IntroductionThe hepatitis E virus (HEV) represents an important cause of viral hepatitis and could cause chronic infections in immunocompromised patients. However, data about immunocompromised patients other than solid organ transplant recipients are limited.MethodsWe identified patients from a laboratory database and retrospectively compiled and analyzed clinical as well as laboratory data in detail.ResultsOverall, 22 severely immunosuppressed patients, excluding solid organ transplant recipients, were identified. Four patients did not experience viral clearance (one without and three despite ribavirin therapy). Three patients acquired the infection after allogeneic hematopoietic stem cell transplantation (alloHSCT) and recovered spontaneously, whereas another patient, infected prior to alloHSCT, developed a chronic infection. Four patients failed to clear HEV, resulting in fatal liver failure in two patients. The CD4+ cell counts increased in all but one patient attaining a sustained virological response (SVR), as compared to patients with clinical failure. Severe immunoglobulin deficiency did not appear to obviate the control of HEV. Six of ten (60%) patients with and nine of twelve (75%) patients without ribavirin therapy achieved a SVR.ConclusionsUpfront ribavirin therapy does not appear mandatory in patients without CD4+ lymphopenia, but a prolonged HEV-replication carries the risk of liver failure. Our data suggest that chronic HEV-infections could cause T-cell exhaustion, which might be overruled with ribavirin therapy.