Abstract
BACKGROUND: Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide, yet its impact in Latin America remains underexplored. Evidence suggests that chronic liver disease (CLD) patients infected with HEV face increased risks of disease progression and mortality. The PROGINS haplotype has been proposed to influence susceptibility to HEV. This study assessed HEV infection in CLD patients from Latin America and potential associated factors, including the PROGINS haplotype. METHODS: A total of 971 individuals-784 with CLD and 187 healthy controls (HC)-from six countries (Argentina, Brazil, Chile, Colombia, Ecuador, and Peru) were analyzed for anti-HEV IgG and IgM (ELISA), HEV-RNA (RT-qPCR and nested PCR with Sanger sequencing and phylogenetic analysis), and the PROGINS haplotype (PCR). RESULTS: The overall anti-HEV IgG seroprevalence was 15.2%: 15.4% in CLD and 14.4% in HC, with no statistical difference. Marked geographical disparities were observed, with Chile showing the highest (45.1%) and Argentina the lowest (4.2%) anti-HEV IgG detection rates. Cirrhosis and alcohol-related liver disease (ALD) were significantly associated with higher detection rates, while neither age nor sex influenced HEV seroprevalences. PROGINS haplotype showed no significant association with HEV infection. Anti-HEV IgM and HEV-RNA were detected in 11.2% and 0.4% of participants, respectively. Phylogenetic analysis confirmed zoonotic HEV-3 circulation in the region. CONCLUSIONS: This first multinational assessment of HEV in Latin America reveals heterogeneous seroprevalence across countries. Findings support considering HEV testing in diagnostic protocols for CLD patients particularly those with cirrhosis or ALD- when presenting with unexplained hepatic decompensation or acute hepatitis.