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Hepatitis E virus infection and hepatic GvHD in allogeneic hematopoietic stem cell transplantation recipients

Bone Marrow Transplantation volume 52, pages 622–624 (2017)Cite this article

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Hepatitis E virus (HEV) is a non-enveloped, single-stranded RNA virus, which can be subdivided into at least four genotypes. Genotypes 1 and 2 are human viruses causing acute hepatitis, mainly in young adults in tropical countries. Genotypes 3 and 4 are zoonotic, with pigs as the main reservoir in Europe and parts of Asia.1 The most prevalent HEV genotype in Europe is genotype 3, which is normally asymptomatic and self-limiting. It does, however, pose a threat to immunocompromised patients who may develop chronic HEV infection (58–93%)2, 3, 4, 5 and liver cirrhosis.3, 6, 7 In a Dutch cohort of 328 allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients, eight cases of HEV infection (2.4%) were found of which five developed chronic hepatitis.8 This suggests that there is a considerable risk of post-transplant HEV infection for alloHSCT recipients. Most patients with HEV infection have increased ALT- levels and most alloHSCT patients experience one or more episodes of elevated transaminase levels post-transplantation. The differential diagnosis of elevated liver enzymes including transaminases following alloHSCT is, however, extensive and includes medication toxicity, pre-existing liver conditions such as fatty liver disease and GvHD of the liver. Moreover, as infections may incite GvHD it can be hypothesized that HEV can provoke GvHD of the liver. Our aim was to identify the prevalence of HEV infection among alloHSCT patients with elevated ALT-levels.

We performed a retrospective analysis of ALT-levels in all 130 patients who received an allogeneic HSCT between 1 January 2005 and 1 April 2015 at our institution. Elevated ALT-levels were defined as: ALT>50 U/L for at least four consecutive weeks, recurrent elevated ALT-levels>50 U/L for a shorter period of time with normal ALT-levels in between, or an episode of peaking ALT of >100 U/L during a period of less than 4 weeks. HEV-RNA was measured at times of ALT-elevation in stored PCR-grade plasma samples using a real-time quantitative PCR amplifying the open reading frame 3 region of HEV.9 For patients with HEV infection, additional serial plasma samples were retrieved and tested to follow HEV infection over time.

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Acknowledgements

This research was not funded by any institution or company.

Author contributions

SBW and DLB gathered clinical data, analyzed results and prepared the manuscript. They contributed equally to the research and the preparation of the manuscript. PB performed the HEV-RNA PCR’s. EK was responsible for the clinical management of patients. JV provided the pictures and description of the liver biopsy of patient 5. HLZ and MDH set up the project, were involved in patient management, and supervised the analysis of the data and preparation of the manuscript.

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Author notes

  1. S B Willemse and D L Bezuur: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands

    S B Willemse

  2. Department of Hematology, Academic Medical Centre, Amsterdam, The Netherlands

    D L Bezuur, E Kneppers & M D Hazenberg

  3. Department of Clinical Virology, Academic Medical Centre, Amsterdam, The Netherlands

    P Blom & H L Zaaijer

  4. Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands

    J Verheij

Authors
  1. S B Willemse
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  2. D L Bezuur
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  5. J Verheij
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  6. H L Zaaijer
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  7. M D Hazenberg
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Correspondence to M D Hazenberg.

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Willemse, S., Bezuur, D., Blom, P. et al. Hepatitis E virus infection and hepatic GvHD in allogeneic hematopoietic stem cell transplantation recipients. Bone Marrow Transplant 52, 622–624 (2017). https://doi.org/10.1038/bmt.2016.327

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