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.

  • Original Article
  • Published:

Post-Transplant Events

The role of liver biopsy in the workup of liver dysfunction late after SCT: is the role of iron overload underestimated?

Bone Marrow Transplantation volume 42, pages 461–467 (2008)Cite this article

Abstract

Abnormalities in liver function tests are common in hematopoietic SCT (HSCT) recipients. We retrospectively investigated the role of liver biopsy in determining the cause of elevated liver enzymes and its impact on the management of patients in the post-HSCT setting. A total of 24 consecutive liver biopsies were obtained from 20 patients from September 2003 to December 2007. A definite histopathologic diagnosis was obtained in 91.7% of the biopsies. Iron overload (IO) was found in 75% and GVHD in 54.2% of the patients. The initial clinical diagnosis of GVHD was confirmed in 56.5% and refuted in 43.5% of the allogeneic HSCT recipients. The median number of post transplant transfusions, percent transferrin saturation and ferritin levels were found to be higher in patients who had histologically proven hepatic IO (p1=0.007, p2=0.003 and p3=0.009, respectively). Regression analysis showed a significant correlation between serum ferritin levels and histological grade of iron in the hepatocytes. Our data suggest that hepatic IO is a frequent finding in the post-HSCT setting, which contributes to hepatic dysfunction and it should be considered in the differential diagnosis, particularly in patients with high serum ferritin levels.

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
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP et al. Prognostic impact of elevated pretransplant serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood 2007; 109: 4586–4588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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 

  3. 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  PubMed  Google Scholar 

  4. Strasser SI, Sullivan KM, Myerson D, Spurgeon CL, Storer B, Schoch HG et al. Cirrhosis of the liver in long term marrow transplant survivors. Blood 1999; 93: 3259–3266.

    CAS  PubMed  Google Scholar 

  5. El Sayed MH, El-Haddad A, Fahmy OA, Salama II, Mahmoud HK . Liver disease is a major cause of mortality following allogeneic bone marrow transplantation. Eur J Gastroenterol Hepatol 2004; 16: 1347–1354.

    Article  PubMed  Google Scholar 

  6. Tomas JF, Pinilla I, Garcia-Buey ML, Garcia A, Figuera A, Gomez-Garcia de Soria V et al. Long term liver dysfunction after allogeneic bone marrow transplantation: clinical features and course in 61 patients. Bone Marrow Transplant 2000; 26: 649–655.

    Article  CAS  PubMed  Google Scholar 

  7. McDonald GB . Review article: management of hepatic disease following haematopoietic cell transplant. Aliment Pharmacol Ther 2006; 24: 441–452.

    Article  CAS  PubMed  Google Scholar 

  8. 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  PubMed  Google Scholar 

  9. Ma SY, Au WY, Ng IOL, Lie AKW, Leung AYH, Liang RHS et al. Role of liver biopsy in the management of liver dysfunction after hematopoietic stem cell transplantation in a hepatitis B virus prevalent patient population. Transplantation 2003; 76: 169–176.

    Article  PubMed  Google Scholar 

  10. Harrison P, Neilson JR, Marwah SS, Madden L, Bareford D, Milligan DW . Role of non transferrin bound iron in iron overload and liver dysfunction in long term survivors of acute leukaemia and bone marrow transplantation. J Clin Pathol 1996; 49: 853–856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Veneri D, Franchini M, Zanetti F, Krampera M, Matteis G, Pizzolo G . Iron overload in acute myeloid leukemia patients is not related to HFE and TFR2 gene mutations. Haematologica 2003; 88: 1069–1070.

    CAS  PubMed  Google Scholar 

  12. Kim BK, Chung KW, Sun HS, Suh JG, Min WS, Kang CS et al. Liver disease during the first posttransplant year in bone marrow transplantation recipients: retrospective study. Bone Marrow Transplant 2000; 26: 193–197.

    Article  CAS  PubMed  Google Scholar 

  13. Kusumi E, Kami M, Kanda Y, Murasbige N, Seki K, Fujiwara M et al. Hepatic injury following reduced intensity unrelated cord blood transplantation for adult patients with hematological diseases. Biol Blood Marrow Transplant 2006; 12: 1302–1309.

    Article  PubMed  Google Scholar 

  14. Azar N, Valla D, Abdel-Samad I, Hoang C, Fretz C, Sutton L et al. Liver dysfunction in allogeneic bone marrow transplantation recipients. Transplantation 1996; 62: 56–61.

    Article  CAS  PubMed  Google Scholar 

  15. Özdoǧan O, Ratip S, Al Ahdab Y, Dane F, Al Ahdab H, İmeryüz N et al. Causes and risk factors for liver injury following bone marrow transplantation. J Clin Gastroenterol 2003; 36: 421–426.

    Article  PubMed  Google Scholar 

  16. Subbarao G, Haut PR, Johnson CS, Gowan D, Molleston JP . Incidence, etiology and risk factors for liver dysfunction in children following hematopoietic stem cell transplantation. Pediatr Transplant 2006; 10: 682–689.

    Article  PubMed  Google Scholar 

  17. Chahal P, Levy C, Litzow MR, Lindor KD . Utility of liver biopsy in bone marrow transplant patients. J Gastroenterol Hepatol 2008; 23: 222–225.

    Article  PubMed  Google Scholar 

  18. Evens AM, Mehta J, Gordon LI . Rust and corrosion in hematopoietic stem cell transplantation: the problem of iron and oxidative stress. Bone Marrow Transplant 2004; 34: 561–571.

    Article  CAS  PubMed  Google Scholar 

  19. Miceli MH, Dong L, Grazziutti ML, Fassas A, Thertulien R, Van Rhee F et al. Iron overload is a major risk factor for severe infection after autologous stem cell transplantation: a study of 367 myeloma patients. Bone Marrow Transplant 2006; 37: 857–864.

    Article  CAS  PubMed  Google Scholar 

  20. Lichtman SM, Attivissimo L, Goldman IS, Schuster MW, Buchbinder A . Secondary hemochromatosis as a long term complication of the treatment of hematologic malignancies. Am J Hematol 1999; 61: 262–264.

    Article  CAS  PubMed  Google Scholar 

  21. Strasser SI, Kowdley KV, Sale GE, McDonald GB . Iron overload in bone marrow transplant recipients. Bone Marrow Transplant 1998; 22: 167–173.

    Article  CAS  PubMed  Google Scholar 

  22. Poli G . Pathogenesis of liver fibrosis: role of oxidative stress. Mol Aspects Med 2000; 21: 49–98.

    Article  CAS  PubMed  Google Scholar 

  23. Allen KJ, Gurrin LC, Constantine CC, Osborne NJ, Delatycki MB, Nicoll AJ et al. Iron overload-related disease in HFE hereditary hemochromatosis. N Engl J Med 2008; 358: 221–230.

    Article  CAS  PubMed  Google Scholar 

  24. McKay PJ, Murphy JA, Cameron S, Burnett AK, Camphell M, Tansey P et al. Iron overload and liver dysfunction after allogeneic and autologous bone marrow transplantation. Bone Marrow Transplant 1996; 17: 63–66.

    CAS  PubMed  Google Scholar 

  25. Waalen J, Felliti VJ, Gelbart T, Beutler E . Screening for hemachromatosis by measuring ferritin levels: a more effective approach. Blood 2008; 111: 3373–3376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kamble RT, Selby GB, Mims M, Kharfan-Dabaja MA, Özer H, George JN . Iron overload manifesting as apparent exacerbation of hepatic graft versus host disease after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2006; 12: 506–510.

    Article  CAS  PubMed  Google Scholar 

  27. Socie G, Salooja N, Cohen A, Rovelli A, Carreras E, Locasciulli A et al. Nonmalignant late effects after allogeneic stem cell transplantation. Blood 2003; 101: 3373–3385.

    Article  CAS  PubMed  Google Scholar 

  28. Dürken M, Nielsen P, Knobel S, Finckh B, Herrnring C, Dresow B et al. Nontransferrin-bound iron in serum of patients receiving bone marrow transplants. Free Rad Biol Med 1997; 22: 1159–1163.

    Article  PubMed  Google Scholar 

  29. Sahlstedt L, Ebeling F, Von Bonsdorff L, Parkkinen J, Ruutu T . Non-transferrin bound iron during allogeneic stem cell transplantation. Br J Haematol 2001; 113: 836–838.

    Article  CAS  PubMed  Google Scholar 

  30. Gordon LI, Brown SG, Tallman MS, Rademaker AW, Weitzman SA, Lazarus HM et al. Sequential changes in serum iron and ferritin in patients undergoing high dose chemotherapy and radiation with autologous bone marrow transplantation: possible implications for treatment related toxicity. Free Rad Biol Med 1995; 18: 383–389.

    Article  CAS  PubMed  Google Scholar 

  31. Morado M, Ojeda E, Garcia Bustos J, Aguado MJ, Arrieta R, Quevedo E et al. Serum ferritin as a risk factor for veno-occlusive disease of the liver. Prospective cohort study. Hematology 2000; 6: 505–512.

    Google Scholar 

  32. Maertens J, Demuynck H, Verbeken EK, Zachee P, Verhoef GEG, Vandenberghe P et al. Mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transplant 1999; 24: 307–312.

    Article  CAS  PubMed  Google Scholar 

  33. Altes A, Remacha AF, Sadra P, Sancho FJ, Sureda A, Martino R et al. Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis. Bone Marrow Transplant 2004; 34: 505–509.

    Article  CAS  PubMed  Google Scholar 

  34. Altes A, Remacha AF, Sadra P, Baiget M, Sureda A, Martino R et al. Early clinical impact of iron overload in stem cell transplantation. A prospective study. Ann Hematol 2007; 86: 443–447.

    Article  PubMed  Google Scholar 

  35. Angelucci E, Muretto P, Nicolucci A, Baronciani D, Erer B, Gaziev J et al. Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation. Blood 2002; 100: 17–21.

    Article  CAS  PubMed  Google Scholar 

  36. Kallianpur AR, Hall LD, Yadav M, Christman BW, Dittus RS, Haines JL et al. Increased prevalance of the HFE C282Y Hemochromatosis allele in women with breast cancer. Cancer Epidemiol 2004; 13: 205–212.

    Article  CAS  Google Scholar 

  37. Barton JC, Bertoli LF, Acton RT . HFE C282Y and H63D in adults with malignancies in a community medical oncology practice. BMC Cancer 2004; 4: 1–8.

    Article  Google Scholar 

  38. Carreras E . Risk assessment in haematopoietic stem cell transplantation: the liver as a risk factor. Best Pract Res Clin Haematol 2007; 20: 231–246.

    Article  CAS  PubMed  Google Scholar 

  39. Varkonyi J, Tarkovacs G, Karadi I, Andrikovics H, Varga Fe, Varga Fa et al. High incidence of hemochromatosis gene mutations in the myelodysplastic syndrome: the Budapest study on 50 patients. Acta Haematol 2003; 109: 64–67.

    Article  PubMed  Google Scholar 

  40. Ko C, Siddaiah N, Berger J, Gish R, Brandhagen D, Sterling RK et al. Prevalence of hepatic iron overload and association with hepatocellular cancer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry. Liver Int 2007; 27: 1394–1401.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Faculty of Medicine, Gazi University, Ankara, Turkey

    G T Sucak, Z A Yegin, Z N Özkurt & Ş Z Akı

  2. Department of Gastroenterology, Faculty of Medicine, Gazi University, Ankara, Turkey

    T Karakan

  3. Department of Pathology, Faculty of Medicine, Gazi University, Ankara, Turkey

    G Akyol

Authors
  1. G T Sucak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Z A Yegin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Z N Özkurt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ş Z Akı
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Karakan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Akyol
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G T Sucak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sucak, G., Yegin, Z., Özkurt, Z. et al. The role of liver biopsy in the workup of liver dysfunction late after SCT: is the role of iron overload underestimated?. Bone Marrow Transplant 42, 461–467 (2008). https://doi.org/10.1038/bmt.2008.193

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.193

Keywords

This article is cited by

Search

Advanced search

Quick links