Status:
Ready to upload
Record number:
1837
Adverse Occurrence type:
MPHO Type:
Estimated frequency:
In 2022, the World Health Organisation (WHO) reported that about 3.3% of the global population, or 245 million people, were infected with the hepatitis B virus (HBV). The incidence rate was 16 cases per 100,000, with a mortality rate of 14 per 100,000. The highest number of infections was in the Western Pacific (96.8 million), followed by Africa (64.7 million), Southeast Asia (61.4 million), the Eastern Mediterranean (15.1 million), Europe (10.6 million), and the Americas (5 million). (https://www.who.int/data/gho/data/themes/chronic-viral-hepatitis).
A systematic review of HBV prevalence in the EU/EEA and the UK from 2005 to 2021 found a low prevalence of < 1% among first-time blood donors, except in Bulgaria, Greece, and Romania, where rates were higher. Taira (2013) estimates the prevalence of HBV surface antigen HBsAg of 0.71% in Japan. This article also notes that 4-13 HBV infections per year are a result of blood product transfusion. Satake et al (2023) published a case report and stated that the rate of HBV transmission in Japan at the time of publication to be less than one case per year. (https://www.ncbi.nlm.nih.gov/pubmed/37498533)
Allain et al (2012) notes that occult HBV infection is identified in 1:1000-1:50,000 of European blood donations. Ramachandran et al (2019) estimates that among US blood donors 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 (recent Hepatitis B infection) and OBI (occult Hepatitis B infection), respectively.
Vermeulen et al (2012) reported "observed" HBV transmission rate in South Africa of 0.34/million based on the number of transfusions compared to identified recipient cases--it is notable that this case was identified by the look back program.
RBI was defined as donors testing HBV DNA-reactive by NAT and nonreactive for HBsAg and HBV core antibody (HBcAb), as well as donors testing HBV DNA reactive and HBsAg confirmed positive but HBcAb nonreactive (Ramachandran et al, 2019). The first group is referred to as HBV DNA yield and the second group is referred to as HBsAg yield. OBI was defined as HBV DNA reactive and HBcAb reactive but HBsAg nonreactive (with or without antibody to hepatitis B surface antigen [HBsAb]).
Time to detection:
Taira et al (2013) indicate for general (representative) transfusion-transmitted HBV infection caused by OBI-derived, ID-NAT-negative blood to a recipient caused recipient elevations in liver function tests (LFTs) in about 3 months, with positive viral markers in about 4 months.
Satake et al (2023) indicate the recipient tested positive for HBV DNA at 72 days post transfusion during routine blood testing of that recipient of multiple blood and blood products.
According to WHO (WHO Guidelines on Hepatitis B and C Testing. Geneva: World Health Organization; 2017 Feb. TABLE 4.2, Summary of markers of HBV infection. Available from: https://www.ncbi.nlm.nih.gov/books/NBK442290/table/ch4.t2/) the time between infection and HBsAg positivity is around 38 days (depending on methodology used), anti-HBcore total becomes positive around 3 months after infection, and HBV NAT is often positive sooner than HBsAg.
Alerting signals, symptoms, evidence of occurrence:
Clinical manifestations amongst blood recipients can range from no symptoms, asymptomatic elevations in liver transaminases, self-limited hepatitis, chronic hepatitis, and rarely fulminant hepatitis. Cases amongst blood recipients may be identified by repeat blood donors having subsequent positive test/s for HBV triggering a lookback study or the search for a cause of elevated liver transaminases or hepatitis symptoms.
Satake et al (2023) report transmission of HBV via blood transfusion from a donor who was negative for ID-NAT, HBsAg, and anti-HBc--the only positive result was for anti-HBs. While the authors postulate vaccine breakthrough infection is the most likely cause of this transmission but OBI is also still a possibility as there was no available information regarding the vaccination status of the donor (lost to follow-up).
Demonstration of imputability or root cause:
Multiple transmission events have occurred and there is no doubt that HBV is a transfusion-transmissible infection. The demonstration of imputability varied across time and country, but genotype sequencing analyses have proven the transmissibility of HBV via blood transfusion.
Imputability grade:
3 Definite/Certain/Proven
Groups audience:
Keywords:
References:
Reference attachment:
Suggest references:
- Allain JP, et al. Infectivity of blood products from donors with occult hepatitis B virus infection. Transfusion. 53(7):1405-15, 2013 Jul.
- Bianco C, Dodd RY. Infectivity of occult hepatitis B from two different points of view. Transfusion. 53(7):1379-81, 2013 Jul.
- Masahiro Satake, et al. Transfusion-transmitted HBV infection with isolated anti-HBs-positive blood. Transfusion. 2023 May 2.
- Ramachandran S, Groves JA, Xia GL, Saá P, Notari EP, Drobeniuc J, Poe A, Khudyakov N, Schillie SF, Murphy TV, Kamili S, Teo CG, Dodd RY, Khudyakov YE, Stramer SL. Recent and occult hepatitis B virus infections among blood donors in the United States. Transfusion. 2019 Feb;59(2):601-611. doi: 10.1111/trf.15057. Epub 2018 Nov 30. PMID: 30499591; PMCID: PMC8190636.
- Vermeulen M, Dickens C, Lelie N, Walker E, Coleman C, Keyter M, Reddy R, Crookes R, Kramvis A. Hepatitis B virus transmission by blood transfusion during 4 years of individual-donation nucleic acid testing in South Africa: estimated and observed window period risk. Transfusion. 2012 Apr;52(4):880-92. doi: 10.1111/j.1537-2995.2011.03355.x. Epub 2011 Oct 7. PMID: 21981386. (THIS IS from Record 1836)
- Taira et al. Residual risk of transfusion-transmitted hepatitis B virus (HBV) infection caused by blood components derived from donors with occult HBV infection in Japan
Note:
Satake, M, Yamagishi, N, Tanaka, A, Goto, N, Sakamoto, T, Yanagino, Y, et al. Transfusion-transmitted HBV infection with isolated anti-HBs-positive blood. Transfusion. 2023. https://doi.org/10.1111/trf.17390
Suggest we add this paper to this record and review all of them -- Done (EP)
MG Comments: record 1720 has another Occult HBV transmission - suggest we link and update records with occult HBV via blood into one record
Record 1836 has HBV transmission via eclipse period donation (so a WP issue) - suggest if any of the papers here deal with those, the records should be linked and combined
Oscar comments and suggestions after reading the four articles (the three originals and the editorial):
1.- The link for the paper from Allain JP is not available -- pdf now available (EP)
2.- Paper from Bianco is not original, it is the editorial comment for the journal. (MG: should be merged with record 1720 that has other occult HBI records) -- Done (EP)
3.- I am uploading the two original papers: Allain JP and Taira R. These articles can be edited as one as both refer to the same problem. (MG: should be merged with record 1720 occult HBI) -- Done (EP)
4.- I suggest to comment the article from Satake in a separate edition as the problem it faces is somehow different. (MG: specifically, positive anti-HBs only - has information about rate of both Occult HBI AND information about WP transmissions): I suggest we merge Satake in with record 1836, and the reviewer could also put additional helpful information from Satake into 1720 about Occult HBI -- Done (EP)
From MG: 5. Taira 2012 could also be merged with 1720 -- Done (EP)
6/19/25 MG: 1404 can be merged into this as there wasn't much different that is didactic and imputability is "possible"-- Done (EP); 1836 should be reviewed more carefully with the full paper available instead of just the abstract to find anything else useful to add to this so we can merge the records.
Expert comments for publication:
Despite donor testing with multiple assays, it has not proven possible to eliminate all transfusion-transmitted HBV. Estimated rates of blood transmission should be understood to likely be underestimates - hepatitis B infection is often asymptomatic, and many of the transmission cases are found either in the course of look back investigations after a repeat blood donor demonstrates viral marker positivity, or when blood recipients have medical issues requiring repeat testing of LFTs.