Breakthrough infection by hepatitis B virus in a vaccinated blood donor: An emerging threat for transfusion safety in low-endemic countries?

We present the case of a breakthrough infection by hepatitis B virus (HBV), intending to warn about the challenge that HBV represents for transfusion safety. Virological markers for HBV infection were assayed during a blood donor screening by detection of HBsAg, anti-HBc, and viral nucleic acid (HBV DNA) by a nucleic acid test (NAT). Additionally, samples were analyzed for detection of immunoglobulin M anti-HBc, HBeAg, anti-HBe, and anti-HBs. A first-time donor repeatedly tested positive for HBV DNA by NAT and nonreactive for HBV-serological markers of infection. He stated having completed the anti-HBV vaccination schedule; thus, study of anti-Hbs resulted in reactive at protective level (18 mIU/mL). The donor denied clinical symptoms of hepatitis and remained healthy during the follow-up period. 95 days postdonation, NAT was negative, seroconversion of anti-HBc ab was detected, and a significant increase in anti-HBs concentration was measured (>1000 mIU/mL). This is the first case of HBV-breakthrough infection reported in Argentina and to our knowledge, this potential threat to transfusion safety is novel in an HBV low-endemic region with high coverage of HBV vaccination. The occurrence of breakthrough infections challenges the current protocols for the identification of HBV-infected subjects, could be a source of silent HBV transmission.

Acute and chronic HBV infection in central Argentina: High frequency of sub-genotype F1b, low detection of clinically relevant mutations and first evidence of HDV.

Introduction: Genomic analysis of hepatitis B virus (HBV) identifies phylogenetic variants, which may lead to distinct biological and clinical behaviors. The satellite hepatitis D virus (HDV) may also influence clinical outcomes in patients with hepatitis B. The aim of this study was to investigate HBV genetic variants, including clinically relevant mutations, and HDV infection in acute and chronic hepatitis B patients in central Argentina. Methods: A total of 217 adult HBV infected patients [acute (AHB): n = 79; chronic (CHB): n = 138] were studied; 67 were HBV/human immunodeficiency virus (HIV) coinfected. Clinical and demographic data were obtained from medical records. Serological markers were determined. Molecular detection of HBV and HDV was carried out by RT-Nested PCR, followed by sequencing and phylogenetic analysis. Results: Overall, genotype (gt) F [sub-genotype (sgt) F1b] was the most frequently found. In AHB patients, the gts/sgts found were: F1b (74.7%) > A2 (13.9%) > F4 (7.6%) > C (2.5%) > A1 (1.3%). Among CHB patients: F1b (39.1%) > A2 (23.9%) > F4 (18.2%) > D (9.4%) > C and F6 (3.6% each) > A1, A3 and B2 (0.7% each). The distribution of sgt A2 and gt D was significantly different between HBV mono and HBV/HIV coinfected patients [A2: 15.9% vs. 35.7% (p < 0.05), respectively and D: 14.6% vs. 1.8% (p < 0.05), respectively]. Mutation frequency in basal core promoter/pre-Core (BCP/pC) region was 35.5% (77/217) [AHB: 20.3% (16/79), CHB: 44.2% (61/138)]. In the open reading frame (ORF) S, mutations associated with vaccine escape and diagnostic failure were detected in 7.8% of the sequences (17/217) [AHB: 3.8% (3/79), CHB: 10.1% (14/138)]. ORF-P amino acid substitutions associated with antiviral resistance were detected in 3.2% of the samples (7/217) [AHB: 1.3% (1/79), CHB 4.3%, (6/138)]. The anti-HDV seropositivity was 5.2% (4/77); one sample could be sequenced, belonging to gt HDV-1 associated with sgt HBV-D3. Discussion: We detected an increase in the circulation of genotype F in Central Argentina, particularly among AHB patients, suggesting transmission advantages over the other genotypes. A low rate of mutations was detected, especially those with antiviral resistance implications, which is an encouraging result. The evidence of HDV circulation in our region, reported for the first time, alerts the health system for its search and diagnosis.