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 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 evidence supporting the notion that autochthonous HEV infections 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 .
Our patient was referred to the department of gastroenterology 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 infection ; second, the detection of specific HEV antibodies by enzyme-linked immunosorbent assay and immunoblot; and, third, the direct detection of virus-specific RNA by reverse transcription-quantitative polymerase chain reaction. Virus genotyping and subgenotyping 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 , our patient was questioned about his alimentary 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 prolonged 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 . In our case, rituximab therapy was stopped because of severe fatigue and increased susceptibility to infections. Consequently, our patient’s lymphocyte count in the blood increased from 0.8/nL at the time of referral to 9.4/nL at month 7. This may be interpreted as an indicator of a simultaneous immune reconstitution and thus could explain the quick spontaneous clearance of the HEV infection and hepatitis between months 7 and 8.
Notably, severe complications have also been observed in patients with HEV infection after liver transplantation. In a recently published case, undetected HEV infection in a liver transplant donor actually caused chronic HEV and cirrhosis in the recipient . In addition to acute and chronic HEV infections in patients with hematological malignancies [3, 5], patients with HIV have been reported with chronic HEV .
In our patient, antiviral treatment was not initiated, because of the spontaneous recovery after immune reconstitution. However, beyond reduction of immunosuppressive therapy, treatment with ribavirin for at least 3 months seems to be the first treatment option for patients with chronic HEV, even though data are still limited .