Abstract
To investigate nationwide the prevalence of hepatitis E virus (HEV) infection in the general population of Japan, serum samples were collected from 22,027 individuals (9,686 males and 12,341 females; age, mean ± standard deviation: 56.8 ± 16.7 years; range: 20–108 years) who lived in 30 prefectures located in Hokkaido, mainland Honshu, Shikoku, and Kyushu of Japan and underwent health check‐ups during 2002–2007, and were tested for the presence of IgG, IgM, and IgA classes of antibodies to HEV (anti‐HEV) by in‐house ELISA and HEV RNA by nested RT‐PCR. Overall, 1,167 individuals (5.3%) were positive for anti‐HEV IgG, including 753 males (7.8%) and 414 females (3.4%), the difference being statistically significant (P < 0.0001). The prevalence of anti‐HEV IgG generally increased with age and was significantly higher among individuals aged ≥50 years than among those aged <50 years (6.6% vs. 2.7%, P < 0.0001). Although 13 individuals with anti‐HEV IgG also had anti‐HEV IgM and/or anti‐HEV IgA, none of them had detectable HEV RNA. The presence of HEV RNA was further tested in 50 or 49‐sample minipools of sera from the remaining 22,014 individuals, and three individuals without anti‐HEV antibodies tested positive for HEV RNA. The HEV isolates obtained from the three viremic individuals segregated into genotype 3 and were closest to Japan‐indigenous HEV strains. When stratified by geographic region, the prevalence of anti‐HEV IgG as well as the prevalence of HEV RNA or anti‐HEV IgM and/or anti‐HEV IgA was significantly higher in northern Japan than in southern Japan (6.7% vs. 3.2%, P < 0.0001; 0.11% vs. 0.01%, P = 0.0056; respectively). J. Med. Virol. 82:271–281, 2010. © 2009 Wiley‐Liss, Inc.