Hepatitis B Virus Nucleic Acid Testing Research Articles

Hepatitis B in Heart Transplant Donors and Recipients: A Systematic Review and Meta-Analysis

IntroductionExpanding the heart donor pool to include patients with hepatitis B virus (HBV) could help ameliorate the organ shortage in heart transplantation. We performed a systematic review and meta-analysis to evaluate the management and recipient outcomes of D+/R- and D-/R+ heart transplants. MethodsAn electronic search was performed to identify all relevant studies published on heart transplants involving HBV+ donors and/or HBV+ recipients. A comparison was performed between two groups where heart transplants were performed a) D+/R- (n = 98) versus b) D-/R+ (n = 65). ResultsOverall, 13 studies were selected, comprising 163 patients. Mean patient age was 55 y (95% CI: 39, 78) and 79% (69, 86) were male. Active post-transplant HBV infection requiring antiviral treatment occurred in 11% (1, 69) of D+/R- recipients and 33% (9, 71) of D-/R+ recipients. Post-transplant antiviral therapy was given to 80% (6, 100) of D+/R- recipients compared to 72% (42, 90) of D-/R+ recipients (P = 0.84). Hepatitis-related mortality was observed in no D+/R- recipients and 7% (2, 27) of D-/R+ recipients. Survival 1-y post-transplant was comparable between both groups at 83% (83, 92) and 81% (61, 92) for D+/R- and D-/R+ transplants, respectively. ConclusionsOur review found that HBV D+/R- heart transplantation was associated with fewer active hepatitis infections and lower hepatitis-related mortality than D-/R+ transplantation, with comparable survival at 1 y. Additional studies utilizing HBV nucleic acid testing (NAT) to compare outcomes with HBsAg+ and anti-HBc+ donors are crucial to reach more definitive conclusions about the risk of donor-derived infections in this context.

Correlation of serological and molecular markers in the screening for hepatitis B virus in blood bank in northern Brazil

IntroductionIn Brazil, the blood donor screening for hepatitis B virus (HBV) includes laboratory testing for serological (HBsAg and Anti-HBc) and molecular (HBV DNA) markers. This study aims to correlate serology reactive results with HBV DNA detection among blood donors with at least one HBV infection marker detected in a blood bank in northern Brazil. MethodA retrospective search for HBV reactive blood donor data from January 2017 to December 2019 was performed. Serological screening was performed by chemiluminescent microparticle immunoassays Architect HBsAg and Architect Anti-HBc, whereas molecular screening was performed by the HBV nucleic acid test (HBV NAT). Main resultsA total of 556 HBsAg reactive results were detected, between positive (47.66%) and inconclusive (52.34%). A total of 3,658 Anti-HBc reactive results were detected, between positive (83.71%) and inconclusive (16.29%). None of the inconclusive results were associated with HBV DNA detection. The HBV DNA detection rates were 47.55% among HBsAg positive samples and 4.08% among Anti-HBc positive samples. The signal-to-cutoff (S/CO) ratio median of HBV NAT positive samples was superior in comparison to HBV NAT negative samples (p < 0.0001). The thresholds found to optimize sensitivity and specificity were 404.15 for Architect HBsAg and 7.77 for Architect Anti-HBc. Three blood donors were in the window period and 1 occult HBV infection case was detected. ConclusionHigh S/CO ratios were more predictive of HBV DNA detection. However, a number of HBV NAT positive samples gave low values, while some HBV NAT negative samples showed high values, reaffirming the significance of molecular testing to enhance transfusion safety.

Use and outcomes of hepatitis B virus-positive grafts in orthotopic liver transplantation in the United States from 1999 to 2021.

The demand for orthotopic liver transplantation (OLT) is projected to increase, which indicates a need to expand the liver donor pool. We aimed to investigate the use of hepatitis B virus (HBV)-positive grafts and the outcomes of recipients undergoing OLT with HBV-positive grafts. We conducted a retrospective cohort study analyzing all deceased donors and OLT recipients in the Organ Procurement and Transplantation Network database from January 1999 through March 2021. Donor HBV status was positive if hepatitis B surface antigen was positive or HBV nucleic acid testing was detectable. Recipients of HBV-positive allografts were matched 1:5 to recipients of HBV-negative allografts based on recipient and donor age, transplant year, recipient sex, donation after circulatory death, recipient location, and Model for End-Stage Liver Disease score at transplant. Among the 185,212 potential donors, 422 (0.2%) were HBV positive, and 265 (63%) of the HBV-positive grafts were transplanted (14 of 265 [5.3%] in HBV-positive recipients). The overall discard rate for HBV-positive donors of 37.2% (157/422) remained significantly higher than the discard rate for HBV-negative donors of 26.5% (49,026/185,212) during the study period ( p < 0.001). Recipients of HBV-positive ( n = 209) grafts had similar mortality (log-rank, p = 0.47) and graft loss (log-rank, p = 0.72) rates to the matched recipients of HBV-negative allografts ( n = 1045). The 3-year graft survival rate was 77.9% for the HBV-positive group and 79.7% in the matched HBV-negative group. Based on this analysis, transplant recipients of HBV-positive liver allografts do not experience increased rates of mortality or graft loss. One strategy that may help expand the donor pool and lower the waitlist mortality rate is using HBV-positive allografts.

Hepatitis B infections among blood donors in England between 2009 and 2018: Is an occult hepatitis B infection a risk for blood safety?

Hepatitis B virus (HBV) is one of the most frequent infections identified in blood donors in England and represents an ongoing blood safety risk. We have analyzed markers of HBV infections in blood donors in England between 2009 and 2018 and used these to estimate the likelihood of non-detection of occult HBV infection (OBI). We collected epidemiological, virological, and genotyping information on HBV cases identified in England, 2009-2018. The estimated risk of non-detection and likely transmission of OBI were compared to lookback and transfusion-transmitted infections surveillance data. Six-hundered and fifty-five HBV-infected blood donors were identified in England during the 10-year period; 598 chronic, 32 acute, and 25 occult HBV infections. However, most donors with chronic and occult infections were born in Eastern Europe, Africa, or Asia (451/544, 83% and 14/24, 58%); acute infections were largely seen in UK-born donors (19/28, 68%). Genotyping of 266 HBV-positive samples revealed five genotypes (A-E), reflecting ethnicity and country of birth. Most OBIs were identified in repeat donors (19/25); lookback data identified a transmission rate of 8.3%. It is estimated that at least 13 potentially infectious donations from donors with OBI remain undetected annually, equating to an overall residual transmission risk of 3.1 per million donations using our current screening strategy of HBsAg screening with HBV nucleic acid testing (NAT) in pools of 24. OBI accounted for the majority of the HBV residual risk in England. Further cost-benefit analysis is required to estimate if our current HBV screening strategy should be changed.

Assessing Solid Organ Donors and Monitoring Transplant Recipients for Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus Infection - U.S. Public Health Service Guideline, 2020.

SummaryThe recommendations in this report supersede the U.S Public Health Service (PHS) guideline recommendations for reducing transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) through organ transplantation (Seem DL, Lee I, Umscheid CA, Kuehnert MJ. PHS guideline for reducing human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission through organ transplantation. Public Health Rep 2013;128:247–343), hereafter referred to as the 2013 PHS guideline. PHS evaluated and revised the 2013 PHS guideline because of several advances in solid organ transplantation, including universal implementation of nucleic acid testing of solid organ donors for HIV, HBV, and HCV; improved understanding of risk factors for undetected organ donor infection with these viruses; and the availability of highly effective treatments for infection with these viruses. PHS solicited feedback from its relevant agencies, subject-matter experts, additional stakeholders, and the public to develop revised guideline recommendations for identification of risk factors for these infections among solid organ donors, implementation of laboratory screening of solid organ donors, and monitoring of solid organ transplant recipients. Recommendations that have changed since the 2013 PHS guideline include updated criteria for identifying donors at risk for undetected donor HIV, HBV, or HCV infection; the removal of any specific term to characterize donors with HIV, HBV, or HCV infection risk factors; universal organ donor HIV, HBV, and HCV nucleic acid testing; and universal posttransplant monitoring of transplant recipients for HIV, HBV, and HCV infections. The recommendations are to be used by organ procurement organization and transplant programs and are intended to apply only to solid organ donors and recipients and not to donors or recipients of other medical products of human origin (e.g., blood products, tissues, corneas, and breast milk). The recommendations pertain to transplantation of solid organs procured from donors without laboratory evidence of HIV, HBV, or HCV infection. Additional considerations when transplanting solid organs procured from donors with laboratory evidence of HCV infection are included but are not required to be incorporated into Organ Procurement and Transplantation Network policy. Transplant centers that transplant organs from HCV-positive donors should develop protocols for obtaining informed consent, testing and treating recipients for HCV, ensuring reimbursement, and reporting new infections to public health authorities.

Occult hepatitis B infection among blood donors from Yaoundé, Cameroon.

In Cameroon, the prevention of hepatitis B virus (HBV) transmission by blood transfusion is still only based on hepatitis B surface antigen (HBsAg) screening. However, occult HBV infection (OBI) characterised by the absence of detectable HBsAg and low level of viral DNA remains a potential threat for blood safety. The prevalence of OBI was investigated in blood donors from Yaoundé to provide evidence-based recommendations to improve HBV blood safety. Blood donations from August 1st, 2016 to March 31st, 2017 were routinely screened for HBV, human immunodeficiency virus (HIV), and hepatitis C virus (HCV) infections (Murex HBsAg Version 3, Murex HIV Ag/Ab Combination, and Murex HCV Ag/Ab Combination [DiaSorin]). Additional HBV investigations were performed, including hepatitis B core antibody ([HBc] Monolisa Anti-HBc PLUS; BIO-RAD) and HBV DNA tested in minipools of two samples using the quantitative Cobas Taqman HBV assay (Roche; LoQ: 6 IU/mL) and HBV DNA genotyping by sequencing. Of 1,162 donations analysed, 91 (7.8%) were reactive for HBsAg. All of them were also anti-HBc positive. Among the 1,071 HBsAg negative samples, 522 (48.7%) were reactive for anti-HBc. Six (0.56% of all donations) samples fulfilled the consensus definition of OBI and showed low HBV DNA loads (all <6 IU/mL). Following nested polymerase chain reaction amplifications, HBV DNA sequences were obtained for 4 of these samples (1 nearly whole genome [3123 nt], 2 Pre-S/S regions [1,356 nt], and 1 S region [445 nt]). Phylogenetic analysis identified genotype E in all samples. Around 1 in 100 Cameroonian blood donors screened who resulted HBsAg negative and anti-HBc positive carried occult HBV infection. HBsAg alone for screening prospective donors is not sufficient to eliminate the risk of HBV transfusion transmission in Cameroon, and because anti-HBc screening does not seem to be feasible without compromising blood supply, implementation of HBV nucleic acid testing could be considered when possible.

Blood donor testing for hepatitis B virus in the United States: is there a case for continuation of hepatitis B surface antigen detection?

In the United States, blood donor testing for hepatitis B surface antigen (HBsAg) was initiated in the early 1970s. More recently, testing for antibody to hepatitis B core antigen (anti-HBc) and hepatitis B virus (HBV) DNA have been added. The incidence of hepatitis B has been declining. This study reviews the current status of testing and questions the need for continuation of HBsAg testing. From July 2011 to June 2015, a total of 22.4 million donations were serologically tested for HBsAg and anti-HBc and for HBV-DNA by nucleic acid testing (NAT). All reactive results were evaluated and a subset of donations that were either potential NAT yield (seronegative) or serologically positive but nonreactive by HBV NAT in minipools (MPs) of 16 were further evaluated by individual donation (ID)-NAT. Samples with detectable HBV DNA were defined as actively infected and considered potentially infectious. Routine testing plus supplemental ID-NAT identified 2035 samples representing active infection including 1965 with anti-HBc, 1602 with HBsAg, and 1453 with HBV DNA by MP-NAT, for respective rates per hundred-thousand donations of 9.10, 8.78, 7.16, and 6.50, continuing the downward trend previously observed. There were 29 HBV DNA-yield samples (1:771,389), 35 HBsAg-yield samples (anti-HBc nonreactive), and 404 with occult hepatitis B infection. There were six samples with HBsAg and HBV DNA detectable only by ID-NAT in the absence of anti-HBc; additional testing was consistent with extremely low or negligible levels of DNA. Point estimates of HBV infection rates among blood donors continue to decline, as do those for incidence and residual risk. Elimination of HBsAg screening would have negligible impact, with a risk less than 1 per 4 million donations.

Significance of HBV NAT Among HBs Antigen-Negative Blood Donors in Saudi Arabia.

Bloodborne hepatitis B virus (HBV) transmission from asymptomatic donors with acute HBV infections who have undetectable surface antigen of HBV (HBsAg), or from donors with chronic infections in whom serological markers were not detected, could cause residual infections leading to relevant transfusion-transmitted infections (RTTIs). HBV nucleic acid testing (NAT) can detect HBV DNA in the HBsAg-negative and total hepatitis B core antibody (anti-HBc)-negative window period of infection and in chronic cases. To assess the presence or absence of HBV DNA in blood donors with HBsAg negativity. We collected 3014 blood specimens from volunteer blood donors at the blood bank of King Khalid University Hospital in Riyadh, Saudia Arabia. Specimens from each donor were tested for HBsAg, anti-HBc, and hepatitis B surface antibody (anti-HBs) by commercial immunoassays and for qualitative assessments of HBV-DNA by HBV-NAT testing. Of the 3014 donors, 7 (0.23%) tested positive for HBsAg and anti-HBc, 1 for HBsAg (0.03%) only, and of those 264 donors (8.8%) for anti-HBc. Of these last, 6.9% also tested positive for anti-HBs and 1.9% tested negative for anti-HBs. HBV-NAT testing was reactive in 75.0% of subjects who tested HBsAg positive, and nonreactive in 100% of subjects who tested anti-HBc positive/HBsAg negative (with or without anti-HBs). Among 2742 donors who tested seronegative, 1 specimen was determined to be reactive via HBV-NAT testing. The frequency of HBV DNA in blood donors who tested seronegative was low. This finding may indicate the significance of the HBV NAT technique in reducing the residual risk of transfusion-transmitted HBV infection.

Low Prevalence of Occult Hepatitis B Infection Among Blood Donors in Beirut, Lebanon: Reconsider the Deferral Strategy of Anti-HBc Positive Blood Donors

Background: Hepatitis B virus (HBV) infection remains one of the major infectious threats to human health. Since the implementation of highly sensitive HBV nucleic acid testing, occult HBV infection (OBI) has been detected. Occult HBV infection is characterized by a positive HBV DNA test with undetectable HBsAg (Hepatits B surface antigen). The prevalence of OBI varies significantly between geographic areas, genotypes, and population depending on the sensitivity of the detection assays used. Objectives: This project aimed at determining the prevalence of OBI in blood donors from a major blood donor center in Beirut, Lebanon through testing for 4 HBV markers (HBsAg, anti-HBs, anti-HBc and HBV DNA). Methods: A total of 7437 blood donors were first tested for anti-HBc marker between August 2013 and March 2015; samples positive for anti-HBc were tested for other serological markers and HBV genome. DNA was extracted from 500 μL of plasma and tested for HBV DNA using Artus HBV TM PCR Kit assay. All anti-HBc positive samples were tested by nested PCR, targeting the S gene. Results: This study revealed a 4.6% prevalence of anti-HBc positive blood donors (341/7437). Among anti-HBc positive blood donors, 21 were HBsAg positive (6.2%) and 75% were positive for anti-HBs. The occurrence of occult hepatitis B virus in healthy seropositive blood donors during a 20 month period was very low; only 1 Syrian blood donor (n = 1/341, 0.3%) was HBsAg negative, HBV DNA-positive with anti-HBs level > 1000 mIU/mL. Conclusions: Our study indicates that HBV DNA is present in a small percentage of HBsAg negative, anti-HBc reactive units. Lebanon has developed its own blood screening strategy, which is to screen for anti-HBc in addition to HBsAg. This is based on HBV prevalence and cost-effectiveness of testing methods. The disadvantage of not implementing nucleic acid testing (NAT) is missing rare blood units from donors in the window period.

Detection and identification of occult hepatitis B virus infection among blood donors

Background: Occult hepatitis B virus infection (OBI) is defined as the presence of circulating hepatitis B virus (HBV) DNA as detected by HBV nucleic acid test (NAT), in the absence of detectable HBV surface antigen (HBsAg), with or without antibodies to hepatitis B core antigen (anti-HBc) or hepatitis B surface antigen (anti-HBs). HBV infection is a continuing threat to transfusion safety, especially in developing counties like India where detection of HBV is primarily based on the screening for HBsAg as a marker of infection. Objective: To know the prevalence of OBI among blood donors and their serological and molecular characterization of NAT yield samples. Materials and Methods: A total of 41,090 blood donor’s samples from February 2014 to August 2015 were tested by individual donor-NAT (ID-NAT) apart from routine serological screening for anti-HIV 1-2, P24 antigen, anti-HCV, and Hepatitis B surface antigen (HBsAg) by Biomerieux (Vironostika® HIV Ag-Ab, Hepanostika® HCV Ultra, and HBsAg Ultra, France). All the samples were tested individually by Procleix® Utrio Plus® Assay (Novartis Emeryville, CA). Blood units that were HBsAg nonreactive but ID-NAT reactive (NAT yield) were further worked up with anti-HBc, anti-HBsAg, viral DNA load, and viral genotyping. Result: Of the 41,090 samples, 29 were reactive for HBV DNA (NAT yield). Among the 29 NAT yields, 24 were individual NAT yield, 4 were HBV–HCV NAT co-yield, and 1was HBV-HIV NAT co-yield. A total of 24 HBV individual NAT yield samples were further tested for OBI. A total of 11 samples were reactive for anti-HBc only, 3 samples carried both anti-HBc and anti-HBs, yielding a total of 14 (58.3%) samples that were classified as OBI and 1 (4.2%) sample was reactive for anti-HBs only. Nine samples (37.5%) did not have any serological marker owing to incomplete antibody, and they remained unclassified, as window period infection could not be excluded. Two HBV-NAT yield samples of genotype D, one with a window period and the second being an OBI had high viral load by qPCR. Conclusion: Blood products from donors with OBI carry a high risk of HBV transmission by transfusion. Because of multiple antigens and antibodies present in blood in response to HBV infection, at present there is no single test to detect the infection. In developing country such as India with high seroprevalence of HBV infection, combination of at least two tests would help us to improve the transfusion safety.

Occult hepatitis B virus infection and blood transfusion.

Transfusion-transmitted infections including hepatitis B virus (HBV) have been a major concern in transfusion medicine. Implementation of HBV nucleic acid testing (NAT) has revealed occult HBV infection (OBI) in blood donors. In the mid-1980s, hepatitis B core antibody (HBc) testing was introduced to screen blood donors in HBV non-endemic countries to prevent transmission of non-A and non-B hepatitis. That test remains in use for preventing of potential transmission of HBV from hepatitis B surface antigen (HBsAg)-negative blood donors, even though anti-hepatitis C virus tests have been introduced. Studies of anti-HBc-positive donors have revealed an HBV DNA positivity rate of 0%-15%. As of 2012, 30 countries have implemented HBV NAT. The prevalence of OBI in blood donors was estimated to be 8.55 per 1 million donations, according to a 2008 international survey. OBI is transmissible by blood transfusion. The clinical outcome of occult HBV transmission primarily depends on recipient immune status and the number of HBV DNA copies present in the blood products. The presence of donor anti-HBs reduces the risk of HBV infection by approximately five-fold. The risk of HBV transmission may be lower in endemic areas than in non-endemic areas, because most recipients have already been exposed to HBV. Blood safety for HBV, including OBI, has substantially improved, but the possibility for OBI transmission remains.

Evaluation of the Procleix Ultrio Plus ID NAT assay for detection of HIV 1, HBV and HCV in blood donors.

Introduction:The Procleix Ultrio Plusassay is a new-generation qualitative in vitro nucleic acid amplification test used to screen for human immunodeficiency virus type 1 (HIV-1) RNA, hepatitis C virus (HCV) RNA and hepatitis B virus (HBV) DNA in blood donors. This study was performed to compare the Procleix Ultrio assay with the new-generation Procleix Ultrio Plus Nucleic Acid Test (NAT) assays.Materials and Methods:Ten thousand three hundred and two donor samples were run in parallel for ID NAT using the Procleix Ultrio and the Procleix Ultrio Plus assay. Simultaneously, enzyme-linked immunosorbent assay testing was performed on an EVOLIS Walk away System for HIV, HCV, HBsAg and anti-HBc. Reactive samples were confirmed using polymerase chain reaction.Results:In the 10,302 samples tested during the study period, we identified 15 NAT yields, and all these revealed HBV DNA in the discriminatory assays. Eight of these were exclusive yields from the Ultrio Plus assay and the remaining seven cases were determined as HBV NAT yield, both by the Procleix Ultrio as well as the Ultrio Plus assays, i.e. “Combined” yields. No HCV or HIV 1 yields were detected during the study period by either of two assays.Conclusion:With an overall yield rate of 1 in 687 and an exclusive yield rate of 1 in 1287, the Procleix Ultrio Plus assay proved to be highly sensitive in detecting occult HBV infections.

Hepatitis B virus DNA viral load determination in hepatitis B surface antigen-negative Swiss blood donors.

Nucleic acid test (NAT) hepatitis B virus (HBV) screening for all blood donations with a sensitivity limit of 25 IU/mL in the individual donation is mandatory in Switzerland since 2009. The aims of the two studies were to define the percentage of antibody to hepatitis B core antigen (anti-HBc) or anti-HBc and antibody to hepatitis B surface antigen (anti-HBs)-positive donors bearing HBV DNA and to gather HBV viral load data on HBV NAT yields during the routine screening since the introduction of the HBV NAT. Archive samples from anti-HBc-positive donors (Group I) were analyzed with a quantitative HBV DNA test and further with anti-HBc and anti-HBs assays. In addition, all the HBV NAT-only-yield samples (Group II) from the routine donor screening performed between July 2007 and May 2013 were included in the study. From the 667 samples investigated (131 donors), three donors (2.3%) had donated eight samples (1.2%) with detectable HBV DNA; however, all had very low viral loads (≤ 10 IU/mL). From the 1,160,426 donations screened with the routine HBV NAT assay, 16 HBV NAT yields were detected: two window period (WP) and 14 occult hepatitis B infection (OBI) cases. In eight of these positive donations (two WP and six OBI), the HBV viral loads were not more than 10 IU/mL, in three cases between 10 and 25 IU/mL, and in the remaining five donations between 37 and 166 IU/mL. The highly sensitive HBV NAT assay with a threshold significantly below 10 IU/mL is a valuable alternative to anti-HBc and a less sensitive HBV NAT screening in blood donor screening.

Risk of hepatitis B infection in pediatric acute lymphoblastic leukemia in a tertiary care center from South India.

The prevalence of hepatitis B virus (HBV) infection is high in Asian countries. Little is known about outcome of leukemia in HBV infected patients in these regions. Hence, we conducted this study in two cohorts of patients. We retrospectively evaluated mortality, reduction in dose intensity and duration of therapy (intensive phase and maintenance phase) in children with acute lymphoblastic leukemia (ALL) who developed HBV infection. Sixty-three patients with ALL were included in the retrospective cohort of the study. These were followed up for a minimum of 5 years. We prospectively investigated the prevalence of anti-HBc antibodies in 105 treatment naïve pediatric patients with ALL and negative for HbsAg. Twenty of the 63 patients developed hepatitis, of which 10 were attributed to HBV. All the 10 patients with HBV hepatitis had significantly reduced dose intensity during maintenance therapy with an average delay in completion of therapy of 140 ± 83 days and also a high mortality (40%). In the prospective cohort of the study, 39% of treatment naive patients who were HBsAg negative were anti-HBc positive at presentation, possibly reflecting occult HBV infection. HBV infection poses a serious problem in patients with ALL. Hence we propose that in India, in addition to screening for HBsAg, patients with leukemia should also be screened for anti-HBc. Improved hepatitis B vaccine coverage in the community under the universal immunization programme and introduction of HBV nucleic acid test (NAT) for blood donations should also help in addressing the problem.

Impact of repeat testing of living kidney donors within 14 days of the transplant procedure: a multicenter retrospective survey

A transmission of human immunodeficiency virus (HIV) from a live kidney donor prompted recommendations by the New York State Department of Health and the US Centers for Disease Control and Prevention that all live donors undergo additional screening for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) within 7-14 days of the donation procedure. There are concerns that re-screening will result in delays and cancelled transplants. We surveyed live-donor transplant centers in New York State to assess their screening protocols and outcomes. Nine live-donor programs (kidney and liver centers) responded. All but 1 program has a formal repeat screening policy. Overall, no cancellations occurred, but 2 centers experienced transplantation delays, generally as the result of technician and laboratory procedural mistakes necessitating repeat phlebotomy. Testing is typically coordinated with pre-surgical visits, additional laboratory tests, and physical examinations. In the initial evaluation, serology was most frequently used (all 9 centers), with few centers utilizing nucleic acid testing (NAT) (HIV NAT, 1; HBV NAT, 2; HCV NAT, 2). Repeat testing modalities varied: HIV antibody (5, 55%), HIV NAT (8, 88%), hepatitis B surface antigen (5, 55%), hepatitis B surface antibody (2, 22%), hepatitis B core antibody (3, 33%), HBV NAT (3, 33%), HCV antibody (3, 33%), and HCV NAT (5, 55%). Most respondents have policies to re-test living donors within 14 days of the transplant procedures. Rarely, centers encountered repeat testing-associated delays, but no cancellations occurred.

Hepatitis B virus nucleic acid amplification testing of Australian blood donors highlights the complexity of confirming occult hepatitis B virus infection

We present an analysis of the first 2 years of hepatitis B virus (HBV) nucleic acid testing (NAT) of the Australian donor population. Between July 5, 2010, and July 4, 2012, all blood donations were screened for HBV DNA and hepatitis B surface antigen (HBsAg). Donors who tested HBsAg negative but HBV NAT positive were assessed as occult hepatitis B infections (OBI) if reactive for antibodies to HBV core antigen (anti-HBc). Donors who were anti-HBc reactive but with nonrepeatable or nondiscriminated NAT results were assessed as HBV inconclusive pending follow-up testing. During the study period a total of 2,673,521 donations were screened for HBV. Forty-two chronic OBI infections (5.55/100,000 donors) were identified compared to eight acute serologic window period infections (1.06/100,000 donors). Of the 42 OBI cases, 23 (54.8%) were detected the first time they were screened for HBV DNA while 19 (45.2%) gave one or more HBV NAT-nonreactive results before detection. Of 68 donors initially assessed as HBV inconclusive and available for follow-up, 10 later confirmed as OBI cases while 51 were NAT nonreactive but remained anti-HBc reactive and OBI could not be excluded. This study demonstrated a substantially higher prevalence of OBI compared to acute serologic window period HBV infections in Australian blood donors. Follow-up testing of OBI cases indicates that HBV DNA is often only intermittently detectable in OBI, highlighting the importance of including anti-HBc to optimize the HBV testing algorithm.

Comparative analysis of triplex nucleic acid test assays in United States blood donors

This study assessed the clinical sensitivity of three fully automated, human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) triplex nucleic acid test (NAT) assays by individual donation (ID-NAT) and at operational minipool (MP-NAT) sizes used worldwide. MPX, Ultrio, and Ultrio Plus were used to test 2222 pedigreed, marker-positive samples with varying viral loads, each from a unique US blood donor. NAT-positive, seronegative yield samples (16 HBV, 156 HCV, and 23 HIV) were tested in replicates of three; undiluted; and in 1:6, 1:8, and 1:16 dilutions (MP6, MP8, and MP16), simulating various MP sizes. Seropositive samples (1276 HBV, 488 HCV, and 263 HIV) were tested by ID-NAT in singlet. MPX-MP6 and Ultrio Plus-MP16 had equivalent HCV sensitivity. Although Ultrio Plus-MP16 for HIV trended toward lesser sensitivity, this was not corroborated in a large substudy of low-viral-load samples in which Ultrio Plus-MP8/MP16 showed 100% reactivity. MPX-ID and Ultrio Plus-ID HBV clinical sensitivity were identical, but MPX-MP6 was significantly more sensitive than Ultrio Plus-MP16; the differential yield projected to one HBV NAT yield per 4.72 million US donations. Ultrio Plus HBV sensitivity did not increase at MP8 versus MP16. Ultrio Plus versus Ultrio sensitivity was significantly increased in HBV-infected donors with early acute, late acute or chronic, and occult infections. No difference in sensitivity was noted for any virus for MPX-MP6 versus Ultrio Plus-ID. Our data support US donation screening with MPX-MP6 or Ultrio Plus-MP16 since the HBV DNA detection of Ultrio Plus was significantly enhanced (vs. Ultrio) without compromising HIV or HCV RNA detection.

The reliability of HBV core antibody in serological screening for hepatitis B virus

Accurate diagnosis of hepatitis B virus (HBV) infection is essential for infection control, treatment and screening of potential blood, organ and tissue donors. We assessed the sensitivity of the HBsAg and HBcAb as screening assays alone and in combination for detecting HBV infection in a series of Australian patients. The performance of the Architect (Abbott Diagnostics, Germany) and the Elecsys (Roche Diagnostics, Germany) platforms were assessed for detection of HBcAb. There were 2778 blood samples assessed using the COBAS Ampliprep/TaqMan test for HBV DNA, of which 331 sera had concurrent HBV serology testing. This allowed determination of the correlation between HBV DNA and different serological markers. Of the 331 sera, 260 had sufficient residual volume to be retested for HBcAb using both Elecsys and the Architect assays. Of the 331 patients, one (0.3%) was negative by the Architect Anti-HBc II assay, in the presence of HBV DNA and positive HBsAg, consistent with recent infection. Positive HBcAb in the absence of HBV DNA was found in 67 of 331 (20.2%) patients. Of these, 18 of 67 had isolated HBcAb with negative results on all other tests, with 12 of 18 (3.6%) demonstrating low HBcAb signals on chemiluminscent microparticle assay. No cases of detectable HBV DNA in the presence of negative serology were found. When the HBcAb was used as a marker for past exposure or chronic HBV infection, the Architect Anti-HBc II assay demonstrated sensitivity and specificity of 98% and 79.9%, respectively, compared to 90% and 78.9%, respectively, for the Elecsys Anti-HBc assay. The combination of the Architect Anti-HBc II and HBsAg assays, as per conventional solid organ donor and recipient screening protocols, had 90% specificity and 100% sensitivity for determining HBV infection. This study shows that the use of combined HBsAg and HBcAb is sensitive and reliable for screening and predicting HBV nucleic acid test (NAT) positivity, whereas HBcAb alone missed an acute infection in this study population. There were no significant differences detectable between the Architect and the Elecsys HBcAb assays (p=0.001), suggesting laboratories should assess individual assays in the local population before use as screening tests.

The results of nucleic acid testing in remunerated and non-remunerated blood donors in Lithuania.

In Lithuania, governmentally covered remuneration for whole blood donations prevails. Donors may choose to accept or reject the remuneration. The purpose of this study was to compare the rate of nucleic acid testing (NAT) discriminatory-positive markers for human immunodeficiency virus-1 (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) in seronegative, first-time and repeat, remunerated and non-remunerated donations at the National Blood Centre in Lithuania during the period from 2005 to 2010. All seronegative whole blood and blood component donations were individually analysed by NAT for HIV-1, HBV and HCV. Only discriminatory-positive NAT were classified. The prevalence of discriminatory-positive NAT per 100,000 donations in the donor groups and the odds ratios comparing the remunerated and non-remunerated donations were determined. Significant differences were observed for HBV NAT results: 47.42 and 26.29 per 100,000 remunerated first-time and repeat donations, respectively, compared to 10.6 and 3.58 per 100,000 non-remunerated first-time and repeat, seronegative donations, respectively. The differences were also significant for HCV NAT results: 47.42 and 51.99 for remunerated first-time and repeat donations, respectively, compared to 2.12 and 0 per 100,000 non-remunerated first-time and repeat, seronegative donations, respectively. No seronegative, discriminatory-positive NAT HIV case was found. The odds of discriminatory HBV and HCV NAT positive results were statistically significantly higher for both first-time and repeat remunerated donations compared to first-time and repeat non-remunerated donations. First-time and repeat remunerated seronegative donations were associated with a statistically significantly higher prevalence and odds for discriminatory-positive HBV and HCV NAT results compared to first-time and repeat non-remunerated donations at the National Blood Centre in Lithuania.

Infectivity of occult hepatitis B from two different points of view

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