2511 Acute Cholestatic Hepatitis E Infection: Immune Dissociation With Intra-Hepatic Replication

Abstract

INTRODUCTION: There is a lack of understanding of immune modulation during acute hepatitis E virus (HEV) infection. We evaluate the immune response during a case of autochthonous acute HEV genotype 3 infection in the Netherlands. CASE DESCRIPTION/METHODS: A 73 y/o patient initially presented with typical features of acute hepatitis. Extensive work up showed detectable HEV RNA in blood with positive IgM and genotype-3 molecular detection. The liver enzymes improved, there was viral clearance from blood and the patient was discharged home. However, on follow up appointment he was found to have severe cholestasis, was readmitted and passed away shortly. Real time PCR of liver biopsy revealed presence of HEV in liver tissue, suggestive of active intrahepatic infection despite clearance in blood. Peripheral immune evaluation performed via Pro-carta multiplex array showed that during the phase of detectable HEV RNA in serum, there was a surge of T-cell related immune mediators, as well as IFN-a and IP-10 characteristic of viral infections. After clearance of the virus in blood and development of cholestatic hepatitis, several inflammatory markers subsided, followed by an increase in immune factors related to anti-inflammatory activity as well as monocyte/macrophage related markers likely due to the intrahepatic presence of the virus. DISCUSSION: Our case describes a dissociation of intra- and extra-hepatic immune responses during acute HEV infection. As the shedding of the virus became solely intrahepatic, we observed an immune profile reflective of the activity of hepatic resident cells reflecting “competing immune interests' during HEV infection. Moreover, it exposes a less-known aspect of HEV: intra-hepatic morbidity despite lack of detection in blood.