Transfusion-transmitted Hepatitis E Virus Research Articles

HEV in Blood Donors in Switzerland: The Route to Safe Blood Products.

The hepatitis E virus (HEV) is an emerging infectious disease with zoonotic potential, causing acute hepatitis in humans. Infections in healthy individuals are often acute, self-limiting and asymptomatic, thus leading to the underdiagnosis of HEV infections. Asymptomatic HEV infections pose a problem for blood transfusion safety by increasing the risk for transfusion-transmitted HEV infections. Here, we describe the journey from determining the HEV seroprevalence among blood donors to the implementation of routine HEV RNA testing of all blood products in Switzerland in 2018 and summarise the HEV cases detected since. In total, 290 HEV-positive blood donations were detected by mini-pool nucleic acid testing (NAT) in Switzerland in the period of October 2018-December 2023, equal to an incidence of 20.7 per 100,000 donations. Thanks to the implemented scheme, no transfusion-transmitted infections occurred in this period. Furthermore, blood donation monitoring has proven to be an effective means of detecting HEV outbreaks in the general population. HEV cases in Swiss blood donors are caused by two major genotypes, the Swiss-endemic subtypes 3h3 and 3c. Interestingly, 11 HEV cases (5%) were of genotype 3ra, a variant found in wild and farmed rabbits. Our results indicate that mini-pool NAT is an efficient method to reduce the risk of transfusion-transmitted HEV infections.

Hepatitis E Virus Infection in Voluntary Blood Donors in the Russian Federation.

Transfusion-transmitted hepatitis E virus (HEV) infection is an increasing concern in many countries. We investigated the detection rate of HEV viremia in blood donors in Russia. A total of 20,405 regular repetitive voluntary non-renumerated blood donors from two regions (Moscow and Belgorod) were screened for HEV RNA using the cobas® HEV test in mini-pools of six plasma samples. Samples from each reactive pool were tested individually. The average HEV RNA prevalence was 0.024% (95% CI: 0.01-0.05%), or 1 case per 4081 donations. No statistically significant differences in HEV RNA prevalence were observed between the two study regions. The PCR threshold cycle (Ct) values ranged from 25.0 to 40.5 in reactive pools, and from 20.9 to 41.4 in reactive plasma samples when tested individually. The HEV viremic donors had different antibody patterns. Two donor samples were reactive for both anti-HEV IgM and IgG antibodies, one sample was reactive for anti-HEV IgM and negative for anti-HEV IgG, and two samples were seronegative. At follow-up testing 6 months later, on average, four donors available for follow-up had become negative for HEV RNA and positive for anti-HEV IgG. The HEV ORF2 sequence belonging to HEV-3 sub-genotype 3a was obtained from one donor sample. The sequencing failed in the other four samples from viremic donors, presumably due to the low viral load. In conclusion, the HEV RNA detection rate in blood donors in Russia corresponds with data from other European countries, including those that implemented universal donor HEV screening. These data support the implementation of HEV RNA donor screening to reduce the risk of transfusion-transmitted HEV infection in Russia.

High Hepatitis E Virus (HEV) Seroprevalence and No Evidence of HEV Viraemia in Vietnamese Blood Donors.

The prevalence of hepatitis E virus (HEV) in the Vietnamese population remains underestimated. The aim of the present study was to investigate the seroprevalence of HEV IgG/IgM antibodies and the presence of HEV RNA in blood donors as a part of epidemiological surveillance for transfusion-transmitted viruses. Serum samples from blood donors (n = 553) were analysed for markers of past (anti-HEV IgG) and recent/ongoing (anti-HEV IgM) HEV infections. In addition, all serum samples were subsequently tested for HEV RNA positivity. The overall prevalence of anti-HEV IgG was 26.8% (n = 148/553), while the seroprevalence of anti-HEV IgM was 0.5% (n = 3/553). Anti-HEV IgG seroprevalence in male and female donors was similar (27.1% and 25.5%, respectively). A higher risk of hepatitis E exposure was observed with increasing age. None of the blood donors were HEV RNA positive, and there was no evidence of HEV viraemia. Although the absence of HEV viraemia in blood donors from Northern Vietnam is encouraging, further epidemiological surveillance in other geographical regions is warranted to rule out transfusion-transmitted HEV.

Seven years (2015-2021) of blood donor screening for HEV-RNA in France: lessons and perspectives.

The French health authorities are considering expanding the current selective HEV-RNA testing procedure to include all donations in order to further reduce transfusion-transmitted HEV infection. Data obtained from blood donors (BDs) tested for HEV-RNA between 2015 and 2021 were used to assess the most efficient nucleic acid testing (NAT) strategy. Viral loads (VLs) and the plasma volume of blood components, as well as an HEV-RNA dose of 3.85 log IU as the infectious threshold and an assay with a 95% limit of detection (LOD) at 17 IU/mL, were used to assess the proportion of: (i) HEV-RNA-positive BDs that would remain undetected; and (ii) blood components associated with these undetected BDs with an HEV-RNA dose >3.85 log IU, considering 4 NAT options (Individual testing [ID], MP-6, MP-12, and MP-24). Of the 510,118 BDs collected during the study period, 510 (0.10%) were HEV-RNA-positive. Based on measurable VLs available in 388 cases, 1%, 15.2%, 21.8%, and 32.6% of BDs would theoretically pass undetected due to a VL below the LOD of ID, MP-6, MP-12, and MP-24 testing, respectively. All BDs associated with a potentially infectious blood component would be detected with ID-NAT while 13% of them would be undetected with MP-6, 19.6% with MP-12, and 30.4% with MP-24 depending on the plasma volume. No red blood cell (RBC) components with an HEV-RNA dose >3.85 log IU would enter the blood supply, regardless of the NAT strategy used. A highly sensitive ID-NAT would ensure maximum safety. However, an MP-based strategy can be considered given that: (i) the risk of transmission is closely related to the plasma volume of blood components; (ii) RBC are the most commonly transfused components and have a low plasma content; and (iii) HEV-RNA doses transmitting infection exceed 4 log IU. To minimise the potential risk associated with apheresis platelet components and fresh frozen plasma, less than 12 donations should be pooled using an NAT assay with a LOD of approximately 20 IU/mL.

Transfusion-transmitted hepatitis E: What we know so far?

Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. There is growing concern about transfusion-transmitted HEV (TT-HEV) as an emerging global health problem. HEV can potentially result in chronic infection in immunocompromised patients, leading to a higher risk of liver cirrhosis and even death. Between 0.0013% and 0.281% of asymptomatic blood donors around the world have HEV viremia, and 0.27% to 60.5% have anti-HEV immunoglobulin G. HEV is infectious even at very low blood concentrations of the virus. Immunosuppressed patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced; ribavirin may be considered as treatment. Pegylated interferon can be considered in those who are refractory or intolerant to ribavirin. Sofosbuvir, a nucleotide analog, showed modest antiviral activity in some clinical studies but sustained viral response was not achieved. Therefore, rescue treatment remains an unmet need. The need for HEV screening of all blood donations remains controversial. Universal screening has been adopted in some countries after consideration of risk and resource availability. Various pathogen reduction methods have also been proposed to reduce the risk of TT-HEV. Future studies are needed to define the incidence of transmission through transfusion, their clinical features, outcomes and prognosis.

Effect of Hepatitis E Virus RNA Universal Blood Donor Screening, Catalonia, Spain, 2017‒2020.

Hepatitis E virus (HEV) is the major cause of acute viral hepatitis in several countries in Europe. HEV is acquired mainly by consumption of contaminated pork but can also be transmitted through blood transfusion. HEV infection is usually self-limited but can become persistent in immunocompromised persons. During the first 30 months of HEV RNA universal screening of blood donations in Catalonia, Spain, we identified 151 HEV RNA–positive donations (1/4,341 blood donations). Most infected donors reported consumption of pates and sausages, and 58% were negative for HEV IgM and IgG. All HEV isolates belonged to genotype 3. All infected donors spontaneously resolved the infection, and no neurologic symptoms and reinfections were observed after 1 year of follow-up. Since the implementation of HEV RNA universal screening, no new cases of transfusion-transmitted HEV infection were reported. Our data indicate HEV screening of blood donations provides safer blood for all recipients, especially for immunosuppressed persons.

Hepatitis E virus seroprevalence and awareness about feco-oral transmission in blood donors at a single center in Puducherry

<b>INTRODUCTION:</b> Asymptomatic hepatitis E virus (HEV) infections have been found in blood donors. Posttransfusion hepatitis E has been reported and raises concern due to cases of HEV-related mortality in patients with underlying cirrhosis or immunocompromised patients. This study aimed to determine the seroprevalence of HEV-associated sociodemographic parameters, awareness about feco-oral transmitted diseases among healthy blood donors attending a tertiary care teaching hospital blood center. <b>MATERIALS AND METHODS:</b> This was a cross-sectional study done for 1 year from January 2019 to January 2020. Our study included a sample size of 920 blood donors attending for donation at a single center. All the samples were tested using HEV IgM kit with the antigen used for coating were four synthetic peptides with conservative epitopes of ORF2 and ORF3 in genotypes 1, 2, 3, and 4. An open-ended questionnaire regarding awareness of the feco-oral transmission of diseases was administered; data regarding clinical, epidemiological, and demographic characteristics were collected from the donors by a structured data collection proforma. The responses were recorded. <b>RESULTS:</b> Our study results showed a seroprevalence of 1.41%. All the reactive donors were asymptomatic during our routine screening procedures. Most of the donors (457 donors), i.e., 49.7%, belonged to the lower middle class; the mean age of the study population was 28.6 years (standard deviation 8.9). <b>CONCLUSION:</b> This study reflects the burden of HEV in the local population, and this result can be considered a preliminary step in quantifying the risk of transfusion-transmitted HEV. Cost-effectiveness in implementing HEV screening as a part of routine TTI screening to be considered.

Hepatitis E: An update on One Health and clinical medicine.

The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV-related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV-1 to HEV-8) with different human and animal hosts and other HEV-related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food-borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre-existing liver disease and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy, Guillain-Barré syndrome and encephalitis, renal injury and haematological disorders. The risk of transfusion-transmitted HEV is increasingly recognized in Western countries where the risk may be because of a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion-transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.

Emerging infectious disease and transfusion-transmitted infection

Hepatitis B, hepatitis C and HIV infections are well-known infectious diseases caused by blood products, but recently there have been almost no reports. In 2011, hepatitis E virus (HEV) antibody test was covered by insurance in Japan, and certain numbers of transfusion-transmitted HEV were reported, and five cases were recognized in 2019. As the Japanese Red Cross has started to examine individual NAT of HEV for all blood donors since August 2020, and the number of transfusion-transmitted HEV will decrease. In addition, Trypanosoma cruzi antibody test for selective blood donors has been examined since August 2016, and the risk of Chagas disease infection by blood transfusion will be decreased. In the future, it is important for protecting against the transfusion-transmitted infection to inspect bacterial tests and know the information of emerging infectious disease occurring overseas. When the emerging infectious diseases such as DENV (dengue virus), WNV (West Nile virus), Zika (Zika virus) and CHIKV (chikungunya virus) occur in Japan, it is necessary to stimulate countermeasures and prepare what kind of tests should be performed for blood donors or criteria for blood donation.

Seroprevalence of hepatitis E virus in Argentinean blood donors.

Hepatitis E virus (HEV) is the main cause of enteric acute viral hepatitis worldwide. In this epidemiological framework, it has become a threat to blood safety and a relevant issue for blood transfusions. However, there is a paucity of data regarding prevalence of HEV infection. The aim of this study was to determine HEV seroprevalence in blood donors from different regions from Argentina. Serum samples from 391 individuals attending five blood donor centers located in different regions from Argentina were analyzed for anti-HEV IgG and anti-HEV IgM. Overall, anti-HEV IgG was detected in 44 out of 391 (11.3%) samples. HEV prevalence ranged from 5.1 to 20.0% among different country regions. A significant difference in blood donors' age was observed between anti-HEV IgG positive and negative individuals [44 (37-51) vs. 35 (27-43), P < 0.001, respectively]. Anti-HEV IgM was detected in 8 out of 44 (18.2%) anti-HEV IgG positive cases. Anti-HEV IgG was detected in blood donor samples from five analyzed Argentinean regions, highlighting the wide distribution of the virus in the country. HEV prevalence was variable among different regions and significantly higher in older donors. Given the evidence of anti-HEV IgM presence in blood donors, suggesting a potential risk of transfusion-transmitted HEV, screening for HEV in blood units to be used in vulnerable population would be desirable. Molecular studies for detection of viremic donors and donor-recipients follow-up are necessary to certainly determine the risk of transfusion-transmitted HEV in Argentina.

Identification of hepatitis E virus subtype 4f in blood donors in Shanghai, China

Hepatitis E virus (HEV) has been divided into eight genotypes and approximately thirty subtypes. Past studies of blood donors have revealed a substantial prevalence of HEV infection. We examined anti-HEV antibodies and HEV RNA in Chinese voluntary blood donors (VBDs). Blood specimens were collected during 2010–2011, 2014–2015, and 2018, and tested for anti-HEV IgG and IgM antibodies. HEV RNA was tested using real-time PCR and nested reverse transcription PCR (RT-PCR). Phylogenetic analysis determined the genotype using MEGA 7.0. Among 4044 VBDs, 2774 were men (68.6%). In total, 19.8% and 1.1% of the VBDs were reactive to anti-HEV IgG and IgM, respectively. The seroprevalence of anti-HEV IgG was significantly associated with age and time period (P < 0.05), whereas anti-HEV IgM was associated with anti-Treponema pallidum and time period (P < 0.05). A total of five specimens were positive for HEV RNA with normal ALT levels. Subtype 4f (n=1; in the specimens reactive to anti-HEV IgM) and 4d (n=3; 1 in the specimens reactive to anti-HEV IgM and 2 in the anti-HEV negative specimens) were found. The last specimen positive for HEV RNA was not genotyped due to failure in amplifying the partial sequence. In conclusion, our study identified HEV subtype 4f for the first time in China. Additionally, we confirmed the high prevalence of HEV in Chinese VBDs. These findings suggest a substantial risk of transfusion-transmitted HEV. Therefore, screening for HEV among Chinese VBDs might be warranted to prevent further transfusion-mediated spread of HEV.

Hepatitis E virus blood donor NAT screening: as much as possible or as much as needed?

The cost-benefit question of general screening of blood products for the hepatitis E virus (HEV) is currently being discussed. One central question is the need for individual nucleic acid amplification techniques (NAT) screening (ID-NAT) versus minipool NAT screening (MP-NAT) approaches to identify all relevant viremias in blood donors. Here, the findings of ID-NAT versus MP-NAT in pools of 96 samples were compared. From November 2017 to January 2018, a total of 10,141 allogenic blood donations from 7650 individual German blood donors were screened for the presence of HEV RNA using MP-NAT (96 samples) (RealStar HEV RT-PCR Kit) compared to ID-NAT (cobas HEV assay) on the fully automated cobas 6800 platform. Parallel screening of MP (n = 122, 96 samples/MP) using both methods detected seven reactive pools. After pool resolution, 8 HEV RNA-positive donations were identified by the in-house detection method, whereas 17 HEV RNA-positive donations were identified by ID-NAT with the cobas HEV assay. This resulted in an incidence of 1:1268 donations (0.079%) for MP-NAT screening and 1:597 donations (0.168%) for ID-NAT screening. The detection frequency of HEV RNA was approximately 50% higher if ID-NAT was used compared to MP-NAT. However, viral loads of ID-NAT-only samples were below 25 IU/mL and will often not result in transfusion-transmitted HEV (TT-HEV) infection, taking into account the currently known infectious dose of 5.0E + 04 IU inevitably resulting in TT-HEV infection. The clinical relevance and need for identification of these low-level HEV-positive donors still require further investigation.

Molecular and serological infection marker screening in blood donors indicates high endemicity of hepatitis E virus in Poland

Until now, markers of hepatitis E virus (HEV) infection have not been studied in blood donors throughout Poland, and no acute case of HEV infection has been closely documented or confirmed by HEV RNA detection. The prevalence of HEV infection markers, including HEV RNA in Polish blood donors and virus genotypes was investigated. In total, 12,664 individual donations from 22 Polish blood transfusion centers were tested for HEV RNA by transcription-mediated amplification. In addition, 3079 first-time donors sampled throughout Poland also were screened for antibodies to HEV. HEV RNA and immunoglobulin M-positive donations were confirmed using real-time reverse transcription-polymerase chain reaction and Western blotting, respectively. Ten donors were identified as RNA initial reactive (one of 1266 donors), and six (one of 2109) were identified as repeat reactive and confirmed by real-time reverse transcription-polymerase chain reaction or seroconversion. Sequence analysis identified HEV Genotype 3c in one donor and Genotype 3i in two others. On average, 43.5% of donors were immunoglobulin G-positive. Immunoglobulin G seroprevalence ranged from 22.7% to 60.8% in group ages 18 to 27 years and 48 to 57 years, respectively and differed between administrative regions from 28.9% in Podlasie to 61.3% in Wielkopolska. Thirty-nine of the donors were immunoglobulin M-positive, and seven donors were IgM positive only (0.2%). Of 37 immunoglobulin M-reactive samples tested by Western blot, 24 (64.9%) were confirmed. The current results indicate a high level of HEV endemicity throughout Poland compared with other countries. There is an urgent need to consider the protection of recipients of blood components against transfusion-transmitted HEV infection.

Hepatitis E virus - key points for the clinical haematologist.

In recent years there has been a paradigm shift in our understanding of the epidemiology and clinical features of hepatitis E virus (HEV) infection. Once classically described as an acute hepatitis associated with waterborne outbreaks in areas of poor sanitation, HEV is now recognised to be endemic in Europe and is probably zoonotic in origin. Evidence for transfusion-transmitted HEV has prompted the introduction of blood donor screening in a number of countries, but the risk to the haematology patient from food sources remains. The aim of this review therefore, is to equip the clinical haematologist with the knowledge required to diagnose HEV infection and to aid decision-making in patient management. The article also provides information on addressing patient concerns about their risk of acquiring hepatitis E and how this risk can be mitigated.

Transfusion-Transmitted Hepatitis E: NAT Screening of Blood Donations and Infectious Dose.

The risk and importance of transfusion-transmitted hepatitis E virus (TT-HEV) infections by contaminated blood products is currently a controversial discussed topic in transfusion medicine. The infectious dose, in particular, remains an unknown quantity. In the present study, we illuminate and review this aspect seen from the viewpoint of a blood donation service with more than 2 years of experience in routine HEV blood donor screening. We systematically review the actual status of presently known cases of TT-HEV infections and available routine NAT-screening assays. The review of the literature revealed a significant variation regarding the infectious dose causing hepatitis E. We also present the outcome of six cases confronted with HEV-contaminated blood products, identified by routine HEV RNA screening of minipools using the highly sensitive RealStar HEV RT-PCR Kit (95% LOD: 4.7 IU/mL). Finally, the distribution of viral RNA in different blood components [plasma, red blood cell concentrate (RBC), platelet concentrates (PC)] was quantified using the first WHO international standard for HEV RNA for NAT-based assays. None of the six patients receiving an HEV-contaminated blood product from five different donors (donor 1: RBC, donor 2–5: APC) developed an acute hepatitis E infection, most likely due to low viral load in donor plasma (<100 IU/mL). Of note, the distribution of viral RNA in blood components depends on the plasma content of the component; nonetheless, HEV RNA could be detected in RBCs even when low viral plasma loads of 100–1,000 IU/mL are present. Comprehensive retrospective studies of TT-HEV infection offered further insights into the infectivity of HEV RNA-positive blood products. Minipool HEV NAT screening (96 samples) of blood donations should be adequate as a routine screening assay to identify high viremic donors and will cover at least a large part of viremic phases.

Transfusion transmission of hepatitis E virus: an emerging issue

Hepatitis E virus (HEV) infections are quite common in developed countries in Europe, North America and China. HEV infected adults commonly are asymptomatic when they are viremic and usually would qualify to donate blood. More than 20 HEV viremic donors have been detected in Japan and have transmitted HEV to patients. Therefore blood donor screening in Northern Japan since 2007 has detected over 230 HEV viremic donors. A study in Southeastern UK detected 79 HEV viremic donors; 18 of 43 recipients of these infected blood products were infected. Currently donor blood in the UK is screened for HEV RNA in minipools. Clinically silent HEV is quite common among adults in China (about 1:1,500–2,500 donors are HEV RNA positive?). A policy to prevent transfusion-transmitted HEV is needed .

Hepatitis E and blood donation safety in selected European countries: a shift to screening?

The public health implications of hepatitis E virus (HEV) in Europe have changed due to increasing numbers of hepatitis E cases and recent reports of chronic, persistent HEV infections associated with progression to cirrhosis in immunosuppressed patients. The main infectious risk for such immunosuppressed patients is exposure to undercooked infected pork products and blood transfusion. We summarised the epidemiology of HEV infections among blood donors and also outlined any strategies to prevent transfusion-transmitted HEV, in 11 European countries. In response to the threat posed by HEV and related public and political concerns, most of the observed countries determined seroprevalence of HEV in donors and presence of HEV RNA in blood donations. France, Germany, Spain and the United Kingdom (UK) reported cases of transfusion-transmitted HEV. Ireland and the UK have already implemented HEV RNA screening of blood donations; the Netherlands will start in 2017. Germany and France perform screening for HEV RNA in several blood establishments or plasma donations intended for use in high-risk patients respectively and, with Switzerland, are considering implementing selective or universal screening nationwide. In Greece, Portugal, Italy and Spain, the blood authorities are evaluating the situation. Denmark decided not to implement the HEV screening of blood donations.

Hepatitis E: the current state of play

The hepatitis E virus (HEV) is a major cause of acute hepatitis globally. Genotypes 1 and 2 (G1 and G2) are obligate human pathogens transmitted faeco-orally, leading to epidemics in developing countries. In contrast, genotypes 3 and 4 (G3 and G4) have a wider host range, including humans, but are primarily porcine viruses and are transmitted from animals to humans as a food-borne zoonosis when meat from an infected animal is consumed. HEV is increasingly recognised as a problem in developed countries, including countries in Europe. G3 HEV is now the most common cause of acute viral hepatitis in the UK and cases continue to rise. The majority of these infections are acquired within the UK and thought to be from insufficiently cooked meat, predominantly processed pork meat. Previously thought to only cause self-limiting disease, HEV infection can persist in immunosuppressed patients, which may lead to chronic hepatitis and the rapid development of cirrhosis. Of particular interest to the transfusion community has been the possibility of transfusion-transmitted HEV, which has been reported from countries classically considered HEV-endemic but also non-endemic countries in Europe and Japan. This has prompted some countries to introduce screening for HEV in blood donations.

Clinical and virological features of acute hepatitis E in Gunma prefecture, Japan between 2004 and 2015.

To evaluate the clinical and virological features of acute hepatitisE (AH-E) in Gunma prefecture and focus on the hepatitisE virus (HEV) infection in immunocompromised patients. A total of 30 patients with AH-E diagnosed at our Gunma University Hospital, and located in 3-39-15 Showa-machi, Maebashi, Gunma 371-8511 Japan, and its affiliated hospitals from 2004 to 2015, were studied. We evaluated the detailed medical histories, laboratory examinations and virological features of these participants. Of the 30 patients, 21 patients were men, with a median age of 61years. Three of these patients had a history of recent oversea travel. A total of 14 patients had eaten raw or undercooked meat/viscera from animals, and two patients had contracted transfusion-transmitted AH-E. Eight patients were immunocompromised, including those with hematological disease, cancer receiving systemic chemotherapy and kidney transplant or connective tissue disease undergoing immunosuppressive medications. The alanine aminotransferase and total bilirubin levels were more significantly reduced in these immunocompromised patients than in the non-immunocompromised patients. Severe thrombocytopenia, an extra-hepatic manifestation of AH-E, occurred in one case. Among the 22 HEV strains whose subgenotype was determined, two were imported strains (1a and 1f), and 11 strains formed four distinct phylogenetic clusters within subgenotype3b. The remaining nine strains differed from each other by 9.8-22.4%, and were classified into four subgenotypes (3a, 3b, 3e and 3f). Markedly divergent HEV strains (3a, 3b, 3e and 3f) were found to circulate in Gunma. Although immunosuppression appears to play a crucial role in establishing chronic sequels, AH-E in eight immunocompromised patients, including transfusion-transmitted HEV infection in two patients, did not become chronic.

Detection of Hepatitis E Virus Genotype 1 Among Blood Donors From Southwest of Iran.

BackgroundInfection with hepatitis E virus (HEV) is endemic in developing countries and reveals significant regional differences. Several studies have reported virus transmission via blood transfusion. To date, however, no cases of HEV RNA detection in blood donors have been reported from Iran.ObjectivesThe aim of this study was to determine the presence of HEV RNA in plasma samples of blood donors referred to a blood transfusion center in Shiraz in the southwest of Iran. The HEV genotypes were also investigated using nucleotide sequencing.Patients and MethodsBlood samples were collected from 700 blood donors who were referred to Fars blood transfusion organization from January to March 2014. Plasma samples were screened for the presence of HEV IgG and IgM antibodies by standard enzyme immunoassay. Samples seroreactive to anti-HEV were further tested for the presence of HEV RNA using nested polymerase chain reaction (PCR) with universal primers for detection of all four HEV genotypes. Positive PCR samples were then subjected to DNA sequencing for further analysis.ResultsFifty (50, 7.1%) out of 700 plasma samples tested positive for anti-HEV antibodies. HEV RNA was detected in 7/50 (12%) of the antibody-positive samples, the majority of which were IgM positive. Sequence analysis of seven isolates of the HEV RNA ORF 2 gene region revealed > 80% similarity with genotype 1.ConclusionsThe analysis indicates that the HEV isolated from blood donors in the southwest of Iran belongs to genotype 1. However, more samples from other geographic regions of Iran are needed to confirm these findings. Because transmission of HEV by administration of blood or blood components is likely to occur, it may be sensible to screen donor blood for HEV to eliminate transfusion-transmitted HEV infection when the recipient is immunocompromised.