Reply: Ferritin and Liver Allocation? Impact on Mortality Not Only on the Waiting List But Also After Orthotopic Liver Transplantation Should Be Considered

Authors

  • Darrell H. G. Crawford M.D., FRACP,

    1. Discipline of Medicine, University of Queensland, Brisbane, Queensland, Australia
    2. Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane Queensland, Australia
    3. Gallipoli Medical Research Foundation, Greenslopes Hospital, Brisbane, Queensland, Australia
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  • Linda M. Fletcher Ph.D.,

    1. Discipline of Medicine, University of Queensland, Brisbane, Queensland, Australia
    2. Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane Queensland, Australia
    3. Gallipoli Medical Research Foundation, Greenslopes Hospital, Brisbane, Queensland, Australia
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  • Katherine A. Stuart Ph.D., FRACP

    1. Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane Queensland, Australia
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  • Potential conflict of interest: Nothing to report.

Reply:

We thank Weismuller et al. for their interesting comments relating to our recent article.1 Although we agree with their view that an ideal allocation parameter should have a low impact on the post–liver transplant outcome, we assert that the severity of liver disease and renal function are independent factors that influence the outcome of orthotopic liver transplantation (OLT). However, these variables are constitutive elements of the Model for End-Stage Liver Disease score, which is currently widely applied to determine organ allocation.2

Weismuller et al. presented novel data showing that patients with a pre-OLT serum ferritin concentration greater than 365 μg/L had reduced survival in comparison with patients with a serum ferritin concentration below this threshold. Our previous studies have shown that patients with cirrhosis-associated iron loading (CAFeL) are more likely to have an elevated serum ferritin concentration and are also more likely to have a higher Child-Pugh score.3 In our study, the Child-Pugh score and serum creatinine concentration were associated with an adverse post-OLT outcome. Thus, the observation that patients with an elevated serum ferritin concentration have higher posttransplant mortality may simply reflect more advanced liver disease in those subjects. We look forward to a complete multivariate analysis of the Hannover data to confirm if this is the case.

The observation that the serum ferritin concentration has important prognostic significance with respect to pre-OLT (and possibly post-OLT) morbidity and mortality demands that the pathophysiological basis of this relationship be explored because a potential therapeutic target may be uncovered. The authors suggested that an elevated serum ferritin concentration may be associated with iron deposition in extrahepatic sites (e.g., myocardium) that could compromise survival after OLT. Should the relationship be due to increased iron stores, then strategies to reduce body iron need to be considered. In previous studies,3 we did not demonstrate a significant impact of CAFeL on the post-OLT outcome when all factors were considered. However, we recognize that this issue remains controversial, and we acknowledge other reports of adverse post-OLT outcomes associated with this condition and experience with hereditary hemochromatosis by which affected patients are at increased risk of posttransplant mortality.4 An exact understanding of the clinical implications of CAFeL requires the proper identification of affected subjects, and this is difficult in patients with cirrhosis because of the regional variation in the distribution of iron in the same cirrhotic liver.5 Studies using magnetic resonance imaging technology, which provides a global measurement of the hepatic iron concentration and thus overcomes the problem of regional variation, may be particularly important in defining the exact clinical importance of this condition.

Darrell H. G. Crawford M.D., FRACP* † ‡, Linda M. Fletcher Ph.D.* † ‡, Katherine A. Stuart Ph.D., FRACP†, * Discipline of Medicine, University of Queensland, Brisbane, Queensland, Australia, † Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia, ‡ Gallipoli Medical Research Foundation, Greenslopes Hospital, Brisbane, Queensland, Australia.

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