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 HBV-immune-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.

Fig. 1.

Flow chart showing the breakdown of American Red Cross HBV-infected blood donors and study participation, June 2009 to April 2015. * Viral load was obtained from 1248 (34%) prevalent, 43 (90%) HBV DNA yield, 51 (71%) HBsAg yield, and 201 (34%) OBI donors. HBV, hepatitis B virus; OBI, occult hepatitis B infection; RBI, recent hepatitis B infection.

Fig. 2.

Viral load (VL; IU/mL) distribution of four classes of HBV-confirmed-positive donations among American Red Cross blood donors, June 2009 to April 2015. The median VL for each class is as follows; RBI: HBV-DNA yield = 40 IU/mL (1.60 log₁₀ IU/mL), RBI: HBsAg yield = 12,400 IU/mL (4.09 log₁₀ IU/mL), prevalent = 650 IU/mL (2.81 log₁₀ IU/mL) and OBI = 9 IU/mL (0.97 log₁₀ IU/mL). A significant difference in VL was observed between the following classes; RBI: HBV-DNA yield vs. all (p < 0.0001), RBI: HBsAg yield vs. OBI (p < 0.0001) and prevalent vs. OBI (p < 0.0001). RBI: HBV-DNA yield = HBV-DNA-confirmed-positive only; RBI: HBsAg yield = HBV-DNA-confirmed-positive and HBsAg reactive only; prevalent = HBV-DNA-confirmed-positive, HBsAg reactive, and HBcAb reactive; OBI = HBV-DNA-confirmed-positive, HBsAg non-reactive, and HBcAb reactive. OBI, occult hepatitis B infection; RBI, recent hepatitis B infection.

Fig. 3.

Phylogenetic tree constructed from a 442-bp DNA segment amplified from the hepatitis B virus (HBV) S gene in recent (RBI) and occult (OBI) American Red Cross (ARC) infected donors for whom HBV S gene was successfully amplified and sequenced (n = 50), and from representative cases from the CDC’s Sentinel Counties and Emerging Infections Program (EIP) surveillance studies, and outbreak cases. HBV references refers to one or more strain sequences for genotypes A, B, C, D and H obtained from GeneBank. The black arrow indicates the S gene sequence shared among 51% of the A2-infected ARC RBI and OBI donors.

Fig. 4.

Alignment of amino acid sequences in a determinant of HBV S protein from infected donors for whom the HBV S gene was successfully sequenced (n = 50). Bach ARC number represents a unique donor, color coded based on case status - HBsAg yield (HBV-DNA-confirmed-positive and HBsAg reactive only [red]), HBV-DNA yield (HBV-DNA-confirmed positive only [blue]) and OBI (HBV-DNA-confirmed-positive/HBsAg non-reactive/HBcAb reactive [black, shaded gray]) donors. ARC22 carried the C121G, D144G and G145R mutations; ARC27 and ARC48 carried the D144B mutation; ARC115 carried theP120T mutation; ARC116 carried the P120K, M133I, D144E, and C147Y mutations. Abbreviations: ARC, American Red Cross; HBV, hepatitis B virus; OBI, occult hepatitis B infection.