Hepatitis A and E in rural northern India: clinico-epidemiological and molecular surveillance from a tertiary care hospital

Background HAV and HEV cause substantial preventable morbidity across India, yet contemporary clinico-epidemiological and molecular surveillance from the rural Indo-Gangetic plain is sparse, with no published series from the eastern Uttar Pradesh catchment of AIIMS Raebareli. We addressed this gap through an integrated hospital-based study of acute viral hepatitis (AVH) combining seroprevalence, clinical phenotyping, seasonality and molecular genotyping, with public deposit of all newly generated sequences. Methods Serum samples from 554 consecutive patients with clinically suspected AVH at AIIMS Raebareli between January 2023 and October 2024 were screened for anti-HAV and anti-HEV IgM by enzyme-linked immunosorbent assay. Seropositive samples underwent RT-PCR targeting the HAV VP1–VP3 and HEV ORF2 regions, and representative amplicons were Sanger-sequenced. Phylogenetic relationships were reconstructed using maximum likelihood in MEGA 11 with 1,000 bootstrap replicates. Results Anti-HAV IgM was detected in 50 patients (9.0%) and anti-HEV IgM in 18 (3.2%); four (0.7%) showed dual seropositivity. The HAV-positive cohort was predominantly pediatric (median 14 years, IQR 7–19), with 44.0% aged 6–15 and 38.0% aged 16–40 years. HEV-positive patients spanned a wider age range (median 13, IQR 4–30). HAV cases peaked pre-monsoon (May–June); HEV occurred year-round. Severe disease was uncommon: one HAV-positive patient developed acute liver failure and died in hospital. RT-PCR confirmed HAV viremia in 11/50 (22.0%) and HEV in 7/18 (38.9%). All sequenced HAV strains were HAV genotype IIIA and HEV strains HEV genotype 1a, with 98–99% nucleotide identity to Indian references. Conclusion HAV remains the dominant cause of enterically transmitted AVH in this previously unstudied rural catchment, with disease now concentrated in older children, adolescents and young adults; HEV-1a circulates at lower volume but year-round. Genotypic uniformity (HAV-IIIA, HEV-1a) indicates a stable transmission pattern, and the present sequences (GenBank PV454657–PV454670) extend the molecular record from northern India. Three operational priorities follow: structured HAV immunization of older children and adolescents, a focused pre-monsoon (March–May) WASH outreach window, and routine anti-HEV IgM screening of pregnant women presenting with jaundice.