Epidemiology and serologic diagnosis of hepatitis E

Hepatitis E occurs in both epidemic and sporadic forms (1). Epidemics have been reported in many Asian and African countries, and in Mexico. Sporadic cases have been identified in developed countries, among travellers from endemic areas. Since there are no simple diagnostic tests, the precise epidemiology of hepatitis E virus (HEV) infection remains unclear. Diagnosis of hepatitis E used to be based on clinical and epidemiological evidence of enterically transmitted non-A, non-B hepatitis (ET-NANBH). In the past few years, several diagnostic tests for hepatitis E have been developed: immune electron microscopy is used to detect aggregated virus-like particles in stool by means of serum taken during convalescence (2); and the fluorescent blocking antibody assay detects antibodies that react against HEV antigen in hepatocytes (3). These tests are, however, laborious, technically difficult, and expensive, so they are unsuitable for general diagnostic purposes. Recent cloning of HEV has allowed the development of serologic assays for the detection of antibodies to recombinant expressed HEV antigens (anti-HEV) (4). The HEV genome consists of a single-stranded, positive-sense RNA of approximately 7.5 kb. There are three open reading frames (ORF) (5). ORF 1 contains the RNA-dependent RNA polymerase and nucleoside triphosphate binding motifs. ORF 2 contains sequences that may code for virus capsid proteins. ORF 3 partially overlaps with both ORF 1 and ORF 2. Enzyme immunoassays (EIAs) using recombinant (E. coli or baculovirus) expressed HEV antigens from ORF 2 and ORF 3 of Burmese, Mexican, and Pakistani isolates to detect anti-HEV (IgM and IgG) have been developed (6-8). Studies using these assays showed that most epidemics of ET-NANBH were due to HEV. These studies also showed that EIAs using HEV antigens from one isolate can detect anti-HEV in sera from patients or primates infected with HEV strains from other geographical regions, confirming the previous finding (based on aggregation of virus-like particles in stools using convalescent sera from different geographical areas, and cross-challenge experiments in primates) that there is only one HEV serotype. Comparison of the sequences of HEV isolates from diverse countries also revealed a high degree of homology (5,9). Recent surveys in Hong Kong and Egypt, countries in which epidemics of ET-NANBH have not been reported, found that IgM anti-HEV could be detected in 6%-22% of patients with acute viral hepatitis (10-12), suggesting that HEV infection is more widespread than previously thought. In these countries, hepatitis A, another enterically transmitted viral hepatitis, is also common; thus, hepatitis E may be endemic and not necessarily imported. This is substantiated by the finding of IgG anti-HEV in 16% of healthy subjects in Hong Kong (10). Interestingly, both Egyptian studies were conducted in children (I 1,12), while previous studies on epidemics of ET-NANBH found that clinical hepatitis was rare among children. This discrepancy may be related to milder clinical illness in children (as with hepatitis A), and underdiagnosis in the absence of a diagnostic test. The incidence of hepatitis E in western countries was examined in two studies reported in this issue of the Journal. Buti et al. (13) studied 341 consecutive patients with acute viral hepatitis who attended their hospital in Barcelona. None of 64 patients who were negative for hepatitis A, B, C, and D markers that were tested for IgM and IgG anti-HEV by EIA at Genelabs was reactive. In the other study, Pham et al. (14) tested 65 French patients with