Hepatitis E virus infection among raw pork products, pig feces, and human cases in Shandong Province, China: A prospective cross-sectional molecular study.

Zoonotic Hepatitis E virus (HEV) genotype 4 (HEV-4) has become the major pathogen responsible for acute viral hepatitis in China, with swine as the principal reservoir. This study aimed to further assess the presence of HEV in swine, raw pork products as food and genetic relationship with concurrent human strains in Shandong Province, China. From April 2023 to March 2025, a total of 358 raw pork products (166 livers, 96 kidneys, and 96 pork meat) from retail markets and slaughterhouses, 388 fecal samples from pig farms, and 110 serum samples from locally diagnosed HEV cases were collected. HEV RNA was detected using real-time RT-qPCR and nested RT-PCR assays. Overall, the detection rates of HEV RNA were 1.8% (3/166) in liver, 1.0% (1/96) in pork meat, and 6.5% (25/384) in pig feces, but not in kidney. Despite a low prevalence, the presence of HEV in commercial pig liver and pork meat represented potential vehicles for the virus to enter the food chain and a route of human HEV exposure. All 59 human and swine sequences obtained in this study were HEV-4. Human-derived sequences (n = 33) fell into subtypes HEV-4a, HEV-4b, HEV-4d, and HEV-4h, with HEV-4d predominated. Notably, all swine sequences (n = 26) were exclusively of the subtype HEV-4d, which clustered closely with local human HEV-4d strains and shared over 92% nucleotide identity. These findings advanced understanding of zoonotic transmission of HEV-4 from pigs to humans, underscoring the need to increase public awareness of hepatitis E as a swine-related foodborne disease.