Low anti-HBs Titers Research Articles

Risk factors of HBV reactivation in leukemia patients with resolved HBV infection after allogeneic hematopoietic stem cell transplantation

BackgroundThe hepatitis B surface antigen (HBsAg)–negative and antibody to hepatitis B core antigen (anti-HBc)–positive patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of HBV reactivation (HBVr). MethodsTo analyze the risk factors for HBVr, a total of 1,042 leukemia patients(≥18years of age), who underwent allo-HSCT from January 2016 to April 2022 in The First Affiliated Hospital of Soochow University, were enrolled in the study. Finally, 193 leukemia patients with resolved HBV infection were included into the study. ResultsHBVr occurred in 22 patients (11.39 %), and the median time to HBVr was 24 months (with a range of 11-51months). Hepatitis flares developed in 22.73 % of patients with HBVr, and hepatic failure occurred in 1 patient. During the follow-up period, only 1(1.3 %) patient experienced HBVr among 79 patients with antiviral prophylaxis. While 21(18.42 %) patients experienced HBVr among 114 patients without antiviral prophylaxis. The cumulative incidence of HBV reactivation at 3 years was 44.4. % for anti-HBs-negative donors/recipients with a low anti-HBs titer (<100IU/L) and 7.1 % for anti-HBs-positive donors/recipients with a high anti-HBs titer (≥100IU/L) respectively. In addition, univariate and multivariate Cox regression analyses confirmed the use of rituximab as a risk factor for HBV reactivation. ConclusionThe univariate and multivariate analyses confirmed that the anti-HBs titer in both recipients and donors are protective indicators to prevent incidence of HBVr. In addition, antiviral prophylaxis can significantly reduce the incidence of HBVr.

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

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. 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). 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.

Acute hepatitis B virus infection despite vaccination in a patient treated by infliximab: a case report

BackgroundDespite an effective vaccine, hepatitis B remains a major global health problem due to its significant morbidity and mortality. Vaccination in immunosuppressed patients such as those treated for an inflammatory bowel disease (IBD) can be less effective. This case describes an uncommon original diagnosis of an acute hepatitis B infection occurring in a vaccinated but immunocompromised IBD patient under long-term infliximab treatment. A low anti-HBs titer and the presence of HBsAg escape mutations are possible hypotheses to explain this unexpected infection.Case presentationA 28-year-old Caucasian male, regularly followed-up for a Crohn’s disease treated by infliximab, was regularly screened for sexually transmissible infections because of at-risk behaviors. Despite a correct immunization scheme against hepatitis B virus (HBV), an active HBV infection was diagnosed during one of those screenings. Retrospective testing of a sample collected 6 months earlier was in favor of an evolution from an acute hepatitis B toward a chronic hepatitis B. The patient has always had a low anti-HBs antibody levels (near the threshold of 10 IU/L) possibly explaining his infection. In addition, HBV sequencing revealed a genotype A2 HBV strain, carrying the sD144A substitution on the S protein, known as a potential immune escape variant. Dual therapy combining tenofovir disoproxil fumarate and emtricitabine, active against HBV but also efficient as an HIV pre-exposure prophylaxis, was initiated. Ten months after treatment initiation, all surrogate biochemical and virological endpoints for HBV functional cure were achieved. Treatment and periodical monitoring are being maintained.ConclusionEmphasis should be placed on HBV screening, vaccination and regular monitoring of patients under long-term immunosuppressive therapy, particularly those with at-risk behaviors.

Estimation of Anti-HBs Titer in Health Care Professionals of a Tertiary Care Centre of Southern Assam

Background- Due to occupational exposure to blood, body fluids and sharps, the health care professionals are at increased risk of contracting the Hepatitis B virus infection than general population. To combat this, all the health care professionals must be immunized with protective level of anti-HBs but anti-HBs titer gradually wanes with passage of time and may be influenced by gender, smoking or chewing tobacco, diabetes mellitus etc. This study was thus carried out to find the percentage of health care professionals with protective titer of anti-HBs and find the association (if any) of low anti-HBs titer and factors like gender, smoking, diabetes mellitus and time elapsed post vaccination. Method- This cross-sectional study has been carried out with proper ethical clearance from May2018- September2019 in Serology section of VRDL under Department of Microbiology in a Medical College of Southern Assam on serum samples collected from 150 health care professionals vaccinated with 3 doses of recombinant HBsAg vaccine atleast 5years back. Anti-HBs IgG concentration was measured by conventional ELISA in multistandard mode. Result- Out of 150 participants,95 were males and 55 were females.27 participants smoked/chewed tobacco,8 had diabetes mellitus. Booster dose was received by 23. Protective level of anti-HBs IgG (&gt;10 IU/ml) was found in 66% (98/150) of HCP only. Low anti-HBs titer has been found to be significantly associated with Diabetes mellitus (p–0.03) and passage of more than 10 years post primary vaccination(p-0.005) but no significant association has been found with gender, smoking and history of blood transfusion. Conclusion- HBsAg vaccine doesn’t impart everlasting protection. So, all HCP, especially those with co-morbidities should get their anti-HBs titer estimated after vaccination to check out for adequate seroconversion and attainment of protective titer. If found inadequate, they should go for repeat vaccination /booster doses. Keywords: Healthcare professionals, Vaccinated, Anti HBs IgG, Assam,

Immune response to hepatitis B vaccination and factors associated with poor immune response among healthcare workers.

Hepatitis B virus (HBV) infection is a major global health problem, and healthcare workers (HCWs) are at high risk for HBV infection. Current guidelines strongly recommend immunization and screening for high-risk groups. We evaluated immunization and screening for HBV vaccination, assessed post-vaccination immune status of HCW's and characterized potential risk factors associated with poor immune response. From January 2010 to December 2018, we retrospectively analyzed comprehensive health checkup data for a total of 303 HCWs who received an HBV vaccination. After vaccination, HBV surface antibody (anti-HBs) titers were collected and the distribution of immune response types was determined. Risk factors for poor immune responses were identified using logistic regression. A total of 213 HCWs were analyzed after exclusion based on the exclusion criteria. In total, 28 (13.2%) HCWs had anti-HBs titers <100 mIU/mL (hyporesponsive/nonresponsive groups), and 185 (86.8%) had anti-HBs titers ≥100 mIU/mL (hyperresponsive group). Follow-up observations found that 75% (21/28) of the hyporesponsive/nonresponsive groups did not have increased anti-HBs titers or did not maintain an increased response. A multivariate analysis showed that HBV antibody titers at the time of employment were a significant risk factor (OR, 6.12; CI, 1.34-27.93; P = 0.019). More attention should be paid to groups that are hyporesponsive/nonresponsive after vaccination and to those with low anti-HBs titers at the beginning of employment. HCWs can be further protected from HBV if their results are discussed at postvaccination follow-ups.

Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study

BackgroundHepatitis B virus (HBV) reactivation consequent to immunosuppressive therapy is an increasingly prevalent problem with serious clinical implications. Treatment with biologic agents conduces to the loss of protective antibody to HBV surface antigen (anti-HBs), which significantly increases the risk of HBV reactivation. Hence, we investigated the risk factors for losing anti-HBs in patients with rheumatic diseases and HBV surface antigen negative/anti-HBs positive (HBsAg−/anti-HBs+) serostatus during treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs).MethodsUsing a nested case-control design, we prospectively enrolled patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis/psoriasis, or juvenile idiopathic arthritis, who were treated with biologic DMARDs at Changhua Christian Hospital, Taiwan, from January 2013 to June 2019 and had HBsAg−/anti-HBs+ serostatus; the analytic sample excluded all patients with HBsAg+ or anti-HBs− serostatus. Anti-HBs titers were monitored 6-monthly and cases were defined as anti-HBs < 10 mIU/ml during follow-up. Cases were matched one-to-all with controls with anti-HBs ≥ 10 mIU/ml on the same ascertainment date and equivalent durations of biologic DMARDs treatment (control patients could be resampled and could also become cases during follow-up). Between-group characteristics were compared and risk factors for anti-HBs loss were investigated by conditional logistic regression analyses.ResultsAmong 294 eligible patients, 23 cases were matched with 311 controls. The incidence of anti-HBs loss was ~ 2.7%/person-year during biologic DMARDs treatment. Besides lower baseline anti-HBs titer (risk ratio 0.93, 95% CI 0.89–0.97), cases were significantly more likely than controls to have diabetes mellitus (risk ratio 4.76, 95% CI 1.48–15.30) and chronic kidney disease (risk ratio 14.00, 95% CI 2.22–88.23) in univariate analysis. Risk factors remaining significantly associated with anti-HBs loss in multivariate analysis were lower baseline anti-HBs titer (adjusted risk ratio 0.93, 95% CI 0.88–0.97) and chronic kidney disease (adjusted risk ratio 45.68, 95% CI 2.39–871.5).ConclusionsBesides lower baseline anti-HBs titer, chronic kidney disease also strongly predicts future anti-HBs negativity in patients with HBsAg−/anti-HBs+ serostatus who receive biologic DMARDs to treat rheumatic diseases. Patients with low anti-HBs titer (≤ 100 mIU/ml) and/or chronic kidney disease should be monitored during biologic DMARDs therapy, to enable timely prophylaxis to preempt potential HBV reactivation.

Heart Retransplantation from an Anti-HBcore Positive Donor

Introduction The number of transplantations from an anti-HBcore positive donor to a seronegative recipient is still low. We present the first documented case in the history of the Silesian Center for Heart Diseases in Zabrze of a successful retransplantation from an HBcAb (+) donor to a seronegative recipient. Case Report A 45-year-old male patient after HTX in 2014 due to NICM was admitted with the signs and symptoms of heart failure. Severe mitral and tricuspid regurgitation and impaired systolic function of the graft were observed (LVEF 25%, RV hypokinesis). Vasculopathy was excluded, endomyocardial biopsy revealed no signs of acute cellular rejection (ACR 0). Due to the further deterioration, a decision of urgent heart retransplantation was made. A suitable donor with positive HBcAb antibodies and a negative HBs antigen was reported. After obtaining written informed consent, urgent orthotopic heart retransplantation was performed. The patient was vaccinated against hepatitis B, but the level of antibodies was undetectable. Pre-transplantation prophylaxis with lamivudine combined with subsequent valgancyclovir CMV prophylaxis was made. Active inflammatory cardiomyopathy of the explanted heart was diagnosed (histological examination). Inflammation of the transplanted heart was present despite no signs of cellular rejection in the endomyocardial biopsy. After the retransplantation signs of ACR in the 3a class were observed twice in the two first biopsies. High levels of GGTP (max. 692 U/l) and ALP (max. 214 U/l) were found in the second month after the transplantation. Transaminase and bilirubin levels were normal, abdominal US showed no pathology. The results improved in the follow-up. No manifestation of ACR and normal graft function were observed. After three months, valganciclovir prophylaxis was completed. The patient still received lamivudine (up to one year). In the repeated assessments, negative HBs antigen and low anti-HBs titers were found. Summary We present a case report of heart retransplantation due to graft failure from an anti-HBcore positive and HBs antigen negative donor to a seronegative recipient. Based on anatomopathological and histopathological examination of the explanted graft, we also suggest that acute cellular rejection in the transplanted heart may exist despite negative findings in right-sided endomyocardial biopsy.

Cryptic HBV Replicative Activity Is Frequently Revealed in Anti-HBc-Positive/HBsAg-Negative Patients with HIV Infection by Highly Sensitive Molecular Assays, and Can Be Predicted by Integrating Classical and Novel Serological HBV Markers.

The anti-HBc-positive/HBsAg-negative status is frequent in HIV-infection and correlates with poor survival. Here, by highly-sensitive assays, we evaluate cryptic HBV replication and factors correlated with its detection in 81 anti-HBc-positive/HBsAg-negative HIV-infected patients. Patients were treated for >12 months with HBV-active modern combined antiretroviral-therapy (cART) and had serum HBV-DNA < 20 IU/mL by commercial Real-Time PCR. Serum HBV-DNA was quantified by droplet digital PCR, serum HBV-RNA by an Abbott research assay, and anti-HBc titer (proposed to infer intrahepatic cccDNA) by Lumipulse/Fujirebio. Cryptic serum HBV-DNA was detected in 29.6% of patients (median (IQR): 4(1–15) IU/mL) and serum HBV-RNA in 3.7% of patients despite HBsAg-negativity and HBV-active cART. Notably, cryptic serum HBV-DNA correlated with an advanced CDC-stage (p = 0.01) and a lower anti-HBs titer (p = 0.05), while serum HBV-RNA correlated with lower nadir CD4+ cell-count (p = 0.01). By analyzing serological HBV-markers, the combination of anti-HBs < 50 mIU/mL (indicating lower immune response) plus anti-HBc > 15COI (reflecting higher HBV replicative activity) was predictive of cryptic serum HBV-DNA (OR: 4.7(1.1–21.7), p = 0.046, PPV = 62.5%, and NPV = 72%). In conclusion, cryptic HBV-replication (not detected by classical assays) characterizes a conspicuous set of anti-HBc-positive HIV-infected patients despite HBsAg-negativity and HBV-active combined antiretroviral therapy (cART). The integration of classical and novel markers may help identify patients with cryptic HBV-replication, thus optimizing the monitoring of anti-HBc-positive/HBsAg-negative HIV-infected patients.

Breakthrough HBV Infection in Children with Acute Lymphocyte Leukemia During Chemotherapy: A Prospective Study

Background: Acute lymphocyte leukemia (ALL) is the most common cancer in children, and chemotherapy is the most effective treatment in clinical practice. The risk of occult hepatitis B virus (HBV) reactivation in adults patients undergoing immunosuppressive therapy has become more and more prominent. However, there were no study about the happening of HBV infection in ALL patients. In this study, we tried to explore the occurrence of HBV infection in child patients with ALL during chemotherapy. Methods: Seven hundred and thirty one child patients were involved in this study, who were diagnosed with ALL and receiving chemotherapy between August 2012 to December 2017. Demographic characteristics, clinical profile and changes of HBV seromarker in subjects pre- and during-chemotherapy were collected. Findings: Breakthrough HBV infection was identified in four subjects between 397 to 560 days after chemotherapy. During chemotherapy, high proportions of anti-HBc and anti-HBe seroconversion were found in child patients with ALL. Significantly low anti-HBs titers was detected in the HBV breakthrough patients. Interpretation: Breakthrough HBV infections could occur in ALL children during immunosuppressive therapy. The reactivation of occult HBV infection and transmit by blood transfusion should be take more attention. For the ALL child patients, the better time point for HBV infection test are between one and two years after chemotherapy. Younger child patients with significantly lower titers of protective anti-HBs during chemotherapy might have higher risk of breakthrough HBV infection. Funding Statement: This study was supported by the National Natural Science Foundation of China (No.81371876), Health and Family Planning Commission of Chongqing [2013] 39-2013-1-025 and Chongqing Municipal Colleges and Universities Outstanding Talent Support Program and Outstanding Youth Foundation of Children's Hospital of Chongqing Medical University. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study was approved by the Ethics Review Committee of Children’s Hospital of Chongqing Medical University.

Prevalence and risk factors of hepatitis B virus reactivation in patients with solid tumors with resolved HBV infection.

BackgroundReports of hepatitis B virus (HBV) reactivation in solid tumors are very limited, and their frequencies and risk factors were previously unknown.AimTo evaluate the prevalence and risk factors of HBV reactivation in patients with solid tumors with resolved HBV infection.MethodsAll 1088 patients with solid tumors were assessed for eligibility; 251 patients had resolved HBV infection (negative for HBs antigen and positive for anti‐HBc antibody and/or positive for anti‐HBs antibody), and HBV‐DNA was assessed for 243 of these patients in whom we analyzed the prevalence of HBV reactivation. Risk factors for HBV reactivation were exploratorily evaluated by analysis of a case–control study.ResultsThe prevalence of HBV‐DNA reactivation was 2.1% (95% confidence interval [CI], 0.3–3.9%). We did not observe any exacerbation of HBV‐DNA by early intervention. A low anti‐HBs antibody titer (<10.0 mIU/mL) and high average daily dexamethasone dose (>1.0 mg/day) were high risk factors, with odds ratios of 5.94 (95% CI, 1.15–30.6, P = 0.03) and 8.69 (95% CI, 1.27–58.8, P = 0.02), respectively.ConclusionHBV reactivation in solid tumor patients was relatively rare. Therefore, risk factors that can identify targets for HBV screening must be determined in future studies.

Immunogenicity of compulsory and booster doses of hepatitis B vaccine among children in Cairo, Egypt.

Although Egypt had adopted implementation of routine infant hepatitis B virus (HBV) vaccination in 1992, its effectiveness is not evaluated on a national scale. Assessment of early and long-term seroprotection after compulsory vaccination is an important measure for monitoring the success of the vaccination program. The aim of this study was to assess HBV seroprotection and immune memory in children and adolescents who were vaccinated during infancy in Cairo Governorate. The study was carried out in two phases. The first phase was a cross-sectional study carried out in five districts in Cairo Governorate, recruiting 819 children in the age range of 9 months to 16 years. All children had received full doses of the compulsory HBV vaccination. Serum samples were taken from each child and assessed for antibody against hepatitis B virus surface antigen (anti-HBs) titer; total antibodies against HBV core antigen, and HBV surface antigen. HBV DNA was investigated by real-time PCR for those who were HBV core antigen or HBV surface antigen positive. In the second phase, nonseroprotected children (anti-HBs <10 IU/I) received HBV booster dose. AntiHBs titer was reassessed after 4 weeks to identify anamnestic response. Individuals showing antibody concentrations ofless than 10 IU/l were then given an additional complete course of vaccination. Four out of 819 children had HBV breakthrough infection. The seroprotection rate was 60.7%, and was significantly higher among children aged less than 5 years compared to the older age groups and among boys compared to girls. Multivariate logistic analysis showed age as the only independent predictor of low anti-HBs titer. About 95% of nonseroprotected children developed anamnestic response postbooster. Anti-HBs geometric mean titer (GMT) increased significantly from pre-booster (13.8±16.9IU/L) compared to post-booster (307±6.0IU/L, P<0.001). Anti-HBs GMT was significantly higher among children with prebooster anti-HBs level ≥1 IU/l (424.9±4.4 IU/l) compared to children with undetectable level (178.3±8.3). Despite waning of anti-HBs over time, long-term protection still exists. The high anamnestic response rate signifies the existence of immune memory and giving a booster dose is not recommended. However, we suggest that prolonged follow up and surveillance of vaccinees immunized at an early age should be continued.

Development of an Allergy Immunotherapy Leads to a New Type of Hepatitis B Vaccine

Hepatitis B is an old disease and the possibility to successfully vaccinate against infection by hepatitis B virus (HBV) was first shown 36 years ago in a convincing trial (Szmuness et al., 1980). Thus, it may appear unspectacular when in this issue of EBioMedicine, a small clinical trial with a new type of hepatitis B vaccine is described (Cornelius et al., 2016). Do we really need this? But the significance of the paper should not be underestimated. The classical hepatitis B vaccine is produced in genetically transformed yeast cells and consists of 20-nm-large particles formed by the small (S) protein of hepatitis B surface antigen (HBsAg). The antibodies against conformational epitopes of HBsAg (anti-HBs) neutralize the infectivity of hepatitis B virus (HBV) in vitro and indicate protection in vivo. However, the classical vaccine has some shortcomings. In spite of multiple injections some persons remain unprotected, particularly those with a weakened immune response. Furthermore, asymptomatic infections by heterologous HBV genotypes with transient viremia are frequent in vaccinated subjects with low or moderate anti-HBs titers (for review see Gerlich, 2015). While the WHO, public health authorities and the main producers of hepatitis B vaccines still consider these drawbacks as insignificant, an enhanced protective capacity against a wider HBV genotype spectrum would not hurt.

High titers of anti-HBs prevent rituximab-related viral reactivation in resolved hepatitis B patient with non-Hodgkin's lymphoma.

Rituximab, an anti-CD20 monoclonal antibody, is associated with an increased risk of hepatitis B virus (HBV) reactivation. This study aimed to determine the predictive factors for rituximab-related HBV reactivation in resolved hepatitis B patients, defined as HBsAg-negative, anti-HBc-positive, and undetectable HBV DNA. Among 840 consecutive patients with CD20-positive B-cell lymphoma who received rituximab-based chemotherapy from 2003 through 2014 at Seoul National University Hospital, 732 patients were excluded because either anti-HBc was not assessed or they were HBsAg-seropositive. This retrospective study included 108 resolved hepatitis B patients. During a median 33.5-month follow-up period, eight cases of HBV reactivation occurred only among the patients with low anti-HBs titers (<100 mIU/ml) at baseline and those who did not receive antiviral prophylaxis. Using multivariate analyses, antiviral prophylaxis and baseline anti-HBs titers were the protective factors for HBV reactivation (hazard ratio [HR], 0.90 and 0.95, respectively). Among those who did not receive antiviral prophylaxis, patients with high baseline anti-HBs (≥100 mIU/ml) experienced significantly lower risk of HBV reactivation (HR, 0.49; P = 0.006) than the patients with low baseline anti-HBs (<100 mIU/ml) whose cumulative HBV reactivation rates at 6 and 24 months after chemotherapy were 8.3% and 17.3%, respectively. High anti-HBs titer at baseline and antiviral prophylaxis prevented HBV reactivation, suggesting antiviral prophylaxis should be considered according to baseline anti-HBs titer. Meticulous follow-up for ALT and HBV DNA without antiviral prophylaxis might be possible for the patients with high baseline anti-HBs (≥100 mIU/ml).

The yield of universal antibody to hepatitis B core antigen donor screening in the Netherlands, a hepatitis B virus low-endemic country.

In the Netherlands, universal antibody to hepatitis B core antigen (anti-HBc) donor screening was introduced in July 2011 to intercept potentially infectious donations slipping through hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA minipool screening (HBV DNA MP6). The yield and donor loss were evaluated after the first 2 years of universal anti-HBc donor screening. A total of 382,173 donors were tested for anti-HBc and, if positive, for antibody to HBsAg (anti-HBs). Anti-HBc-reactive donors with anti-HBs of less than 200 IU/L were deferred, but repeat donors were allowed retesting after 6 months if anti-HBs was less than 10 IU/mL. Anti-HBc false positivity was estimated using the crude anti-HBc signal, family name-based ethnicity scoring, and donor follow-up. Anti-HBc screening identified 13 confirmed or potential HBsAg- and HBV DNA MP6-negative recent HBV infections. In addition, 820 anti-HBc-reactive donors with low anti-HBs titers (<200 IU/mL), potentially harboring occult HBV infection (OBI), were identified and deferred. Overall, 1583 (0.41%) donors were deferred: 1178 (0.31%) during first-time anti-HBc screening, 361 (0.09%) anti-HBc seroconverters, and 44 (0.01%) donors with waning anti-HBs titers. Only 188 of 1583 (12%) deferred donors could be reentered upon retesting. Estimated anti-HBc false positivity was 16%, but varied greatly among anti-HBc-reactive donors with and without anti-HBs (8% vs. 62%). Anti-HBc testing has improved the safety of the Dutch blood supply but its exact yield remains difficult to determine, due to the complexity of confirming anti-HBc reactivity and OBI. In a low-endemic country, donor loss associated with anti-HBc screening is sustainable, but adds to the already considerable list of donor exclusions.

Hepatitis B Immunoglobulin Prophylaxis after Liver Transplantation: Experience in a Tertiary Transplant Centre

Prophylaxis with hepatitis B immunoglobulin (HBIG) and nucleoside analogs can prevent hepatitis B virus (HBV) recurrence after liver transplant (LT). To determine the efficacy and cost of maintaining immunoprophylaxis with HBIG and hyperimmune plasma (HIP) for 6 months after LT. The study included 22 HBV related LT recipients who were on entecavir and either HBIG or HIP for 6 months. Post transplant HBIG or HIP dose and cost incurred towards prophylaxis were noted. The cost of 200IU of HBIG at the time of study was Rs 8250/- (US Dollars 135) and that of 2000IU of HIP was Rs 8000/- (USD 130.7). The loading and maintenance costs at end of 6 months were compared between the two groups. Response to HBIG and HIP was assessed by checking for HBsAg reactivity, anti HBs titer response and HBV DNA viral load. Median and range, Kruskal Wallis (KW) sign rank Sum Test and Correlation Coefficient (r2) was used for analysis. Thirteen recipients received HBIG and 9 recipients HIP. The anti HBs response to HIP was significantly high compared to HBIG (KW Sign rank Sum test P<0.05); titers remained high until the study period. Between 8 and 30 days, the titer achieved by both HBIG and HIP was similar (KW Sign rank Sum test not significant). Despite low anti HBs titer of <100IU/L, none of the recipients on HBIG had HBsAg reactivity while 3 on HIP had transient HBsAg positivity. The total cost with HBIG was 13.9 times the cost of HIP. HIP immunoprophylaxis in combination with entecavir achieves a high anti HBs titer at a significant low cost during anhepatic and loading phase. HBV reactivation rates with HBIG and HIP is low despite low anti HBs titer.

Infectivity of occult hepatitis B from two different points of view

Infectivity of occult hepatitis <scp>B</scp> from two different points of view

Occupational exposure to blood borne viruses among healthcare workers in a tertiary care referral hospital in tehran.

Dear Editor, Occupational exposure to blood-borne viruses (BBVs) is a major concern in the health care setting. The BBVs of primary concern are the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Health care workers (HCWs) can be exposed to these viruses through needle-stick and other injuries through contaminated material with blood and other infectious body fluids. Nurses, health technicians, cleaning personnel and physicians are potentially targets for such accidents. The Center for Disease Control and Prevention (CDC) estimates that hospital-based healthcare personnel sustain an estimated 385,000 percutaneous injuries (needle-sticks and other sharp-devices) (1) annually. In Iran, the annual incidence of occupational exposure to BBVs is unknown due to the limited data in this area. The World Health Organization (WHO) estimates that more than two million injuries causes about 66,000 HBV, 16,000 HCV and about 1,000 HIV infections among 35 million HCWs each year (2). The key in reducing accidental exposure to BBVs is through promoting educational awareness of health care staff on suitability of HBV vaccination, in house training courses concerning preventive measures of such accidents and implementing proper postexposure prophylaxis (PEP) and following-up. Here, we reviewed case notes of 193 HCWs accidently exposed to BBVs over four-years, from January 2009 to January 2013. The data were reviewed in Labbafinejad hospital, which is a specialized 231 bed public tertiary care referral hospital with a total number of 915 HCWs who are potentially at accidental risk of acquiring BBVs. The study was approved by the ethics committee in the hospital. The reviewed HCWs cases (193) were classified into 75 nurses, 39 medical doctors, 35 cleaning personnel, 30 medical technicians (17 surgical operation technicians, 10 lab technicians and 3 radiology technicians), 13 nursing students and 1 medical student. In this study, the nurses were in top list of accidental exposure, which is in line with other studies (3, 4). Injuries were categorized as follows; 150 had needle-stick injuries, 22 cases had sharp cuts like scalpel and broken glasses and 21 cases had blood splashes on their eyes. Among these 193 cases, 132 HCWs were exposed to known serologically tested HIV, HBV and HCV negative patients, 24 had exposure to HBsAg positive patient, 5 had exposure to anti-HCV positive patients and two were exposed to HIV seropositive patient (one was co-infected with HCV infection). A total of 30 HCWs had occupational exposures to unknown sero-status patients. Anti-HBs antibody titer of the 24 HCWs, who had HBV exposure, was higher than 200 mIU/mL. Therefore, no intervention was done for them expect one who, despite being vaccinated had low anti-HBs titer. Thus, he was treated with hepatitis B immunoglobulin (HBIG) with another full course of hepatitis B vaccine, as routine schedule. Six patients were exposed to HCV seropositive patients; they underwent lab investigations, the result of that was normal for everyone. In these patients, follow up 2 weeks RT-PCR was negative. Thereafter, 1, 3, 6 months lab investigations were repeated and results were negative. One HCW was exposed to seropositive HIV patient, as the result of which he received PEP for HIV infection and underwent follow up and the result was negative. Another HCW was exposed to seropositive HIV coinfected with HCV. He also received PEP for HIV and underwent follow up lab investigation for HCV infection and lab results were negative. Hence, no further action was advised. PEP therapy has been shown to reduce the risk of transmission of HIV following accidental exposure by 80% (5). In conclusion, avoiding accidental occupational exposure to BBVs is an important safety issue, which can be achieved to some extent by health awareness of the problem and further by strengthening health control measures and providing a safe hospital work environment.

Variable presentation of primary immune deficiency: Two cases with CD3 gamma deficiency presenting with only autoimmunity

CD3 chain expression defects including CD3 gamma, epsilon, delta, and zeta chain subunits, are autosomal recessive inherited severe combined immunodeficiencies (SCID). The phenotype is usually T-B+NK+ SCID with lymphopenia where the clinical findings may be mild (CD3γ) or severe (CD3δ, ε, ζ) owing to the underlying molecular defect. There is limited information about the disease in literature. Here, we present two siblings from non-consanguineous family with autoimmunity including Evans syndrome, autoimmune hepatitis, nephrotic syndrome, and Hashimoto's thyroiditis and with no previous history of infections. To define the molecular basis of the disease, we performed linkage analysis around the CD3 receptor cluster and found consistent linkage to this region. The patient one displayed low TCRαβ expression, low IgG, low IgA, low IgM, low CD3, low CD4, low CD8. The patient two also displayed low TCRαβ expression and low anti-HBs titer. We went onto identify a homozygous splicing mutation (IVS2-1G>C) in the two affected individuals in the CD3γ gene. To date, only four cases have been reported with CD3γ deficiency. Occasionally, the patients present with only autoimmunity including autoimmune hemolytic anemia, vitiligo, Hashimoto's thyroiditis, and autoimmune enteropathy. However, Evans syndrome, autoimmune hepatitis, and nephrotic syndrome have not been reported in previous cases. We believe that our cases will contribute to the literature.

Excellent Liver Transplantation Survival and Prevention of Hepatitis B Recurrence Using Hepatitis B Immunoglobulin and Nucleoside or Nucleotide Analogue Along With Treating Physician Adherence to Treatment Protocol

IntroductionThe introduction of hepatitis B immunoglobulin (HBIG) in the early 1990s dramatically reduced recurrence of hepatitis B after orthotopic liver transplantation (OLT) and thus improved survival. Today a combination of HBIG and a nucleoside or nucleotide analogue (NUC) is recommended as prophylaxis. The optimal protocol is yet to be commonly agreed upon. The aim of this study was to review our results over 25 years. Patients and MethodsAll 56 patients (45 males and 11 females) who underwent OLT due to hepatitis B infection between 1985–2009 were included in the review. Median age at transplantation was 51 years (range, 18–66). Seventeen patients (30%) had hepatocellular carcinoma (HCC) at transplantation. ResultsThe 1- and 5-year overall survival rates were 89% and 77%, respectively. The 23 patients who underwent transplantation before 2000 showed 1- and 5-year survival rates of 82% and 61%, respectively; the 33 who underwent transplantation between 2000 and 2009, the rates were 94% and 90%, respectively (P < .01). There was no difference in the 5-year survival rate between patients who had or did not have been HCC (75% vs 78%, respectively). Recurrence of hepatitis B, defined as seroconversion to HBsAg positivity, was observed in 9 patients. Three transplantation cases before 1992 consequently did not receive HBIG. The remaining 6, who all underwent OLT between 1993 and 2001, were administered HBIG. In all 6 cases periods of low anti-HBs titers were registered prior to recurrence; treating physician noncompliance with the protocol may have contributed to the low anti-HBs titers. No recurrence was registered after 2001. ConclusionWith a combination of HBIG and NUC, excellent OLT results can be achieved for hepatitis B. It is, however, still important to maintain sufficient anti-HBs titers to prevent recurrence.

Efficacy of hepatitis B vaccine boosters among neonatally vaccinated university freshmen in Taiwan

Long-term protection against hepatitis B virus (HBV) after vaccination remains widely debated. We evaluated the efficacy of a modified 3-dose booster protocol in neonatally vaccinated university students in Taiwan. Changes in the levels of antibodies to the hepatitis B surface antigen (anti-HBs) were examined in 250 university students over a 3-year period. Group A (n=39) lacked seroprotective levels of anti-HBs, and declined to receive a booster dose of the HBV vaccine. Group B (n=128) lacked seroprotective levels of anti-HBs, and received booster doses of the HBV vaccine according to a modified 3-dose booster protocol. Group C (n=83) possessed seroprotective levels of anti-HBs, and did not receive a booster dose. The levels of seroprotective anti-HBs increased in 12.8% of Group A and 14.5% of Group C, suggesting that our entire cohort had experienced booster effects from natural HBV exposure. However, no new HBV infections were observed, and 53.9% of Group B maintained protective levels of anti-HBs during the follow-up period. The use of the modified 3-dose booster protocol induced significant long-term increases in the titer of anti-HBs in over 50% of the neonatally vaccinated participants with previously non-protective titers. However, in the absence of a vaccine booster, some neonatally vaccinated people with low anti-HBs titers may nonetheless produce anamnestic responses to HBV upon exposure, suggesting that protection from neonatal vaccination may persist, despite low titers of anti-HBs.