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 22-year old male patient had been treated with eculizumab from 2013 to 2015 for two years followed by RTX due to an atypical hemolytic-uremic syndrome and immune thrombocytopenia. RTX was administered from May to June 2015 (three cycles). In the following years, the patient suffered from recurrent infections including several episodes of bacterial bloodstream infections. A severe immunoglobulin deficiency was diagnosed and the patient was treated with intravenous immunoglobulin G substitutions. The patient also received long-term treatment with corticosteroids. Elevated aminotransferases were noticed from the end of 2015. In September 2017, he was admitted to our intensive care unit with a septic shock caused by an abscess in the left axilla. During recovery from the sepsis, jaundice was noticed and HEV RNA was detected in his blood (413 mio copies/mL) and feces. RBV therapy was initiated at a reduced dose of 200 mg/d due to his impaired renal function and was subsequently reduced to 200 mg three times per week. In the further course, RBV treatment was increased to a dose of 200–400 mg/d but had to be terminated after 4.5 months due to severe anemia and leukopenia. HEV replication remained continuously detectable throughout the complete RBV treatment period, confirming non-response in this patient.