Yes, a negative HBsAg (Hepatitis B surface antigen) blood test result isn’t 100% reliable and this answer explains how that could happen. Escape is the outcome of multiple dynamic donor and recipient variables that intersect with each other in a highly unpredictable manner (below from 1) so pinning down its percentage in hard numbers isn’t feasible.
Occult describes cases of Hepatitis B (Hep-B) infection where HBsAg is undetectable while replication-competent HBV (Hepatitis B virus) DNA may or may not be detectable in the blood (below from 1, text modified as bullet points by me and table).
“We have identified 25 published cases of recipient HBV infection acquired from donors in the HbsAg-negative window period and have summarized these data in Table 10. Cases (usually published as part of a case series) have been reported from the United Kingdom, Japan, and Germany and have been found either through donor-initiated lookback or via recipient-based surveillance systems that have captured and investigated cases of reported post-transfusion HBV infection.105-111
- In the large majority of cases reported in Table 10, the transmitting donation was found to be positive for HBV DNA if tested by ID NAT [Individual donation Nucleic Acid Amplification Technology];
- however, in three cases (Table 10, Case 1, and a single case in Case Series 3 and 5), HBV ID NAT was negative.
- In two of these cases (Table 10, Case 1, and Table 10, Case Series 3), transmission was proven by sequence homology between donor and recipient isolates.
- In one of these cases (Table 10, Case 1),105 the donor tested positive for HBsAg and HBV DNA 2 months after index donation. The recipient was under treatment for leukemia and when evaluated 12 weeks after transfusion tested HBV DNA positive despite the presence of passively transfused anti-HBs (from a HBV-vaccinated PLT [platelet] donor) at a concentration of 58 IU/L.
- In the other case (Table 10, Case Series 3),107 the donor was positive for HBsAg 6 weeks after index donation but HBV DNA results were not reported.
- In addition to the transmitting cases, several of these publications also included cases (one case in Case Series 2 and 11 cases in Case Series 4) 106,108 in which HBV DNA– positive components did not transmit infection to the recipient.”
“OBI [occult Hepatitis B infection] is defined as the presence of HBV DNA in the absence of HBsAg in patients who are not in the HBsAg negative window phase of acute infection.38,40 Almost all such donors have detectable anti-HBc [anti-HBV core antibody] and about half have anti-HBs [anti-HBV surface antibody]. The majority of these OBIs are thought to represent past HBV infections that have been controlled but not completely cleared by the immune system, but some may represent chronic HBV carriers that lost detectable HBsAg over time. In either case, HBV DNA is generally present in low concentration (<100 IU/mL) and can fluctuate over time, being detectable only intermittently even with the use of highly sensitive NAT assays. Recent studies of OBI donors in Europe have shown that, at least in this location, most OBI donors harbored mutated HBV strains.47-49 Many of these mutations occurred in the S gene encoding the major immunodominant region of HBsAg and it is possible that in some OBI cases, an altered form of HBsAg could be present but not detectable by at least some commercial HBsAg assays.”
In essence, OBI means HBV in liver but at much lower levels, and both its DNA and surface antigen, HbsAg, practically undetectable in blood (figures below from 2).
A more recent 2019 study (3) better clarifies how transmission could be possible under such circumstances. It examined 3 repeat donors from Slovenia who were not only HBsAg negative but also had undetectable HBV DNA by highly sensitive NAT and yet transmitted HBV to 9 recipients who were transfused with various blood components from these donors.
Long-term evaluation of these OBI donors showed that they alternated between phases where viremia (detectable virus in blood) was apparently absent and phases with very low but detectable virus loads. Blood products from these 3 OBI donors had been transfused into 47 patients and follow-up data was retrieved from 31 of them.
- Seven of them (22.5%) had anti-HBs antibodies and weren’t infected.
- Nine (29%) were definitely infected; >99% donor-recipient sequence homology in 5, probable in 3 and possible in 1.
Based on the specifics of the blood products transfused in these cases, this study revealed that OBI blood products such as ~200ml of fresh frozen plasma that presumably contained ~3200 virions or red blood cells containing ~20ml plasma (~320 virions) could transmit HBV to naive recipients. The study concluded
- Transmission was possible with a minimal dose of as few as ~3.0 IU/ml (~<16 copies/ml) of HBV DNA, far lower than the previous infectious dose of 20 IU/ml (~1017 copies/ml).
- The NAT sensitivity threshold necessary to prevent transmission needs to be lowered from the current 3.4 IU/ml to an even lower 0.15 IU/ml (or 0.8 genome equivalent/ml).
Lowering these cut-off thresholds won’t be easy to implement and aren’t cost-free since they necessitate testing much larger volumes of single donations and would preclude minipool testing (small sample derived from a large group of blood donors).
Another approach would be to treat blood donation components with specific pathogen reduction steps such as treatment with amotosalen, a Psoralen – Wikipedia, and UVA light.
Bibliography
1. Kleinman, Steven H., Nico Lelie, and Michael P. Busch. “Infectivity of human immunodeficiency virus‐1, hepatitis C virus, and hepatitis B virus and risk of transmission by transfusion.” Transfusion 49.11 (2009): 2454-2489. http://www.academia.edu/download/46065816/Infectivity_of_human_immunodeficiency_vi20160530-32615-16m0xmb.pdf
2. Raimondo, Giovanni, et al. “Update of the statements on biology and clinical impact of occult hepatitis B virus infection.” Journal of hepatology (2019). Update of the statements on biology and clinical impact of occult hepatitis B virus infection
3. Candotti, Daniel, et al. “Multiple HBV transfusion transmissions from undetected occult infections: revising the minimal infectious dose.” Gut 68.2 (2019): 313-321. https://dl.uswr.ac.ir/bitstream/Hannan/57032/1/2019%20GUT%20Volume%2068%20Issue%202%20February%20%2817%29.pdf