Hepatitis E in suspected acute hepatitis cases in Brazil: A comparison with hepatitis A

Hepatitis E virus (HEV) is an underrecognized cause of acute viral hepatitis worldwide, with growing public health relevance, particularly in settings where routine diagnostic testing is limited. Hepatitis A virus (HAV) is another epidemiologically related hepatitis virus, but few studies have directly compared these infections in Brazil. This study aimed to (1) determine the frequency of acute hepatitis E (AHE) and evaluate the contribution of HEV infection to the burden of hepatitis among patients with suspected acute disease attended in public healthcare institutions in Brazil; (2) assess the prevalence of acquired immunity to HEV and HAV; and (3) compare demographic characteristics, risk factors, and clinical-laboratory findings associated with HEV and HAV infections. We enrolled 1,721 adults (≥18 years) with suspected acute hepatitis from 16 Brazilian states between October 2019 and May 2023. Serum samples were tested for anti-HEV IgG/IgM and anti-HAV IgG/IgM by immunoassay and for HEV and HAV RNA by RT-PCR. Demographic, behavioral, clinical, and laboratory data were collected using a standardized questionnaire. Group comparisons were performed using univariate analyses and logistic regression, with statistical significance set at p < 0.05. Anti-HEV IgG was detected in 89 individuals (5.2%), whereas anti-HAV IgG was detected in 1,352 (78.6%). Anti-HEV IgG seroprevalence was higher in the South, Southeast, and Central West regions and among heterosexuals, and it increased with age, reaching 13.0% among individuals aged ≥65 years. Seropositivity was associated with markers of previous exposure or immunity, including HAV, HBV, Leptospira, and Toxoplasma. A total of 124 acute hepatitis cases were identified: 16 (12.9%) AHE and 108 (87.1%) acute hepatitis A (AHA). Compared with AHA cases, AHE cases occurred in older individuals and were more frequent among women and heterosexual participants. All AHA cases occurred in urban areas, whereas AHE cases were observed in both urban and rural settings. AHA cases showed higher aminotransferase levels and more frequent jaundice than AHE cases. HEV accounts for a small but distinct proportion of suspected acute hepatitis cases in Brazil and shows epidemiological and clinical characteristics that differ from HAV. Incorporating HEV testing into routine diagnostic algorithms may improve etiological clarification and surveillance of acute hepatitis.