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.     

Antibody to hepatitis B core antigen in blood donors with a history of hepatitis

Sera and questionnaires from 3,230 prospective U.S. volunteer blood donors were obtained in an earlier study to determine the prevalence of serologic markers of hepatitis B virus (HBV) and hepatitis A virus (HAV) among prospective blood donors with or without a history of either hepatitis or blood transfusion. These sera were reevaluated using a radioimmunoassay for antibody to hepatitis B core antigen (anti- HBc). Anti-HBc in the absence of hepatitis B surface antigen (HBsAg) or its antibody (anti-HBs) was detected in 30 of 1,151 (2.6%) prospective donors with a history of hepatitis, compared to four of 1,086 (0.4%) with no history of hepatitis (p less than 0.001). Although end-point dilution titers of anti-HBc greater than or equal to 1:100 and the presence of IgM anti-HBc were more frequently detected among donors with a history of hepatitis than among donors with no history of hepatitis, the difference was not statistically significant. Unlike a history of hepatitis, a history of transfusion or a history of exposure to persons with hepatitis had no significant association with the detection of anti-HBc in the absence of other HBV serologic markers.     

The clinical features of chronic hepatitis C are not affected by the coexistence of hepatitis B virus DNA in patients negative for hepatitis B surface antigen

Hepatitis B virus (HBV) DNA has been detected in the sera of hepatitis patients who are negative for hepatitis B surface antigen (HBsAg) by polymerase chain reaction (PCR). The purpose of the present study was to clarify the clinical characteristics of patients with chronic hepatitis C who are negative for serum HBsAg and positive for HBV DNA. The subjects included 49 patients with chronic hepatitis C who were negative for serum HBsAg and 119 blood donors who served as healthy controls. Serum samples were tested for the presence of HBV DNA by the nested PCR method. Serum HBV DNA was detected in 18 (37.7%) of the 49 chronic hepatitis C patients and in none (0%) of the 119 blood donors. Among the hepatitis C patients, HBV DNA was detected in 20.7% of those who were negative for all HBV-associated markers and in 57.1% of those who were positive for one or more HBV-associated marker. The HBV DNA-positive rate among those in each F stage did not significantly differ. The liver function parameters of the HBV DNA-positive and the HBV DNA-negative chronic hepatitis C patients did not significantly differ. These results suggest that hepatitis C virus is frequently coinfected with serum HBsAg-negative HBV, and that the incidence of HBV infection in blood donors is low. However, it is considered that HBsAg-negative HBV infection does not modify the blood biochemical features of chronic hepatitis C.     

Anti-hepatits B core antigen testing, viral markers, and occult hepatitis B virus infection in Pakistani blood donors: implications for transfusion practice

BACKGROUND: The purpose of this study was to determine the seroprevalence of anti-hepatitis B core antigen (HBc) and the impact of its testing along with other markers of hepatitis B, hepatitis B virus (HBV) DNA, hepatitis C virus antibody (anti-HCV), and syphilis in Pakistani blood donors. STUDY DESIGN AND METHODS: The study design was cross-sectional. A total of 966 donors were selected randomly for testing of anti-HBc and HBV markers, including HBV DNA, of 94,177 blood donors who were routinely screened for hepatitis B surface antigen (HBsAg), anti-HCV, human immunodeficiency virus antibody (anti-HIV), Treponema pallidum hemagglutination assay (TPHA), and malarial parasites from 2003 to October 2005. RESULTS: The seroprevalence of various infectious markers was as follows: HBsAg, 2.16 percent; anti-HCV, 4.16 percent; anti-HIV, 0.004 percent; TPHA, 0.75 percent; and malaria, 0.002 percent. Anti-HBc prevalence in HBsAg-negative, HBV DNA-negative blood donors was 167 of 966 (17.28%), with 76 percent demonstrating anti-HBs positivity. Younger donors with mean age of 25 years were exposed to HBV to a lesser extent compared to those with a mean age of 29 years. Anti-HBc positivity was significantly higher in anti-HCV-reactive individuals. HBV DNA was detectable in 5 blood donors who were HBsAg-, anti-HBc-positive and were categorized as having occult HBV infection. CONCLUSIONS: The study shows that more than 17 percent of healthy, young blood donors in Pakistan are already exposed to HBV, with two-thirds showing anti-HBs levels of greater than 100 mIU per mL. One in 200 blood donors who are HBsAg-, anti-HBc-positive, however, have occult HBV infection, with likelihood of transmission of hepatitis B in recipients of blood components derived from them. HBsAg-negative individuals who are anti-HBc-negative and those who are anti-HBc-positive, anti-HBs-positive, and HBV DNA-negative should be selected as regular blood donors to minimize transmission due to occult hepatitis B infection.     

Hepatitis B virus DNA in blood donors with anti-HBc as a possible indicator of active hepatitis B virus infection in Yucatan, Mexico

Hepatitis B virus (HBV) may be present in serum even when negative for HBV surface antigen (HBsAg). If routine screening of sera for anti-HBV core antigen (anti-HBc) is not done, low-level HBV viraemia may not be identified. A study was done on the presence of HBV DNA in serum samples from Mexican blood donors negative for HBsAg. Sera from 158 volunteer blood donors, negative for HBsAg and anti-HBs, but positive for anti-HBc, were analysed using nested polymerase chain reaction (PCR). HBV DNA was detected in sera from 13 (8.23%) of the 158. Specificity of the PCR-amplified products was corroborated using Southern blot. Single strand conformation polymorphism (SSCP) analysis showed identical SSCP-banding patterns for all 13 PCR products, suggesting similar cDNA sequences. Occult HBV infection was observed in approximately 8% of anti-HBc only donors. The absence of HBsAg in the blood of apparently healthy individuals may not be sufficient to ensure lack of circulating HBV, and blood containing anti-HBc only may be infectious until proven otherwise.     

Hepatitis B core antigen antibody as an indicator of a low grade carrier state for hepatitis B virus in a Saudi Arabian blood donor population

Blood donor screening for anti-hepatitis B core antigen (anti-HBc) was introduced as a surrogate marker of non-A, non-B hepatitis prior to the availability of a specific test for hepatitis C. In areas endemic for hepatitis B virus (HBV), such as Saudi Arabia, earlier studies indicated that up to 30% of blood donors might disqualify if screened for anti-HBc. The issue was readdressed in a study of 6035 consecutive first-time Saudi national blood donors in an attempt to identify a subgroup of anti-HBc positive donors who might be at high risk of being low grade carriers of HBV. An isolated anti-HBc of high titer in a donor with a low or absent anti-hepatitis B surface antigen (anti-HBsAg) was taken as an indicator of increased risk of a low grade carrier state. Using this algorithm, an additional 125 (2%) donors would disqualify. HBsAg immune complex assays and polymerase chain reaction of donor samples with an isolated anti-HBc identified two donors with immune complexes and two donors with HBV DNA. All four donor samples expressed over 90% neutralization in the anti-HBc supplementary testing, indicating high titer anti-HBc. These findings seem to support the suggested policy of donor exclusion based on the anti-HBc and anti-HBsAg serology as a means to eliminate low grade carriers of HBV in endemic areas without jeopardizing the blood supply.     

Posttransfusion hepatitis B transmitted by blood from a hepatitis B surface antigen-negative hepatitis B virus carrier

A female blood donor at our institution was implicated in three cases of clinical posttransfusion hepatitis B. She had given blood 25 times in 8 years. Twenty-seven recipients were followed up, and about one-half of those who were still living had serologic markers of hepatitis B virus (HBV) infection. The donor was repeatedly negative for hepatitis B surface antigen (HBsAg) and antibody, but she had high titers of antibody to hepatitis B core antigen. We conclude that blood from this HBsAg-negative blood donor was capable of transmitting hepatitis B.     

Infectivity of blood components with low hepatitis B virus DNA levels identified in a lookback program

BACKGROUND: Japanese Red Cross (JRC) blood centers implemented anti-hepatitis B core antigen (HBc) screening in 1989 and 50-minipool (MP)-nucleic acid testing (NAT) in 2000. A systematic lookback study has been conducted to determine the hepatitis B virus (HBV) transmission risk of donations drawn in the pre-hepatitis B surface antigen (HBsAg) and/or MP-NAT window phase and by donors with occult HBV infection. STUDY DESIGN AND METHODS: JRC blood centers have been storing aliquots of every blood donation since 1996. On the basis of the complete repository tube archives, all donations from repeat donors received from 1997 to 2004 were subjected to a lookback study. When repeat donors turned positive for HBV viral marker(s), repository tubes from their previous donations were tested for HBV with individual-donation (ID)-NAT. The frequency of ID-NAT-only-positive donations and the HBV transmission risk by the transfusion of those components were investigated. RESULTS: HBV ID-NAT was performed on 15,721 repository tubes, and 158 tubes (1.01%) were found positive for the presence of HBV DNA. Of these 158 ID-NAT-only-positive donations, 95 (60%) were derived from carriers with low anti-HBc titers. Of 63 patients transfused with ID-NAT-only-positive components, 12 (19%) proved to be infected with HBV. Only 1 of 33 components with low anti-HBc titers could be identified as infectious, whereas 11 of 22 anti-HBc-negative components proved to be infectious. None of the 16 identified hepatitis B surface antibody-positive components showed serologic evidence of infection. CONCLUSION: The clinically observed HBV infection risk caused by blood components from occult HBV carriers with low anti-HBc titers who slip through the JRC screening system is more than 10-fold lower than the transmission risk by donations in the pre-HBsAg and/or MP-NAT window phase.     

Detection and characterization of hepatitis B virus of anti-hepatitis B core antigen-reactive blood donors in Quebec with an in-house nucleic acid testing assay

BACKGROUND: Hepatitis B virus (HBV) infection can be detected in blood donations by many serologic markers. Since the introduction of routine anti-hepatitis B core antigen (HBc) donor screening at Héma-Québec in April 2003, a large number of donors have been deferred on the basis of reactive anti-HBc test results. The objective of this study was to evaluate the correlation between the anti-HBc–reactive donations and the detection of HBV DNA with an in-house nucleic acid testing (NAT) assay.
STUDY DESIGN AND METHODS: The in-house HBV NAT assay is a conventional polymerase chain reaction amplifying part of the viral S  gene. From October 2004 to November 2005, a total of 1169 anti-HBc–reactive donations were tested with this in-house assay. The results were correlated with hepatitis B surface antigen (HBsAg) and anti-HBs markers. HBV DNA–positive samples were further investigated by DNA sequencing.
RESULTS: All HBsAg-positive samples were detected by the NAT assay. Overall, 38 (3.25%) of anti-HBc–positive samples were found to be positive for the presence of HBV DNA. Of these 38, a total of 12 donations with a low level of HBV DNA were HBsAg-negative. The sequencing results clearly showed various genotypes and subtypes within a same genotype.
CONCLUSION: The 3.25 percent HBV DNA positivity rate among the anti-HBc–reactive donations and more particularly the low level of HBV DNA observed in occult donations underline the importance of the use of a sensitive assay to detect HBV DNA in conjunction with other markers. The HBV genetic diversity found in our donor population reflects the province demographics, particularly in the Montreal area where most of the positive donors were from.     

Value of anti-HBc screening of blood donors for prevention of HBV infection: results of a 3-year prospective study in Northwestern Greece

BACKGROUND: The risk of infection with transfusion-transmitted viruses has been reduced remarkably. However, a zero-risk blood supply remains a popular goal. Some authorities have introduced the screening for antibody to HBc (anti-HBc) as a surrogate test for the presence of several infectious agents. A 3-year prospective study was conducted in the Epirus region of Greece to determine the prevalence of several blood-borne viruses. One component of the study was the prevalence of HBV infection markers and the potential value of anti-HBc testing of donors in this area. STUDY DESIGN AND METHODS: Between January 1, 1995, and December 31, 1997, some 6696 donors were investigated for the presence of HBV infection markers by standard EIAS: Every sample that tested HBsAg-negative but anti-HBc-reactive alone or in combination with either or both antibodies to HBV e antigen (anti-HBe) and low-titered antibodies to HBsAg (anti-HBs <20 mIU/mL) was further investigated for the presence of HBV DNA by a combination of PCR and DNA EIA. RESULTS: Of these 6696 donors, 15.8 percent tested positive for at least one serologic marker of HBV infection (HBsAg prevalence, 0.85%). Anti-HBc reactivity alone or in combination with either or both anti-HBe and low-titered anti-HBs was found in 282 donors (4.2%). None tested HBV-DNA positive. No transfusion-associated HBV infections were recorded in the recipients of the above 282 blood units. CONCLUSION: A moderate prevalence of HBV infection markers was found. However, taking into account previous studies from this region, it appears that the HBsAg prevalence has declined. In addition, the present study cannot recommend the introduction of anti-HBc screening as a surrogate marker of occult HBV infection. The adoption of this exclusion criterion in this region would result in unacceptably high rejection rates among otherwise healthy donors. The absence of any case of transfusion-associated HBV infection after the transfusion of all HBsAg-negative, anti-HBc-positive units appears to provide further support for the negative HBV DNA results. Before a consideration of screening donors, efforts must be focused on reducing the number of false-positive anti-HBc results.     

Hepatitis B virus DNA-positive, hepatitis B surface antigen-negative blood donations intercepted by anti-hepatitis B core antigen testing: the Canadian Blood Services experience

BACKGROUND: The benefit of introducing anti-hepatitis B core antigen (HBc) screening for intercepting potentially infectious donations missed by hepatitis B surface antigen (HBsAg) screening in Canada was studied. STUDY DESIGN AND METHODS: Anti-HBc testing of all donations was implemented in April 2005, along with antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B virus (HBV) DNA supplemental testing of anti-HBc repeat-reactive, HBsAg-negative donations. The proportion of potentially infectious donations intercepted by anti-HBc over the initial 18 months of testing was calculated based on three assumptions relating infectivity of HBV DNA-positive units to anti-HBs levels. Lookback was conducted for all DNA-positive donations. RESULTS: Of 493,344 donors, 5,585 (1.13%) were repeat-reactive for the presence of anti-HBc, with 29 (0.52%) being HBV DNA-positive and HBsAg-negative. The proportion of potentially infectious donations intercepted by anti-HBc screening was 1 in 17,800 if all HBV DNA-positive donations were infectious, 1 in 26,900 if infectivity was limited to donations with an anti-HBs level of not more than 100 mIU per mL, and 1 in 69,300 if only donations with undetectable anti-HBs were infectious. For 279 components in the lookback study, no traced recipients were HBsAg-positive and 7 recipients were anti-HBc-reactive in association with 4 donors, 3 of whom had an anti-HBs level of more than 100 mIU per mL and 1 of whom had a level of 61 mIU per mL. CONCLUSION: Implementation of anti-HBc screening reduced the risk of transfusing potentially infectious units by at least as much as had been expected based on the literature. The lookback did not provide proof of transfusion transmission of HBV from HBV DNA-positive, anti-HBc-reactive, HBsAg-negative donors but it did not establish lack of transmission either.     

New hepatitis B virus mutant form in a blood donor that is undetectable in several hepatitis B surface antigen screening assays

BACKGROUND: Envelope mutant forms of hepatitis B virus (HBV), impairing HBV antibody recognition, have been reported with mutations in single or multiple sites of the hepatitis B surface antigen (HBsAg) group- specific "a" determinant. Blood donors infected with such an HBsAg mutant form of HBV may escape detection by HBsAg screening assays and therefore may affect the safety of the blood supply. CASE REPORT: A repeat blood donor became HBsAg-reactive in an enzyme immunoassay. Confirmatory testing yielded negative results for HBsAg in a radioimmunoassay and in four enzyme immunoassays used in blood donor screening. The specificity of the HBsAg reactivity in the first enzyme immunoassay was confirmed by HBsAg neutralization with antibody to HBsAg. Additional HBV confirmatory test results were positive for antibody to hepatitis B core antigen and antibody to hepatitis B e antigen; negative for antibody to HBsAg and for hepatitis B e antigen; and positive for HBV DNA. DNA sequence analysis of the "a" determinant region of HBsAg revealed amino acid substitutions from Q (Gln) to R (Arg) at codon 129 and from M (Met) to T (Thr) at codon 133. CONCLUSION: This case illustrates the presence of HBsAg mutant forms of HBV in a West European blood donor population that were undetected by several HBsAg screening assays. Adaptation of HBsAg screening is indicated to overcome deficiencies in sensitivity in detecting HBsAg mutant forms of HBV. Screening for antibody to hepatitis B core antigen or HBV DNA may also detect blood donors infected with HBsAg mutant forms of HBV     

Feasibility and usefulness of an efficient anti-HBc screening programme in blood donors

SUMMARY. Post-transfusion hepatitis B remains a risk for recipients of hepatitis B surface antigen (HBsAg) screened blood. Anti-hepatitis B core antibody (anti-HBc) screening may help reduce this risk. To evaluate its usefulness, 9,238 East Anglian blood donors were screened for anti-HBc. Those with isolated anti-HBc were identified with two confirmatory anti-HBc and anti-HB surface antibody (anti-HBs) assays. The prevalence of anti-HBc reactions in screening and confirmatory assays was 1.29% and 0.35%, respectively. The level of reactivity was significantly higher when two anti-HBc assays gave concordant results or, being concordant, were anti-HBs positive. All isolated anti-HBc-positive units (0.04%) were negative for additional HBV markers including DNA tested with nested polymerase chain reaction (PCR).
A 0.31% prevalence of past HBV infection was found in this population, all carrying both anti-HBc and anti-HBs antibody, most above the protective level (0.IU/ml).
The proposed screening schemes would limit the number of deferred donors and discarded units and keep the testing time within the remit of routine blood banking practices for an additional cost of approximately £1 per unit. However, no evidence was found in this donor population to suggest that anti-HBc screening would significantly reduce the incidence of post-transfusion hepatitis B.     

Evaluation of a multiplex human immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus nucleic acid testing assay to detect viremic blood donors in northern Thailand

BACKGROUND: Screening of blood donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) has been implemented recently in the United States. There are limited data, however, on the additional NAT yield of donors in developing countries in Asia where the prevalence of infection is higher. In addition, data on hepatitis B virus (HBV) NAT in high prevalence areas are minimal. STUDY DESIGN AND METHODS: A total of 5083 whole-blood donors at the Chiang Mai University Hospital, Thailand, blood bank were evaluated with a commercially available NAT assay (Procleix Ultrio, Gen-Probe, Inc.) to screen individual donations. RESULTS: No NAT yield cases were found for HIV-1 or HCV. There were 17 samples with discrepant HBV DNA NAT and hepatitis B surface antigen (HBsAg) tests, however. Seven of these were HBV DNA NAT-positive, HBsAg-negative; of these 7, 1 was NAT-positive at baseline, but negative on follow-up, and considered a false-positive, 1 had an acute infection, and 5 had chronic prevalent HBV infections, for a NAT yield of 6 in 4798 HBsAg negative donors (1:800). In addition there were 10 NAT-negative, HBsAg-positive serum samples. All were anti-hepatitis B core antigen immunoglobulin G-positive; on testing with a more sensitive NAT target capture assay, 5 were positive (1.8-20.6 IU/mL) and 5 were negative. CONCLUSION: Multiplex NAT screening of individual-donor serum samples in Northern Thailand detected approximately 1 per 800 HBV NAT-positive, HBsAg-negative donors. The especially high prevalence of HBV infection in Thailand and other Asian countries suggests that HBV NAT screening of donors will be more cost-effective than in other areas.     

Prevalence of serologic markers for hepatitis B and C viruses in Brazilian blood donors and incidence and residual risk of transfusion transmission of hepatitis C virus

BACKGROUND: We evaluate the current prevalence of serologic markers for hepatitis B virus (HBV) and hepatitis C virus (HCV) in blood donors and estimated HCV incidence and residual transfusion‐transmitted risk at three large Brazilian blood centers. STUDY DESIGN AND METHODS: Data on whole blood and platelet donations were collected from January through December 2007, analyzed by center; donor type; age; sex; donation status; and serologic results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti‐HBc), and anti‐HCV. HBV and HCV prevalence rates were calculated for all first‐time donations. HCV incidence was derived including interdonation intervals that preceded first repeat donations given during the study, and HCV residual risk was estimated for transfusions derived from repeat donors. RESULTS: There were 307,354 donations in 2007. Overall prevalence of concordant HBsAg and anti‐HBc reactivity was 289 per 100,000 donations and of anti‐HCV confirmed reactivity 191 per 100,000 donations. There were significant associations between older age and hepatitis markers, especially for HCV. HCV incidence was 3.11 (95% confidence interval, 0.77‐7.03) per 100,000 person‐years, and residual risk of HCV window‐phase infections was estimated at 5.0 per million units transfused. CONCLUSION: Improvement in donor selection, socioeconomic conditions, and preventive measures, implemented over time, may have helped to decrease prevalence of HBV and HCV, relative to previous reports. Incidence and residual risk of HCV are also diminishing. Ongoing monitoring of HBV and HCV markers among Brazilian blood donors should help guide improved recruitment procedures, donor selection, laboratory screening, and counseling strategies.     

Significance of antibody to hepatitis B core antigen in blood donors as determined by their serologic response to hepatitis B vaccine

Because large numbers of volunteer blood donors may be disqualified for "false-positive" results on tests for antibody to hepatitis B core antigen (anti-HBc), a more specific definition of anti-HBc enzyme immunoassay (EIA)-reactive was evaluated, including only those donor samples that were "strongly" reactive (sample-to-cutoff absorbance ratio, < 0.45). Results using this definition and other anti-HBc test methods were compared to the serologic response (antibody to hepatitis B surface antigen [anti-HBsAg]) to hepatitis B vaccination. Fifty-eight volunteer blood donors who had previously been deferred as donors, because of reactive anti-HBc tests (all other blood screening tests were negative, including those for HBsAg and anti-HBsAg) on two occasions, were vaccinated for hepatitis B. It was assumed that an anamnestic response to vaccine indicated past infection with hepatitis B, while a primary response to vaccine indicated lack of past infection. One (2%) of 43 donors with a historically "weak" anti-HBc (reactive absorbance ratio, > or = 0.45) had an anamnestic response to vaccine, compared to 8 (53%) of 15 with historically "strong" anti-HBc (reactive absorbance ratio, < 0.45) (p < 0.005). Anti-HBc testing using the microparticle EIA method also correlated well with hepatitis B vaccination results. The use of a narrower definition of "reactive" for anti-HBc EIA testing yielded much more specific, but slightly less sensitive, results.     

闽南地区无偿献血者隐匿性乙型肝炎病毒感染研究

目的研究闽南地区无偿献血者中隐匿性乙型肝炎病毒感染(OBI)情况,探讨现有输血传播乙肝病毒(HBV)的检测方法的有效性。方法依据多种与HBV相关血清学指标的检测情况对献血者标本进行HBV携带风险评价分级,对较高携带风险的标本做单份多区段巢式-PCR检测其HBV DNA,对低携带风险的标本做10份混合的巢式-PCR检测。采用这一方案,对闽南地区19 360例HBsAg阴性的无偿献血者标本做检测分析。结果闽南地区HBsAg阴性献血者中的HBV DNA阳性检出率为0.21%(40/19 360,95%CI:0.15%—0.28%),属于OBI;其中抗-HBc阳性检出率85%(34/40),但阳性预测值仅为3.4%(34/995,95%CI:2.4%—4.7%);HBV NRAg阳性预测值30%(6/20),但灵敏度为15%(6/40)。结论现有筛查体系下无偿献血者中仍存在一定比例的OBI,需要寻求更为有效的检测方法。     

Efficacy of individual nucleic acid amplification testing in reducing the risk of transfusion‐transmitted hepatitis B virus infection in Switzerland,a low‐endemic region

BACKGROUND: The risk of transfusion‐transmitted hepatitis B virus (HBV) in Switzerland by testing blood donors for hepatitis B surface antigen (HBsAg) alone has been historically estimated at 1:160,000 transfusions. The Swiss health authorities decided not to introduce mandatory antibody to hepatitis B core antigen (anti‐HBc) testing but to evaluate the investigation of HBV nucleic acid testing (NAT). STUDY DESIGN AND METHODS: Between June 2007 and February 2009, a total of 306,000 donations were screened routinely for HBsAg and HBV DNA by triplex individual‐donation (ID)‐NAT (Ultrio assay on Tigris system, Gen‐Probe/Novartis Diagnostics). ID‐NAT repeatedly reactive donors were further characterized for HBV serologic markers and viral load by quantitative polymerase chain reaction. The relative sensitivity of screening for HBsAg, anti‐HBc, and HBV DNA was assessed. The residual HBV transmission risk of NAT with or without anti‐HBc and HBsAg was retrospectively estimated in a mathematical model. RESULTS: From the 306,000 blood donations, 31 were repeatedly Ultrio test reactive and confirmed HBV infected, of which 24 (77%) and 27 (87%) were HBsAg and anti‐HBc positive, respectively. Seven HBV‐NAT yields were identified (1:44,000), two pre‐HBsAg window period (WP) donations (1:153,000) and five occult HBV infections (1:61,000). Introduction of ID‐NAT reduced the risk of HBV WP transmission in repeat donors from 1:95,000 to 1:296,000. CONCLUSIONS: Triplex NAT screening reduced the HBV WP transmission risk approximately threefold. NAT alone was more efficacious than the combined use of HBsAg and anti‐HBc. The data from this study led to the decision to introduce sensitive HBV‐NAT screening in Switzerland. Our findings may be useful in designing more efficient and cost‐effective HBV screening strategies in low‐prevalence countries.     

Transfusion-transmitted HBV infection in an endemic area: the necessity of more sensitive screening for HBV carriers

BACKGROUND: By NAT, HBV DNA is occasionally detectable in blood donors with past HBV infection but negative for HBsAg. Whether or not these donors can cause transfusion-transmitted HBV infections is uncertain. STUDY DESIGN AND METHODS: To determine whether or not donors with past HBV infection but negative for HbsAg can cause HBV transfusion-transmitted infections, recipients followed for blood transfusion in a university medical center in Taiwan were studied. HBV DNA and serologic markers were tested in donors and recipients. RESULTS: Of 1,038 enrolled recipients, 910 completed the 6-month post-transfusion follow-up visit. Of these, only 39 patients (4.3%) tested negative on the pretransfusion sample for HBsAg, anti-HBs, anti-HBc, and HBV DNA by PCR. These 39 HBV-naive recipients had been transfused with blood from 147 donations for which stored samples were available for HBV DNA testing by PCR; 11 of these HBsAg-negative samples tested positive for HBV DNA and anti-HBc. Two of the 11 patients who received the HBV-DNA-positive donations (18%) became positive for HBV DNA, and one seroconverted to anti-HBc and finally to anti-HBs, with a mild transient elevation of serum ALT activities. Based on the one confirmed case of HBV transmission, a projection was made that approximately 200 post-transfusion HBV infections could occur in one million units of transfused blood in Taiwan. CONCLUSIONS: In HBV-endemic areas like Taiwan, where blood donors are screened for HBsAg only, the risk of transfusion-transmitted HBV appears to be substantial. Implementation of NAT for blood screening in these settings warrants consideration.