Cell Tissue Bank DOI 10.1007/s10561-013-9409-6

ORIGINAL PAPER

Comparison of hepatitis B, core, HBc, and hepatitis B antibody, anti HBs, in a presumed low risk donor population Ellen Heck • H. Dwight Cavanagh

Received: 6 August 2013 / Accepted: 15 November 2013 Ó Springer Science+Business Media Dordrecht 2013

Abstract Donors screened by medical social history interview negative for high risk behavior or communicable disease history, but subsequently exhibiting reactive serological markers, emphasize importance of duel safe guarding factors for determining donor suitability. This report examines a relationship between two immunoabsorption assay tests, hepatitis B core (HBc) antibody, a required food and drug administration (FDA) test, and hepatitis B antibody (anti HBs), non-required test. Reactive serology results, 129 cases, 3,581 donors (2008–2012) for HBc as the only initially positive serological marker were subjected to anti HBs testing in this history prescreened donor population. Enzyme linked immunoabsorption assay kits hepatitis B, core and antibody, were used in this study. All samples were initially tested for human immunodeficiency virus, hepatitis B, and hepatitis C, utilizing nucleic acid testing and antigen antibody immunoabsorption assay. Testing was performed by a FDA-registered CLEA-certified reference laboratory. Samples were deceased donor blood samples and a limited number of pre-mortem samples, separated, stored and analyzed according to manufacturer recommendation and FDA regulations. E. Heck (&)  H. D. Cavanagh Transplant Services Center, University of Texas Southwestern Medical Center, Dallas, TX, USA e-mail: [email protected] H. D. Cavanagh e-mail: [email protected]

129 reactive HBc only samples, were subsequently tested for anti HBs. Of these 129, 94 were found to be reactive for anti HBs. This represented 72 % of samples tested for antibody, a higher percentage than anticipated for a medical history negative, low risk population. Keywords Hepatitis B  Antibody  Core  Allograft safety Abbreviations HIV Human immunodeficiency virus (HIV-1, HIV-2) HBV Hepatitis B virus HBc Hepatitis B core HCV Hepatitis C virus NAT Nucleic acid testing CDC Centers for disease control FDA Food and drug administration

Introduction Donor allograft safety and the possibility of communicable disease transmission is a continuing concern for eye, tissue and organ procurement organizations. Since donors are pre-screened for risk factors both prior behavioral and disease, with a medical social history questionnaire and the resulting donor population is conventionally considered to be of low risk for communicable disease. Thus, a finding of hepatitis B

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core (HBc) only reactivity in samples which had been previously tested for all food and drug administration (FDA) required serologies(Food and Drug Administration 2001) has raised perplexing questions of clinical significance. Can these findings in a low risk population indicate a false-positive test reaction or are they indicative of a marker of recent or chronic hepatitis B infection? (University of Washington 2012; Mayo Clinic 2011) This report examines the relationship between HBc antibody, HBc, an FDA required test and anti-HBs, a non-required test.

Methods Blood samples drawn from deceased donors or premortem samples from hospital donors were routinely tested for HIV 1-2 antibody, hepatitis B surface antigen, hepatitis C antibody, and HBc antibody, and with nucleic acid testing for HIV, HBV and HCV. All samples were tested according to FDA regulation 21 CFR Part 1271. FDA-approved enzyme immunoassay test kits supplied by Ortho, Bio-Rad, and Abbott Laboratories (Bio-Rad laboratories Redmond Washington, Ortho Clinical Diagnostics, Raritan New Jersey), were used for this testing. Samples were separated and stored according to manufactures test kit recommendations, FDA regulations, and testing laboratory specifications. The assay for NAT testing was Procleix (GenProbe Incorporated, San Diego) or Ultrio (Gen Probe Inc.).

Results One hundred twenty-nine samples previously tested and found to be reactive for HBc only were subsequently tested for hepatitis B antibody (anti HBs). Of these 129, 94 were found to be reactive for anti HBs. This represented 72.8 % positivity an unexpectedly high ratio given negative medical social history prescreening which would suggest this to be a low risk donor population. Donors subjected to prior medical social history screening from knowledgeable individuals conducted prior to acceptance of the donor, along with a review of medical records and in some cases history from the treating or family physicians conventionally are considered to constitute a ‘‘low risk’’ group for transmission of infectious disease. The

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Table 1 Cause of death

Anoxia

4

Cancer

13

Cardiac

78

ICH Renal

12 2

Respiratory (COPD etc.) Trauma Total Table 2 Ethnicity

9 11 129

Asian

5

Black

30

Caucasian

83

Hispanic Total

11 129

medical social history questionnaire contains specific questions designed to identify high risk for communicable disease or known history of communicable disease. The demographics for the study population reported here were examined for trends in age, sex, race, and cause of death to determine any effect these parameters might have on the percent of antibody positive reactions: (Food and Drug Administration 2001) Donors were 64 % male and 36 % female similar to the overall donor gender distribution, (no correlation); (University of Washington 2012) Also there was no correlation with age with the majority of donors ranging in age from mid-40 s to mid-60 s; (Mayo Clinic 2011) Sixty-one percent (61 %) of the 129 donors died from cardiac related events or cardiac disease, and eight percent (8 %) of the deaths were from a trauma related cause or event. For the purposes of this report trauma included motor vehicle accidents, gunshot wounds, stabbing, hanging and other violent acts or activities, (Table 1). For this donor population 64 % were Caucasian, 23 % Black, 9 % Hispanic, and 4 % Asian, (Table 2). While hepatitis B is known to occur at higher rates in certain populations, specifically in individuals from Eastern Europe, Asia and Africa, the donor represented population studied was not influenced by a specific endemic population. Other investigators in reporting blood donor demographics have reported a 0.4–1.7 % frequency of HBc antibody in low prevalence areas (CDC 2010). These results for tissue and eye donors indicate a 3.6 % occurrence in what as previously stated is also presumed to be at low risk population.

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Discussion The findings of 94 positive hepatitis antibody tests in a sampling of 129 reactive HBc samples was, given the prior screening for risk factors and prior disease history, an unexpected high indication of reactivity and prior or pre-mortem disease. The Centers for disease control and prevention (CDC) reported in 2010 that the incidence of hepatitis B was declining in all age groups.(CDC 2010) Other investigators have indicated in the absence of detectable antigen (HBsAg) or antibody (anti-HBs), core alone in low risk populations should be considered a false positive test.(Lab Tests Online 2012; Kukka and HBV 2008) The results reported in this study would indicate, that the classification as low risk of the eye and tissue donors based solely on the medical social history and available medical records alone does not appear to be adequate to define this population as low risk or to insure recipient safety. In the 2010 CDC study of 1,784 hepatitis B case reports 3.5 % of the patients indicated no risk behaviors or exposure yet did have reactive serology results.(CDC 2010) Recent reports from Public Health Reports extensively discuss relationship of risk to the presence of disease markers for assessing organ donor suitability(Seem et al. 2013) further, emphasizing the importance of comprehensive testing along with the interview process in determining transmission risks. The remaining 35 core-only reactive donors in this study cannot absolutely be categorized as false-positive results as it is possible that in at least some cases exposure and/or infectivity may have occurred within the weeks prior to antibody development. HBc antibodies are the first antibodies, either with or after the resolution of positive antigen tests. Core antibody is detectable usually approximately 8 weeks after infection. anti HBs, (c) develops later during the recovery phase and general is viewed as an indication of immunity. Collectively the results reported in this study offer at least two major areas for consideration by those involved in allograft recovery. First, is there some amenable flaw in the medical social history screening

or is this an irresolvable short-coming of second-hand family or other historian’s information especially when obtained under stressful conditions? Second, if presence of anti-HBs indicates immunity are these individuals then potential suitable donors especially of organs where availability is constantly at issue or possibly in certain circumstances also of eyes and tissues? Finally it would appear obvious that it is the combination of skilled interview and infectious disease serologic testing that provides maximum allograft recipient safety. Acknowledgments The authors acknowledge Valerie Winkleman, MT (ASCP), MB, and Sherri Cyrus, MT (ASCP), SBB (Creative Testing Solutions, Phoenix, AZ) for their technical expertise and assistance with testing; and William D. Timmons, RN, for his assistance with data. Conflict of interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

References CDC (2010) Centers for disease control and prevention. Viral Hepatitis Surveillance, USA Food and Drug Administration (2001) Guidance for industry: eligibility determination for donors of human cells, tissues, and cellular and tissue-based products (X. References) 21 CFR Part 1270. Silver Springs, MD: US Food and Drug Administration Kukka, Christine M (2008) HBV: How to Interpret Hepatitis B antibody and viral tests. Hepatitis C Support Project. HCSP. Version 2.0. p. 1–3 Lab Tests Online (2012) Hepatitis B Mayo Clinic (2011) Mayo Clinic Staff. Hepatitis B. Mayo Foundation of Medical Education and Research Seem, Debbie L., Lee, Ingi., Umscheid, Craig A., Kuehnert, Matthew J (2013) PHS Guideline for reducing human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission through organ transplantation. Public Health Reports. PHS Guideline Vol 128: 247–344 University of Washington (2012) Interpretation of isolated hepatitis B core antibody: hepatitis web study. Normal formation of hepatitis B core antibody (Anti-HBc). Frequency of isolated hepatitis B core antibody. potential transmission of HBV by patient

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Comparison of hepatitis B, core, HBc, and hepatitis B antibody, anti HBs, in a presumed low risk donor population.

Donors screened by medical social history interview negative for high risk behavior or communicable disease history, but subsequently exhibiting react...
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