An Update on the Clinicopathologic Features and Pathologic Diagnosis of Hepatitis E in Liver Specimens

Infection with the hepatitis E virus (HEV) is globally seen a leading cause of hepatitis. Now increasingly recognized also in industrialized countries, hepatitis E constitutes a significant health problem worldwide. The patient's immune status determines the clinical course and histopathology of hepatitis E. In immunocompetent patients, hepatitis E usually follows an asymptomatic or subclinical course, but may also present with acute hepatitis. In contrast, immunocompromised patients may develop chronic hepatitis, and patients with preexisting liver diseases are at risk for liver decompensation with potentially fatal outcome. Whereas pathologists only occasionally encounter liver biopsies from immunocompetent individuals with hepatitis E, they are more likely exposed to biopsies from patients with preexisting liver disease or immunocompromised individuals. Histopathologic hallmarks of hepatitis E in immunocompetent patients comprise lobular disarray, lobular, and portal inflammation, as well as hepatocyte necrosis of varying extend and regeneration. Thus, it is similar to acute non-E viral hepatitis, yet further differential diagnoses include autoimmune hepatitis and drug-induced liver injury. Histopathologic findings of hepatitis E in preexisting liver disease are determined by the underlying pathology, but may be more severe. Histopathologic presentation of hepatitis E in immunocompromised patients is highly variable, ranging from minimal active hepatitis to chronic hepatitis with severe activity and progressive fibrosis. Taken together, the variability of the histologic features depending on the clinical context and the overlap with other liver diseases make the histopathologic diagnosis of hepatitis E challenging. Immunohistochemistry for HEV open reading frame 2 protein and molecular testing for HEV RNA are useful tissue-based ancillary tools.