Relationship between hepatocellular injury and transfusional iron overload prior to and during iron chelation with desferrioxamine: a study in adult patients with acquired anemias.
The role of iron overload as cause of liver dysfunction has never been studied in detail in patients without concomitant hepatotropic infections who receive multiple transfusions. We therefore investigated the relationship between the extent of hepatocellular injury as reflected by serum levels of aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and several iron status indices in 39 anti-hepatitis C virus-negative (HCV(-)) nonthalassemic patients with transfusional iron overload owing to acquired anemias. In 12 patients, we monitored aminotransferase levels and indices of iron status during iron chelation treatment. Before treatment, elevated aminotransferase activity was seen only at liver iron concentrations more than 300 microM/g. During treatment all aminotransferase values were normal if the liver iron concentration returned below 350 microM/g. At the start of treatment, ALT (R(2) = 0.64, P =.006) and AST activity (R(2) = 0.57, P =.01) were closely related to urinary iron excretion, reflecting the size of the chelatable or the labile iron pool. During treatment, a comparable pattern was seen and the urinary iron excretion was also directly related to the liver iron concentration at concentrations above approximately 400 microM/g. All elevated ALT values were associated with a urinary iron excretion more than 15 mg/24 h. In conclusion, our data suggest the existence of a critical liver iron concentration range, above which hepatocellular injury is seen. The extent of the injury seems to be determined mainly by the size of the chelatable or labile iron pool, supporting the concept of the labile iron pool as the compartment directly involved in iron toxicity. Our findings may be helpful in establishing criteria for safety from complications of transfusional iron overload.
Jensen
Peter D
PD
Department of Hematology and Center for Nuclear Magnetic Resonance, Aarhus University Hospital, Denmark. d222615@inet.uni2.dk
Jensen
Finn T
FT
Christensen
Thorkil
T
Nielsen
Johan L
JL
Ellegaard
Joergen
J
D000328:Adult; D000368:Aged; D000740:Anemia / Q000209:etiology / Q000473:pathology; D015913:Chelation Therapy; D003676:Deferoxamine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007501:Iron / Q000032:analysis / Q000652:urine; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000188:drug therapy / Q000209:etiology*; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000637:Transaminases / Q000097:blood; D065227:Transfusion Reaction
D007502:Iron Chelating Agents; D007501:Iron; D000637:Transaminases; D003676:Deferoxamine