Therapy for HH is relatively simple and quite effective. Phlebotomy has been shown to effectively remove excess iron stores without significant side effects. If therapeutic phlebotomy is started before the development of cirrhosis, morbidity and mortality are significantly reduced. Some clinical features of iron overload respond better to phlebotomy than others. Malaise, fatigue, abdominal pain, skin pigmentation, and insulin requirements in diabetic patients tend to improve, whereas arthropathy and hypogonadism are less responsive. Given these findings, early identification and initiation of therapeutic phlebotomy should be the goal.
Therapeutic phlebotomy (500 mL of blood) should be initiated weekly with approximately 250 mg of iron removed with each unit of blood. Some patients can tolerate biweekly phlebotomy; in contrast, some petite older women can only tolerate half a unit every other week. The goal should be to continue weekly phlebotomy until the patient's serum ferritin level is < 50 ng/mL and the transferrin saturation is < 50%. Before each phlebotomy, the hematocrit should be checked. According to the American Association for the Study of Liver Diseases practice guidelines, the hematocrit should not fall > 20% with each phlebotomy. In the uncomplicated patient, each unit of blood removed will result in a decrease in the serum ferritin level by about 30 ng/mL. This can be used as a rough guideline to predict phlebotomy requirements to deplete excess iron stores. It is important to remember that some patients with symptomatic HH may have in excess of 30 g of stored iron, and thus may require several years of weekly to biweekly phlebotomy to remove the excess stored iron. The goal of treatment is not to make patients iron deficient and/or anemic, but rather to deplete excess iron stores and to achieve serum iron values in the low normal range.
Once initial therapeutic phlebotomy has been accomplished, maintenance phlebotomy should be performed. In most patients, one unit of blood should be removed every 2 to 4 months with subsequent assessment of iron status by measuring serum ferritin and transferrin saturation. Some patients will require more frequent maintenance phlebotomies, whereas others will be on a less frequent maintenance schedule.
Occasionally, patients with significant iron loading will present with anemia that precludes frequent phlebotomy. This rarely occurs in HH, and is more often seen in patients with anemia due to ineffective erythropoiesis with secondary and/or parenteral iron overload when it can be used. In these patients, chelation therapy may be warranted. Chelation therapy with deferoxamine using continuous subcutaneous infusion results in urinary excretion of 50 to 100 mg iron per day. However, it should be noted that phlebotomy remains the easier, quicker, and less expensive therapy for iron reduction.
Cirrhosis does not improve with iron reduction therapy. Despite therapeutic phlebotomy, hepatocellular carcinoma (HCC) continues to be a threat in patients who have cirrhosis. In fact, HCC accounts for about 30% of all deaths in HH patients. Orthotopic liver transplantation is a viable alternative for patients who develop decompensated liver disease due to HH. However, it is important to note that in undetected and thus untreated HH patients, the post-transplant survival rate is lower than for other types of chronic liver disease, largely in part to increased perioperative cardiac and infection-related complications.
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