A 68-year old male patient had been diagnosed with marginal zone lymphoma in 2011. He had received chemotherapy (R-CHOP) and autologous hematopoietic stem cell transplantation in 2012. After recurrence of his lymphoma in 2015 he had been treated with ibrutinib from 2015 to 2017 followed by bendamustine and RTX from January to October 2018. He had increased aminotransferases in March 2019, and HEV RNA was measured at 43 mio copies/mL in June 2019, prompting the initiation of treatment with ribavirin at a dose of 600 mg/d, which led to HEV clearance in July 2019. RBV treatment was terminated and the patient showed no HEV replication in October 2019. In November 2019, a viral relapse was detected and retreatment with 600 mg RBV/d was initiated.
A 69-year old male received seven cycles of R-CHOP plus two cycles of RTX in 2008 and 2009 for non-Hodgkin’s, lymphoma leading to long-term remission. A regular follow-up examination in July 2016 revealed elevated aminotransferases indicating hepatitis. An extended laboratory examination including HEV serology without HEV RNA testing failed to unravel the underlying cause. A liver biopsy obtained in September 2016 exhibited histological features of viral hepatitis, but laboratory results remained negative for hepatotropic viruses. The patient remained undiagnosed until HEV RNA quantitation was performed in March 2018, revealing a HEV load of 4.15 E6 copies/mL despite persistent HEV seronegativity until present (recomWell HEV IgG/IgM and for confirmation recomLine HEV IgG/IgM, both Mikrogen Neuried, Germany). Weight-based RBV was administered at a dose of 1000 mg/day for three months and the patient cleared HEV, which led to the termination of therapy. HEV relapsed after 4 weeks and RBV treatment was re-induced at a dose of 1000 mg/d for 4 additional months without achieving viral clearance. After a treatment pause of two months RBV was continued at a reduced dose of 800 mg/d due to increasing fatigue and insomnia of the patient, who shows persisting HEV replication and constantly elevated aminotransferases until present.