Epidemiology and Genetic Surveillance of Human Hepatitis E Virus Infections in Shandong Province, Eastern China, 2019–2023

Hepatitis E virus (HEV) has emerged as a major agent of acute viral hepatitis, with zoonotic genotype 4 (HEV-4) representing a public health concern in China. In this study, we integrated province-wide enhanced hepatitis E surveillance data and molecular profiling from Shandong Province of eastern China, 2019-2023, with the aim of elucidating the epidemiology, genetic diversity, and clinical correlations of autochthonous HEV infections. In total, 5826 cases were reported during the study period, with 72.8% in males and 90.6% aged ≥ 40 years. 695 sequences were obtained from 553 males, 142 females, and an age range of 3-96 years (median 59 years). HEV-4d was predominant (84.0%), followed by 4b (9.9%), 4a (3.7%), and 4h (1.6%). Three HEV-3 strains and two imported HEV-1 strains were also identified. A high degree of nucleotide similarity was observed between dominant HEV-4d strains circulating in human populations and indigenous strains previously isolated from swine, cattle, and sheep within the province. Comparative analysis revealed no statistically association between the four principal HEV-4 subtypes and specific clinical manifestations, likely reflecting conserved pathogenic potential across these subtypes. Ongoing molecular surveillance is essential to monitor evolutionary trends and transmission dynamics of HEV within the framework of One Health.