Prevalence of antibodies to hepatitis B core antigen and occult hepatitis B virus infections in Korean blood donors

BACKGROUND: This study was performed to determine the prevalence of antibodies to hepatitis B core antigen (anti‐HBc) among Korean blood donors and frequencies of hepatitis B virus (HBV) DNA and antibodies to hepatitis B surface antigen (anti‐HBs) in anti‐HBc–positive donors. STUDY DESIGN AND METHODS: A total of 12,461 consenting blood donors were consecutively enrolled from Korean Red Cross Blood Services from April to October 2008. All of the donors were screened for anti‐HBc with an electrochemiluminescence immunoassay. Repeat‐reactive anti‐HBc–positive donors were assayed for anti‐HBs and for HBV DNA using a multiplex test (Cobas TaqScreen, Roche Molecular Systems) on individual donation. RESULTS: Of the 12,461 donors, 1682 (13.5%) were reactive for anti‐HBc. Among different age groups, there was a steady increase in the anti‐HBc–positive rate, ranging from 2.0% in the age group of less than 20 years to 80.0% in the age group of 60 years and older (p < 0.0001). Of the anti‐HBc–positive donors, 1523 (90.5%) were anti‐HBs positive. HBV DNA was detected in two donors who were anti‐HBc positive and hepatitis B surface antigen negative. The prevalence of occult HBV infection was 0.016%, and the HBV nucleic acid test (NAT) yield was 1 in 838 (0.12%). CONCLUSION: This study helps to determine the current status of hepatitis B infection and the prevalence of occult HBV infection in the blood donor population in Korea. We estimate that in Korea, up to 161 units per million donated units from blood donors may contain HBV DNA. Although the potential infectivity of these units has been debated upon, the HBV NAT assay could prevent certain transfusion‐transmitted HBV infections.     

Donor screening for antibody to hepatitis B core antigen and hepatitis B virus infection in transfusion recipients

BACKGROUND: Testing for antibody to hepatitis B core antigen (anti-HBc) as a surrogate for hepatitis C viremia is no longer needed for blood donor screening. Currently, the important question is how much its use supplements hepatitis B surface antigen (HBsAg) donor screening in preventing transfusion-transmitted hepatitis B virus (HBV) infection. STUDY DESIGN AND METHODS: In a study conducted in the 1970s, 64 blood donors were associated with 15 cases of HBV (1.0%) in 1533 transfusion recipients. Sera from 61 donors at donation and 29 follow-up visits were available for present-day assays for HBsAg, HBV DNA, anti-HBc, and antibody to HBsAg (anti-HBs). RESULTS: HBsAg was found in four previously negative blood donors; HBV DNA was limited to three of these four. Anti-HBc was detected in six HBsAg-negative donors. Two other donors were negative in all assays at donation, but positive for anti- HBc and anti-HBs 2 to 4 months later. The remaining donors were negative for all HBV markers, which left five recipient cases unexplained. No HBV transmission was observed when anti-HBs sample-to- negative control values were > or = 10. CONCLUSION: Some 33 to 50 percent of cases of hepatitis B that could be transmitted by transfusion of blood from HBsAg-negative donors are prevented by anti- HBc screening. Anti-HBc-positive donors unequivocally positive for anti- HBs should be considered noninfectious for HBV and should be allowed to donate. Anti-HBc screening of paid plasmapheresis donors, supplemented by anti-HBs testing, would reduce the amount of HBV to be processed by virus inactivation and increase the content of anti-HBs in plasma pools.     

HBsAg和HBsAb双阳患者前C/C区基因突变分析

目的 探讨乙型肝炎表面抗原(HBsAg)和乙型肝炎表面抗体(HBsAb)同时阳性(以下简称双阳)患者前C/C区基因突变的特点及其与S区基因突变的关系.方法 选取18例双阳患者,对前C/C区及S区基因序列扩增并测序,分析测序结果.结果 18例双阳患者中,检出前C/C区氨基酸突变者7例;前C/C区发生突变与未发生突变者比较,其S区氨基酸的突变次数及突变率明显增加(P<0.05);7例前C/C区氨基酸突变患者中,4例为前C区nt1896突变,其中1例为HBeAg(-),3例为HBeAg(+).结论 双阳患者不仅S区氨基酸突变增多,其前C/C区氨基酸突变也明显增加;双阳患者前C区nt1896突变更常见于HBeAg阳性者,可能与双阳患者病毒株的复杂性有关.     

Transmission of serologically silent hepatitis B virus along with hepatitis C virus in two cases of posttransfusion hepatitis

The polymerase chain reaction (PCR) was used to investigate the presence of hepatitis B virus (HBV)-related DNA sequences in blood from three blood donors and two transfusion recipients who developed posttransfusion non-A, non-B hepatitis (NANBH). In the first case, the sole donor was positive for antibody to hepatitis B surface (HBs) and core (HBc) antigens and had elevated alanine aminotransferase (ALT) levels, while the recipient had no HBV serologic markers. Both the donor and the recipient had serologic markers of hepatitis C virus (HCV) and were found positive for HBV DNA and HCV RNA sequences by PCR. The second case involved two donors and one recipient. Serologic tests for conventional HBV markers were negative in all three individuals, but one of the donors had elevated ALT. HBV DNA sequences were detected by PCR in the serum of the recipient and of the donor with high ALT, but not in the serum of the donor with normal ALT. Anti-HCV was detected in the serum of the recipient and of the suspect donor but not in that of the donor with normal ALT. The sequences amplified in the S region and determined after cloning of PCR products for both donor-recipient pairs were indistinguishable from each other and identical to the sequence of the major HBV subtype of adw in the first case and ayw in the second case. Furthermore, for the second case, an identical single-point mutation was found in both the donor and the recipient. These data confirm the transmission of conserved HBV sequences together with HCV in posttransfusion NANBH.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性乙型肝炎乙型肝炎病毒核心启动子区和前核心区基因变异后的预后分析

目的 为了解慢性乙型肝炎患者乙型肝炎病毒(HBV)核心启动子(BCP)区和前核心(前C)区基因变异后的临床转归及其预后。方法 采用DNA序列分析法检测123例HBV DNA阳性的慢性乙型肝炎患者血清HBV BCP区(nt1762、nt1764)和前C区(nt1896)基因序列,并同步进行乙型肝炎e抗原(HBeAg)、乙型肝炎e抗体(抗-HBe)定量及肝功能检测。结果 123例患者HBV BCP区(A1762T、G1764A)和前C区(G1896A)基因变异检出率为76.42％;其中肝炎肝硬化(HLC)患者双变异(A1762T、G1764A)和联合变异(A1762T、G1764A、G1896A)率最高(52．94％与29．41％);慢性重型肝炎患者终止变异(G1896A)率最高(42．86％);HBeAg／抗HBe转换率分别为：双变异组23.91％,终止变异组75．00％,联合变异组84．00％,无变异组13．79％。结论 HBV BCP双变异、前C终止变异和联合变异均可引起慢性乙型肝炎病情加重及肝硬化的发生,但严重肝损伤与这3种变异之间可能无因果关系,只是HBV减少病毒蛋白的产生,逃避免疫监视的一种方式;推测BCP双变异和联合变异可能是引起HLC的重要病因之一;BCP区变异患者时干扰素治疗敏感。     

A revised method for estimating hepatitis B virus transfusion residual risk based on antibody to hepatitis B core antigen incident cases

BACKGROUND: To take into account the transient nature of hepatitis B virus (HBV) antigenemia, the calculation of HBV residual risk (RR), based on the incidence/window period model, is adjusted by a correction factor that adds uncertainty to the RR estimates. STUDY DESIGN AND METHODS: This new method to estimate the RR for HBV is a weighted sum of the RR derived from hepatitis B surface antigen (HBsAg) incident cases and the one derived from antibody hepatitis B core antigen (HBc) incident cases. An anti‐HBc incident case was defined as a donation from a blood donor who had made at least one anti‐HBc–negative donation followed by a donation that was found positive with two different assays within a 3‐year period and positive for at least one of the following markers: 1) antibody to hepatitis B e antigen or hepatitis B e antigen, 2) anti‐HBc immunoglobulin M, 3) HBV DNA, 4) hepatitis B surface antibody without HBV vaccination history, or 5) HBV DNA retrospectively found in the previous donation. Five overlapping 3‐year study periods between 2000 and 2006 were analyzed. RESULTS: The HBV RR estimated with the classical method ranged from 1.51 (2000‐2002) to 0.69 per million donations in 2004 through 2006 with a decrease in 2002 through 2004 due to only two HBsAg incident cases reported in this period. By applying the revised model, the HBV RR ranged from 1.06 (2000‐2002) to 0.49 per million donations (2004‐2006), with a regular decrease. CONCLUSION: The new presented model provides HBV RR estimates that do not statistically differ from those obtained with the classical model; however, it provides more accurate data, especially in low endemic areas where the HBsAg incidence is low.     

Detection of pre-C and core region mutants of hepatitis B virus in chronic hepatitis B virus carriers.

We analyzed the pre-C and core region of hepatitis B virus (HBV) DNA by a polymerase chain reaction in 22 chronic carriers. In 9 hepatitis B e antigen-positive asymptomatic carriers, a single DNA band was detected at the expected size, whereas additional shorter DNA bands were observed in 7 out of 11 patients with chronic hepatitis. The smaller-sized DNAs from one chronic hepatitis patient had various lengths of deletions spanning from 105 to 183 bp in the middle of the core gene, and all deletions included common nucleotide sequences. All of the smaller-sized DNAs from the other patients proved to be variant core genes. They were deleted in similar regions by Southern analysis using oligonucleotide probes. A follow-up study revealed that four out of seven chronic hepatitis patients with a short core gene seroconverted to antibody to hepatitis B e antigen, but those with only a "wild type" did not. In another set of sequence studies, clones isolated from two chronic carriers displayed heterogeneity of the pre-C and core gene which was more often present in sera with normal alanine aminotransferase levels than with abnormal levels. These results suggest that mutant HBV alters the host immune response, and may modulate the clinical course of HBV infection. An alternative possibility is that chronic hepatitis selects for mutant forms.     

Performance of an algorithm for the reentry of volunteer blood donors deferred due to false-positive test results for antibody to hepatitis B core antigen

BACKGROUND: Blood donor testing for antibody to hepatitis B core antigen (anti‐HBc) has been used in the United States for more than 20 years as a surrogate to prevent transmission by transfusion of non‐A,non‐B hepatitis, as a human immunodeficiency virus surrogate, and to reduce transmission of hepatitis B virus (HBV). Nonspecific anti‐HBc assays have caused deferral of hundreds of thousands of otherwise qualified donors. A more specific anti‐HBc test and a sensitive HBV DNA test should permit donor reentry after false‐positive anti‐HBc. STUDY DESIGN AND METHODS: A total of 1324 otherwise eligible volunteer donors, deferred for anti‐HBc reactivity on more than one occasion, were recruited from four collection facilities. They were tested using a licensed, more specific anti‐HBc test, a licensed hepatitis B surface antigen (HBsAg) test, and a licensed HBV DNA assay with a 95 percent limit of detection of not more than 10 copies per mL. RESULTS: From 11 to 32 percent of donors contacted by participating sites entered the study. Overall, 488 (37%) of the donors were negative on the more specific anti‐HBc test. The proportion of putative false‐positive samples varied according to the test responsible for the original deferral. A single donor, negative for the presence of anti‐HBc and HBsAg, was positive for the presence of HBV DNA in one of three replicates. Repeat testing of this donor 10 months later was negative for the presence of all markers of HBV infection, and the donor had a history of HBV vaccination with documented postimmunization anti‐HBs seroconversion 10 years before her anti‐HBc deferral, and was considered HBV DNA false positive. CONCLUSION: These data support reentry of donors with false‐positive anti‐HBc results on the relatively nonspecific assays that have been in use in the United States for more than 20 years.     

Nucleic acid sequence analysis of basal core promoter/precore/core region of hepatitis B virus isolated from chronic carriers of the virus from Kolkata, eastern India: low frequency of mutation in the precore region

OBJECTIVE: The aim of the present study was to characterize the predominant hepatitis B virus (HBV) strains and their molecular variants present in the HBV isolates of the different genotypes found among the chronic carriers of the virus in our community. METHODS: Precore/core and core promoter regions of HBV DNA were amplified by polymerase chain reaction and then subjected to direct sequencing. Of the 64 hepatitis B surface antigen (HBsAg)-positive chronic HBV carriers investigated, 44 were HBeAg negative and 20 were HBeAg positive. RESULTS: In addition to genotype D, which was the predominant genotype, 12 genotype C (18.7%) and 6 genotype A (9.4%) were also detected. Presence of T at nt 1858 has often been related to the development of precore stop mutation at nt 1896, while that of C has been related to the development of 1762-1764 double mutation. In our study group, 39 of the 44 HBeAg-negative samples have T1858. The precore stop codon mutation was found in only 8 (18%) of the HBeAg-negative samples. More than half of the HBeAg-negative samples had wild-type sequence in the precore region. The core promoter region could be sequenced from 40 samples, and 1762-1764 double mutation was detected in 13 (32.5%) of them. No significant changes could be detected in the core amino acid sequence of these isolates. CONCLUSION: The pattern of core promoter and precore mutation of HBV isolates in the present study is atypical and not in accordance with reports from other parts of the world, where genotype D and genotype C with T at codon 1858 are common.     

乙型肝炎病毒C基因启动子和前C终止变异与乙型肝炎标志物模式的关系及临床意义

目的研究乙型肝炎病毒C基因启动子和前C基因终止变异与乙型肝炎标志物模式的关系,并分析其临床意义。方法通过基因测序法分析检测104例乙型肝炎患者血清中C基因启动子和前C基因终止变异情况,采用微粒子发光分析法和荧光定量聚合酶链法(PCR),分别检测血清中乙型肝炎e抗原(HBeAg)和乙型肝炎病毒脱氧核糖核酸(HBV—DNA)含量,并进行比较分析。结果乙型肝炎表面抗原(HBsAg)、HBeAg、乙型肝炎核心抗体(抗-HBc)阳性患者1762T／1764A双变异率显著高于HBsAg、乙型肝炎e抗体(抗-HBe)、抗-HBc阳性患者,而1896G→A终止变异率和联合变异(双变异合并终止变异)率显著低于HBsAg、抗-HBe、抗-HBc阳性组,73例HBsAg、HBeAg、抗-HBc阳性患者中32例无变异者,其HBeAg定量值显著高于其他有变异者．31例HBsAg、抗-HBe、抗-HBc阳性患者中有4例无双变异和终止变异,其HBV-DNA定量值显著低于其他患者。结论1762T／1764A双变异和1896G→A终止变异可使HBeAg含量显著下降,其变异株并不影响病毒的复制。1762T／1764A双变异和1896终止变异株的优蛰积累并逐渐取代野生株是HBeAg向抗抗-HBe转化的原因之一．     

Serological characterization of occult hepatitis B virus infection among blood donors in India

IntroductionDiscovery of hepatitis B infections characterized by the presence of viral genome without detectable HBsAg (Occult Hepatitis; OBI) has initiated a considerable amount of research in this regard. Our study is a serological and molecular characterization of OBI among the donors who donated at our blood bank during the study period.Material and MethodDuring the study period HBsAg ELISA non reactive ID-NAT reactive donors samples were screened for presence of antibody against HBc, HBs and HBe. Molecular analysis of these NAT yield samples was undertaken for detection of the viral load and genotyping.ResultWe studied 28,134 HBsAg ELISA non reactive donor samples. On testing them with ID-NAT, HBV DNA was detected in 25 samples. Eighteen samples out of these 25 NAT yield were further worked up. The 66.6% of the NAT yield samples (12 out of 18) were reactive for antibody against HBc. The 25% (3 out of 12) of these NAT yield samples having antibody against core antigen also had antibody against HBs. The 27.7% (5 out of 18) of NAT yield detected by ID-NAT did not have any detectable serological marker in blood. Four out of 12 core antibody positive NAT yield samples had genotype A HBV infection.ConclusionAs per our study molecular detection of HBV DNA by ID-NAT, we were able to analyze 18 HBV NAT yield cases among 28,134 HBsAg ELISA non reactive donors. Out of 18, 12 donors were OBI whereas the rest (6) were in window period (WP yield) of HBV infection. One out of every 3.6 NAT yield detected by ID-NAT was non reactive for all serological markers.     

Residual risk of transfusion‐transmitted hepatitis B virus (HBV) infection caused by blood components derived from donors with occult HBV infection in Japan

BACKGROUND: Nucleic acid amplification testing (NAT) for hepatitis B virus (HBV) during blood screening has helped to prevent transfusion‐transmitted HBV infection (TT‐HBV) in Japan. Nevertheless, 4 to 13 TT‐HBV infections arise annually. STUDY DESIGN AND METHODS: The Japanese Red Cross (JRC) analyzed repository samples of donated blood for TT‐HBV that was suspected through hemovigilance. Blood donations implicated in TT‐HBV infections were categorized as either window period (WP) or occult HBV infection (OBI) related. In addition, we analyzed blood from 4742 donors with low antibody to hepatitis B core antigen (anti‐HBc) and antibody to hepatitis B surface antigen (anti‐HBs) titers using individual‐donation NAT (ID‐NAT) to investigate the relationship between anti‐HBc titer and proportion of viremic donors. RESULTS: Introduction of a more sensitive NAT method for screening minipools of 20 donations increased the OBI detection rate from 3.9 to 15.2 per million, while also the confirmed OBI transmission rate increased from 0.67 to 1.49 per million. By contrast the WP transmission rate decreased from 0.92 to 0.46 per million. Testing repository samples of donations missed by minipools of 20 donations NAT showed that 75 and 85% of TT‐HBV that arose from WP and OBI donations, respectively, would have been interdicted by ID‐NAT. The ID‐NAT trial revealed that 1.94% of donations with low anti‐HBc and anti‐HBs titers were viremic and that anti‐HBc titers and the frequency of viremia did not correlate. CONCLUSIONS: The JRC has elected to achieve maximal safety by discarding all units with low anti‐HBc and anti‐HBs titers that account for 1.3% of the total donations.     

Precore wild-type hepatitis B virus with G1896 in the resolution of persistent hepatitis B virus infection

OBJECTIVE: Factors influencing the resolution of persistent hepatitis B virus (HBV) infection were sought for. METHODS: The loss of hepatitis B surface antigen (HBsAg) from serum was correlated with mutations in HBV DNA for a hepatitis B e antigen (HBeAg)-minus phenotype in patients infected with HBV genotype C and positive for HBeAg at presentation. RESULTS: HBeAg turned negative in all the 22 patients in whom HBV infection resolved, but only in 11 of the 25 patients with severe liver diseases (100 vs. 44%, p = 0.0001). The precore wild type (G1896) persisted significantly more frequently in the 22 patients in whom HBV infection resolved than in the 11 patients who developed decompensated liver cirrhosis or hepatocellular carcinoma (15/22 or 68% vs. 1/11 or 9%, p = 0.005). The double mutation in the core promoter (T1762/A1764) was comparably frequent in the two groups of patients at presentation (14/22 or 64% vs. 7/11 or 64%) and >15 years thereafter (18/22 or 82% vs. 10/11 or 91%). CONCLUSION: The precore wild type (G1896) would seem to facilitate the resolution of HBV infection, while the precore mutant (A1896) may induce severe liver diseases in patients with HBeAg-positive chronic hepatitis who have lost HBeAg from serum.     

Quantitative analysis of hepatitis B virus precore mutant in hepatitis type B.

Active liver disease has been detected in chronic hepatitis B after seroconversion from positive HBe antigen to positive anti-HBe antibody. Active replication of HB virus (HBV) containing a precore stop-codon mutation has been implicated in this condition. The usual methods, such as direct sequencing, to characterize the responsible mutant of HBV are not suitable for routine clinical use. Here we employed the competitive mutation site specific assay (CMSSA) to detect precore mutant HBV-DNA in patients with positive HB surface antigen. In patients with HBe antigen, precore mutant HBV-DNA was significantly higher than in patients with HBe antibody. The level of precore mutant HBV-DNA in patients with elevated serum ALT was significantly higher than in patients with normal serum ALT. Sex, age and the level of serum HBV-associated DNA polymerase levels were not correlated with levels of precore mutant HBV-DNA. Ten of 11 negative patients for the precore mutant by polymerase chain reaction followed by restriction fragment length polymorphism assay (PCRRFLP) were positive for the precore mutant by CMSSA. These results suggest that the precore mutant has already emerged in the HBeAg-positive phase as determined by CMSSA, which is more sensitive than PCR-RFLP and is useful for evaluating the clinical course of patients with chronic hepatitis B.     

Infectious source factors affecting the severity of sexually transmitted acute hepatitis due to hepatitis B virus genotype C

OBJECTIVE: The aim of this study was to identify clinical features and virological aspects of infectious sources that are related to the severity of sexually transmitted acute hepatitis B virus (HBV) infection in patients, especially in cases of genotype C. METHODS: Nineteen patients with acute HBV infection, 10 classified with severe acute hepatitis (SH) (prothrombin time; PT <40%) and 9 with typical acute hepatitis (AH) (PT >40%), and their infectious sources (all were sexual partners) were studied. Infectious source factors were analyzed in relation to the severity of hepatitis in the patients' partners. RESULTS: The nucleotide homology of HBV-DNA between each pair was >/=98.9%. Sixteen were infected with HBV genotype C. Among the 16 infectious sources, age, numbers with elevated alanine aminotransferase (ALT, 7/9 vs. 1/7), anti-HBe positivity (8/9 vs. 1/7) and core promoter mutations at nt 1762 (7/9 vs. 1/7), nt 1764 (8/9 vs. 1/7) and precore mutation at nt 1896 (8/9 vs. 1/7) were significantly higher in the sources of SH than in those of AH. CONCLUSION: Higher age, elevated ALT, anti-HBe positivity and core promoter/precore mutations were possible risk factors for an infectious source of the severe form of sexually transmitted acute hepatitis due to HBV genotype C.     

Preemptive use of lamivudine in breast cancer patients carrying hepatitis B virus undergoing cytotoxic chemotherapy: a longitudinal follow-up

Reactivation of hepatitis B virus (HBV) after cytotoxic chemotherapy is a serious problem, and it occurred to 41% of breast cancer patients carrying HBV. Previous studies have demonstrated that lamivudine was effective for HBV flare-up during cytotoxic chemotherapy. We aimed to monitor the HBV status of breast cancer patients undergoing chemotherapy with preemptive lamivudine over time. Six breast cancer patients carrying hepatitis B surface antigen (HBsAg) were monitored during chemotherapy, five in the adjuvant setting and one with metastatic disease. Preemptive lamivudine was given throughout the chemotherapy course. HBsAg, HBV envelope antigen (HBeAg), anti-HBV envelope antibody (HBe Ab), serial serum alanine transaminase (ALT), quantitative HBV viral DNA analysis, and HBV DNA precore promoter and precore sequence were monitored. One patient carried wild type and the other five precore mutant strain of HBV by examination of HBV sequence in precore promoter and precore region. No evident HBV reactivation developed, and all patients tolerated lamivudine well. During the 6-to-8-month follow-up after cessation of cytotoxic therapy and withdrawal of lamivudine, serum ALT remained unchanged, although an increase of HBV DNA levels in four patients was found. No emergence of the tyrosine-methionine-aspartate-aspartate (YMDD) lamivudine-selective resistant strain was observed in the six patients. Preemptive use of lamivudine can effectively prevent reactivation of HBV in breast cancer patients receiving postoperative adjuvant chemotherapy. Lamivudine can be discontinued safely without emergence of lamivudine-resistant HBV strain or rebound HBV flare-up. The candidate for the use of preemptive lamivudine in HBV carriers who need short-term chemotherapy remained to be investigated.     

Evaluation of algorithms for the diagnostic assessment and the reentry of blood donors who tested reactive for antibodies against hepatitis B core antigen

BACKGROUND: Screening of blood donations for antibodies against hepatitis B core antigen (anti‐HBc) is an accepted method to prevent some transfusion‐transmitted hepatitis B virus (HBV) infections. However, anti‐HBc testing may result in donor loss due to unspecific results in the currently available anti‐HBc tests. Algorithms to distinguish true‐positive from false‐positive results and for reentry of those donors who tested false anti‐HBc positive were evaluated retrospectively. STUDY DESIGN AND METHODS: Samples that tested reactive for anti‐HBc by chemiluminescent microparticle immunoassay (CMIA) were investigated for anti‐HBc by microparticle immunoassay, for anti‐HBs and hepatitis B surface antigen (HBsAg) by CMIA, and for HBV DNA by individual‐donor nucleic acid testing. Results were classified true positive, indeterminate, and false positive for anti‐HBc. Donors who tested indeterminate and false positive were admitted for reentry if follow‐up testing for anti‐HBc became negative and no further evidence for an HBV infection was apparent. RESULTS: A total of 554 of 148,000 samples, taken from 30,000 individuals within 3 years tested reactive for anti‐HBc by CMIA. Of those, 553 could be further classified: 142 (26%) true positive, 76 (14%) indeterminate, and 335 (60%) false positive. A total of 214 of 411 (52%) samples termed indeterminate or false positive were admitted for reentry and able to provide further donations. In one donor, anti‐HBc–positive/HBsAg‐ and HBV DNA–negative HBV DNA was detectable during follow‐up. CONCLUSION: According to our proposed algorithm, 26% of anti‐HBc–reactive results tested by CMIA were true positive. Many donors tested indeterminate or false positive can provide future donations if our proposed algorithm for reentry is applied. One donor at risk for transmitting HBV was identified solely by anti‐HBc testing.     

Distribution of hepatitis B virus DNA sequences in different peripheral blood mononuclear cell subsets in HBs antigen-positive and negative patients

Abstract. Hepatitis B virus (HBV) DNA sequences have been detected in leucocytes from HBV-infected individuals. The aim of this study was to assess the specificity of HBV for a special leucocyte subset in nine healthy chronic HBV carriers, nine HBs antigen-positive patients with chronic active hepatitis, 16 HBs antigen-negative haemophiliacs with HBc and/or HBs antibodies, and 10 patients with HBV-related systemic necrotizing vasculitis. HBV-DNA sequences were found by Southern blot hybridization in the leucocytes of 15 out of the 44 (34%) patients. The prevalence was not significantly different between the four groups. HBV-DNA was found in the CD4+ cells (9/11) as well as in the CD8+ cells (4/11), B cells (4/12) and monocytes (2/12). In conclusion, leucocytes, and particularly CD4+ lymphocytes, are frequently infected by HBV in patients with HBV serum markers.     

Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis.

Infection with hepatitis B virus leads to a wide spectrum of liver injury, including self-limited acute hepatitis, fulminant hepatitis, and chronic hepatitis with progression to cirrhosis or acute exacerbation to liver failure, as well as an asymptomatic chronic carrier state. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes. To investigate the reason why the extreme immunological attack occurred in fulminant hepatitis and severe exacerbation patients, the entire precore and core region of hepatitis B virus DNA was sequenced in 24 subjects (5 fulminant, 10 severe fatal exacerbation, and 9 self-limited acute hepatitis patients). No significant change in the nucleotide sequence and deduced amino acid residue was noted in the nine self-limited acute hepatitis patients. In contrast, clustering changes in a small segment of 16 amino acids (codon 84-99 from the start of the core gene) in all seven adr subtype infected fulminant and severe exacerbation patients was found. A different segment with clustering substitutions (codon 48-60) was also found in seven of eight adw subtype infected fulminant and severe exacerbation patients. Of the 15 patients, 2 lacked precore stop mutation which was previously reported to be associated with fulminant hepatitis. These data suggest that these core regions with mutations may play an important role in the pathogenesis of hepatitis B viral disease, and such mutations are related to severe liver damage.