised and included in an intention-to-treat analysis. They were dialysed on polysulfone (n = 11) or PMMA (n = 14) for 40 weeks. Fifty percent of the PMMA patients versus 54.5% of the polysulfone patients achieved seroconversion (p = 1.00). The median anti-HBs antibody titre in responders at week 40 was 496 (92–750) versus 395 (43–572) UI/mL for PMMA and polysulfone, respectively (p = 0.46). The median CD40s titre at week 12 was 306 (193–448) versus 491 (281–515) pg/mL (p = 0.21). The CD40s median variation between week 0 and week 12 was 5 (–105 to 90) versus 64 (–63 to 123) pg/mL (p = 0.55). The CD40s level at week 12 in non-responders was slightly inferior to that of the responders: median 193 (168–331) versus 413 (281–512) pg/mL (p = 0.08). Conclusion: We did not observe a better vaccine response with the PMMA membrane compared to high-flux polysulfone. The PMMA membrane did not decrease the CD40s more than the polysulfone membrane probably because the titre was previously low in the 2 groups.

Outcome of Repeated Vaccination to Hepatitis B Virus in Patients Failing to Respond to Vaccination Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): If at First You Don't Succeed, Try Try Again

Background: Recipient immunity is compromised after HSCT, obligating patients (pts) to take prophylactic antimicrobial and antiviral agents and to be reimmunized to viral and bacterial pathogens. Hepatitis B virus (HBV) infection is a major public health problem, with about 30% of the world population having serological evidence of current or past HBV infection. HBV vaccination post-HSCT is imperative in these pts, as most lose protective HBV surface antibodies (anti-HBs) following conditioning, placing them at high risk for HBV reactivation. Guidelines recommend delaying vaccination (including HBV) for 6-12 months following transplantation to allow for cellular and humoral immune recovery. Even with delaying vaccination, immunosuppression, graft-versus-host disease (GVHD), and delayed immune reconstitution hinder the effectiveness of vaccines. The efficacy of HBV vaccination is not well defined in pts on immunosuppressive therapy (IST) and/or in those with GVHD. Further, little data exists on the efficacy of HBV revaccination in pts failing to respond to the 1st vaccination series. We studied factors impacting the success of vaccination in pts undergoing one to four HBV vaccination series after HSCT. Methods: This single-center, retrospective study evaluated the effectiveness of HBV vaccine in HSCT pts by assessing protective antibody generation after vaccination. Fifty-two pts (25 female, 27 male) who received at least one 3-dose HBV vaccination series post-HSCT and who had evaluable post-vaccine anti-HBs titers were included in the analysis. Pts with negative or indeterminate anti-HBs titers following the first vaccine series were eligible to receive one or more additional series of HBV vaccinations. All pts were treated with cyclophosphamide and fludarabine based conditioning (± anti-thymocyte globulin) and received GVHD prophylaxis with either cyclosporine/tacrolimus with or without mycophenolate mofetil. The vaccine response rate over a series of vaccinations was estimated by Kaplan-Meier methods. The development of response after the first vaccination was correlated with patient baseline and post-HSCT factors including pretransplant HBV titers, vaccination time post-transplant, use of rituximab and IST and absolute lymphocyte count (ALC), CD4, and CD8 cell counts and history of acute or chronic GVHD. Results: The studied cohort included 52 HSCT pts with a median age of 22 years (range 7-62) and a variety of diagnoses (38 aplastic anemia, 6 myelodysplastic syndrome and 8 hematological malignancies). Thirty-five pts underwent HSCT from an HLA-matched donor and 17 pts received a combined haploidentical and umbilical cord blood transplant. The median time to first HBV vaccination was 12 months (8-37) post-HSCT. Following the 1st vaccination series; 19, 4 and 2 pts received a 2nd, 3rd and 4th vaccination series. The estimated cumulative anti-HBs response rates were 51.9%, 82.3%, 91.1% and 100% for the four vaccination series, respectively (Figure). A logistic regression analysis revealed: a) Pts who achieved a response after the initial vaccination series had higher CD4 counts compared to those who failed to mount a response (median CD4 count 450 vs. 300/μL, P= 0.024, Figure); b) Pts without a history of acute GVHD (n=23) were significantly more likely to respond to the 1st vaccination series compared to those with acute GVHD (n=29) (response: 69.6% vs 37.9%, P= 0.029). Other factors included in this analysis were not found to be correlated with the anti-HBs response after the initial vaccination series. Conclusions: Multiple rounds of HBV vaccination may be required before a protective antibody response is achieved. After the first vaccination series, only 51.9% of pts achieved a response, with lower pre-vaccination CD4 counts and a prior history of acute GVHD being negatively associated with vaccine success. Remarkably, with continued vaccination attempts (up to four vaccination series), all evaluable pts ultimately developed a protective anti-HBs response. Figure Disclosures Shalabi: GlaxoSmithKline: Other: Spouse is employed by GSK Pharma.

The Real-Life Data on the Outcome of Hepatitis B Infection in Patients with B-Cell Lymphoproliferative Neoplasms Treated with Ibrutinib

Background: Ibrutinib has become a widely used drug in the management of B-cell lymphoproliferative neoplasms (BLPNs). Past or active HBV infection is an exclusion criteria for the clinical trials of ibrutinib and for patients (pts) treated outside clinical trials there are contradictory data or suggestions concerning hepatitis B virus (HBV) prophylaxis. In this study, we evaluated the real-life data on the outcome of HBV infection status of pts with BLPNs receiving ibrutinib. Methods: Demographic features, previous treatments (including rituximab (RTX)) and follow-up durations, HBV infection and reactivation status, prophylaxis information, serum transaminase and total bilirubin levels of the pts were noted retrospectively. Past HBV infection was defined as concurrent detectable HBV core IgG antibody (Ab) (anti-HBc IgG) and undetectable HBV surface Ag (HbsAg) ± HBV surface Ab (anti-HBs). Active HBV infection was defined as HbsAg and/or HBV core IgM Ab (anti-HBc IgM) positivity. Quantitative HBV-DNA PCR results are also recorded, when available. Results: Twenty-seven consecutive pts were included, and pts' characteristics are displayed in Table 1. Median durations of ibrutinib therapy and entire follow-up were 9 and 108 months, respectively. All pts had received RTX prior to ibrutinib. Among the 27 patients, 8 had past HBV infection, while 2 had active HBV infection. HBV prophylaxis or treatment was started before ibrutinib in 5 pts, and simultaneously with ibrutinib in one. The remaining 4 pts with past HBV infection were not given any prophylaxis. Among these 4 cases with anti-HBc IgG positivity, three were also positive for anti-HBs. Currently, these 4 pts, including the one with a negative anti-HBs status, are at the 2nd, 4th, 12th, and 16th cycles of ibrutinib. To date, no signs of HBV reactivation was detected in our cohort. Discussion &amp; Conclusion: All pts in our cohort had received RTX containing regimens prior to ibrutinib. In our analysis, 5 pts were under HBV prophylaxis or treatment when ibrutinib was started. Two of these had active HBV infection. Simultaneous HBV prophylaxis was started with ibrutinib for one pt and the remaining 4 pts with past HBV infection (anti-HBs + anti-HBc IgG positivity) did not receive any prophylaxis, but they were planned to be followed by monitoring the anti-HBs titers. In a study, 21 BLPN pts (10 treated with RTX previously) with occult HBV infection with a median follow-up of 9.5 months treated with ibrutinib without anti-HBV prophylaxis, and only two HBV reactivations were reported (Hammond et al. Blood. 2018;131(17):1987-1989). In another study, no HBV reactivation was detected in 7 CLL pts with past HBV infection, with a median follow-up duration of 25 months under ibrutinib, without any anti-viral prophylaxis (Tedeschi et al. Leuk Lymphoma. 2017; 58(12):2966-2968). The increase in the number of pts treated with ibrutinib, is followed by the awareness about the infectious complications including HBV reactivation. The consecutive use of RTX and ibrutinib has increased the risk of HBV-related complications. This issue has become more important in areas with a higher prevalence of HBV. Although the number of pts is limited and follow-up periods are relatively short, our results may indicate that pts with occult HBV infection treated with ibrutinib for BLPNs, might only be closely followed for HBV reactivation, rather than routine anti-HBV prophylaxis. Since pts with previous RTX exposure are likely to lose anti-HBs antibodies, ibrutinib-treated pts with both anti-HBs and anti-HBc IgG positivity should be closely monitored for possible risk of HBV reactivation. Anti-viral prophylaxis under ibrutinib therapy might still be an option for the selected cases. Disclosures No relevant conflicts of interest to declare.

Stability of hepatitis B viral load during pregnancy and implications for antepartum prophylaxis: A prospective cohort study.

We examined changes in hepatitis B virus (HBV) viral loads (VLs) in pregnancy, their association with hepatitis B e antigen (HBeAg), and the associated infant outcomes. We prospectively followed 132 mothers positive for hepatitis B surface antigen (HBsAg) and their 135 infants from 2011 to 2015 in Vancouver, British Columbia. Outcome measures included association between maternal HBeAg and high (>200,000 IU/mL) or low (≤200,000 IU/mL) HBV VL, changes in HBV VL through pregnancy, infant HBsAg status, and infant completion of the HBV vaccination series. f the 91 participants with an available HBV VL, 13 (14.3%) had an HBV VL of more than 200,000 IU/mL. Of 59 participants with paired HBeAg and HBV VL in pregnancy, 6 had an HBV VL of more than 200,000 IU/mL; of interest, 2 of the 6 (33.3%) were HBeAg-negative. Thirty-eight participants had HBV VL results at both mid-trimester and delivery. For these 38 participants, Wilcoxon signed-ranks test for paired data found that an HBV VL remained stable (p = .58). We observed no perinatal transmissions. However, 20.7% of infants did not have a documented complete HBV vaccination series, 20.0% did not have post-vaccination HBsAg testing completed, and 18% did not have anti-HBs titres measured by age 12 months. Our study demonstrates that HBeAg and HBV VL are not reliably predictive of each other. This supports the improved predictive value of VL measurement in pregnancy to risk stratify pregnant patients to offer antiviral treatment when indicated and further minimize the risk of perinatal transmission.

Assessment of immune response to Hepatitis B vaccine by estimation of anti - HBs antibody titer among immunized health care workers

Background: Hepatitis B vaccination is recommended for all health care workers as they constitute a high-risk group for acquiring blood borne hepatitis B infection. Anti HBs level ≥10 mIU/ml at any time after vaccination is considered as a marker of sustained immunity, which provides protection against infection. Poor sero-protection rates to hepatitis B vaccine are recognized and some individuals do not develop sufficient levels of anti-HBs antibodies. Hence, it is necessary to identify the individuals who are non-protective responders to vaccination. With this background, the present study was undertaken to determine immune response to hepatitis B vaccine amongst the health care workers. Material and Methods: The present cross-sectional study included 200 health care workers in a tertiary teaching hospital, who were immunized with three complete doses of hepatitis B vaccine. Quantitative determination of anti HBs levels was done by ELISA. The effect of gender, age, smoking, body mass index and duration after immunization on antibody levels were analyzed. Results: The association of anti-HBs status and gender was not statistically significant. Increase in age leads to decline of anti-HBs protective responders. Smoking and higher body mass index are significantly associated with less anti HBs titers (<10 mIU/ml). Conclusion: The highest number of protective responders is seen in initial 5 years post vaccination duration and least protective responders are observed in >10 years post vaccination duration, indicating decline in antibody response over a period of time.

Low-dose anti-hepatitis B immunoglobulin regimen as prophylaxis for hepatitis B recurrence after liver transplantation.

Combination of anti-hepatitis B immunoglobulin (HBIg) and antiviral nucleotide/nucleoside is the most common regimen for prophylaxis against hepatitis B virus (HBV) recurrence. However, what the optimal regimen is for HBIg administration remains subject to debate. Two hundred and thirty-two HBV patients who had liver transplantation were included in this study. According to the decline rate of HBIg, the patients were divided into quick (group Q, n=95) and slow decline groups (group S, n=137). Quick HBIg decline was defined as anti-HBs titer <200IU/mL at postoperative month (POM) 1, when 24000IU of HBIg was given perioperatively. HBV recurrence was defined as reappearance of hepatitis B surface antigen (HBsAg). After a mean (range) follow-up of 42.2 (24.1-76.8) months, the HBV recurrence rate was 12.1% for all 232 patients. The median (interquartile) HBIg titer was 96.2 (41.0-158.0) IU in group Q patients, compared to 418.0 (298.8-692.8) IU in group S patients at POM 1 (P<.001). For the patients in group Q, 18 patients (18.9%) had HBV recurrence; this was higher than the 10 (7.3%) patients in group S (P=.013). Multivariate analysis showed that quick HBIg decline and hepatocellular carcinoma recurrence were the risk factors for HBV recurrence. Perioperative low-dose HBIg and antiviral nucleotide/nucleoside can effectively prevent HBV recurrence in patients with slow HBIg decline. For patients with quick HBIg decline, the idealized HBIg and antiviral agent regimen should be adjusted to establish an effective regimen as prophylaxis against HBV recurrence.

Serological response to three alternative series of hepatitis B revaccination (Fendrix, Twinrix, and HBVaxPro-40) in healthy non-responders: a multicentre, open-label, randomised, controlled, superiority trial

Serological non-response can be present after hepatitis B vaccination in healthy adults. We aimed to establish which of three revaccination regimens is most effective at inducing protective immunity METHODS: Healthy adults (aged 18-80 years) from 16 Dutch centres (13 public health services, two university hospitals, and one travel clinic) were included in this multicentre, parallel group, randomised, controlled, superiority trial. The inclusion criterion was vaccine non-response (hepatitis B surface antibody [anti-HBs] titre <10 IU/L) after a primary series with three doses of one type of recombinant vaccine against hepatitis B virus (either HBVaxPro-10 or Engerix-B at months 0, 1, and 6). Participants were individually randomly assigned (1:1:1:1) to a vaccination series of repeated initial vaccination (HBVaxPro 10 μg or Engerix-B 20 μg) as the control, or to Twinrix 20 μg, Fendrix 20 μg, or HBVaxPro 40 μg. We used a web-based randomisation programme, stratified by centre, with a block size of four. Participants and centres were unmasked to assignment after randomisation. Laboratory staff and investigators were masked to vaccine-group assignment. All revaccination schedules were identical, with intramuscular vaccinations at 0, 1, and 2 months. Anti-HBs was measured at 0, 1, 2, and 3 months. The primary outcome was the percentage of responders (anti-HBs titres ≥10 IU/L) at 3 months. Immunogenicity and safety analyses were based on an intention-to-vaccinate analysis, the immunogenicity analysis with last observation carried forward for missing data, and the Bonferroni and the Benjamini-Hochberg method were applied to correct for multiple testing. The trial was registered in the Dutch National Trial Register and inclusion has been stopped (identifier NL3011; EudraCT-number 2011-005627-40). The participants were recruited between Nov 1, 2012, and Sept 1, 2017. 480 participants were randomly assigned and included in intention-to-vaccinate analyses: 124 (26%) to control, 118 (25%) to Twinrix, 114 (24%) to HBVaxPro-40, and 124 (26%) to Fendrix. At month 3 the percentage of responders was 83 (67%) of 124 (95% CI 57·9-75·1 in the control group, 94 (80%) of the 118 (71·3-86·5) in the Twinrix group, 95 (83%) of 114 (75·2-89·7) in the HBVaxPro-40 group, and 108 (87%) of 124 (79·9-92·4) in the Fendrix group. Compared with the control group, the percentage of responders was superior for the HBVaxPro-40 group (adjusted difference 21·6% [95% CI 10·4-32·7], p=0·0204 [Bonferroni corrected p value]) and the Fendrix group (26·3% [15·4-37·3], p=0·0006), but not the Twinrix group (25·0% [13·0-37·0]; p=0·0846). One serious adverse event occurred (herpes zoster ophthalmicus) in the Fendrix group, which was not attributed to the vaccine. Revaccinating healthy non-responders with Fendrix or HBVaxPro-40 resulted in significantly higher proportions of responders and therefore indication for these vaccines should be expanded to enable revaccination of non-responders. National Institute for Public Health and the Environment.

Long-term persistency of hepatitis B immunity: an observational cross-sectional study on medical students and resident doctors.

SummaryHepatitis B virus (HBV) is a main cause of chronic and acute hepatitis. Healthcare workers (HCWs), including medical students and resident doctors, have an occupational risk of HBV infection.The study aimed to evaluate the long-term persistence of protective anti-HBs antibody levels in healthcare students and resident doctors at risk for occupational exposure to HBV at 15 years after primary vaccination course. Further objective was to evaluate the anamnestic response observed in non-seroprotected subjects receiving a booster dose.Data were collected from the clinical documentation filled in during the occupational medical check of medical students and resident doctors undergoing Occupational Health Surveillance by the University of Ferrara.Of the 621 included individuals, 27.7% had an anti-HBs concentration < 10 mIU/mL. Subjects vaccinated during infancy had more frequently a concentration < 10 mIU/mL than those vaccinated during adolescence (42.7% vs 6.9%; p-value < 0.001). Multivariate analysis confirmed the statistical significance of the vaccination age. 94 subjects who had an anti-HBs concentration < 10 mIU/mL received a booster dose. The proportion of subjects who had an anamnestic response was higher in those vaccinated in infancy rather than during adolescence (94.1% vs 77.8% respectively).These findings suggest that the anti-HBs concentration decreases below 10 mIU/mL more frequently in subjects vaccinated during infancy. Immunological memory seems to persist after the decline of the anti-HB titer, as observed in response to a booster dose. In conclusion, vaccinated subjects at increased risk of HBV infection should be monitored and a booster dose administered if anti-HBs titer is below 10 mIU/mL.

Response to hepatitis B vaccination is co-determined by HLA-DPA1 and -DPB1

Background and aimsNo report explored the combined effects of HLA-DPA1 and -DPB1 with long-term response to hepatitis B (HB) vaccination (HBVac). The specific aims of the study were to assess the combined effects and relative contributions of DPA1 and DPB1 genes. MethodsThe cases were 152 adolescents who had undetectable (<1.0 mIU/mL) post-booster anti-HBs titers and the controls were adolescents who had residual anti-HBs ≥ 10 mIU/mL at aged 16 years (n = 207) or had detectable (≥1.0 mIU/mL) anti-HBs titers after booster HBVac (n = 481). HLA-DPA1 and -DPB1 genotypes were determined by sequence-based typing. ResultsHLA-DPA1*01:03:01 was correlated with lower ORs of undetectable anti-HBs titers, while -DPA1*02:02:02 and -DPB1*05:01:01 were correlated with higher ORs. The ORs for HLA-DPA1*01:03:01-DPB1*05:01:01 and DPA1*02:02:02-DPB1*protective combinatory types were significantly less than 1.0. As compared with subjects who had no protective allele, the adjusted ORs (95% CI) were 0.545 (0.328–0.906), 0.350 (0.174–0.702), and 0.122 (0.058–0.257), for subjects who had protective alleles on DPA1only, DPB1 only, and both genes, respectively. Analyses of amino acid polymorphisms showed that subjects who carried Arg81-Pro158-Val191-Pro259α + Met234β and Gln62-Arg82α + Met234β combinations had 4.3-to-4.6 folds of risks. ConclusionBoth DPA1 and DPB1 genes contribute to the persistence of immunological response to primary infantile HBVac. The effects of HLA-DP risk alleles were dominated by the protective alleles and there were significant gene-gene interactions. Our findings provide evidences for the design of more potent HB vaccine.

New Markers in Monitoring the Reactivation of Hepatitis B Virus Infection in Immunocompromised Hosts.

Hepatitis B virus (HBV) persistence is at the basis of HBV reactivation as a consequence of chemotherapy and immunosuppressive treatments. The identification of early viral replication indicators and markers of effective HBV immunological control would be useful in monitoring patients who are at risk of potential viral reactivation during the course of immunosuppressive treatment. Currently, international guidelines have shared some criteria to identify patients with a low, medium or high risk of HBV reactivation; however, permanently placing a patient in a definitive category is not always easy. More often, patients move from one category to another during the course of their immunosuppressive treatment; therefore, in many cases, there are no precise indicators or tools for monitoring possible reactivation and establishing the duration and suspension of antiviral prophylaxis. Historically, the sequence of HBV antigens and antibodies and HBV DNA levels has been used to evaluate the different stages of the acute and chronic phases of an HBV infection. In the last few years, new biomarkers, such as anti-HBs and anti-HBc titres, HBV core-related antigen (HBcrAg), ultra-sensitive HBsAg evaluation and HBV RNA, have been used in patients with an HBV infection to evaluate their diagnostic and prognostic potential. The aim of this review is to evaluate the published results on the use of new infection markers in the diagnosis and monitoring of HBV reactivation over the course of immunosuppressive treatments. Moreover, the importance of viral genotypic studies was emphasized, given the diagnostic and therapeutic implications of the mutational profiles of HBsAg during the HBV reactivation phase.

Association between Body Mass Index and Hepatitis B antibody seropositivity in children.

BackgroundThe seropositivity rate of hepatitis B surface antigen (anti-HBs) antibodies is known to be ≥95% after hepatitis B virus vaccination during infancy. However, a low level or absence of anti-HBs in healthy children is discovered in many cases. Recent studies in adults reported that a reduced anti-HBs production rate is related to obesity.PurposeTo investigate whether body mass index (BMI) affects anti-HBs levels in healthy children following 3 serial dose vaccinations in infancy.MethodsWe recruited 1,200 healthy volunteers aged 3, 5, 7, or 10 years from 4-day care centers and 4 elementary schools. All subjects completed a questionnaire including body weight, height, and vaccine type received. Levels of serum hepatitis B surface antigen (HBsAg) and anti-HBs in all subjects were analyzed using electrochemiluminescence immunoassay. The standardized scores (z score) for each sex and age were obtained using the lambda-mu-sigma method in the 2017 Korean National Growth Charts for children and adolescents.ResultsOur subjects (n=1,200) comprised 750 males (62.5%) and 450 females (37.5%). The overall anti-HBs seropositivity rate was 57.9% (695 of 1,200). We identified significant differences in mean BMI values between seronegative and seropositive groups (17.45 vs. 16.62, respectively; P<0.001). The anti-HBs titer was significantly decreased as the BMI z score increased adjusting for age and sex (B=-15.725; standard error=5.494; P=0.004). The probability of anti-HBs seropositivity based on BMI z score was decreased to an OR of 0.820 after the control for confounding variables (95% confidence interval, 0.728–0.923; P=0.001).ConclusionThere was a significant association between anti-HBs titer and BMI z score after adjustment for age and sex. Our results indicate that BMI is a potential factor affecting anti-HBs titer in healthy children.