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 46-year-old Caucasian man who worked as a mechanic was transferred to the gastroenterology out-patient clinic by the department of hematology, where he was regularly treated for B-CLL. The reason for the visit was a continuous increase of transaminases over the previous 7 months (months 0 to 7). The patient reported persistent exhaustion and occasional right-side abdominal pain. B-CLL had been diagnosed 4 years earlier (initially Binet stage B; actual blood cell counts: leukocytes 13.6/nL, thrombocytes 224/nL, and hemoglobin 16.3g/dL). Owing to increasing night sweats and compression of the urinary bladder by lymphomas 2 years earlier (leukocyte count 61/nL), he was treated with rituximab, pentostatin, and cyclophosphamide for 3 months, resulting in partial remission. Maintenance therapy was performed by using rituximab and was finally abandoned in month 4 of increased transaminases because of severe fatigue and susceptibility to infections, after which the patient took no medication. At the time of referral to our department, the patient was in stable partial remission and B symptoms were absent. He had no history of recent travels to countries outside Germany, contact with animals, or consumption of venison, liver sausage, or offal. He had not received a blood transfusion prior to the infection.\nNormal alanine transaminase (ALT) was documented in our patient until 10 months prior to his admission to the gastroenterology department. No ALT results are available in the 3-month interval from 10 months until 7 months prior to his transfer to the department of gastroenterology. Therefore, there is a 3-month window during which the first increase of transaminases must have occurred. An elevated ALT concentration of 234U/L was first detected 7 months before referral to the department of gastroenterology (the month of referral is denoted as “month 0”). After the initial discovery of increased transaminases, moderate fluctuating transaminitis – month 1: aspartate transaminase (AST) 61U/L, ALT 139U/L; month 3: AST 108U/L, ALT 220U/L; month 5: AST 142U/L, ALT 337U/L; and month 6: AST 161U/L, ALT 408U/L – was observed. Bilirubin concentrations were repeatedly within the reference interval. A diagnostic workup ruled out autoimmune and metabolic liver disease, hepatitis A-C, and herpes virus infection. A physical examination revealed enlarged axillary lymph nodes. The results of an abdominal ultrasound examination were otherwise unremarkable. Finally, HEV was diagnosed in a blood sample by detection of anti-HEV antibodies and HEV RNA (month 7: 3.0×105 copies/mL). Retrospectively, the presence of HEV RNA in serum was confirmed in two earlier samples (month 0: 2.0×107 copies/mL and month 6: 1.0×107 copies/mL). Samples from earlier visits were not available for analysis. Figure shows ALT concentrations, HEV viral load, and phases of immunosuppressive therapy over time. Sequence determination and phylogenetic analysis revealed a novel HEV genotype 3 strain clustering with other European subgenotype 3c isolates (Figure ).\nLaboratory analyses ordered 10 days after referral to our department showed that transaminases had rapidly decreased to concentrations within the reference intervals without therapeutic intervention (Figure ). Four weeks later (month 8), our patient was seen again in the department of hematology; transaminase concentrations were still normal, and HEV-RNA was not detectable from blood. Thus, it may be concluded that HEV infection was spontaneously cleared 7 to 8 months after the first referral. Lymphocyte counts in our patient’s blood were 0.8/nL at month 0, 0.7/nL at month 6, 9.4/nL at month 7, and 1.4/nL at month 8.