Four-year long (2014-2017) clinical and laboratory surveillance of hepatitis E virus infections using combined antibody, molecular, antigen and avidity detection methods: Increasing incidence and chronic HEV case in Hungary

Background: Hepatitis E virus (HEV) is a pathogen of viral hepatitis. Since 2006, the number of reported HEV cases has ten-fold increase in Hungary. Objectives: The aim of this clinical and laboratory surveillance study was to analyse and confirm HEV IgM-positive sera with different methods in four consecutive years (2014-2017) in Hungary. Study design: Between 2014 and 2017, a total of 1439 sera samples were tested for HEV from in/out-patients with unknown hepatitis from university and county hospitals and general practitioners from three counties in Southwest Hungary (covered population: Sigma 894.000 persons) using combined antibody (serology), various molecular (RT-PCR and RT-qPCR), novel antigen (Ag) and avidity detection methods. Results: Total of 162 (11.3%) of the 1439 sera were HEV IgM-positive including 13 (8%) HEV RT-PCR-positive (confirmed as HEV genotype 3 sub-genotypes 3a/c/e/f/i in genus Orthohepevirus A) with up to 1.1383 x 108 RNA copy/ml, 30 (18.5%) HEV Ag-positive and 16 with low avidity index for HEV, respectively. Total of 6 samples were positive simultaneously with the combined four methods and 31 with three methods. If the quotient of serum sample's OD/cut-off of anti-HEV ELISA IgM and IgG scores is higher than >= 1 it predisposes for acute HEV infection. No rat or ferret HEV RNA (genus Orthohepevirus C) were identified from these specimens by RT-PCR. During our surveillance period a 68-year-old professional (meat-packing) hunter with kidney transplantation and immunosuppressive therapy was confirmed and treated as the first documented case of chronic HEV infection in Hungary. Conclusion: This four-year-long clinical and laboratory surveillance highlights the increasing importance of acute and chronic HEV infections in Hungary and supports the use of confirmatory assays for laboratory diagnosis of HEV in human.