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Background/Aims There have been numerous efforts to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV) with antiviral agents during pregnancy. However, there are limited data regarding the outcomes of pregnant women after delivery. This study was performed to evaluate the efficacy of antiviral agents in preventing MTCT of HBV and maternal long-term outcomes. Methods The HBV-infected pregnant women treated with antiviral agents to prevent MTCT were retrospectively reviewed. Forty-one pregnant women who received telbivudine or tenofovir during late pregnancy (28-34 week) were analyzed. Hepatitis B virus surface antibody (HBsAb) positivity was tested in 43 infants after 7 months of birth. Eleven mothers were followed >1 year after delivery. Results The mean HBV DNA titer before antiviral therapy was 8.67 (6.60–9.49) log copies/mL, and the median age at delivery was 32 years (range, 22–40). Eleven patients were treated with tenofovir and 30 with telbivudine. The median duration was 57 days (range, 23–100), and the median HBV DNA titer at birth was 5.06 log copies/mL (range, 2.06–6.50). Antiviral treatments were associated with significant HBV DNA reduction (P12 months, and an antiviral agent was administered. Conclusions Antiviral treatment during late pregnancy effectively reduced MTCT. Long-term follow-up should be required in such cases. In addition, given that maternal biochemical flare occurred in 18% of mothers, re-administration of antiviral agents might be required.

From December 2006 to December 2016, 1093 human immunodeficiency virus (HIV) individuals < 70 years enrolled in Korea human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) cohort were analyzed to investigate the prevalence of HIV/HBV co-infection rate and hepatitis B virus surface antibody (HBsAb) positive rate based on birth year. The HBV co-infection prevalence rate was the highest (8.8%) in patients born between 1960 and 1964 and the lowest (0%) among those born between 1995 and 1999. A decreasing linear trend of HBV co-infection rate was observed according to the 5-year interval changes. HBsAb-positive rate was only 58.1% in our study. The national HBV vaccination programs have effectively lowered the HBV co-infection rate in HIV population. However, it is identified that the HIV population has low HBsAb positive rate. Further evidences supporting efficacy of booster immunization for HBsAb negative HIV patients are required and efforts should be made to increase HBsAb positive rates among HIV patients to prevent horizontal transmission., Graphical Abstract

Background Although several cases of hepatitis B virus reactivation have been described in patients with a history of hepatitis B virus infection while undergoing treatment for hepatitis C virus infection with direct acting antivirals, the question of whether hepatitis B virus surface antigen immune-escape mutations might play a role has not been addressed so far. Case presentation We report a case of hepatitis B virus reactivation in a Caucasian patient infected with hepatitis C virus during treatment with sofosbuvir and velpatasvir. A 50-year-old man with a genotype 1a hepatitis C virus infection was considered for therapy. His serological profile was hepatitis B virus surface antigen-negative, hepatitis B virus core antibody-positive, hepatitis B virus surface antibody-negative, and anti-hepatitis D virus-positive. The detection of hepatitis B virus deoxyribonucleic acid (DNA) indicated active viral replication during the direct acting antiviral treatment that spontaneously returned to undetectable levels after treatment completion. Starting from week 12 after the end of treatment, hepatitis B virus surface antibody titers and hepatitis B virus e antibody developed. Sequencing analysis revealed the hepatitis B virus genotype D3 and the presence of two relevant immune-escape mutations (P120S and T126I) in the major hydrophilic region by analyzing the S region. Conclusions We speculate that the presence of the hepatitis B virus surface antigen mutations, endowed with the enhanced capability to elude the immune response, could play a role in hepatitis B virus reactivation. This observation confirms that occult hepatitis B infection should also be carefully monitored, through surveillance of the hepatitis B virus viral load before and during direct acting antiviral treatment of hepatitis C virus.

Chronic hepatitis B (CHB), caused by persistent hepatitis B virus (HBV) infection, significantly increases the risk of leading to liver diseases. Despite the successful development and implementation of HBV prophylactic vaccines for several decades, the development of therapeutic vaccine, a substantially potential strategy to eradicate HBV and achieve CHB cure, remains a great challenge. Herein, we applied flash nanocomplexation (FNC) technology to prepare nanovaccines with narrow size distribution and high encapsulation via the charge complexation between chitosan and heparin to encapsulate recombinant hepatitis B virus surface antigen (rHBsAg) or core antigen (rHBcAg), with CpG as adjuvant. The two nanovaccines enhanced the uptake of antigen and adjuvant into Raw264.7 cells and their co-administration further promoted maturation and activation of bone marrow-derived dendritic cells (BMDCs). Meanwhile, they exhibited excellent lymph nodes (LNs) targeting ability, draining to proximal and distal LNs with prolonged retention time, following subcutaneous injection. Co-administered nanovaccines could break immune tolerance and restore HBV-specific immune responses. In a mouse model of CHB, 90% and 80% of mice achieved hepatitis B virus surface antigen (HBsAg) seroclearance and hepatitis B virus surface antibody (HBsAb) seroconversion, respectively. Moreover, the vaccines induced long-term immune memory in HBV-cured mice to protect them from HBV reinfection. Thus, this work offers a promising and translational alternative for therapeutic CHB vaccine.

Previous epidemiological and experimental studies have shown that legacy perfluoroalkyl acids (PFAAs) are immunotoxic. However, whether the immunosuppressive effects in PFAA alternatives which recently have been widely detected in the environment are unknown. To address this knowledge gap, we investigated the relationship of serum legacy PFAAs and PFAA alternatives with the antibody of hepatitis B virus in adults. We recruited 605 participants from a cross-sectional study, the Isomer of C8 Health Project in China. We measured two representative legacy PFAAs (perfluorooctane sulfonate, PFOS and perfluorooctanoic acid, PFOA), and three PFAA alternatives (two chlorinated polyfluorinated ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) in serum using ultra-performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS). We applied linear and logistic regression models to analyze associations between serum PFAAs and hepatitis B surface antibody (HBsAb) with multivariable adjustments. We found negative associations between serum PFAAs concentrations and HBsAb. Lower serum HBsAb levels (log mIU/mL) were observed for each log-unit increase in linear PFOS (β = −0.31, 95% confidential interval: 0.84, −0.18), 6:2 PFESA (β = −0.81, 95% CI: 1.20, −0.42), 8:2 PFESA (β = −0.29, 95% CI: 0.43, −0.14) and PFBA (β = −0.18, 95% CI: 0.28, −0.08). The association between PFAAs and HBsAb seronegative seemed to be higher for 6:2 PFESA (odds ratio = 3.32, 95% CI: 2.16, 5.10) than its predecessors, linear PFOS (OR = 1.96, 95% CI: 1.37, 2.81) and branched PFOS isomers (OR = 1.64, 95% CI: 1.05, 2.56). We report new evidence that exposure to PFAA alternatives are associated with lower HBsAb in adults. This association seems to be stronger in 6:2 PFESA than PFOS. Our results suggest that more studies are needed to clarify the potential toxicity of PFAA alternatives in human which will facilitate better chemical regulations for PFAAs.

Background Our aim was to investigate dynamic changes in hepatitis B virus (HBV) surface antibody (HBsAb) titer and the associated risk of HBV reactivation and clinical course in patients with HBV surface antigen negative/core antibody positive (HBsAg−/HBcAb+) serostatus during antirheumatic therapy with biologic agents. Methods In a prospective study from January 2013 to June 2017, we monitored the HBV serostatus of HBsAg−/HBcAb+ patients undergoing biologic therapy for rheumatic diseases. From HBsAb titers at baseline and subsequent time points, we calculated the person-years (PY) contributed by patients with different HBsAb levels: 100 mIU/mL (high). We analyzed the incidence of detectable HBV DNA and HBV reactivation in each group, and documented the clinical courses of patients. Results Among 380 participants, 83 (21.8%) had baseline HBsAb 100 mIU/mL. Total PY at study end were 169.3 PY from the HBsAb-negative group, 362.7 PY from the low-titer group, and 285.8 PY from the high-titer group. Seventeen patients had detectable HBV DNA, with respective incidence rates in negative, low- and high-titer groups of 4.7/100 PY, 2.5/100 PY, and 0/100 PY. Two HBsAb-negative patients subsequently developed HBV reactivation, an incidence of 1.2/100 PY. Conclusions The risk of HBV reactivation varied with HBsAb titer, which changed during biologic therapy. Neither HBV DNA nor reactivation were detected in patients with HBsAb > 100 mIU/mL, whereas HBV DNA without reactivation occurred periodically in patients with HBsAb 10–100 mIU/mL; HBsAb-negative serostatus was associated with a risk of HBV reactivation. Electronic supplementary material The online version of this article (10.1186/s13075-018-1748-z) contains supplementary material, which is available to authorized users.

UNLABELLED In the past 50 years there have been considerable efforts to identify the cellular receptor of hepatitis B virus (HBV). Recently, in vitro evidence from several groups has shown that the sodium-taurocholate cotransporting polypeptide (NTCP, which is encoded by SLC10A1 and transports bile acids into hepatic cells in enterohepatic recirculation) is a strong candidate. In particular, in vitro the p.Ser267Phe variation of SLC10A1 results in loss of HBV receptor function. We tested the role of NTCP as a receptor for HBV in chronic hepatitis B patients using a genetic association study. We selected SLC10A1 variants from 189 exomes. We used Sanger sequencing to follow up the association of the various SLC10A1 variants in a Han Chinese cohort of 1899 chronic hepatitis B patients and 1828 healthy controls. We further investigated the potential impact of the p.Ser267Phe variant on NTCP function using structural analysis. The p.Ser267Phe variant was associated with healthy status (P = 5.7 × 10(-23) , odds ratio = 0.36) irrespective of hepatitis B virus surface antibody status (P = 6.2 × 10(-21) and 1.5 × 10(-10) , respectively, when the cases were compared with hepatitis B virus surface antibody-positive and -negative controls). The variation was also associated with a lower incidence of acute-on-chronic liver failure (P = 0.007). The estimated heritability explained by this single variation was ∼3.2%. The population prevented fraction was around 13.0% among the southern Chinese. Our structural modeling showed that the p.Ser267Phe variant might interfere with ligand binding, thereby preventing HBV from cellular entry. CONCLUSION The p.Ser267Phe NTCP variant is significantly associated with resistance to chronic hepatitis B and a lower incidence of acute-on-chronic liver failure. Our results support that NTCP is a cellular receptor for HBV in human infection.

There are a limited number of studies on the seroprevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection in Turkey. This study aimed to compare HBV and HCV seroprevalence rates before and after the implementation of national hepatitis B vaccination program (NHPVP) and to explore age-related changes in the seroprevalences.Results of Hepatitis B surface antigen (HBsAg), Hepatitis B virus surface antibody (antiHBs) and anti-HCV tests performed during 2009 and 2010 in a state hospital laboratory were reviewed retrospectively. As NHPVP was started in 1998, 12 years of age and younger children were considered post- NHPVP period subjects.A total of 3280 HBsAg, 2444 antiHBs and 3188 anti-HCV test results were reviewed, representing approximately 3% of the population of the city where the study was conducted. HBsAg, antiHBs and anti-HCV positivity were 3.2%, 36.12% and 0.97%, respectively. HBsAg and antiHBs positivity were higher among males (p0.001). When assessed by age groups, HBsAg positivity was found to be the lowest in the age group 0-12 and highest in the age group 51-60. HBsAg positivity was lower in the post-NHPVP period versus pre-NHPVP period (p=0.01). Anti-HCV positivity was similar for pre- and post- NHPVP periods (p0.05).Owing to the use of NHPVP, HBsAg seropositivity has decreased, and it is expected to decrease further in the next years with a wider implementation of the program. Efforts should be continued to increase the level of awareness in the community for HBV and the importance of immunization.Türkiye’de Hepatit B virüs (HBV) ve Hepatit C virüs (HCV) enfeksiyonu seroprevelansının araştırıldığı çalışmalar sınırlı sayıdadır. Bu çalışmada ulusal hepatit B aşı programı (UHBAP) sonrası ve öncesi dönemde HBV ve HCV seroprevalansının karşılaştırılması ve bu seroprevalanstaki yaşa bağlı değişimin ortaya konulması amaçlanmıştır.Bir hizmet hastanesi laboratuarında 2009 ve 2010 yıllarında çalışılan Hepatit B yüzey antijeni (HBsAg), Hepatit B virüs yüzey antikoru (antiHBs) ve anti-HCV test sonuçları retrospektif olarak incelendi. UHBAP 1998 yılında başladığı için 12 yaş ve daha küçükler UHBAP sonrası dönem olarak kabul edildi.Çalışmanın yapıldığı il nüfusunun yaklaşık %3’üne tekabül eden 3280 HBsAg, 2444 antiHBs ve 3188 anti-HCV test sonucu değerlendirmeye alındı. HBsAg, antiHBs ve anti-HCV pozitifliği sırasıyla %3,2, %36,12 ve %0,97 bulundu. HBsAg ve antiHBs pozitifliği erkeklerde kadınlardan daha yüksekti (p0,001). Yaş gruplarına göre HBsAg pozitifliği en düşük 0–12 yaş arası, en yüksek 51–60 yaş arası bulundu. UHBAP öncesi dönemde UHBAP sonrası döneme göre HBsAg pozitifliği daha düşüktü (p=0,01). Anti-HCV pozitifliği UHBAP öncesi ve sonrası dönemde benzerdi (p0,05).UHBAP ile beraber HBsAg seropozitifliği azalmış ve programın daha geniş bir şekilde uygulanmasıyla önümüzdeki yıllarda daha da azalacağı beklenmektedir. HBV ile bağışıklamanın önemi hakkında toplumun farkındalık düzeyini artırıcı faaliyetlere devam edilmelidir.

AIM To investigate the relationship between serum titers of anti-Helicobacter pylori (H. pylori) immunoglobulin G (IgG) and hepatitis B virus surface antibody (HBsAb). METHODS Korean adults were included whose samples had positive Giemsa staining on endoscopic biopsy and were studied in the hepatitis B virus surface antigen (HBsAg)/HBsAb serologic assay, pepsinogen (PG) assay, and H. pylori serologic test on the same day. Subjects were excluded if they were positive for HBsAg, had a recent history of medication, or had other medical condition(s). We analyzed the effects of the following factors on serum titers of HBsAb and the anti-H. pylori IgG: Age, density of H. pylori infiltration in biopsy samples, serum concentrations of PG I and PG II, PG I/II ratio, and white blood cell count. RESULTS Of 111 included subjects, 74 (66.7%) exhibited a positive HBsAb finding. The serum anti-H. pylori IgG titer did not correlate with the serum HBsAb titer (P = 0.185); however, it correlated with the degree of H. pylori infiltration on gastric biopsy (P < 0.001) and serum PG II concentration (P = 0.042). According to the density of H. pylori infiltration on gastric biopsy, subjects could be subdivided into those with a marked (median: 3.95, range 0.82-4.00) (P = 0.458), moderate (median: 3.37, range 1.86-4.00), and mild H. pylori infiltrations (median: 2.39, range 0.36-4.00) (P < 0.001). Subjects with a marked H. pylori infiltration on gastric biopsy had the highest serological titer, whereas in subjects with moderate and mild H. pylori infiltrations titers were correspondingly lower (P < 0.001). After the successful eradication, significant decreases of the degree of H. pylori infiltration (P < 0.001), serum anti-H. pylori IgG titer (P < 0.001), and serum concentrations of PG I (P = 0.028) and PG II (P = 0.028) were observed. CONCLUSION The anti-H. pylori IgG assay can be used to estimate the burden of bacteria in immunocompetent hosts with H. pylori infection, regardless of the HBsAb titer after HBV vaccination.

We studied clinical outcome and clinico-virological factors associated with hepatitis B virus reactivation (HBV-R) following cancer treatment in hepatitis B virus surface antigen (HBsAg)-negative/anti-hepatitis B core antibodies (anti-HBcAb)-positive patients. Between 11/2003 and 12/2005, HBV-R occurred in 7/84 HBsAg-negative/anti-HBcAb-positive patients treated for haematological or solid cancer. Virological factors including HBV genotype, core promoter, precore, and HBsAg genotypic and amino acid (aa) patterns were studied. Patients presenting with reactivation were men, had an hepatitis B virus surface antibody (HBsAb) titre 1 line of chemotherapy (CT) significantly more frequently than controls. All were treated for haematological cancer, 3/7 received haematopoietic stem cell transplantation (HSCT), and 4/7 received rituximab. Using multivariate analysis, receiving >1 line of CT was an independent risk factor for HBV-R. Fatal outcome occurred in 3/7 patients (despite lamivudine therapy in two), whereas 2/4 survivors had an HBsAg seroconversion. HBV-R involved non-A HBV genotypes and core promoter and/or precore HBV mutants in all cases. Mutations known to impair HBsAg antigenicity were detected in HBV DNA from all seven patients. HBV DNA could be retrospectively detected in two patients prior cancer treatment and despite HBsAg negativity. HBV-R is a concern in HBsAg-negative/anti-HBcAb-positive patients undergoing cancer therapy, especially in males presenting with haematological cancer, a low anti-HBsAb titre and more than one chemotherapeutic agent. HBV DNA testing is mandatory to improve diagnosis and management of HBV-R in these patients. The role of specific therapies such as rituximab or HSCT as well as of HBV aa variability deserves further studies.

Quantum dots (QDs) are widely used in the immune detection. Yet, the sensitivity and specificity of the immune detection are not satisfactory because the binding sites of QDs onto antibody (Ab) are often arbitrary and the influence of the large surface electronic potential energy of QDs on the directly conjugated Ab is nonnegligible. In this work, we provide a "flexible" coupling method, in which protein G (PG) is selected as the flexible bridge between the QDs and the Hepatitis B virus surface antibody (HBsAb), to improve the sensitivity and specificity of the fluoroimmunoassay compared to the directly covalent conjugation. Successful coupling of the HBsAb to our highly luminescent CdTe/CdS core/shell QDs is proven with Gel electrophoresis and atomic force microscopy (AFM). The assay results, based on the microelisa well plate as matrix to immobilize the sandwich structure, show that both sensitivity and specificity can be improved greatly through the flexible coupled QDs-PG-Ab conjugates.

A patient with chronic hepatitis B and C undergoing treatment with interferon and ribavirin showed an upsurge in hepatitis B virus surface antibody (anti-HBs) titer, accompanied by a decrease in hepatitis B virus surface antigen (HBsAg) during the early treatment phase. Simultaneously, elevation of alanine aminotransferase (ALT) was observed. Subsequently, the hepatitis B virus (HBV) DNA titer decreased and HBV e antigen (HBeAg) to anti-HBe seroconversion occurred. The anti-HBs titer gradually returned to the pretreatment level after cessation of ribavirin treatment and HBV-DNA became undetectable. We found no nucleotide mutations in HBV-DNA that could explain the sudden elevation in anti-HBs titer. The appearance of anti-HBs was considered to be a break in immune tolerance against some epitopes in HBsAg, possibly the r epitope, stimulated by interferon/ribavirin treatment. The immunomodulatory effect of ribavirin might have caused this unexpected early immune response to HBsAg that preceded seroconversion to anti-HBe.

High rates of vertical transmission of hepatitis B virus (HBV) infection from carrier mothers to their babies are observed in hepatitis B e antigen (HBeAg)-positive mothers under the existing protocol. The current status suggests that the existing protocol may be insufficient for the prevention of mother-to-child transmission (MTCT) in HBeAg-positive mothers. To achieve complete prevention of HBV vertical transmission, we designed a protocol implementing intravenous administration along with ordinary intramuscular administration of HBV immune globulin (HBIG) to the baby after birth.We compared the HBV surface antibody (HBsAb) titer in babies who were simultaneously administered HBIG both intravenously and intramuscularly after birth with that in babies who received HBIG only intramuscularly.The HBsAb titer rose rapidly after administration in the combined administration group, and the elevated titer was maintained for approximately 2 months. Although the antibody titer at the peak was nearly 6 times greater in the combined administration group than in the intramuscular administration group, the combined administration of HBIG did not have any effect on total IgG antibody levels in the bloodstream.The combined protocol was demonstrated to be safe and superior to the protocol of only intramuscular HBIG administration with respect to rapid elevation of HBsAb in the bloodstream. It could be an effective method for the prevention of MTCT in HBeAg-positive mothers.

In this paper we report attempts to directly detect the behaviors of hepatitis B virus surface antigen (HBsAg) binding procedures and interactions between HBsAg and hepatitis B virus surface antibody (HBsAb) on the liquid–solid interfaces. In the work, an optical transmittance interferometry based transducer was used to detect the film thickness change in real time. Several hundred nanometer polystyrene films were deposited on the glass slides to construct polymer matrix and HBsAg was immobilized on their surfaces through physisorphtion. At the incubation end, film thickness increase 5.7, 4.3, 3.1, 2.4 and 1.2 nm at the HBsAg concentrations of 5, 4, 3, 2 and 1 mg ml−1, respectively. On the 5 mg ml−1 HBsAg coated film surfaces, HBsAg–HBsAb interactions resulted in 5.3, 3.4, 2.7, 1.8 and 0.6 nm film thickness increase at the concentrations of 15, 20, 36, 50, and 100 μg ml−1, respectively. The mass transport effects and reaction effects were obtained using the biosensor. Nonlinear regression analysis indicated that the association constant between HBsAg and HBsAb is 9.5×104 M−1s−1 and the dissociation rate kd is 1.21×10−3 s−1, respectively.

In this paper we report attempts to directly detect the different binding property between monoclonal hepatitis B virus surface antibody (Mab) and multiclonal hepatitis B virus surface antibody (Multiab) with hepatitis B virus surface antigen, which was coated on a pretreated glass slide. In the procedure, an optical transducer based transmittance interferometry was used to detect this interaction in real time. At the end of the interaction, an increase in protein layer thickness of about 7nm and 4.1nm for Mab as well as 6nm and 2nm for Multiab were obtained at the concentrations of 10μg/ml and 1μg/ml, respectively. The dynamic data derived from the film thickness change were evaluated with bimolecular model. Compared with the interaction between Multiab and antigen. higher kinetic constant between Mab and its corresponded antigen was obtained.

We report a case of autoimmune thrombocytopenia associated with acute reverse seroconversion of hepatitis B in a patient who was initially hepatitis B virus surface antigen negative and hepatitis B virus surface antibody positive. Reactivation occurred 9 months after chemotherapy with anti-CD 20 monoclonal antibodies and autologous hematopoietic stem cell transplantation for lymphoma had been performed. After non specific polyglobulin injections and treatment with adefovir dipivoxil, thrombocytopenia and viral replication were controlled. Seroconversion for both HBe and HBs occurred at 5 months. Adefovir was stopped 4 months later with no relapse during fifteen months of follow-up. This case shows that patients who have had previous contact with hepatitis B virus should be monitored if they become immunosuppressed, even if anti-HBs were initially present.

Background The risk associated with transplantation of renal allografts from hepatitis B virus core antibody-positive (HBcAb(+)), hepatitis B virus surface antigen-negative (HBsAg(-)) donors is not well defined. Methods. Over 4 years, we performed 45 kidney transplants from IgG HBcAb(+), IgM HBcAb(-), HBsAg(-) donors into recipients with a history of prior hepatitis B virus (HBV) infection or reported vaccination. We examined HBV-related outcomes in these 45 patients, in comparison with 45 recipients of allografts from HBcAb(-) donors (matched for transplant type, date, and pretransplant HBV antibodies). We sought evidence for HBV transmission by testing posttransplant sera for the presence of HBcAb, hepatitis B virus surface antibody, and HBsAg. Additionally, we analyzed alanine aminotransferase profiles and allograft survival rates for all patients. Results. No patient receiving an allograft from an HBcAb(+) donor developed clinical HBV infection. No patient receiving an allograft from an HBcAb(+) donor had HBsAg detected through retrospective testing of stored sera or through prospective routine clinical evaluation and care. However, among the HBcAb(+) kidney recipients, 27% developed new HBcAb and/or hepatitis B virus surface antibody after transplant; in contrast, only 4% of control patients developed new antibody responses (relative risk=4.94; confidence interval 1.07-22.83). Among the recipients of HBcAb(+) organs, 18% developed elevated transaminases after transplant, in comparison with 36% of the controls. No association was found between seroconverter status and elevated alanine aminotransferase profiles in either group. Conclusions. Transplantation of renal allografts from HBcAb(+), HBsAg(-) donors was not associated with clinically detectable HBV disease or antigenemia. However, recipients had a significantly increased risk of HBV seroconversion, consistent with exposure to HBV antigen. These results suggest that HBcAb(+) kidneys can be safely used if transplanted into appropriate recipients, but highlight the need for effective HBV vaccination and vaccine-response monitoring in potential recipients.

In order to determine the impact of screening potential organ donors for hepatitis B virus DNA using a standardized test, the serum of 145 donor candidates was tested. All of the candidates were negative for hepatitis B virus DNA, but the status of one donor was doubtful for hepatitis B virus surface antigen and seven donors tested positive for hepatitis B virus core antibody without hepatitis B virus surface antigen. Nine transplant recipients tested positive for hepatitis B virus surface antibody; they were given kidneys from the donor with a doubtful hepatitis B virus surface antigen result and from four of the seven donors who tested positive for hepatitis B core antibody. Follow-up revealed no case of hepatitis B transmission. In this study, screening for hepatitis B virus DNA was useful and did not lead to donor organ shortage. Patients with hepatitis B virus surface antibodies can safely be given kidneys from donors who are positive for hepatitis B core antibody but negative for hepatitis B virus DNA.

We conducted a multicenter trial in Canada to assess the value of using trueness controls (TC) for rubella virus IgG and hepatitis B virus surface antibody (anti-HBs) serology to determine test performance across laboratories over time. TC were obtained from a single source with known international units. Seven laboratories using different test systems and kit lots included the TC in routine assay runs of the analytes. TC measurements of 1,095 rubella virus IgG and 1,195 anti-HBs runs were plotted on Levey-Jennings control charts for individual laboratories and analyzed using a multirule quality control (MQC) scheme as well as a single three-standard-deviation (3-SD) rule. All rubella virus IgG TC results were “in control” in only one of the seven laboratories. Among the rest, “out-of-control” results ranged from 5.6% to 10% with an outlier at 20.3% by MQC and from 1.1% to 5.6% with an outlier at 13.4% by the 3-SD rule. All anti-HBs TC results were “in control” in only two laboratories. Among the rest, “out-of-control” results ranged from 3.3% to 7.9% with an outlier at 19.8% by MQC and from 0% to 3.3% with an outlier at 10.5% by the 3-SD rule. In conclusion, through the continuous monitoring of assay performance using TC and quality control rules, our trial detected significant intra- and interlaboratory, test system, and kit lot variations for both analytes. In most cases the assay rejections could be attributable to the laboratories rather than to kit lots. This has implications for routine diagnostic screening and clinical practice guidelines and underscores the value of using an approach as described above for continuous quality improvement in result reporting and harmonization for these analytes.

Immune thrombocytopenia is a disease mediated by platelet autoantibodies that accelerate platelet destruction and inhibit their production. Most cases are considered idiopathic, whereas others are secondary to coexisting conditions such as infectious diseases. All hepatotropic viruses seem able to cause thrombocytopenia. The advent of molecular techniques has revealed the possible persistence of hepatitis B virus genome in HBsAg-negative individuals with or without serologic markers of previous infection. This form of infection is named occult. We report a case of autoimmune thrombocytopenia associated with acute reverse seroconversion of hepatitis B in a patient who was initially hepatitis B virus surface antigen negative and hepatitis B virus surface antibody positive. The search for occult HBV infection before immunosuppressive therapy and monitoring for reactivation is today diagnostic standard and several reports have been presented in literature about HBV reactivation following immunosuppressive therapy. In our patient, reactivation of dormant HBV happened prior to any immunosuppressive therapy. The case we report offers the occasion to emphasize the importance of medium-term and long-term hemovigilance also in other kind of patients than in subjects on immunosuppressive therapy. A deeper follow-up is advisable even in patients showing an unexplainable worsening of their hematological conditions.

We used regimens containing rituximab in the treatment of five hepatitis B virus surface antibody (HBsAb)-positive patients with non-Hodgkin's lymphoma (NHL). Serum levels of HBsAb were obtained and analyzed in four of these patients. Two patients were HBs antigen (HBsAg) positive. One of these HBsAg-positive patients was treated with lamivudine because the patient developed fulminant hepatitis from hepatitis B virus (HBV) infection prior to chemotherapy. However, none of the other patients were administered lamivudine. An HBsAg-positive patient who did not receive lamivudine treatment later developed fulminant hepatitis. Another HBsAg-positive patient receiving lamivudine prophylaxis did not develop severe hepatitis arising from HBV. In the three patients not receiving lamivudine treatment, serum HBsAb titers decreased soon after the administration of rituximab. These results suggest that rituximab reduced the antibody titer for HBV, thus inducing an immunological environment leading to easy reactivation of HBV. Lamivudine prophylaxis was effective, at least when rituximab was given to an HBsAg-positive patient with non-Hodgkin's lymphoma.

In some patients with chronic liver disease induced by hepatitis B virus, viral DNA is known to persist in low concentration in serum after seroconversion to hepatitis B surface antibody-positivity. This phenomenon has, however, not been documented in asymptomatic black African carriers of hepatitis B virus. Using nested amplification by the polymerase chain reaction, we detected low concentrations of hepatitis B virus DNA in the serum of 6 of 23 (26%) healthy black African adults with normal liver function and with hepatitis B virus surface antibody as the only serological marker of the virus. This finding offers one explanation for the earlier observation of integrated hepatitis B virus DNA in hepatocellular carcinomas in black Africans whose serum was positive for surface antibody alone. A number of genetic changes were found in the six isolates that might be responsible for evasion of the immune response and persistence of the virus. Isolated mutations were detected in the “a” determinant of the surface gene and in the encapsidation signal. In all five isolates sequenced in the core promoter, mutations were present in the upstream regulatory region. Recombination between genotypes A and D was present in three of the isolates, including both of those in which the entire genome was sequenced. This change in genotype also overlapped the amino end of the polymerase domain and may result in sufficiently low levels of replication to allow viral persistence. Topoisomerase 1 specific trinucleotides were concentrated in the vicinity of the recombination breakpoints. J. Med. Virol. 64:441–454, 2001. © 2001 Wiley-Liss, Inc.

We report a case of acute hepatitis B after autologous stem cell transplantation (ASCT) in a patient with low-grade non-Hodgkin's lymphoma. At diagnosis of the hematological disease, the patient had the characteristic serology of a previous hepatitis B infection, being Ag HBs negative, hepatitis B virus core antibody positive (anti-HBC) and hepatitis B virus surface antibody weakly positive. He developed fatal hepatitis B after autologous stem cell transplantation, suggesting reactivation consequent to immunosuppression.

Hepatitis B core antibody (anti-HBc) has recently been recognized as a paradoxical (surrogate) marker for non-A, non-B hepatitis agents in donated blood. We studied prospectively the hepatitis B virus antigen and antibody status and liver functions in 63 uremic patients admitted consecutively to our dialysis program. Nineteen percent of uremic patients, negative for hepatitis B surface antigen (HBsAg), hepatitis B virus surface antibody (anti-HBs), hepatitis B virus DNA, and antibody to delta agents, had anti-HBc in their sera at the time of admission to maintenance dialysis. This prevalence was significantly higher than that of the medical personnel working in the dialysis unit (P = 0.043) and healthy controls (P = 0.027). The prevalence of persistent presence of isolated anti-HBc increased to 31% in these uremic patients on long-term maintenance dialysis. Four patients had developed anti-HBc alone during their course of maintenance dialysis, and the appearance of anti-HBc was preceded by blood transfusion within 4 to 8 weeks. Transient or recurrent hepatic dysfunction occurred in three of these four patients. Patients with isolated anti-HBc were characterized by a higher incidence of repeated liver dysfunction (P less than 0.005), elevated alanine transaminase levels (P less than 0.005), and a higher transfusion requirement (P less than 0.01). Our data strongly suggest that these patients with isolated anti-HBc may have acquired either hepatitis B virus infection or non-A, non-B hepatitis through repeated blood transfusions despite careful screening of the donated blood to exclude transmission of hepatitis B virus.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE: To determine the duration of protection from hepatitis B vaccine given in infancy and early childhood. DESIGN: Cross sectional serological study of hepatitis B virus infection in children of various ages 14 years after the start of a trial of vaccination regimens. SETTING: Two villages in the Gambia. PARTICIPANTS: Children and adolescents given hepatitis B vaccine in infancy or early childhood: 232 were aged 1-5 years, 225 aged 5-9 years, 220 aged 10-14 years, and 175 aged 15-19 years. MAIN OUTCOME MEASURES: Vaccine efficacy against infection and against chronic infection in the different age groups. RESULTS: Vaccine efficacy against chronic carriage of hepatitis B virus was 94% (95% confidence interval 89% to 97%), which did not vary significantly between the age groups. Efficacy against infection was 80% (76% to 84%). This was significantly lower in the oldest age group (65%, 56 to 73). Of the uninfected participants in this age group, 36% had no detectable hepatitis B virus surface antibody. Time since vaccination and a low peak antibody response were the most powerful risk factors for breakthrough infection (P