In the past the combination of elevated serum iron and abnormal liver enzymes led to a liver biopsy for the majority of hemochromatosis patients. Other iron tests eventually came into use: transferrin (TF) and serum ferritin (SF) along with total iron binding capacity (TIBC). The iron picture sharpened thanks to the results of these iron-related tests. Genetics and publication of clinical studies about patient outcomes eventually led to wide medical acceptance that unless a patient’s serum ferritin is 1,000 ng/mL the risk of liver disease is very low, possibly less than 1%. However, if SF is greater than 1,000 ng/mL risk of liver disease soars to 20-200 fold.
Liver biopsy is invasive since a needle is used to puncture the skin and penetrate the liver. The procedure provides no direct information about iron in other organs such as the heart, pancreas, pituitary, joints, or the hormone producing system. Like the liver, these vital organs are vulnerable to disease when burdened with too much iron.
As researchers addressed the need for new techniques to see iron in the body, they began to experiment with magnetic resonance imaging (MRI). Some of the first studies were done with sickle cell and thalassemia patients but the findings were also helpful for people with iron overload due to other causes such as hereditary hemochromatosis. In these studies, liver iron content obtained by liver biopsy was compared to readings generated by specialized MRI. Both methods delivered reliable results for seeing iron and determining how much of it was present.
Is magnetic resonance imaging (MRI) or ultrasound (Fibroscan®) a more accurate means of evaluating liver iron? As with any procedure, there are limitations. MRI shows the presence of iron but identifying the liver as the primary cancer requires a biopsy. Fibroscan® helps to determine the extent of fibrosis by staging the stiffness of the liver. This is done by pressing an instrument against the abdomen and sending pulses to the liver. These pulses correlate to the degree of stiffness and generate a reading. The higher the reading, the greater the fibrosis, which is the early stages of liver disease and can be reversible in some cases. Fibrosis can develop into cirrhosis and liver cancer. Obese patients or ones with swollen bellies (ascites) are not good candidates for Fibroscan®.
Liver enzymes commonly measured to assess liver, heart and bone health include: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Gamma Glutamyl Transferase (GGT) is another liver enzyme test we encourage physicians to include because elevated GGT levels measure oxidative stress and have recently been shown to correlate strongly with decreased plasma glutathione, which is considered the body’s most important antioxidant.
When doctors were informed that patients are not at risk for disease until SF is over 1,000 ng/mL, we suffered a blow that created gaps in clinical management. Some healthcare providers decided to monitor organ function as iron continued to build in vital organs. Free iron in tiny amounts can damage the pituitary, and in modest amounts can destroy delicate islet cells of the pancreas and harm tissues of the heart, gonads, thyroid, joints, and eyes. By the time SF reaches 1,000 ng/mL disease can be measured because it is present.
If your SF is at the top end of normal, begin iron reduction strategies right away. In early stages a few blood donations a year and modest diet changes can lower iron levels and slow the absorption and progression of disease. Look for our handout, Iron Zones, which provides some useful tips on how to keep body iron in a healthy range.
References:
Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of abnormal liver chemistries. American Journal of Gastroenterology. 2017 Jan; 112(1):18-35. doi: 10.1038/ajg.2016.517. Epub 2016 Dec 20.
Wood JC, Enriquez C, Ghugre N, Tyzka JM,Carson S,Nelson MD, and Coates TD. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood. 2005 Aug 15; 106(4): 1460-1465. Prepublished online 2005 Apr 28. doi: 10.1182/blood-2004-10-398
Stark DD, Bass NM, Moss AA, Bacon BR, McKerrow JH, Cann CE, Brito A, Goldberg HI. Nuclear magnetic resonance imaging of experimentally induced liver disease. Radiology. 1983 Sep; 148(3):743-51.
Bonkovsky HL, Ponka P, Bacon BR, Drysdale J, Grace ND, Tavill AS. An update on iron metabolism: Summary of the Fifth International Conference on Disorders of Iron Metabolism. Hepatology. 1996 Sep;24(3):718-29.
Kinner S, Reeder SB, Yokoo T. Quantitative imaging biomarkers of NAFLD. Digestive Diseases and Sciences. 2016 May; 61(5): 1337-1347.
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