Hepatitis E Pathogenesis

Abstract

Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years.

Keywords: chronic infection; extra-hepatic manifestation; fulminant hepatitis; hepatitis E virus; pathogenesis.

Figure 1

Hepatitis E virus (HEV) genome. The 5′ end of the RNA genome is capped with a 7-methylguanosine (7 mG), and the 3′ end is polyadenylated (poly(A)). Open reading frame 1 (ORF1) encodes nonstructural proteins, including a methyl transferase (MT), cysteine protease (P), helicase (Hel), and RNA polymerase (RdRp), as well as three regions of unknown function (Y domain, polyproline region (PPR), and X domain). ORF4 has only been described in hepatitis E virus genotype 1 (HEV1).

Figure 2

Phylogenetic tree based on full-length sequences of HEV strains. Sequences were aligned using ClustalW (MEGA5) and BioEdit (version 7.0). The phylogenetic tree was created by the neighbour-joining (Kimura two-parameter) method, with a bootstrap of 100 replicates. The species Orthohepevirus A includes 7 genotypes (HEV1−7).

Figure 3

Biopsies of a kidney allograft in a patient with membranoproliferative glomerulonephritis at the acute phase of HEV infection. (a) kidney-allograft biopsy at diagnosis; (b) kidney-allograft biopsy seven months after HEV clearance (Masson’s trichrome, magnification: × 400).

Figure 4

Course of an acute HEV infection.

Figure 5

Histological patterns of liver biopsies taken from a patient with a chronic HEV infection. (a) initial liver biopsy; (b) inflammation after 15 months of chronic HEV infection; (c) cirrhosis after 38 months of chronic HEV infection. (Masson’s trichrome, magnification × 100).