Discussion
HEV is known to cause acute hepatitis in developing countries, and
regional outbreaks occur often.1,2 HEV is an
approximately 7.2-kb single-stranded RNA virus belonging to the genusOrthohepevirus of the family Hepeviridae . Genotypes 1 to 4
infect humans, with types 3 and 4 reported in Japan, mainly in Hokkaido
and eastern Japan.3 HEV causes zoonotic infections.
Known sources of infection include venison, pork, boar meat, and
contaminated water, but there are also reports that the consumption of
wild plants such as blackberries and blueberries poses a risk for
infection. Transfusion is another known risk factor for infection.
However, in some cases, even with detailed interviews, the source of
infection remains unknown.4 The incubation period is
2–10 weeks, but in most cases, the disease develops within 4–5 weeks
after infection. Anti-HEV IgM and IgG antibody levels rise during the
incubation period. IgM is detected only for 3–12 months, whereas IgG
can be detected for several years after infection.5The symptoms of hepatitis include general fatigue, slight fever, nausea,
and dark urine. HEV infection often resolves spontaneously, but caution
should be exercised because it can become severe in pregnant women and
immunocompromised patients and progresses to acute liver failure in rare
cases.4,6-8 Recent studies have shown that HEV is a
more common pathogen than previously thought, even in industrialized
countries. In the United States, the prevalence of anti-HEV IgG
antibodies among adults is 21.0%.3 In Japan, although
there have been few reports of chronic HEV infection in conventionally
healthy people, the proportions of subclinical infections and
undiagnosed cases are thought to be high.9 Although
anti-HEV IgM is used as a reliable and sensitive marker of recent HEV
infection, the specificity of the solid-phase assay for anti-HEV IgM has
been questioned in some cases, particularly in patients with IgM
rheumatoid factors in their serum that exert activity against the Fc
portion of IgG directed to the HEV antigen and may elicit a
false-positive result.9-12 Virus-specific IgA has been
detected during the acute stage of infection with hepatitis A or B
virus.13,14 HEV IgA has been detected in sera from
patients with hepatitis10 and was included in the
national health insurance scheme in 2011. Since then, the number of
reports has been increasing.9
Chronic HEV infection has been reported in patients who have undergone
organ transplantation. Lasting viremia in such cases has been mainly
caused by immunosuppression due to the administration of
immunosuppressive drugs or induced by specific HEV
genotypes.2,15,16 Patient factors associated with
higher disease severity and mortality include being male and having
comorbidities, such as tumors, diabetes, liver dysfunction, respiratory
disease, and renal dysfunction.4,6 In the present
case, the patient had no history of immunodeficiency, and there was no
obvious cause of the HEV infection. RNA testing can reliably identify
the virus, but it is not covered by health insurance in Japan; it is
more practical to follow up with blood tests for liver dysfunction and
HEV IgA to determine whether acute hepatitis or liver failure develops.
A previous study showed that in some cases, negative results were
obtained within a few dozen days of onset, whereas in others, there were
positive results after 140 days; therefore, it is not clear how long a
patient remains positive after onset.9 In the present
case, the patient did not develop acute hepatitis; however, HEV IgA
remained positive for more than eight months. The clinical significance
of long-term persistently positive HEV IgA remains unclear, and more
data are needed. The patient was young, had no comorbidities, and had a
low risk of severe disease; however, careful follow-up is necessary.