Hepatitis E Virus (HEV) ORF2 Antigen Levels Differentiate Between Acute and Chronic HEV Infection.

BACKGROUND Hepatitis E virus (HEV) genotype 3 infections are frequent in Europe and North America, with acute and chronic courses described in the literature. HEV RNA detection by real-time polymerase chain reaction (PCR) is the gold standard for diagnosis. Recently, an anti-HEV antigen (Ag)-specific enzyme-linked immunosorbent assay (ELISA) directed against the HEV capsid became commercially available. The effectiveness of anti-HEV Ag-specific ELISA at detecting HEV genotype 3 infections remains undefined. METHODS The performance of anti-HEV Ag-ELISA was compared with that of real-time PCR, using sera from a cohort of acutely infected individuals, in addition to a cohort of chronically infected patients undergoing ribavirin therapy. Furthermore, virion properties were evaluated by density fractionation. RESULTS Anti-HEV Ag-specific ELISA was less sensitive than real-time PCR at detection of HEV infection. Anti-HEV Ag-specific ELISA revealed significantly higher HEV Ag in chronically infected individuals as compared to acutely infected patients, with high sensitivity and specificity to distinguish acute from chronic HEV infection. Of note, HEV Ag remained detectable for >100 days after HEV RNA clearance in ribavirin-treated patients with chronic HEV. Density gradients revealed the presence of membrane-associated virions in the sera, with a different distribution as compared to HEV RNA. CONCLUSIONS The anti-HEV Ag-specific ELISA is less sensitive than HEV RNA real-time PCR but represents a useful tool to discriminate chronic from acute infection.