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.
A 22-year old male patient had been treated with eculizumab from 2013 to 2015 for two years followed by RTX due to an atypical hemolytic-uremic syndrome and immune thrombocytopenia. RTX was administered from May to June 2015 (three cycles). In the following years, the patient suffered from recurrent infections including several episodes of bacterial bloodstream infections. A severe immunoglobulin deficiency was diagnosed and the patient was treated with intravenous immunoglobulin G substitutions. The patient also received long-term treatment with corticosteroids. Elevated aminotransferases were noticed from the end of 2015. In September 2017, he was admitted to our intensive care unit with a septic shock caused by an abscess in the left axilla. During recovery from the sepsis, jaundice was noticed and HEV RNA was detected in his blood (413 mio copies/mL) and feces. RBV therapy was initiated at a reduced dose of 200 mg/d due to his impaired renal function and was subsequently reduced to 200 mg three times per week. In the further course, RBV treatment was increased to a dose of 200–400 mg/d but had to be terminated after 4.5 months due to severe anemia and leukopenia. HEV replication remained continuously detectable throughout the complete RBV treatment period, confirming non-response in this patient.