Prevalence of antibodies to hepatitis E virus among Japanese blood donors: identification of three blood donors infected with a genotype 3 hepatitis E virus.

Risk factors for acquiring hepatitis E among individuals in industrialized countries including Japan are not fully understood. We investigated whether Japanese blood donors with or without an elevated alanine aminotransferase (ALT) level are likely to have hepatitis E virus (HEV) infection. Serum samples were collected from 5,343 voluntary blood donors including 1,087 donors with elevated ALT of 61-966 IU/L and 4,256 donors with normal ALT (< or = 60 IU/L) at two Japanese Red Cross Blood Centers, and were tested for the presence of anti-HEV IgG by in-house enzyme-linked immunosorbent assay (ELISA). Overall, 200 donors (3.7%) were positive for anti-HEV IgG, including 32 (2.9%) with elevated ALT and 168 (3.9%) with normal ALT. Serum samples with anti-HEV IgG were further tested for the presence of anti-HEV IgM by in-house ELISA and for HEV RNA by reverse transcription (RT)-polymerase chain reaction (PCR). Three donors with ALT of 966, 62 or 61 IU/L were positive for anti-HEV IgM and HEV RNA. The HEV isolates obtained from the three viremic donors segregated into genotype 3, were 91.5-93.4% similar to each other in the 412 nucleotide sequence of open reading frame 2, and had the highest identity of 91.5-94.9% with the JRA1 isolate which was recovered from a Japanese patient with sporadic acute hepatitis E who had never been abroad, suggesting that these three HEV isolates are indigenous to Japan. This study suggests that a small but significant proportion of blood donors in Japan with or without elevated ALT are viremic and are potentially able to cause transfusion-associated hepatitis E.