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.
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.