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.
In December 2009, a 32-year-old Caucasian woman was diagnosed with acute myeloid leukemia [t(11;19)]. She had no history of recent travel, contact with animals, or consumption of venison, liver sausage, or offal. She received a blood transfusion prior to undergoing consecutive cycles of chemotherapy. In February 2010, she underwent hematopoietic stem cell transplantation with cells obtained from her brother. A standard screening protocol performed prior to the transplantation showed she was seropositive for HSV, CMV, varicella zoster virus (VZV), EBV, and T. gondii. Further virologic investigation revealed vaccine-derived immunity to HBV, but no evidence of HAV, HCV, or HIV. One month post-transplantation, in March 2010, CMV reactivated and was treated with consecutive antiviral agents (valacyclovir, foscavir, ganciclovir, and cidofovir). In May 2010, pathologic laboratory values were obtained for alanine aminotransferase (ALT; 544 IU/L), aspartate aminotransferase (259 IU/L), and gamma-glutamyltransferase (GGT; 92 IU/L). Findings from an abdominal ultrasound were negative. She underwent a liver biopsy, with histologic findings compatible with acute viral hepatitis. In September 2010, she developed CMV-ventriculitis, which was confirmed by magnetic resonance imaging and presence of viral DNA in cerebrospinal fluid, and was successfully treated with ganciclovir plus cidofovir.\nLiver function tests remained abnormal, and in November 2010, a serum test for HEV RNA was conducted, revealing a high viral load (>5×106 copies/mL). Thus, a diagnosis of HEV infection (genotype 3f) was made, and the patient was treated with ribavirin monotherapy. Serologic HEV testing (RecomWell Hepatitis IgG/IgM; Mikrogen GmbH, Neuried, Germany) remained negative. Although no serum samples were available to evaluate pretransplant serostatus, the hematopoietic stem cell donor was HEV-seronegative. The HEV viraemia remained stable (5×106 copies/mL) for several months. In February 2011, Aspergillus pneumonia with pleural effusion appeared, without hepatic involvement, which was treated with caspofungin plus amphotericin B. One week later, the patient became extremely confused and suffered from dizziness and reduced consciousness. Examination of a plasma sample showed 2,565 copies/mL of adenovirus in addition to the persistent, high HEV viral load (5×106 copies/mL), and a sample of cerebral spinal fluid was positive for HEV RNA (3,700 copies/mL); CMV, adenovirus, EBV, and Toxoplasma were excluded.\nThe patient died in March 2011 due to multiple organ failure. Based on the chronic (>3 months), high-level detection of HEV RNA and no reported recent travel to endemic areas, an autochthonous, chronic HEV infection was most likely. An alternative origin of infection, such as the ingestion of contaminated food during the post-transplant period or transplantation of contaminated cells or blood products could not fully be excluded. Furthermore, no remaining stem cell preparation (prepared in an external laboratory) could be tested for the presence of HEV RNA.