Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Significant nutrient deposition in the liver after allogeneic hematopoietic stem cell transplantation: pathological analysis of 25 autopsy cases

Bone Marrow Transplantation volume 52, pages 781–782 (2017)Cite this article

Subjects

Hepatobiliary abnormalities are rather common after allogeneic hematopoietic stem cell transplantation (allo-HSCT).1 These abnormalities have various causes, such as drug toxicity, sinusoid obstructive syndrome (SOS), GvHD, infectious diseases, total parenteral nutrition (TPN) and iron overload. The correct diagnosis of hepatobiliary abnormalities is important so as to select the most effective treatment. However, liver biopsy after allo-HSCT is considered to have significant risks.2 Therefore, the prevalence of each type of liver dysfunction is still unclear. Out of various causes of hepatobiliary abnormalities, deposition of nutrients is underrecognized in the field of allo-HSCT, as liver biopsy is often omitted due to a risk of complications, and provisional diagnosis of hepatobiliary abnormalities can be GvHD- or drug toxicity-related in clinical practice after allo-HSCT. However, if the cause of hepatobiliary abnormalities is the deposition of nutrients, the appropriate treatment can be different. As representative of a tissue sample of liver obtained from patients after allo-HSCT, we focused on the autopsy samples, since it is possible to assess the deposition of the nutrients in the liver retrospectively. We hypothesized that some of the patients after allo-HSCT had deposition of nutrients in the liver, and it was associated with liver dysfunction. In this study, we assessed the hepatic deposition of fat, iron and copper in 25 post-allo-HSCT autopsy cases from 2007 to 2013. This study was approved by the institutional review board of the National Cancer Center. We chose these three nutrients in this study as the technique to assess the deposition is practically available in general.

In this study, we demonstrated that overdeposition of fat, iron and copper in the liver was commonly observed in autopsy cases after allo-HSCT. It is possible that nutrient overdeposition plays a significant role in the pathogenesis of hepatobiliary dysfunction after allo-HSCT. Nutrient overdeposition should be included in the differential diagnosis of hepatobiliary dysfunction, as treatments differ significantly depending on the underlying condition. In terms of copper deposition, one study reported its presence in conditions other than Wilson’s disease.3 Our study is the first to assess its status after allo-HSCT. Although we found copper deposition in four patients, the deposition was mild in comparison to Wilson’s disease cases. Therefore, we assume that it was not a direct cause of liver dysfunction but rather a result of reduced biliary excretion of copper due to liver dysfunction. Several studies demonstrated that a significant proportion of patients had iron overload after allo-HSCT, but other than these reports few were based on liver biopsies.4, 5, 6 Though the present study had similar findings, its ability to estimate the incidence of nutrient deposition was limited by the small sample size. In particular, there were few patients without iron deposition, which made it difficult to assess the association between iron deposition and laboratory data. Thus, more studies are needed to assess the actual incidence and its implications. In patients with nutrient overdeposition, it might be beneficial to modify nutritional support so as to reduce the burden of the deposited nutrient(s). The relevance of fat deposition should be determined in larger case series, even though there was no significant association with liver damage in this study.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Levitsky J, Sorrell MF . Hepatic complications of hematopoietic cell transplantation. Curr Gastroenterol Rep 2007; 9: 60–65.

    Article  Google Scholar 

  2. Oshrine B, Lehmann LE, Duncan CN . Safety and utility of liver biopsy after pediatric hematopoietic stem cell transplantation. J Pediatr Hematol Oncol 2011; 33: e92–e97.

    Article  Google Scholar 

  3. Blaszyk H, Wild PJ, Oliveira A, Kelly DG, Burgart LJ . Hepatic copper in patients receiving long-term total parenteral nutrition. J Clin Gastroenterol 2005; 39: 318–320.

    Article  Google Scholar 

  4. Ho GT, Parker A, MacKenzie JF, Morris AJ, Stanley AJ . Abnormal liver function tests following bone marrow transplantation: aetiology and role of liver biopsy. Eur J Gastroenterol Hepatol 2004; 16: 157–162.

    Article  Google Scholar 

  5. Choi SW, Islam S, Greenson JK, Levine J, Hutchinson R, Yanik G et al. The use of laparoscopic liver biopsies in pediatric patients with hepatic dysfunction following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2005; 36: 891–896.

    Article  CAS  Google Scholar 

  6. Iqbal M, Creger RJ, Fox RM, Cooper BW, Jacobs G, Stellato TA et al. Laparoscopic liver biopsy to evaluate hepatic dysfunction in patients with hematologic malignancies: a useful tool to effect changes in management. Bone Marrow Transplant 1996; 17: 655–662.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was conducted in collaboration with Terumo Medical Corporation, Tokyo, Japan.

Author information

Authors and Affiliations

  1. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    S Fuji, S-W Kim & T Fukuda

  2. Department of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan

    A M Maeshima

Authors
  1. S Fuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A M Maeshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S-W Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Fuji.

Ethics declarations

Competing interests

SF received research funding from Terumo Medical Corporation, Tokyo, Japan. The remaining authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fuji, S., Maeshima, A., Kim, SW. et al. Significant nutrient deposition in the liver after allogeneic hematopoietic stem cell transplantation: pathological analysis of 25 autopsy cases. Bone Marrow Transplant 52, 781–782 (2017). https://doi.org/10.1038/bmt.2016.367

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2016.367

Search

Advanced search

Quick links