Viral Hepatitis

Hepatitis E (HEV) Antibody Detection Assays

Hepatitis E virus (HEV) is a waterborne disease mainly found in areas with poor sanitation and typically results from ingesting fecal matter that contaminates the water supply. The disease is usually acute but can be particularly dangerous in pregnant women.

GENOME ORGANIZATION OF THE HEPATITIS E VIRUS

Hepatitis E infection has a clinical course comparable to Hepatitis A and is mostly a self-limiting disease with low death rates. However, in individuals with a weakened immune system, there is a high risk of developing chronic hepatitis. In addition, in pregnant women (particularity those in the third trimester), the disease can be severe with a death rate of 25% and it is often associated with a clinical syndrome called fulminant liver failure. HEV was once an understudied and neglected virus. However, in recent years, the safety of blood products with respect to HEV has increasingly been considered to be a public health problem. In total there are four main genotypes of Hepatitis E. Genotypes 1 and 2 have been found only in humans. Genotypes 3 and 4 are linked to zoonotic transmission (pigs, wild boar and deer) and cause sporadic infections in industrialized countries through ingestion of undercooked animal meat. Structurally, HEV is a nonenveloped virus with a genome consisting of three open reading frames (ORFs). ORF1, which encodes the nonstructural proteins (NS) necessary for replication, ORF2 which encodes the core protein for the viral capsid, and ORF3 which partially overlaps ORF1 and encodes a viroporin-like protein.

ORF2 encodes the core protein that forms the capsid, and the ORF3 protein is essential for viral release via the ESCRT pathway

DIAGNOSIS The commonly used tests for HEV infection include detection of IgM and IgG anti-HEV antibodies and detection of HEV RNA. HEV IgM antibodies appear early (from 1-4 weeks) in the course of illness and disappear over 4–5 months. Assays detecting anti-HEV are usually qualitative sandwich immunoassay developed with recombinant HEV antigens that provide broad coverage of all 4 major HEV genotypes. The antigens typically represent part of the ORF2 and ORF3 proteins. Simultaneous assessment of anti-HEV IgA has been recommended to improve specificity as the IgM assay may cross-react with other IgM-based assays such as rheumatoid factor IgM.