Kris V. Kowdley
The American College of Gastroenterology released a new clinical guideline for the screening, diagnosis and treatment of hereditary hemochromatosis, a genetic disease that alters the body’s ability to regulate iron absorption and one of the most common genetic disorders among people of northern European descent.
“There have been several recent advances in our management of hemochromatosis, in particular the use of noninvasive diagnostic tests using MRI technology and a better understanding of the use of genetic testing in this disorder,” Kris V. Kowdley, MD, FACG, clinical professor at Washington State University, director of the Liver Care Network at the Swedish Medical Center in Washington, and lead guideline author, told Healio Gastroenterology and Liver Disease. “This is clinically relevant now that direct-to-consumer gene testing and genetic testing platforms have become widely available, and patients are increasingly coming in with this information asking for interpretation and management.”
According to Kowdley, the updated guideline follows recent clinical discoveries and provides evidence-based and grade-system scaled recommendations.
High-level recommendations in the guideline state that genetic testing should be used appropriately in patients with elevated results on serum iron studies, such as transferrin-iron saturation and ferritin results.
The guideline clarifies the different mutation patterns associated with iron overload in hemochromatosis, especially the C282Y homozygous mutation and the C282Y/H63D compound heterozygous mutation.
Kowdley explained that some of the key updates to the guideline include the role of noninvasive imaging, particularly the use of MRI scanning to estimate liver iron concentration and the use of transient elastography or FibroScan (Echosens) for identifying patients with increased risk for advanced fibrosis or cirrhosis.
“In light of the increased prevalence and increased significance of fatty liver disease, we discuss that elevated ferritin can be seen in patients with fatty liver disease and the role of the use of serum ferritin to identify patients with more severe disease progression,” Kowdley said.
While phlebotomy remains the cornerstone recommendation for therapy, the guideline discusses alternative therapies including iron chelators. Chelation is not recommended as a first-line therapy for hereditary hemochromatosis, given the safety and efficacy of phlebotomy as an established therapy, but is recommended for patients who are intolerant or refractory to phlebotomy.
“Understanding and interpreting the use of genetic testing for hemochromatosis remains confusing for clinicians,” Kowdley said. “Even though some of the material here is previously known, this review and guideline will provide clear and evidence-based recommendations for physicians using the PICO question format and GRADE methodology.” – by Talitha Bennett
Disclosure: Kowdley reports he is on the advisory boards of AbbVie, Allergan, Conatus, CymaBay, Dicerna, Dova Pharma, Gilead, Intercept, IQVIA Inc., Mavupharma, Merck, Novartis, Oxford Pharmagenes, Patera Pharma, Trio Health and Verlyx; consults for AbbVie, Ambys Medicines, Arena, Corcept Therapeutics, Dova Pharmaceuticals, Enanta, Gilead, Intercept, NGM Biopharma, Protagonist Therapeutics and Verlyx; is on the speaking bureaus of AbbVie, Gilead and Intercept; has received grants or research support from Allergan (Tobira), Conatus, Enanta, Galectin, Genfit, Gilead, GlaxoSmithKline, HighTide, Immuron, Intercept, LaJolla, Merck, NGM Biopharma, Novartis, Prometheus, Taiwan Pharmaceuticals and Zydus Discovery; and has received royalties from Up-To-Date. Please see the full guideline for all other authors’ relevant financial disclosures.