Recent and occult hepatitis B virus infections among blood donors in the United States

Abstract

BACKGROUND: Characteristics of US blood donors with recent (RBI) or occult (OBI) hepatitis B virus (HBV) infection are not well defined. METHODS: Donors with RBI and OBI were identified by nucleic acid and serologic testing among 34.4 million donations during 2009-2015. Consenting donors were interviewed and their HBV S-gene sequenced. RESULTS:The overall rate of HBV-infected donors was 7.95 per 100,000; of these, 0.35 per 100,000 and 1.70 per 100,000 were RBI and OBI, respectively. RBI (n = 120) and OBI (n = 583) donors constituted 26% of all HBV-infected (n = 2735) donors. Detection of HBV DNA in 92% of OBI donors required individual donation nucleic acid testing. Donors with OBI compared to RBI were older (mean age, 48 vs 39 years; p < 0.0001) with lower median viral loads (9 vs. 529 IU/mL; p < 0.0001). A higher proportion of OBI than RBI donors were born or resided in an endemic country (39% vs. 5%; p = 0.0078). Seventy-seven percent of all RBI and OBI donors had multiple sex partners, an HBV-risk factor. Of 40 RBI and 10 OBI donors whose S gene was sequenced, 33 (83%) and 6 (60%), respectively, carried HBV subgenotype A2; 18 (55%) and 2 (33%), respectively, shared an identical sequence. Infection with 1 or more putative HBVimmune-escape mutants was identified in 5 (50%) of OBI but no RBI donors. CONCLUSION: RBI and OBI continue to be identified at low rates, confirming the importance of comprehensive HBV DNA screening of US blood donations. HBV-infected donors require referral for care and evaluation and contact tracing; their HBV strains may provide important information on emergent genotypes. ABBREVIATIONS: ARC = American Red Cross; CI = confidence interval; HBcAb = hepatitis B core antibody; HBsAb = antibody to hepatitis B surface antigen; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; ID = individual; MPs = minipools; NAT = nucleic acid testing; OBI = occult HBV infection; OR = odds ratio; PCR = polymerase chain reaction; RBI = recent HBV-infected; TMA = transcription-mediated amplification From the

International Forum on Occult hepatitis B infection and transfusion safety

“…HBV subgenotype A2 was predominant in all donors (83% in recent infections vs 60% in OBI) versus non‐A2 subtypes (17 and 40%, respectively) with overall more molecular diversity observed in sequences from OBI donors including 50% having 1 or more immune‐escape mutations identified. We conclude that additional surveillance using sensitive NAT methods is needed to measure trends over time .…”

“…Finally, in another recent study, the rates, demographics, risk factors for infection and molecular characteristics of recently HBV‐infected Red Cross donors were compared to those with OBI . In this study, recently infected donors were defined as those lacking anti‐HBc but confirmed for HBV DNA with or without HBsAg‐confirmed positivity.…”

“…">a.The LODs of the 3 available, FDA‐licensed NAT assays, based on ID screening (which does not routinely occur in the US) is as follows: TaqScreen MPX, version 2·0, which processes samples on the cobas s201 (Roche), and more recently, the FDA‐licensed MPX assay which processes samples on the cobas 6800/8800 platform (Roche) have 95% LODs of 2·3 IU/ml (95% CI: 2·0–2·8) and 1·4 IU/ml (95% CI: 1·2–1·7), respectively; these assays continue to be used in MPs of 6 . For comparison, the Ultrio Plus 95% LOD is 3·4 IU/ml (95% CI: 3·0–4·1) and continues to be used in MPs of 16 . b.With the use of the Ultrio Plus assay, 24·2 million donations have been screened by the American Red Cross from implementation on April 28 2013 to Oct 31 2017 with a seronegative yield of 37 confirmed positives (based on an independent sample from the plasma unit at index or donor follow‐up confirming HBV DNA and seroconversion as appropriate) for a rate of 1:654 000 which is similar to that cited above for the period of 2009–2015 of 1:781 000.…”

“…No further testing of OBI donors in the United States is performed outside of the context of studies [2–5,7,8]. FDA requires in‐date components from HBV‐reactive donations to be retrieved but does not require recipient tracing.…”

Overt and occult hepatitis B among immigrants and native blood donors in Madrid, Spain

“…3 In the United States, these two groups represent 26% of the overall rate of 8 per 100,000 HBV donors. 4 Similar figures are not well known in Europe, but certainly the large migration flows from HBV endemic regions in recent times could have changed the former scenario.…”