Debes JD, et al. - During a case of acute HEV genotype 3 infection in the Netherlands, who initially presented with typical features of acute viral hepatitis with detectable HEV RNA in blood, the immune response was determined via performing cytokine evaluation via multiplex cytokine array for 67 immune markers in plasma during different phases of hepatitis. Following peripheral clearance of the virus, this evolved into a cholestatic disease resulting in the death of the patient. Liver tissue displayed the presence of HEV in real-time PCR, suggestive of active intrahepatic infection despite clearance in blood. They noted a surge of T-cell related immune mediators, as well as IFN-α and IP-10 characteristic of viral infections during the phase of detectable HEV RNA in serum. They observed subsidence of several inflammatory markers, 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, following clearance of the virus in blood and development of cholestatic hepatitis. These findings suggest the shedding of the virus, solely intrahepatic, and an immune profile reflective of the activity of hepatic resident cells following peripheral clearance of the virus.