AIM To conduct a prospective assessment of anti-hepatitis E virus(HEV) Ig G seroprevalence in the Western Cape Province of South Africa in conjunction with evaluating risk factors for exposure.METHODS Consenting participants attending clinics and wards of Groote Schuur, Red Cross Children’s Hospital and their affiliated teaching hospitals in Cape Town, South Africa, were sampled. Healthy adults attending blood donor clinics were also recruited. Patients with known liver disease were excluded and all major ethnic/race groups were included to broadly represent local demographics. Relevant demographic data was captured at the time of sampling using an interviewer-administered confidential questionnaire. Human immunodeficiency virus(HIV) status was self-disclosed. HEV Ig G testing was performed using the Wantai? assay.RESULTS HEV is endemic in the region with a seroprevalence of 27.9%(n = 324/1161) 95%CI: 25.3%-30.5%(21.9% when age-adjusted) with no significant differences between ethnic groups or HIV status. Seroprevalence in children is low but rapidly increases in early adulthood. With univariate analysis, age ≥ 30 years old, pork and bacon/ham consumption suggested risk. In the multivariate analysis, the highest risk factor for HEV Ig G seropositivity(OR = 7.679, 95%CI: 5.38-10.96, P < 0.001) was being 30 years or older followed by pork consumption(OR = 2.052, 95%CI: 1.39-3.03, P < 0.001). A recent clinical case demonstrates that HEV genotype 3 may be currently circulating in the Western Cape.CONCLUSION Hepatitis E seroprevalence was considerably higher than previously thought suggesting that hepatitis E warrants consideration in any patient presenting with an unexplained hepatitis in the Western Cape, irrespective of travel history, age or ethnicity. AIM To conduct a prospective assessment of anti-hepatitis E virus (HEV) Ig G seroprevalence in the Western Cape Province of South Africa in conjunction with evaluating risk factors for exposure. METHODS Consenting participants attending clinics and wards of Groote Schuur, Red Cross Children’s Hospital and their affiliated teaching hospitals in Cape Town, South Africa, were sampled. Healthy adults attending blood donor clinics were also recruited. Patients with known liver disease were excluded and all major ethnic / race groups were included to broadly represent local demographics. Relevant demographic data was captured at the time of sampling using an interviewer-administered confidential questionnaire. Human immunodeficiency virus (HIV) status was self-disclosed. HEV Ig G testing was performed using the Wantai® assay .RESULTS HEV is endemic in the region with a seroprevalence of 27.9% (n = 324/1161) 95% CI: 25.3% -30.5% (21.9% when when-adjusted) with no significant differences between ethnic g With the univariate analysis, age ≥ 30 years old, pork and bacon / ham consumption suggested risk. In the multivariate analysis, the highest risk factor for HEV Ig G seropositivity (OR = 7.679, 95% CI: 5.38-10.96, P <0.001) was being 30 years or older followed by pork consumption (OR = 2.052, 95% CI: 1.39-3.03, P <0.001) that HEV genotype 3 may be currently circulating in the Western Cape. CONCLUSION Hepatitis E seroprevalence was high higher than previously thought suggesting that hepatitis E warrants consideration in any patient presenting with an unexplained hepatitis in the Western Cape, irrespective of travel history, age or ethnicity .