Delayed recurrence of hepatitis E virus RNA in serum and feces after ribavirin therapy for chronic hepatitis E: importance of extended follow-up.

A 56-year-old man receiving immunosuppressive therapy with methotrexate (MTX) for a T-cell lymphoproliferative disorder developed acute hepatitis caused by hepatitis E virus (HEV). Persistent HEV viremia was observed, and the patient was diagnosed with chronic HEV infection based on the continued presence of HEV RNA in both serum (106-107 copies/mL) and feces (~ 109 copies/mL in 15% suspensions) 6 months after the initial infection. A 12-week course of ribavirin (RBV) therapy, combined with gradual tapering of MTX, resulted in undetectable HEV RNA levels in serum and feces at the end of the RBV treatment. However, 6 months after completion of RBV therapy and MTX cessation, HEV RNA reappeared at low levels in serum (10 copies/mL) and feces (~ 103 copies/mL in 15% suspensions). This low-level viremia persisted for approximately 4 months without any clinical symptoms or additional treatment. Eventually, HEV RNA became spontaneously undetectable in both serum and feces, and the patient was considered cured based on sustained HEV RNA negativity 1129 days after the onset of hepatitis. This case highlights the importance of extended follow-up-beyond the standard 6 months-when assessing the viral clearance in HEV-infected patients following antiviral therapy.