Gauss et al. Journal of Medical Case Reports 2012, 6:334 http://www.jmedicalcasereports.com/content/6/1/334 Germany, contact with animals, or consumption of ven- ison, liver sausage, or offal. He had not received a blood transfusion prior to the infection. Normal 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 gastro- enterology. Therefore, there is a 3-month window during which the first increase of transaminases must have oc- curred. 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 trans- aminases, 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 dis- ease, hepatitis A-C, and herpes virus infection. A phys- ical examination revealed enlarged axillary lymph nodes. The results of an abdominal ultrasound examination were otherwise unremarkable. Finally, HEV was diag- nosed in a blood sample by detection of anti-HEV anti- bodies 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 cop- ies/mL and month 6: 1.0×107 copies/mL). Samples from earlier visits were not available for analysis. Figure 1 shows ALT concentrations, HEV viral load, and phases of immunosuppressive therapy over time. Sequence de- termination and phylogenetic analysis revealed a novel HEV genotype 3 strain clustering with other European subgenotype 3c isolates (Figure 2). Laboratory analyses ordered 10 days after referral to our department showed that transaminases had rapidly decreased to concentrations within the reference inter- vals without therapeutic intervention (Figure 1). 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 infec- tion 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. Discussion In this case report, our patient is a man from southern Germany with chronic autochthonous HEV infection. In industrialized countries, HEV is generally perceived as an imported disease, and travel to endemic regions is considered Page 3 of 5 the primary risk factor. The disease is endemic in many countries in Asia and Africa and occurs both in sporadic forms and in waterborne outbreaks. However, recent evi- dence supporting the notion that autochthonous HEV infec- tions are also widespread in many industrialized countries has accumulated. Phylogenetic analyses have shown that HEV genotype 1 is responsible for the majority of cases in developing countries, whereas the prevalent HEV genotype in Europe and North America is genotype 3 [10]. Our patient was referred to the department of gastro- enterology with hepatitis of unknown origin. During a diagnostic workup, HEV was identified as the underlying disease. The diagnosis was based on three factors: first, a moderate fluctuating transaminitis with an ALT ranging from 61 to 408U/L, a typical pattern in chronic HEV in- fection [14]; second, the detection of specific HEV anti- bodies by enzyme-linked immunosorbent assay and immunoblot; and, third, the direct detection of virus- specific RNA by reverse transcription-quantitative poly- merase chain reaction. Virus genotyping and subgenotyp- ing were performed by sequencing and in silico phylogenetic analysis and revealed HEV subgenotype 3c. HEV RNA was detectable in three serum samples taken over an 8-month period. Thus, our patient tested positive for HEV RNA for more than 6 months, and this fits the definition of chronic HEV infection. In the course of an acute HEV infection, the highest level of viral nucleic acid in the blood is present before the occurrence of the first clinical symptoms and then rapidly declines in immunocompetent patients. After the onset of clinical symptoms, HEV RNA is usually detectable by polymerase chain reaction for only 14 to 28 days from blood, plasma, or serum. HEV genotype 3 has been reported for non- travel-associated infections in industrialized countries. Interestingly, a sequence database search revealed several closely related HEV sequences derived from swine as well as from humans in different European countries. In light of these findings and a recent report on the detection of HEV in porcine livers sold as food in southeastern Germany [3], our patient was questioned about his ali- mentary habits. However, ingestion of raw meat or offal and contact with animals (including pigs) were denied. Thus, the source of infection and mode of transmission remain unclear. Several reports in the literature suggest that patients under immunosuppression are at increased risk of acquiring autochthonous HEV infection with pro- longed viral replication and potentially severe clinical consequences. Our patient had received therapy with anti- CD20 antibodies, pentostatin, and cyclophosphamide for his hematological malignancy. It is tempting to speculate that the chronic course of his HEV infection was, in fact, fueled by his therapeutically induced immunosuppression. The first step in treating patients with chronic infections is to reduce or stop immunosuppressive agents [14]. In