Prolonged Cholestatic Hepatitis A With Transient Epstein-Barr Virus IgM Reactivity and Marked Hyperferritinemia in an HFE H63D Heterozygote

Hepatitis A virus (HAV) infection is usually self-limited and does not progress to chronic liver disease. However, atypical courses such as prolonged cholestatic hepatitis may occur in adults, posing diagnostic and therapeutic challenges. We report the case of a 55-year-old man with hypertension, obesity, and known hepatic steatosis who presented with jaundice, choluria, acholic stools, fatigue, epigastric pain, and nausea. Laboratory evaluation revealed a mixed hepatocellular-cholestatic pattern with predominantly direct hyperbilirubinemia. Acute HAV infection was confirmed (anti-HAV IgM positive), and alternative causes were excluded. Imaging showed no biliary obstruction. Epstein-Barr virus (EBV) serology obtained during the first admission was consistent with past infection (viral capsid antigen (VCA) IgG positive, VCA IgM negative, and EBV nuclear antigen-1 (EBNA-1) IgG positive). The patient improved with supportive care and was discharged after one week. He was readmitted one week later with clinical relapse and severe hyperbilirubinemia (total bilirubin 25.3 mg/dL). Given a household contact with a mononucleosis-like illness, repeat EBV serology showed weak/low-level VCA IgM reactivity (12.1 UA/mL) with persistent VCA IgG positivity. However, subsequent reassessment results returned to VCA IgM negativity with persistent VCA IgG and EBNA-1 IgG positivity, supporting remote EBV infection and suggesting non-specific IgM reactivity (or, less likely, reactivation) rather than primary acute EBV infection. EBV DNA PCR was not pursued due to low clinical and serologic suspicion of active infection and the subsequent resolving course. A genetic study requested during the first admission revealed HFE H63D heterozygosity, with a ferritin level >11,000 ng/mL and transferrin saturation of >80%. The patient improved with ursodeoxycholic acid (UDCA) and individualized iron management. Corticosteroids were not used, given progressive improvement with supportive care and UDCA. Follow-up quantitative liver MRI showed only mild iron overload (43 µmol/g), supporting an acute-phase/inflammatory iron contribution during severe hepatitis, and FibroScan® revealed mild fibrosis (5.3 kPa). This case highlights the importance of stepwise reassessment in prolonged cholestatic HAV, the pitfalls of interpreting transient EBV VCA IgM reactivity in a patient with serology consistent with prior EBV infection, and careful interpretation of marked hyperferritinemia in HFE H63D heterozygotes.