Chronic hepatitis E virus (HEV) infection is nowadays an accepted cause of chronic liver disease in immunocompromised individuals.1 Although that first series from Kamal et al. focused on solid-organ transplant recipients in 2008,2 there is increasing evidence of the risk of chronic hepatitis E in patients with other sources of immune impairment such as hematopoietic stem cell transplantation,3 human immunodeficiency virus (HIV) infection4, 5 or even underlying liver disease,6, 7 the latter especially in the context of unexplained alanine aminotransferase (ALT) flares.1

The importance of chronic hepatitis E lies in the rapid development of liver fibrosis and progression to cirrhosis due to the immune dysfunction of these patients.8 Screening of chronic hepatitis E in immunocompromised patients with normal transaminases levels has shown an extremely low performance,9 and for this reason it is not systematically recommended.1

Overall, the prevalence of antibodies against hepatitis E in the blood banks throughout Europe range from 5% to 25%.10 The HEV seroprevalence may be influenced by many factors such as geographical region, the assay employed and the individual's age. However, to date, prevalence of chronic hepatitis E defined by persistent HEV viraemia for more than 3–6 months remains unknown. Preliminary data from a cross-sectional cohort in the United Kingdom in transplant patients receiving tacrolimus has shown an overall HEV-RNA prevalence of 0.67%, ranging from 0.6% in solid-organ to 2.1% among stem cell transplant recipients, though all individuals on tacrolimus were tested, regardless of the ALT levels.11

Concerning risk factors for chronic hepatitis E, it is well-known that the deeper the immunosuppression, the higher the risk of chronicity.2, 12 Nevertheless, data on predisposing factors associated with increased risk of chronic infection are scarce and usually based on retrospective cohorts of solid-organ transplant patients.13 Most commonly reported factors linked to augmented rate of chronic hepatitis E are the use of tacrolimus and time from the transplant.2, 13 Recently, Cornberg et al. reported the experience of Sofosbuvir monotherapy for the treatment of chronic hepatitis E in a small number of cases.14 Although no patient achieved undetectable HEV-RNA at the end of therapy, it seems that those on mammalian target of rapamycin (mTOR) inhibitors presented a weaker antiviral response, as previously shown in in vitro studies.15, 16

Our multicenter prospective study, entitled CHES (Chronic Hepatitis E Screening in patients with immune impairment) aimed to assess the prevalence of chronic hepatitis E among subjects with immune dysfunction and persistently elevated transaminases, and to identify risk factors for chronic HEV infection.