Asian Journal of Transfusion Science
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Year : 2013  |  Volume : 7  |  Issue : 1  |  Page : 1-3
Hepatitis E- Is it a risk to transfusion safety?

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

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Date of Web Publication2-Feb-2013

How to cite this article:
Kumar N, Sarin SK. Hepatitis E- Is it a risk to transfusion safety?. Asian J Transfus Sci 2013;7:1-3

How to cite this URL:
Kumar N, Sarin SK. Hepatitis E- Is it a risk to transfusion safety?. Asian J Transfus Sci [serial online] 2013 [cited 2022 May 24];7:1-3. Available from:

Hepatitis E virus (HEV) has long been considered an enterically transmitted virus causing self-limiting acute viral hepatitis. The virus was first described in samples collected retrospectively in an outbreak of jaundice in 1955 in New Delhi. [1] The disease is endemic in many developing countries in Southeast and Central Asia, the Middle East, Central America and Africa, primarily due to contaminated drinking water. The disease causes large-scale epidemics of viral hepatitis in several developing countries and is the most common cause of acute sporadic hepatitis and occasionally fulminant hepatic failure in such countries. Pregnant females, patient's with pre-existing chronic liver disease and immunocompromised patients are at a much higher risk of developing hepatic failure. [2],[3],[4] Recently, it has been reported that worldwide HEV infection causes more than 3 million symptomatic cases of acute hepatitis E each year that result in approximately 70,000 deaths. [5] Although HEV hepatitis has been classically described as an acute illness, recently there have been reports of chronicity in immunosuppressed patients. Chronic infections are rare, and have been seen in solid organ transplant recipients. [6] Persistent infection may also occur in individuals with compromised immune systems including cancer patients undergoing chemotherapy, Human immunodeficiency virus (HIV)-infected patients, and individuals with drug induced liver failure and liver damage due to alcohol abuse.

Viremia in individuals infected with HEV is usually of a short duration with a brief incubation period followed by a symptomatic phase. There is also increasing evidence that asymptomatic infections constitute majority of the disease burden. The ratio of symptomatic to asymptomatic cases ranged from 1:2 to 1:13 in the developing world. [7] In recent years, studies have also shown asymptomatic viremia in blood donors which is suggestive of ongoing subclinical infection. Arankalle and Choube from Pune, India, have shown 1.5% (3/200) of blood donors to be positive for HEV RNA and suggested the possibility of transmission by transfusion. [8] Since then, many studies have shown that HEV RNA is present in the serum of healthy blood donors and there is a potential risk for transmission of HEV through blood.

Transfusion safety has been of paramount importance for the transfusion services and with time the transfusion safety has been constantly improving secondary to screening of blood and blood products with regular introduction of better tests. Currently screening of blood and blood products for HEV is not done and there are also no recommendations. But the question is largely unanswered whether parenterally transmitted HEV is a risk to transfusion safety.

The presence of anti-HEV IgG antibody has generally been taken as evidence of prior exposure to HEV. In developed countries, anti-HEV immunoglobulin G (IgG) prevalence rates range between 1% and above 20%. These appear to be higher than those expected from the low rate of clinically evident hepatitis E disease in developed countries, suggesting that subclinical or unrecognized infection is common. [9],[10],[11],[12] Endemic regions have a very high seroprevalence. In India, the seroprevalence of HEV IgG has been reported up to 35%. [8],[13] The seroprevalence of HEV in different countries is shown in [Table 1]. In India, seroprevalence of HEV rises with age peaking in young adults but studies from China, Japan, and Denmark have shown a continuous rise in prevalence with age with peaks at around 60 years or higher.
Table 1: The seroprevalence of HEV in blood donors in different regions[8-12]

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In one of largest studies by Gotanda et al., out of 6,700 Japanese blood donors with elevated ALT, 479 (7.1%) were positive for anti-HEV IgG, including eight donors with anti-HEV IgM and seven donors with anti-HEV IgA. Among the nine donors with anti-HEV IgM and/or anti-HEV IgA, six had detectable HEV RNA. Three donors, including one without anti-HEV IgG, were found to be positive for HEV RNA. [14] Sakata et al., have also shown the presence of HEV RNA in blood donors with elevated ALT levels. [15] Studies have thus shown that HEV RNA is present in the serum of healthy blood donors, and there is a potential risk for transmission of HEV through blood. There have been several instances of post transfusion HEV reported in developed countries including Japan, the United Kingdom, France, and Saudi Arabia. [16]

There are several high risk groups of patients, such as patients with chronic hemodialysis (CHD) who are likely to develop transfusion associated hepatitis (TAH). [17] The previous studies done for seroprevalence have been unclear whether prevalence of anti-HEV antibodies in patients with CHD is higher than normal population. Study done by Sylvan et al., didn't find any increased seropositivity among patients with CHD as compared to healthy controls. [18] A study by Ayoola et al., indicated a significantly higher risk of acute HEV infection among patients on chronic haemodialysis although anti HEV IgG antibodies prevalence was not different. [19] A recent study by Harrrison et al., has shown a higher prevalence of anti-HEV IgG antibodies in CHD patients compared to normal controls and post renal transplant patients, which could be attributed to parenteral transmission. [20]

A current study by Reza et al., examined this possibility. They have shown that the prevalence of HEV antibodies was more than two times higher in the CHD patients, compared to the healthy controls. The difference was not significant. Furthermore, the authors examined the levels of alanine aminotransferase (ALT) in the CHD patients and the controls; there was no significant difference between the two. This is not unexpected as patients on CHD, are likely to have relatively lower alanine aminotransferase/aspartate aminotransferase (ALT/AST) levels. [21] The study is, however, wanting in examining whether these CHD patients had IgM anti-HEV or IgG anti HEV and whether these patients had circulating HEV RNA. The transmission of HEV through blood transfusion is only likely to occur when patients are viremic. Furthermore, it is likely that the increased transfusion of blood and blood products may be the cause of increased seroprevalence rather than the chronic hemodialysis per se. Future studies in this direction would indeed be a great addition to the knowledge base.

The below [Table 2] mentions the cases reported till date that have been proven as transfusion transmitted hepatitis E. The first case of transfusion transmitted HEV was reported from Hokkaido, Japan in 2004 when a Japanese male patient who developed acute hepatitis after receiving a transfusion of blood from 23 voluntary donors during open heart surgery. [16] Most reported cases were patients receiving multiple blood and blood products due to their underlying disease. Many cases are likely to go undiagnosed due to the general belief that hepatitis E is an enterically transmitted disease and can be asymptomatic, and thus these reported cases may represent only the tip of the iceberg.
Table 2: Proven cases of transfusion associated hepatitis E

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Clinical relevance of transfusion-transmitted HEV is unclear. Studies from endemic areas have suggested the possibility of transmission through blood transfusion on retrospective evaluation in transfusion recipients. Khuroo et al., had shown a significantly higher prevalence of markers for acute HEV (anti-IgM and HEV RNA) in multitransfused patients (13/145) as compared to controls (2/250). [22] It was also shown that patients who were positive for HEV markers had received more transfusions, had a higher incidence of icteric disease and higher ALT levels. Arankalle and Choube from Pune and Irshad and Peter from Delhi have also shown a significantly higher prevalence of markers of acute HEV in transfusion recipients. [8],[23]

The natural course of transfusion associated hepatitis E is not known but in high risk recipients like pregnant females, patient's with pre-existing chronic liver disease and immunocompromised patients, it is supposed to be associated with considerable morbidity and mortality. We are now well-aware of the entity of acute or chronic liver disease (ACLF), which has a very high mortality rate, and HEV is one of the most common insults leading to acute deterioration of the liver function and the irony is that the chronic liver disease may be previously undiagnosed in many patients. [4],[24],[25]

There has been a paradigm shift from Hepatitis E being considered as an enterically transmitted virus to a virus transmitted parenterally, and it is being also considered as a re-emerging infectious disease. It will be wise to consider hepatitis E as a risk to transfusion safety especially in high risk recipients due to two reasons, the first being that the HEV positive donor may be asymptomatic with normal AST/ALT and that the disease severity may be higher in the high risk individuals. In light of the current knowledge, at the presence or the absence of any effective vaccination or treatment, it will be worthwhile to introduce HEV screening for blood products in endemic areas and in high risk population considering the influence it can have on the disease course. HEV viremia is most commonly associated with IgM anti-HEV antibodies and less frequently with IgG anti-HEV antibodies. Screening for these antibodies should be introduced into clinical practice by the blood banks and wide scale implementation is likely to make it cost effective.

   References Top

1.Wong DC, Purcell RH, Sreenivasan MA, Prasad SR, Pavri KM. Epidemic and endemic hepatitis in India: Evidence for a non-A, non-B hepatitis virus aetiology. Lancet 1980;2:876-9.  Back to cited text no. 1
2.Nelson KE, Kmush B, Labrique AB. The epidemiology of hepatitis E virus infections in developed countries and among immunocompromised patients. Expert Rev Anti Infect Ther 2011;9:1133-48.  Back to cited text no. 2
3.Jilani N, Das BC, Husain SA, Baweja UK, Chattopadhya D, Gupta RK, et al. Hepatitis E virus infection and fulminant hepatic failure during pregnancy. J Gastroenterol Hepatol 2007;22:676-82.  Back to cited text no. 3
4.Ramachandran J, Eapen CE, Kang G, Abraham P, Hubert DD, Kurian G, et al. Hepatitis E superinfection produces severe decompensation in patients with chronic liver disease. J Gastroenterol Hepatol 2004;19:134-8.  Back to cited text no. 4
5.Rein, D. B., Stevens, G. A., Theaker, J., Wittenborn, J. S. and Wiersma, S. T. (2012), The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology, 55: 988-997. doi: 10.1002/hep.25505.  Back to cited text no. 5
6.Kamar N, Garrouste C, Haagsma EB, Garrigue V, Pischke S, Chauvet S, et al. Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. Gastroenterology 2011;140:1481-9.  Back to cited text no. 6
7.Center for Disease Control and Prevention. Hepatitis E Information for Health Professionals. Available from: [Last accessed on 2012 Dec 26].   Back to cited text no. 7
8.Arankalle VA, Chobe LP. Retrospective analysis of blood transfusion recipients: Evidence for post-transfusion hepatitis E. Vox Sang 2000;79:72-4.  Back to cited text no. 8
9.Kaufman A, Kenfak-Foguena A, André C, Canellini G, Bürgisser P, Moradpour D, et al. Hepatitis E virus seroprevalence among blood donors in southwest Switzerland. PLoS One 2011;6:e21150.  Back to cited text no. 9
10.Park HK, Jeong SH, Kim JW, Woo BH, Lee DH, Kim HY, et al. Seroprevalence of anti-hepatitis E virus (HEV) in a Korean population: Comparison of two commercial anti-HEVassays. BMC Infect Dis 2012;12:142.  Back to cited text no. 10
11.Guo QS, Yan Q, Xiong JH, Ge SX, Shih JW, Ng MH, et al. Prevalence of hepatitis E virus in Chinese blood donors. J Clin Microbiol 2010;48:317-8.  Back to cited text no. 11
12.Fukuda S, Sunaga J, Saito N, Fujimura K, Itoh Y, Sasaki M, et al. Prevalence of antibodies to hepatitis E virus among Japanese blood donors: Identification of three blood donors infected with a genotype 3 hepatitis E virus. J Med Virol 2004;73:554-61.  Back to cited text no. 12
13.Begum N, Devi S, Husain S, Kumar A, Kar P. Seroprevalence of subclinical HEV infection in pregnant women from north India: A hospital based study. Indian J Med Res 2009;130:709-13.  Back to cited text no. 13
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14.Gotanda Y, Iwata A, Ohnuma H, Yoshika A, Mizoguchi H, Endo K, et al. Ongoing subclinical infection of hepatitis E virus among blood donors with an elevated alanine aminotransferase level in Japan. J Med Virol 2007;79:734-42.  Back to cited text no. 14
15.Sakata H, Matsubayashi K, Takeda H, Sato S, Kato T, Hino S, et al. A nationwide survey for hepatitis E virus prevalence in Japanese blood donors with elevated alanine amino transferase. Transfusion 2008;48:2568-76.  Back to cited text no. 15
16.Matsubayashi K, Kang JH, Sakata H, Takahashi K, Shindo M, Kato M, et al. A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route. Transfusion 2008;48:1368-75.  Back to cited text no. 16
17.Zekavat OR, Makarem A, Karami MY, Amanat A, Maesoomeh M, Habibagahi M. Serological investigation for hepatitis E virus infection in the patients with chronic maintenance hemodialysis from southwest of Iran. Asian J Transfus Sci 2013;7:21-5.   Back to cited text no. 17
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18.Sylvan SP, Jacobson SH, Christenson B. Prevalence of antibodies to hepatitis E virus among hemodialysis patients in Sweden. J Med Virol 1998;54:38-43.  Back to cited text no. 18
19.Ayoola EA, Want MA, Gadour MO, Al-Hazmi MH, Hamza MK. Hepatitis E virus infection in haemodialysis patients: A case-control study in Saudi Arabia. J Med Virol 66:329-34.  Back to cited text no. 19
20.Harrison A, Scobie L, Crossan C, Parry R, Johnston P, Stratton J. Hepatitis E seroprevalence in recipients of renal transplants or haemodialysis in southwest England: A case-control study. J Med Virol 2013;85:266-271.   Back to cited text no. 20
21.Fabrizio F, Giovanna L, Finazzi S, Colucci P, Pagano A, Ponticelli C, et al. Decreased serum aminotransferase activity in patients with chronic renal failure: Impact on the detection of viral hepatitis. Am J Kidney Dis 2001;38:1009-15.   Back to cited text no. 21
22. Khuroo MS, Kamili S, Yattoo GN. Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area. J Gastroenterol Hepatol 2004;19:778-84.  Back to cited text no. 22
23.Irshad M, Peter S. Spectrum of viral hepatitis in thalassemic children receiving multiple blood transfusions. Indian J Gastroenterol 2002;21:183-4.   Back to cited text no. 23
24.Sarin SK, Kumar A, Almeida JA, Chawla YK, Fan ST, Garg H, et al. Acute-on-chronic liver failure: Consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2009;3:269-82.   Back to cited text no. 24
25.Monga R, Garg S, Tyagi P. Superimposed acute hepatitis E infection in patients with chronic liver disease. Indian J Gastroenterol 2004;23:50.  Back to cited text no. 25

Correspondence Address:
Shiv Kumar Sarin
Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi - 110 070
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-6247.106708

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