A 33-year-old white man’s alanine aminotransferase (ALT) has been elevated for approximately two years. At initial evaluation, his ferritin level was >1,000 ng/mL. Additional laboratory studies, including a hepatitis panel and autoimmune determinations, were normal. Eventually, his liver biopsy showed marked fatty liver without fibrosis. His hepatic iron index was <1, and genetic testing for hemochromatosis was negative. A repeat ferritin was 900. Does this patient need phlebotomy to get his ferritin down?
—Patrick Leong, MD, Nashua, N.H.

An acute-phase reactant, ferritin can increase markedly in hepatocellular necrosis or inflammatory states, such as infection or chronic disease. When assessing iron stores, ferritin should be evaluated alongside the serum transferrin saturation. A transferrin saturation >50% is considered abnormal and should trigger genetic testing for hemochromatosis. Additional testing is necessary because an elevated transferrin saturation is also seen in conditions that do not involve iron overload, such as alcoholic liver disease.

The patient described has no indication for phlebotomy since he does not have hemochromatosis or evidence of iron overload based on his biopsy and genetic testing. I would, however, be concerned about alcoholic liver disease or nonalcoholic steatohepatitis as both can result in the clinical picture you have described.
—Susan Kashaf, MD, MPH (101-3)

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