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 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.