Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload

Abstract

The rate and pattern of iron deposition and accumulation are important determinants of liver damage in chronically transfused patients. To investigate iron distribution patterns at various tissue iron concentrations, effects of chelation on hepatic iron compartmentalization, and differences between patients with sickle cell disease (SCD) and thalassemia major (TM), we prospectively investigated hepatic histologic and biochemical findings in 44 patients with iron overload (35 SCD and 9 TM). The median hepatic iron content (HIC) in patients with TM and SCD was similar at 12.9 and 10.3 mg Fe/g dry weight, respectively (P = 0.73), but patients with SCD had significantly less hepatic fibrosis and inflammation (P < 0.05), less hepatic injury, and significantly less blood exposure. Patients with SCD had predominantly sinusoidal iron deposition, but hepatocyte iron deposition was observed even at low HIC. Chelated patients had more hepatocyte and portal tract iron than non-chelated ones, but similar sinusoidal iron deposition. These data suggest that iron deposition in patients with SCD generally follows the traditional pattern of transfusional iron overload; however, parenchymal hepatocyte deposition also occurs early and chelation removes iron preferentially from the reticuloendothelium. Pathophysiological and genetic differences affecting iron deposition and accumulation in SCD and TM warrants further investigation.

Trial registration: ClinicalTrials.gov NCT00675038.

Conflict of interest statement

Conflicts of interest

The authors have no conflicts of interest to declare.

Figures

Figure 1

Iron distribution in the three liver compartments for transfused patients with sickle cell disease according to the hepatic iron burden. The percentage of the maximum iron score was calculated for each of the three liver compartment scores (HIS, SIS, and PIS) and the TIS in patients with low (HIC n = 12), moderate (HIC 7–15 mg Fe/g dry weight, n = 13), and high (HIC > 15 mg Fe/g dry weight, n = 10). The percentage of the maximum score for all three liver compartments and TIS increased as HIC increased; however, SIS was always higher (i.e., more saturated) than HIS. Results are the mean (±SE) for the % maximum value for each liver compartment. HIC, hepatic iron content; HIS, hepatocytic iron score; PIS, portal iron score; SIS, sinusoidal iron score; TIS, total iron score.

Figure 2

Relationship of biopsy-proven hepatic iron content and iron scores for all three liver compartments as a percentage of the total histologic iron score in patients with sickle cell disease. Iron saturates the reticuloendothelium (sinusoidal compartment) very fast, with SIS representing approximately 50% of the total iron score (TIS) at lowest iron burden. The amount of iron deposited in hepatocytes increases proportionally with increasing iron burden, so that HIS represents approximately 70% of the TIS at higher iron burdens. HIS, hepatocytic iron score.