D. Westhölter

HEV-positive blood donations represent a relevant infection risk for immunosuppressed recipients

BACKGROUND & AIMS Routine HEV testing of blood products has recently been implemented in Great Britain and the Netherlands. The relevance of transfusion-transmitted HEV infections is still controversially discussed in Europe. METHODS All blood donations at the University Medical Center Hamburg-Eppendorf were prospectively tested for HEV RNA by pooled PCR from October 2016 to May 2017. Reactive samples were individually retested. Additionally, stored samples from previous donations of positive donors were tested to determine the duration of HEV viraemia. HEV RNA-positive donors and a control cohort were asked to answer a questionnaire. RESULTS Twenty-three out of 18,737 HEV RNA-positive donors were identified (0.12%). Only two of the positive donors (8.7%) presented with elevated aminotransferases at time of donation (alanine aminotransferase: 192 and 101 U/L). The retrospective analysis of all positive donors revealed that four asymptomatic donors had been HEV viraemic for up to three months with the longest duration of HEV viraemia exceeding four months. Despite the HEV-testing efforts, 14 HEV RNA-positive blood products were transfused into 12 immunocompromised and two immunocompetent patients. One recipient of these products developed fatal acute-on-chronic liver failure complicated by Pseudomonas septicemia. The questionnaire revealed that HEV RNA-positive donors significantly more often consumed raw pork meat (12 out of 18; 67%) than controls (89 out of 256; 35%; p = 0.01). In two donors, undercooked pork liver dishes were identified as the source of infection. HEV genotyping was possible in 7 out of 23 of HEV viraemic donors and six out of seven isolates belonged to HEV Genotype 3, Group 2. CONCLUSIONS Prolonged HEV viraemia can be detected at a relatively high rate in Northern German blood donors, leading to transfusion-transmitted HEV infections in several patients with the risk of severe and fatal complications. Eating raw pork tartare represented a relevant risk for the acquisition of HEV infection. LAY SUMMARY The relevance of transfusion-transmitted hepatitis E virus infections has been discussed controversially. Herein, we present the first report on routine hepatitis E virus screening of blood donations at a tertiary care centre in Germany. Hepatitis E viraemia was found at a relatively high rate of 0.12% among blood donors, which represents a relevant transfusion-related risk for vulnerable patient populations.

Lack of evidence for human serum albumin as major source of HEV infections: Letter to the Editor

Dear Sir, We read with interest the recent article by Juhl et al., regarding transmission of the hepatitis E virus (HEV) by coagulation factor concentrates (Juhl et al., 2017). Based on seroprevalence data, the authors interpret their results as evidence that HEV is efficiently inactivated during the manufacturing process of coagulation factor concentrates. In our region, HEV genotype 3 infections can be acquired autochthonously (Hoofnagle et al., 2012). The most relevant sources of transmission are swine contact and consumption of undercooked swine meat. Individuals in contact with swine have a two-fold increased risk for anti-HEV positivity compared to healthy controls (blood donors without swine contact) (Krumbholz et al., 2012). Within the last few years, blood products have been identified as a relevant source of HEV transmission. Transmission via blood products is assumed to be less frequent compared to transmission via swine consumption. However, detailed epidemiological data are still lacking. Recently, we demonstrated, in a large cohort of almost 19·000 blood donations, that approximately 1/1000 blood donations in Germany tested positive for positive by polymerase chain reaction (PCR) (Westholter et al., 2018). Therefore, in our opinion, it is crucial to further investigate other products derived from blood donations as potential source of infection: Human serum albumin (HSA) is a product manufactured from mixed pools of plasma donations (1000 to 1660 L) of several thousands of donors (Horowitz et al., 2004). Human albumin is usually administered to patients with liver cirrhosis and refractory ascites (8 g L−1 of removed ascites) (EASL, 2010). Some of these patients develop acute-on-chronic liver failure, with potentially fatal outcomes. It still needs to be determined if HEV infection transmitted by HSA infusions can play a role in this context, perhaps as a trigger or additional hit. In 2015, in a British/French study of 343 patients with decompensated chronic liver disease demonstrated, it was found that 11 patients (3·2%) had acute hepatitis E, and 3 of these 11 died (Blasco-Perrin et al., 2015). How many of these patients received albumin, and whether this could have been their source of infection, is unknown. As HSA is a product derived from pooled human plasma, it represents a potential source of HEV transmission.

Hepatitis E seroprevalence in the Americas: A systematic review and meta-analysis

While hepatitis E virus infections are a relevant topic in Europe, knowledge about epidemiology of hepatitis E virus infections in the USA and Latin America is still limited. Aim of this study was to estimate anti‐hepatitis E virus IgG seroprevalence in the Americas and to assess whether low socioeconomic status is associated with hepatitis E virus exposure.

Course of HEV viremia and anti-HEV IgM/IgG response in asymptomatic blood donors

BACKGROUND Globally, an estimated 20 million Hepatitis E infections occur every year. The course of viremia and antibody response has been investigated in patients with symptomatic hepatitis E. However, the majority of HEV infections in industrialized countries take a subclinical course. OBJECTIVES To investigate the course of HEV viremia and epitope specific anti-HEV IgM/IgG response in asymptomatic blood donors in order to understand the immune response and viral clearance in asymptomatic blood donors with HEV infections. METHODS In this study 27 HEV viremic donors were identified by HEV-PCR during routine screening of blood donors and the course of anti-HEV IgM/IgG and HEV-RNA was retrospectively studied using RT-PCR and a commercial immunoblot (Mikrogen®) allowing classification of the antibody response according to HEV epitopes. RESULTS At time of donation, serological testing failed to identify viremic donors as 70.4% had no detectable antibody response. Anti-HEV IgM could be detected in 22.2% of viremic donors while anti-HEV IgG could be found in 7.4%. At least three donors experienced prolonged viremia beyond 100 days. Spontaneous HEV-RNA clearance within a median time span of 57 days was observed in all 27 donors. In all donors anti-HEV IgG specific for the immunogenic viral epitope O2C could be detected in close temporal association with viral clearance. CONCLUSION Serological testing is inappropriate for identifying HEV-viremic blood donors. Acute HEV infection in asymptomatic blood donors can persist for more than 100 days. HEV-RNA clearance coincided with the appearance of anti-HEV IgM/IgG confirming the importance of a B-cell mediated response in clearing acute infections. Anti-HEV IgM and IgG specific for the epitope O2C are associated with the clearance of HEV-viremia.

Hepatitis E: Still Waters Run Deep

Abstract Hepatitis E is an infectious inflammatory disease of the liver caused by the hepatitis E virus (HEV), a single-stranded RNA virus. Today, it is estimated that there are more than 20 million HEV infections every year, leading to 3.3 million symptomatic cases and more than 56,000 deaths. For a long time it was believed that HEV was a travel-associated disease, endemic in developing countries with poor hygienic standards and unsafe water supply. However, over the past years, publications have demonstrated that autochthonous HEV infections in industrialized countries are far more common than previously thought. Awareness for HEV amongst health care practitioners in industrialized countries is still limited. This relatively rare disease is of great importance, especially in immunocompromised patients where it can cause chronic liver disease. This article comprehensively reviews current literature to give an overview on clinically important topics. It will focus on epidemiological aspects, acute and chronic HEV infection as well as extra-hepatic manifestations, diagnostic approach and treatment options. Furthermore, the article is concluded with a brief outlook on perspectives and urgent problems to be addressed in the future.