Epstein-Barr Virus Infection With Hepatic Involvement in a Pediatric Patient: An Atypical Presentation

Epstein-Barr virus (EBV) infection is a self-limited disease, generally asymptomatic in children, and most cases of EBV hepatitis are mild. We report a pediatric case of EBV hepatitis with prolonged course, use of antiviral therapy, and screening for immunodeficiency associated with autoimmunity. School-age female, 8 years old, non-consanguineous parents, with a clinical history of fever, abdominal pain, and jaundice for 9 days. Complete blood count showed lymphocytic atypia; serologic investigation showed reactive EBV IgG and IgM, and non-reactive hepatitis A, HIV, CMV, and parvovirus. She remained clinically stable and was discharged for outpatient follow-up. She was readmitted 30 days later due to relapse of symptoms, painful cervical lymphadenopathy, elevated liver transaminases, and hepatosplenomegaly. Liver biopsy was indicated ‒ acute hepatitis with mild fibrosis and intense mononuclear portal and lobular inflammation. Immunohistochemistry for antibodies (CD3, CD4, CD8, CD20, and CD34 positive; CD21 negative; TDT negative; and nonspecific EBV) was suggestive of EBV-related hepatic inflammation, and workup for autoimmune hepatitis showed p-ANCA and c-ANCA, anti-LKM-1, anti-mitochondrial, anti-smooth muscle, and ANA all non-reactive. Immunologic screening ‒ serum immunoglobulins: IgA 209 mg/dL (between the P75 and P97 percentiles), IgM 190 mg/dL (above the P97 percentile), IgG 1,460 mg/dL (between the P75 and P97 percentiles) ‒ immunophenotyping: total lymphocytes 1,842 cells/μL, CD4+ (40.5%; 746 cells/μL), CD8+ (28.7%; 529 cells/μL), CD19+ (9.9%; 196 cells/μL) ‒ and quantitative serum PCR for EBV negative. Acyclovir was started due to altered liver function and later outpatient normalization. Epstein–Barr virus (EBV) is a ubiquitous herpesvirus that establishes lifelong latency in B cells and is typically controlled by robust T-cell and NK-cell responses. Severe and persistent forms of EBV hepatitis are uncommon and may be a manifestation of autoimmune hepatitis or an underlying inborn error of immunity. EBV-associated autoimmunity is still not fully understood, but there is evidence supporting its role in inducing T and/or B lymphocytes to produce liver-specific autoantigens. The relationship between inborn errors of immunity and EBV infection and hepatitis is multifaceted and clinically significant. In such cases, diagnostic investigation with liver biopsy and EBV-specific diagnostic tests (serology, PCR, in situ hybridization) are vital to confirm the diagnosis and guide treatment.