Medical education
Lessons from practice
Volume 206 - Issue 7
First confirmed case of transfusion-transmitted hepatitis E in Australia
Authors: Veronica C Hoad, Tristan Gibbs, Madhur Ravikumara, Monica Nash, Avram Levy, Samantha L Tracy, Catherine Mews, Zofia Perkowska-Guse, Helen M Faddy and Scott Bowden
Med J Aust 2017; 206 (7): 289-290. || doi: 10.5694/mja16.01090
Published online: 17 April 2017
Published online: 17 April 2017
Clinicians should remain alert to the possibility of HEV infection, particularly in immunocompromised patients
Clinical record
In July 2014, a 6-year-old boy underwent a split liver transplant following liver failure of unknown cause and received 18 blood components peri-operatively. In January 2015, routine monitoring revealed elevated levels of serum liver enzymes (alanine aminotransferase, 289 U/L; reference interval, < 30 U/L). Two biopsies showed possible but inconclusive evidence of rejection, and alanine aminotransferase levels continued to rise, reaching 1170 U/L, despite anti-rejection treatment. Hepatitis E virus (HEV) testing was performed on a third biopsy sample and HEV RNA was detected by reverse transcription polymerase chain reaction. Retrospective testing of the patient’s blood and liver samples showed that he was HEV RNA negative before transplantation, but HEV RNA positive in post-transplant blood from September 2014. After 3 months of ribavirin therapy, the patient’s liver enzyme levels normalised and HEV RNA became undetectable.
The patient had not consumed uncooked pork products and had no history of contact with swine, a known zoonotic HEV source, or overseas travel. HEV RNA was not detected in donor liver samples tested retrospectively. In July 2015, the case was referred to the Australian Red Cross Blood Service (Blood Service) for investigation into possible transmission by transfusion. HEV RNA and IgG testing was performed on archived samples from all 18 blood donations manufactured into the transfused components. HEV RNA was detected in one donation manufactured into a transfused fresh frozen plasma component. The donor of this component reported no symptoms but had travelled to the south of France, a known high HEV prevalence area,1 in the 2 months before donation and had eaten local pork products. The timing of travel was consistent with overseas-acquired infection and donation during the infectious period. HEV IgG was detected in a subsequent donation with RNA clearance, demonstrating seroconversion. This, together with molecular characterisation of patient and blood product HEV (see the Appendix at mja.com.au), strongly supported transmission by transfusion.
Hepatitis E virus (HEV) is a single-stranded RNA virus spread by various routes — including faecal–oral, foodborne, bloodborne, mother to child during pregnancy or birth, and animals to humans — typically causing a self-limiting viral hepatitis after an incubation period of 2–6 weeks.1 Chronic HEV infection has been identified almost exclusively among immunocompromised people and has been found to lead to cirrhosis in liver transplant patients.1 However, early recognition and addition of ribavirin treatment has generally good outcomes with viral clearance.2
Hepatitis E is a disease of emerging importance in developed nations,1 especially in the context of blood donation. HEV is a known transfusion-transmission agent,3 and the prevalence of asymptomatic blood donor viraemia internationally has been found to be considerably higher than expected. England has reported a viraemic prevalence of 1 in 28483 blood donors, and the Netherlands has reported a prevalence of 1 in 762.4 In addition, the potential for adverse outcomes is highest in immunosuppressed recipients who typically receive blood components. Laboratory testing for HEV is not performed on Australian blood donors during the donation process.
We report the first confirmed case of the transmission of HEV by transfusion in Australia; although transmission by transfusion was not definitely excluded in a previously described case.5 The risk that HEV poses to blood safety is specific to the Australian context. Hepatitis E is a rarely notified disease in Australia with about 30–40 notifications to health authorities each year.6 The vast majority of HEV infections notified in Australia are acquired overseas. Asymptomatic infections from most overseas-acquired infections are expected to be covered by existing Blood Service malarial risk travel deferrals, which prevent donation for fresh component manufacture for 4 months.7 However, the assumption that locally acquired infections are rare may be influenced by past external laboratory practice, where testing for HEV infection only occurred in individuals with a history of overseas travel.6 Given that infection with HEV genotype 3 has a high asymptomatic proportion — reportedly as high as 98%1 — the true infection burden in the Australian population remains unknown.
A preliminary Blood Service study found a rate of HEV viraemia of 1 in 14 799 donations,8 which is considerably lower than in other countries such as the United Kingdom that supply an HEV-safe inventory for high risk recipients. Compared internationally, adverse outcomes from transfusion-transmitted HEV in Australia are likely to be a rare event and Australia’s blood supply is at considerably lower risk. In Australia, potential risk management approaches include options such as accepting the risk as tolerable, HEV-specific travel deferrals, universal screening, and targeted screening for high risk recipients. Quarantine and donor deferrals have very limited effectiveness for infections with a high asymptomatic proportion. To guide risk management, the Blood Service has commenced a large Australia-wide HEV RNA prevalence study in blood donors. In the interim, given the uncertain incidence of HEV infection in Australia, we suggest that clinicians remain alert to the possibility of HEV infection, especially in immunosuppressed patients.Lessons from practice
Hepatitis E is a disease of emerging importance for blood safety in developed nations, with the published prevalence of blood donor viraemia reported to be approximately 1 in 750 in the Netherlands, 1 in 3000 in England and 1 in 15 000 in Australia.
HEV is a known transfusion-transmissible agent; while the risk in Australia is low compared with other countries, we report the first confirmed Australian case of transmission by transfusion.
Chronic infection can occur in immunocompromised individuals and may lead to cirrhosis; however, early recognition and treatment generally results in viral clearance.
Clinicians should remain alert to the possibility of HEV infection, particularly in immunocompromised patients.
Competing interests
No relevant disclosures.
Acknowledgements
We thank the donor and the recipient and family for agreeing to the publication of this article. We thank Ashish Shrestha for viral load testing and Anthony Keller and George Kotsiou for their comments on the manuscript. Australian governments fund the Australian Red Cross Blood Service to provide blood, blood products and services to the Australian community.
References
- Kamar N, Dalton HR, Abravanel F, et al. Hepatitis E virus infection. Clin Microbiol Rev 2014; 27: 116-138.
- Aggarwal A, Perumpail RB, Tummala S, et al. Hepatitis E virus infection in the liver transplant recipients: clinical presentation and management. World J Hepatol 2016; 8: 117-122.
- Hewitt PE, Ijaz S, Brailsford SR, et al. Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet 2014; 384: 1766-1773.
- Hogema BM, Molier M, Sjerps M, et al. Incidence and duration of hepatitis E virus infection in Dutch blood donors. Transfusion 2016; 56: 722-728.
- Speers DJ, Ma MX, Faddy HM, et al. Domestically acquired hepatitis E successfully treated with ribavirin in an Australian liver transplant recipient. Med J Aust 2015; 202: 209-211.
- Yapa CM, Furlong C, Rosewell A, et al. First reported outbreak of locally acquired hepatitis E virus infection in Australia. Med J Aust 2016; 204: 274.
- Shrestha AC, Flower RLP, Seed CR, et al. Hepatitis E virus infections in travellers: assessing the threat to the Australian blood supply. Blood Transfus 2016; doi: 10.2450/2016.0064–16.
- Shrestha AC, Flower RLP, Seed CR, et al. Hepatitis E virus RNA in Australian blood donations. Transfusion 2016; 56: 3086-3093.