Hepatitis E virus: an underestimated opportunistic pathogen in recipients of allogeneic hematopoietic stem cell transplantation

Abstract

Key Points• The incidence of acute HEV infection after alloHSCT is relatively low, in contrast to a high probability of developing chronic hepatitis.• HEV infection or reactivation should be included in the differential diagnosis of liver enzyme abnormalities in alloHSCT recipients.Hepatitis E virus (HEV) is increasingly acknowledged as a cause of hepatitis in healthy individuals as well as immunocompromised patients. Little is known of HEV infection in recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT). Therefore, we set out to study the incidence and sequelae of HEV as a cause of hepatitis in a recent cohort of 328 alloHSCT recipients. HEV RNA was tested in episodes of liver enzyme abnormalities. In addition, HEV RNA and HEV serology were assessed pre-and postalloHSCT. We found 8 cases (2.4%) of HEV infection, of which 5 had developed chronic HEV infection. Seroprevalence pre-alloHSCT was 13%. Four patients died with HEV viremia, with signs of ongoing hepatitis, having a median time of infection of 4.1 months. The 4 surviving patients cleared HEV after a median period of 6.3 months. One patient was diagnosed with HEV reactivation after a preceding infection prior to alloHSCT. Although the incidence of developing acute HEV post-alloHSCT is relatively low, the probability of developing chronic hepatitis in severely immunocompromised patients is high. Therefore, alloHSCT recipients should be screened pretransplantation by HEV serology and RNA. Furthermore, a differential diagnosis including hepatitis E is mandatory in all alloHSCT patients with severe liver enzyme abnormalities. (Blood. 2013;122(6):1079-1086

Hepatitis E virus infection in a hematopoietic stem cell donor

“…1 Versluis et al 2 recently studied the incidence and course of HEV-infection in a large cohort of patients undergoing allogeneic hematopoietic SCT (HSCT). In contrast to previously published studies from our group 3 and others, 4 they identified a considerable number of patients with chronic HEV infection with a significant lethality.…”

Hepatitis E Virus (HEV) Genotype 3 Infection of Human Liver Chimeric Mice as a Model for Chronic HEV Infection

“…Since no animal model for chronic HEV infection is available, we examined the infectivity of HEV gt3 samples of different clinical origins in the humanized liver urokinase-type plasminogen activator (uPA) transgenic mouse model on a severely immunodeficient NOD/Shi-scid/IL-2R␥ null background (uPA-NOG) and compared this to the established adenocarcinoma human alveolar basal epithelial cells (A549) culture system (19)(20)(21)(22). We demonstrate that in vitro infectivity differences of feces-, liver-, and plasma-derived HEV are paralleled in vivo.…”

Hepatitis E virus infection

“…In both studies, ongoing HEV infection was absent. Prior to allogeneic stem cell transplantation, Versluis et al recently reported an anti-HEV IgG prevalence of 13% (287). HEV RNA was found in 8 of 328 stem cell transplant patients (2.4%) (287), and 5 patients developed chronic hepatitis (287).…”

“…Case reports of chronic HEV infection in hematological patients include a patient with myeloma who required a stem cell transplant (284), a child with HEV-associated cirrhosis following bone marrow transplantation (288), and a case of HEV reactivation in a patient with acute lymphoblastic leukemia after allogeneic stem cell transplantation (289). Very recently, another case of HEV reactivation was suspected in a hematological patient (287), but no HEV reactivation was seen in a study from France (286). There are still some unresolved questions in the setting of stem cell transplantation, i.e., should all patients undergoing stem cell transplantation be screened for HEV RNA, especially if liver enzyme levels are increased?…”

“…Prior to allogeneic stem cell transplantation, Versluis et al recently reported an anti-HEV IgG prevalence of 13% (287). HEV RNA was found in 8 of 328 stem cell transplant patients (2.4%) (287), and 5 patients developed chronic hepatitis (287). Case reports of chronic HEV infection in hematological patients include a patient with myeloma who required a stem cell transplant (284), a child with HEV-associated cirrhosis following bone marrow transplantation (288), and a case of HEV reactivation in a patient with acute lymphoblastic leukemia after allogeneic stem cell transplantation (289).…”