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

Abstract

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.

Cross-Species Transmission of Swine Hepatitis E Virus Genotype 3 to Rabbits

“…In humans, portal inflammation and interface hepatitis are observed in acute HEV patients [43,44]. However, fibrosis is increased in patients with chronic HEV infection [44,45]. The histopathological findings in our study indicate that mild inflammation and fibrosis are reproducible in the liver tissues of rabbits infected with swine HEV or rabbit HEV.…”

“…A histopathological study of HEV infection has also been conducted in gerbils, which showed lymphocyte and eosinophil infiltration and histiocytic hepatitis [42]. In humans, portal inflammation and interface hepatitis are observed in acute HEV patients [43,44]. However, fibrosis is increased in patients with chronic HEV infection [44,45].…”

Genotype specific pathogenicity of hepatitis E virus at the human maternal-fetal interface

“…Lessons from the TORCH (Toxoplasma, Others, Rubella virus, Cytomegalovirus, and Herpes simplex virus) infections have revealed that viral replication at the maternal-fetal interface is associated with tissue damage and adverse pregnancy outcome 15 , 16 . Furthermore, apoptotic and necrotic features were previously reported in liver biopsies from HEV infected patients 17 , 18 . Accordingly, we assessed whether HEV infection impairs the morphology of the maternal-fetal interface.…”

Synanthropic rodents as virus reservoirs and transmitters

“…Mortality rates are higher among infected people presenting previous liver disease, immunocompromised patients, and pregnant women, as they present higher chances of renal failure leading to death 33,41,42 .…”

“…Detection methods for HEV include serological (specific IgG), histopathological, and molecular (RT-PCR) techniques 41 . Commercially, there are no specific prophylatic measures available on the market, although Chinese researchers have developed the HEV p239 vaccine from the HEV1 genotype 51 .…”