The Value of Hepatitis E Screening Sensitivity: Lookback Investigation in German Blood Donors.

Hepatitis E virus (HEV) is the leading cause of hepatitis globally and poses particular risks for immunocompromised individuals. Mandatory screening of blood donations for HEV RNA and retrospective individual testing of previous donations (lookback investigations) following a reactive result have been implemented in several countries to protect these patients. This includes Germany, where a sensitivity limit of 2000 IU/mL applies to index donations. In total, 334 HEV RNA-positive blood donations were detected at our blood donation service between 2018 and 2024. Lookback testing was applied in 211 cases, revealing previous HEV RNA-positive donations in 23.1% of donors (n = 48, 76 donations). Although 16 of these retrospectively tested HEV RNA-positive donations have already been transfused, no transfusion-transmitted HEV infection has been reported. The HEV RNA viral load in the lookback donation was below 50 IU/mL in 72.4% of cases. Routine testing effectively prevents highly viremic blood products entering the supply, significantly reducing the infection risk. While the administration of virus particles with low-viremic products cannot be ruled out, the remaining risk appears to be minimal and has been deemed so far acceptable for the safety of blood products. The lookback strategy further supports the screening strategy by retrospectively identifying blood products from low-viremic donations and enabling appropriate risk management.