Iron deficiency anemia in chronic liver disease: etiopathogenesis, diagnosis and treatment

Abstract

Chronic liver disease is accompanied by multiple hematological abnormalities. Iron deficiency anemia is a frequent complication of advanced liver disease. The etiology is multifactorial, mostly due to chronic hemorrhage into the gastrointestinal tract. The diagnosis of iron deficiency anemia is very challenging, as simple laboratory methods, including serum iron, ferritin, transferrin saturation (Tsat), and mean corpuscular volume are affected by the liver disease itself or the cause of the disease, resulting in difficulty in the interpretation of the results. Several new parameters, such as red blood cell ferritin, serum transferrin receptor test and index, and hepcidin, have been studied for their utility in indicating true iron deficiency in combination with chronic liver disease. Once iron deficiency anemia is diagnosed, it should be treated with oral or parenteral iron as well as portal pressure reducing drugs. Blood transfusion is reserved for symptomatic anemia despite iron supplementation.

Keywords: Iron deficiency anemia; chronic liver disease; cirrhosis; ferritin; hepcidin; homeostasis.

Figure 1

Iron homeostasis. (A) Iron absorption. Fe³⁺ is reduced to Fe²⁺ by duodenal cytochrome B (Dcytb) and is transported from enteral lumen into the enterocyte by the divalent metaltrasporter-1 (DMT-1). Iron is transported by the ferroportin (FPN) to the circulation, after oxidization by hephaestin and binding to transferrin (Tf) (B) Cellular iron uptake takes place via the transferrin receptors (TfR) on the membrane of the cell and iron is internalized and released from Tf with the help of DMT-1 (C) The hepcidin is produced mainly in the liver after activation of the BMP/SMAD pathway via the interaction of transferrin with TfR2, protein HFE and the co-receptor hemojuvelin (HJV) BMPR, bone morphogenetic protein receptor, HAMP, hepcidin antimicrobial protein.

Figure 2

Hepcidin production by the liver. The production of hepcidin causes ferroportin (FPN) internalization, degradation and thus inhibition of iron export to the circulation. Hepcidin also inhibits divalent metal transporter-1 (DMT-1), blocking the absorption of iron in the duodenum. The production of hepcidin is inhibited by hypoxia, iron deficiency and erythroblastic activity, and triggered by inflammation and iron excess Tf, transferrin