S3294 Acute Hepatitis E Infection With False Positive Cross-Reactivity to Epstein-Barr Virus

Abstract

Introduction: Hepatitis E virus (HEV) can cause acute or chronic viral hepatitis and is a common cause of acute viral hepatitis worldwide and is an important public health concern. A high level of HEV, hepatitis A virus (HAV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) cross reactivity can occur, which indicates that serology can sometimes be unreliable in the diagnosis of acute viral hepatitis. Case Description/Methods: A 28-year-old Pakistani male presented with right upper quadrant abdominal pain, general malaise, and deranged liver function tests. Work-up for his abnormal liver tests was unremarkable except for detection of Hepatitis E antibody, Hepatitis E IgM antibody, and Epstein-Barr Virus IgM antibody with polymerase chain reaction (PCR) analysis revealing no detection of Epstein-Barr Virus DNA. The patient was diagnosed with acute hepatitis E with a false-positive EBV infection due to serological cross-reactivity. Supportive care was continued, liver function tests trended down, and the patient clinically improved and was discharged with outpatient follow-up. Discussion: The incubation time for HEV infection can last up to six weeks and HEV RNA, anti-HEV IgM, and anti-HEV IgG antibodies can be detected at the time of diagnosis. Anti-HEV IgM antibodies have a short window of positivity at three to four months, whereas HEV RNA can be detected in the blood within three weeks with viral shedding lasting up to six weeks in the stool. The enzyme immunoassay is the most widely used serological method for the identification of anti-HEV IgG and IgM antibodies, but the identification of anti-HEV IgM and rising titers of anti-HEV IgG antibodies are inadequate for diagnosis due to the lack of specificity for these antibodies. Confounding the diagnosis of HEV is the incidence of HEV, HAV, CMV, and EBV cross reactivity, which is posited to be due to polyclonal B-cell stimulation. The diagnosis of HEV infection in the clinical setting relies on the performance of assays of anti-HEV IgM, and subsequently the awareness of factors influencing diagnostic accuracy is crucial regarding potential treatment options. This case suggests that both anti-HEV IgM and EBV IgM should be interpreted with caution in acute HEV infection and that confirmatory testing with PCR analysis should be conducted to evaluate for false-positive serological cross-reactivity. We conclude that the diagnosis of viral hepatitis should be based on characteristic symptoms, elevated liver enzymes, serology, and confirmatory PCR testing.