Prevalence of Occult Hepatitis B Virus Infection in Blood Donors with Negative ID-NAT in Switzerland

Abstract

<b><i>Introduction:</i></b> Screening of hepatitis B surface antigen (HBsAg) and individual-donation nucleic acid amplification testing (ID-NAT) of blood donors have become standard to detect hepatitis B virus (HBV) infection. However, there is still a residual risk of HBV transmission by blood components of donors suffering from occult HBV infection (OBI). Therefore, many countries implemented universal testing of anti-HBV core antigen (anti-HBc) antibodies in order to increase blood safety. In Switzerland, anti-HBc testing is not part of the routine blood donor-screening repertoire. Therefore, we sought to assess prevalence of donors with OBI in a Swiss blood donor collective. <b><i>Methods:</i></b> Blood donations were prospectively investigated for the presence of anti-HBc antibodies during two time periods (I: all donors, March 2017; II: first-time donors only, April 2017 until February 2018). Anti-HBc-positive findings were confirmed by an anti-HBc neutralization test. Discarded plasma samples of anti-HBc-confirmed positive donors were ultracentrifuged and subsequently retested by regular HBV-ID-NAT to search for traces of HBV. <b><i>Results:</i></b> During time period I, 78 (1.6%) individuals out of 4,923 donors were confirmed anti-HBc-positive. Sixty-nine (88%) anti-HBc-positive samples were available and processed by ultracentrifugation followed by repeat HBV-ID-NAT. Four samples (5.8%) were found positive for HBV DNA. Sixty-five (94.2%) samples remained HBV NAT-negative upon ultracentrifugation. During time period II, 56 (0.9%) donor samples out of 6,509 exhibited anti-HBc-confirmed positive. Fifty-five (98%) samples could be reassessed by HBV-ID-NAT upon ultracentrifugation. Three (5.5%) samples contained HBV DNA and 52 (94.5%) samples remained HBV NAT-negative. <b><i>Conclusion:</i></b> Overall, we detected 7 viremic OBI carriers among 11,432 blood donors, which tested negative for HBV by standard HBV-ID-NAT and HBsAg screening. In contrast, OBI carriers showed positive anti-HBc findings which could be confirmed in 83.8% of the cases. Thus, OBI might be missed by the current HBV screening process of Swiss blood donors. We suggest to review current HBV screening algorithm. Extended donor screening by anti-HBc testing may unmask OBI carriers and contribute to blood safety for the recipient of blood products.

Ultrasensitive PCR system for HBV DNA detection: Risk stratification for occult hepatitis B virus infection in English blood donors

“…The DNA positivity rate in the current study of 8/412 (1.9%, CI [0.8–3.8]) (Figure 5) is slightly lower than a Swiss study's finding of 7/124 (5.6%, CI [2.3–11.3]; p = 0.055) of anti‐HBc‐positive donors with detectable DNA 20 despite our more sensitive assay. Moreover, that study did not stratify by anti‐HBs levels, where blood donations with levels less than 100 IU/L are considered more infectious 8 and more likely to contain HBV DNA.…”

“…Moreover, that study did not stratify by anti-HBs levels, where blood donations with levels less than 100 IU/L are considered more infectious8 and more likely to contain HBV DNA. This suggests a lower but still significant proportion of OBI donors in England compared to Switzerland, which follows the lower anti-HBc positivity rate amongst all blood donors 7,20. Considering the DNA positivity rate in our study cohort, an average of 106 [45-213] anti-HBc-positive donations would be DNA-positive per year based on an average of 1 864 484 yearly…”

Efficacy of combined HBsAg, anti-HBc and anti-HBs screening in minimizing transfusion transmission risk of hepatitis B infection in low resource setting

“…4 , current policy misses about 22.8% of anti-HBc positive donors, 3 % of whom may have a higher risk of transmission due to presence of HBV DNA. A recent study on Swiss blood donors found that some occult HBV infections with potential transmission risk were missed by HBsAg and ID NAT [ 31 ]. Introducing anti-HBc testing along with ID-NAT testing can greatly reduce the risk of transfusion-mediated transmission.…”

Laboratory Assessment of Viral Hepatitis B Prevalence, Including Occult Viral Hepatitis B, Among People Living With Hiv and General Population in the Far Eastern Federal District

“…Крупномасштабное исследование среди доноров компонентов крови в Канаде (обследованы 1 401 603 первичных доноров с 2005 по 2020 год) показало, что распространённость оккГВ среди них составляла 0,004% [16] . В Швейцарии среди доноров с первичным отрицательным анализом на HBsAg и ДНК ВГВ, которым в последующем провели повторный ПЦР анализ для выявления ДНК вируса после концентрирования плазмы крови, распространённость HBsAg-негативного ГВ равнялась 0,06% (у 7 из 11 432 доноров) [17] .…”