Are recipients of solid organ transplantation a high‐risk population for hepatitis E virus infection?

We read the articles by Kamar et al. and Haagsma et al. with interest. The authors reported for the first time a few cases of chronic hepatitis related to hepatitis E virus (HEV) infection in organ transplant recipients with progression to cirrhosis, and they suggested that these subjects could be long-term carriers of the infection. Hepatitis E infection typically causes acute hepatitis with spontaneous recovery in almost all cases. Very few cases have been associated with fulminant hepatitis. The disease predominates in developing countries with tropical or subtropical climates because HEV is mainly transmitted enterically through contaminated water. In industrialized countries, hepatitis E is considered an emerging disease formerly associated with travel to highly endemic regions. However, in the last few years, sporadic cases of HEV infection related to the spread of autochthonous viral strains have been detected, and this suggests a zoonotic transition from pigs. The potential risk of persistent HEV infection with chronic liver disease has been described in select clinical situations characterized by reduced immunocompetence, such as those induced by chemotherapy or immunosuppression. This possibility has not been widely analyzed because of the difficulties in establishing the diagnosis of HEV infection. Its diagnosis is limited by the lack of commercial assays for detecting HEV RNA and the lack of assays that are able to determine anti-HEV immunoglobulin M (IgM) antibodies. We recently reported a prevalence of anti-HEV immunoglobulin G (IgG) of 7.33% in healthy adults in Spain. There are no data regarding the frequency of anti-HEV antibodies in solid organ recipients in our area. Therefore, we tested for anti-HEV immunoglobulin antibodies in 108 serum samples from consecutive liver and kidney recipients who were controlled in our center between July and August 2008 and who had elevated alanine aminotransferase (ALT) levels greater than 1.5 times the upper normal limit. Among them, 71 (65.7%) were males with a mean age of 54.9 years (range: 1975). Eighty-two were liver recipients, 21 were renal transplant recipients, and 5 were dual-organ recipients. Serum samples positive for anti-HEV IgG were also tested for serum anti-HEV IgM and HEV RNA. Anti-HEV IgG and IgM were determined with immunoenzymatic assays (Bioelisa HEV IgG and Bioelisa HEV IgM, Biokit, Barcelona, Spain), and HEV RNA was determined by real-time polymerase chain reaction. Anti-HEV IgG antibodies were detected in only 3 solid organ recipients (2.7%). All 3 patients were liver recipients diagnosed with chronic hepatitis C, and they were negative for anti-HEV IgM and serum HEV RNA. Two were males (mean age: 65.9 years; range: 65-73), with a mean time after transplantation of 60.73 months (range: 19-94 months), and they had median ALT levels 1.9 times the normal values. Among patients without anti-HEV IgG antibodies, 69 (65.7%) were males, with a mean age of 54.5 years (range: 19-75), a mean time after transplantation of 47.49 months, and mean ALT levels 2.7 times the normal values. There were no statistically significant differences between the groups. Second serum samples from those 3 patients with anti-HEV IgG antibodies, obtained 6 months later, showed the persistence of these antibodies; the samples were negative for anti-HEV IgM and HEV-RNA, and an active HEV infection was ruled out. Our results showed similar frequencies of detection of anti-HEV IgG antibodies in the general population and in solid organ transplant recipients; the frequency was even lower in comparison with the anti-HEV IgG detection rate of 12% in the same age group in the general population. These results contradict previous reports from areas with a low rate of HEV prevalence suggesting that solid organ transplant recipients and even selected patients with abnormal ALT levels could be a risk population for HEV infection. A previous report from Spain found a higher prevalence of HEV antibodies neither in patients with hemophilia nor in patients on hemodialysis. Further studies are needed to determine the real prevalence of hepatitis E in transplant recipients and the possible causes of the epidemiological differences between regions in Europe.