Prospective Seroepidemiological Study of Hepatitis E Virus Infection in an Occupational Health-Checkup Cohort in Mie Prefecture, Japan

Aims: Reported cases of hepatitis E have increased in Japan; however, the true burden of hepatitis E virus (HEV) infection is likely underestimated due to the high proportion of asymptomatic infections. We prospectively evaluated anti-HEV immunoglobulin G (IgG) seroprevalence, seroconversion-based incidence, and questionnaire-reported exposures in an occupational health-checkup cohort in Mie Prefecture, central Japan. Methods: A total of 608 individuals (189 men and 419 women) who underwent annual health checkups between fiscal years 2023 and 2025 were included. Serum anti-HEV IgG was measured. At baseline, participants completed a 10-item questionnaire on potential HEV-related exposures. Incident infection was evaluated by identifying IgG seroconversion during follow-up. Results: Anti-HEV IgG was detected in 5 of 608 participants (0.82%), all of whom were men (5/189, 2.65% vs. 0/419 women, 0%; p = 0.0028). Age was not significantly associated with IgG seropositivity. As no women were seropositive, exploratory age-adjusted analyses were conducted among men only; no questionnaire item was significantly associated with IgG positivity. Sex differences were observed in reported consumption of pork liver/offal, pork tongue, and venison/wild boar meat. One participant seroconverted during follow-up, corresponding to an incidence of 138 per 100,000 (1/724; 95% CI, 3–770) person-years. The seroconverter reported frequent consumption of raw or undercooked pork products. Conclusions: Anti-HEV IgG seroprevalence was low in this relatively young, predominantly female cohort. However, prospective follow-up identified incident infections, with an incidence consistent with previous domestic estimates, suggesting that a substantial proportion of the Japanese population remains at risk of HEV infection.