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.
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.