A 64-year old male with elevated aminotransferases presented himself at our outpatient clinic. He had been diagnosed with a monoclonal gammopathy of undetermined significance in 1992. In 2012, he had received eight cycles of bendamustine and RTX for Waldenstrom macroglobulinemia. Due to a relapse in 2016 he had been retreated with six cycles of bendamustine and RTX until February 2017, with stable remission since then. In November 2017, elevated aminotransferases were noted for the first time and the patient reported a short period of jaundice and fatigue. Extended laboratory testing revealed a HEV load of 6.1 E7 copies/mL. HEV IgG was positive and HEV IgM negative. After three months of persistent HEV replication, weight-based RBV treatment was started at a dose of 800 mg/d leading to virus clearance after three months of RBV treatment. RBV was stopped, but HEV relapsed only one month later and the patient was retreated with 800 mg RBV/d for an additional three months, achieving a sustained virological response.
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.