ACG Clinical Guideline: Hereditary Hemochromatosis

Abstract

Hereditary hemochromatosis (HH) is one of the most common genetic disorders among persons of northern European descent. There have been recent advances in the diagnosis, management, and treatment of HH. The availability of molecular diagnostic testing for HH has made possible confirmation of the diagnosis for most patients. Several genotype-phenotype correlation studies have clarified the differences in clinical features between patients with the C282Y homozygous genotypes and other HFE mutation patterns. The increasing use of noninvasive tests such as MRI T2* has made quantification of hepatic iron deposition easier and eliminated the need for liver biopsy in most patients. Serum ferritin of <1,000 ng/mL at diagnosis remains an important diagnostic test to identify patients with a low risk of advanced hepatic fibrosis and should be used routinely as part of the initial diagnostic evaluation. Genetic testing for other types of HH is available but is expensive and generally not useful in most clinical settings. Serum ferritin may be elevated among patients with nonalcoholic fatty liver disease and in those with alcoholic liver disease. These diagnoses are more common than HH among patients with elevated serum ferritin who are not C282Y homozygotes or C282Y/H63D compound heterozygotes. A secondary cause for liver disease should be excluded among patients with suspected iron overload who are not C282Y homozygotes. Phlebotomy remains the mainstay of therapy, but emerging novel therapies such as new chelating agents may have a role for selected patients.