From the Guidelines
High serum iron in liver transplant patients is concerning and requires immediate attention to prevent graft dysfunction, increased infection risk, and reduced survival rates. Patients with elevated serum iron should undergo additional testing including transferrin saturation, ferritin levels, and possibly liver biopsy to confirm iron overload, as recommended by the American Association for the Study of Liver Diseases 1. Management typically involves phlebotomy, which is a safe and effective treatment for hereditary hemochromatosis, as stated in the EASL clinical practice guidelines: liver transplantation 1. The target levels of phlebotomy should be a ferritin level of 50-100 lg/L, as recommended by the American Association for the Study of Liver Diseases 1. Regular monitoring of iron parameters is essential, and patients with end-organ damage due to iron overload should undergo regular phlebotomy to the same endpoints as indicated above 1. It is also important to note that iron overload impairs immune function, increasing susceptibility to bacterial and fungal infections, which are already major concerns in immunosuppressed transplant recipients, as mentioned in the diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases 1. Some key points to consider in the management of high serum iron in liver transplant patients include:
- Therapeutic phlebotomy is the general treatment for hereditary hemochromatosis, which is safe and effective 1
- Phlebotomies are recommended if serum ferritin is >1000 ng/ml, usually started at 500 ml/week, and continued until reaching normalized iron store levels (serum) 1
- Patients with hemochromatosis and iron overload should be monitored for reaccumulation of iron and undergo maintenance phlebotomy 1
- Iron overload is particularly problematic in transplant patients because the liver is the primary site of iron storage, and excessive iron can generate free radicals causing oxidative stress, hepatocellular damage, and fibrosis 1.
From the Research
Implication of High Serum Iron in Liver Transplant Patients
- High serum iron levels can lead to iron overload, which is a risk factor for hepatic ischemia-reperfusion injury in liver transplantation 2
- Iron overload can cause damage to the liver and other organs through oxidative stress and promote fibrogenesis and carcinogenesis 3
- Ferroptosis, an iron-dependent cell death, contributes to the pathogenesis of hepatic ischemia-reperfusion injury in liver transplantation 2
- Iron chelation therapy can reduce iron overload and prevent organ damage, and may be beneficial for liver transplant patients with high serum iron levels 4, 5, 6
- Optimizing iron management before and after liver transplantation is crucial to improve clinical outcomes, as both iron overload and iron deficiency are associated with poor prognosis 6
Risk Factors and Clinical Outcomes
- High serum ferritin levels, a marker of iron overload, are an independent risk factor for liver damage after liver transplantation 2
- Iron overload is associated with poor prognosis in end-stage organ failure in patients awaiting liver transplantation, and this negative prognostic impact persists after transplantation 6
- Iron deficiency and anemia are also associated with poor prognosis in patients with end-stage heart failure, highlighting the need for careful management of iron status in transplant patients 6