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.
In June 2014, a 66-year-old Caucasian man was admitted for investigation of bilateral shoulder pain associated with remarkably dark urine. He revealed a ten-day history of general malaise, loss of appetite, anorexia, and an influenza-like syndrome with diffuse myalgia. The shoulder pain was evolutive, followed by progressive neurologic complaints, including muscular weakness and loss of force in the left hand accompanied by paresthesia of the fingers and dysesthesia of the palm of the hand. The patient reported a recent trip to Southeast Asia. Magnetic resonance imaging of the head and cervical spine showed no abnormalities, as did computed tomography of the thorax and abdomen. Liver function tests showed elevated ALT (188 IU/L), alkaline phosphatase (159 IU/L), total bilirubin (29.1 μmol/L), and GGT (814 IU/L). Serology was negative for CMV, EBV, HIV, HSV, VZV, T. gondii, parvovirus B19, and Coxiella burnetii. Serology for HBV was weakly positive for the core antibody (signal-to-cutoff ratio: 9.19), and negative for surface and envelope antigens and antibodies. Polymerase chain reaction for HBV was negative. Anti-HEV IgG (174 IU/mL) and IgM (137 IU/mL) were positive, although no serum HEV RNA could be detected at the time of diagnosis. Immunoblot analysis (RecomLine Hepatitis E IgG/IgM; Mikrogen GmbH) confirmed the presence of the antibody with high suspicion of a genotype 3 infection (no bands for genotype 1 visible). It is likely that cross-reactivity with acute HEV infection lead to a false-positive HB core antibody reactivity, which became undetectable during the convalescent phase of HEV infection. Electromyography confirmed bilateral (idiopathic) brachial plexopathy suggestive of Parsonage–Turner syndrome. Therefore, the patient was diagnosed with an acute HEV infection triggering a bilateral Parsonage–Turner syndrome.\nThe patient was managed conservatively with physical therapy and nonsteroidal anti-inflammatory drugs and opiates for pain relief, without any antiviral therapy. Neurologic signs and symptoms improved within two months, and laboratory parameters returned to values within the physiologic reference range within one month. The patient recovered completely after eight months of intensive revalidation exercise.