Hallmarks of liver lesions in pigs naturally infected by hepatitis E virus genotype 3

Abstract

Histopathological evaluation of liver from 33 pigs slaughtered for human consumption in Amazon region, previously tested by serology and molecular techniques for hepatitis E virus infection (HEV), was analysed in three groups: Group 1, negative for both HEV-RNA and anti-HEV IgG (n=10); Group 2, positive for HEV-RNA (n=13); Group 3, positive for anti-HEV IgG (n=10). Group 2 showed a significant difference among the groups for liver lesions such as lobular activity (P=0.007), periportal interface hepatitis (P=0.004), portal inflammation (P=0.028) hepatitis with lobular, portal and periportal interface activity (P=0.001). HEV detection by immunohistochemistry was performed and 3 of 6 samples of group 2 were positive. Pigs naturally infected by HEV genotype 3 present microscopic necroinflammatory liver lesions similar to HEV in humans. Liver histopathology showed be important in the diagnosis of active asymptomatic HEV infection in pigs slaughtered for human consumption because hepatic liver lesions may present distinct profiles according to molecular and serological diagnosis and in this sense, histopathology and immunohistochemistry may be an important complementary diagnostic tool.

Immunohistochemical analysis of ORF2 protein and ORF3 protein of hepatitis E virus in livers of swine in Mato Grosso state, Brazil

“…Immunohistochemical studies using only isolated commercial antibodies to HEV ORF2 protein were previously reported in swine, revealing of pORF2 immunostaining with spatial localization in hepatocyte cytoplasm (Ha & Chae 2004, Lee et al 2009, with minimal or no histopathological lesions, presenting characteristics and spatial location similar to those observed in this study. In a study by Lana et al (2014), no statistical association was observed between the presence of viral RNA in the liver and the occurrence of microscopic lesions (mild lymphoplasmacytic periportal hepatitis), which reiterates the immunolabeling observed in intact hepatocytes in this study; however, in contrast, De Souza et al (2018) reported the occurrence of marked histological lesions in swine hepatocytes associated with cytoplasmic immunolabeling of HEV using the primary antibody to pORF3. In humans are reported severe and disseminated hepatocellular necrosis associated with an expression and subcellular localization of pORF2 in human hepatocytes with cytoplasmic localization and in the nucleus of hepatocytes (Friedman et al 2016, Lenggenhager et al 2017, Ankavay et al 2019.…”

“…The liver sections were evaluated using optical microscopy (Axio Imager A2, Carl Zeiss) to verify the presence, intensity, and location of immunolabeling of the HEV antigen according to the zones of the liver lobes and the cell types involved. The positivity criteria established in this study were based on morphological characteristics and defined by immunolabeling in hepatocytes (cytoplasmic and/or nuclear), with a granular appearance and intensely brownish color (Lenggenhager et al 2017, De Souza et al 2018.…”

“…Detection of HEV using immunohistochemistry is related to the production of viral proteins in certain cell types (Lee et al 2009). Previous IHC studies have been described viral antigen detection in paraffin-embedded human HEV infected livers (Gupta et al 2012, Friedman et al 2016, Lenggenhager et al 2017) and swine (Ha & Chae 2004, Lee et al 2009, Lana et al 2014, De Souza et al 2018. Lenggenhager et al (2017) carried out a comparative immunohistochemical study to identify and localize viral proteins in human livers using different polyclonal and monoclonal antibodies to the three ORFs of the viral genome, relating the sensitivity of the immunohistochemical technique to molecular detection, in situ hybridization, and immunofluorescence techniques to establish reliable diagnoses of HEV infection.…”

Seroprevalence of Hepatitis E Virus in Moose (Alces alces), Reindeer (Rangifer tarandus), Red Deer (Cervus elaphus), Roe Deer (Capreolus capreolus), and Muskoxen (Ovibos moschatus) from Norway

“…Additionally, genotype 7 was described in an immunocompromised man who developed chronic hepatitis [ 14 ]. In HEV-positive pigs, necroinflammatory hepatic lesions similar to those observed in human cases have been reported by histopathology [ 68 ]. Given this study’s results in Norwegian reindeer and moose in Norway, we believe that wildlife necropsies should include HEV in their differentials when hepatic lesions are observed.…”