Blood-borne Hepatitis E Virus Transmission: A Relevant Risk for Immunosuppressed Patients

T o the E ditor —The relevance of blood-borne hepatitis E virus (HEV) infections has been discussed controversially during recent months [ 1 ]. Despite 0.022% of blood products in Germany testing HEV RNA positive [ 2 ], HEV testing of blood products has still not been generally implemented [ 1 ]. Hereby we describe the course of 3 immunosuppressed individuals exposed to HEV by 1 HEV-positive blood donation (genotype 3). Patient 1 was a 33-year-old male stem cell transplant recipient who was diagnosed with chronic HEV infection (Figure 1A ). The patient had received an HEV-positive erythrocyte concentrate from an apparently healthy blood donor in whom retrospective testing revealed an occult HEV infection (alanine aminotransferase [ALT] level of 15 U/L, HEV viral load 10 5 IU/mL, anti-HEV immunoglobulin [IgG] positive). The erythrocyte concentrate contained a calculated HEV concentration of 8 × 10 5 IU/mL. The recipient's ALT levels strongly increased within 60 days after transfusion (Figure 1A ). Aminotransferases were interpreted as possible signs of graft-vs-host disease, as they occurred during tapering of immunosuppression. After termination of immunosuppression, aminotransferase levels remained elevated but stable. Subsequently, chronic HEV infection was diagnosed. Ribavirin therapy was initiated (800 mg/day), and HEV viral load decreased. Due to side effects (headache, weakness, nausea), the dose was reduced to 600 mg/day within 8 weeks. However, the patient stopped ribavirin treatment and a relapse of HEV occurred (initial 100 IU/mL, then 60 IU/mL). Course of alanine aminotransferase (ALT) levels, hepatitis E virus (HEV) viral load (VL), and anti-HEV immunoglobulin G (IgG) status in a stem cell transplant recipient ( A ) and a heart transplant recipient ( B ) chronically infected by 1 HEV-positive blood donation. Patient 2 was a 61-year-old woman with acute myeloid leukemia. She received a platelet transfusion prepared from pooled buffy coats enclosing 1 buffy coat from the HEV-infected donor (HEV concentration, 2.5 × 10 6 IU/mL). Stored serum samples of this patient tested negative for HEV RNA and positive for anti-HEV IgG 13 days before and 49 days after transfusion. Patient 3 was a 71-year-old male heart transplant recipient, who had been treated for rejection with a plasma product containing 3 × 10 7 IU/mL HEV (immunosuppressants: cyclosporine and mycophenolate). The ALT level increased within 54 days after transfusion and normalized within 3 months. This compromised patient presented fluctuating HEV concentrations (Figure 1B ) without HEV clearance. Due to risk factors (creatinine value >3.5 mg/dL, hemoglobin <9 g/dL, repeated rejection episodes), we decided against ribavirin treatment and opted to observe the further course of the disease. One HEV-infected blood donor with normal aminotransferase levels and without apparent symptoms can be a source of HEV infection in immunosuppressed individuals. To date, HEV testing of blood products is not mandatory. In line with a recently published report about a kidney transplant recipient infected by an HEV-positive plasma product [ 3 ], we recommend testing of blood products administered to immunosuppressed individuals. Patient 1 demonstrated that HEV infection established under immunosuppression in stem cell transplant recipients may persist even after immunosuppressive medication is stopped. This observation is in line with a recent report depicting that chronic HEV infection persisted in an human immunodeficiency virus patient despite restoration of his immunostatus [ 4 ]. The incubation period for HEV infection (genotype 3) in immunosuppressed individuals with blood-borne HEV infection has never been determined. We observed an interval between 50 and 60 days following transfusion, while an incubation period of <30 days has been described for immunocompetent individuals infected with genotype 1 [ 5 ]. In allogeneic stem cell transplant patients, an increase in ALT may coincide with tapering of immunosuppression and thus mimic graft-vs-host disease. Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.