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.