Abstract
Asymptomatic hepatitis E virus (HEV) infections have been found in blood donors from various European countries, but the natural course is rarely specified. Here, we compared the progression of HEV viraemia, serostatus and liver-specific enzymes in 10 blood donors with clinically asymptomatic genotype 3 HEV infection, measuring HEV RNA concentrations, plasma concentrations of alanine/aspartate aminotransferase, glutamate dehydrogenase and bilirubin and anti-HEV IgA, IgM and IgG antibodies. RNA concentrations ranged from 77.2 to 2.19×105 IU/mL, with viraemia lasting from less than 10 to 52 days. Donors showed a typical progression of a recent HEV infection but differed in the first detection of anti-HEV IgA, IgM and IgG and seropositivity of the antibody classes. The diagnostic window between HEV RNA detection and first occurrence of anti-HEV antibodies ranged from eight to 48 days, depending on the serological assay used. The progression of laboratory parameters of asymptomatic HEV infection was largely comparable to the progression of symptomatic HEV infection, but only four of 10 donors showed elevated liver-specific parameters. Our results help elucidate the risk of transfusion-associated HEV infection and provide a basis for development of screening strategies. The diagnostic window illustrates that infectious blood donors can be efficiently identified only by RNA screening.
Highlights
The hepatitis E virus is a single-stranded RNA virus; there are currently four human pathogenic genotypes 1 to 4 [1]
The day of the detection of hepatitis E virus (HEV) RNA by PCR screening was defined as day 0, but HEV infection is most likely to have occurred before the beginning of our study period
Figure panels B–D show the course of anti-HEV IgM, anti-HEV IgG and anti-HEV IgA
Summary
The hepatitis E virus is a single-stranded RNA virus; there are currently four human pathogenic genotypes 1 to 4 [1]. Genotypes 3 and 4 are responsible for sporadic cases of HEV infection. Symptomatic infection presents as an acute, mostly self-limiting hepatitis with clinical characteristics similar to hepatitis A [2]. Clinical manifestations of HEV infections caused by the different genotypes are indistinguishable. HEV genotype 3 and 4 infection proceed asymptomatically in immunocompetent individuals [8], but severe or fatal HEV infections have been observed in individuals with chronic liver disease [11,12], in transplant patients [13,14] and in immunosuppressed individuals [8]. Asymptomatic HEV infection has often been observed in blood donors [15,16,17], with reported prevalence rates of HEV RNA-positive donors of 1:2,848 (England [18]), 1:1,240 (Germany [17]) and 1:1,761 (the Netherlands [19])
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