Increased Risk of Death From Iron Overload Among 422 Treated Probands With HFE Hemochromatosis and Serum Levels of Ferritin Greater Than 1000 μg/L at Diagnosis
Increased Risk of Death From Iron Overload Among 422 Treated Probands With HFE Hemochromatosis and Serum Levels of Ferritin Greater Than 1000 μg/L at Diagnosis
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DOI：
10.1016/j.cgh.2011.11.032
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发表时间：
2012-04-01
影响因子：
12.6
通讯作者：
Adams, Paul C.
中科院分区：
文献类型：
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作者：
Barton, James C.;Barton, J. Clayborn;Adams, Paul C.
背景与目的：我们研究了在接受治疗的血色素沉着症先证者中铁超负荷死亡的风险，这些先证者是HFE C282 Y纯合子，诊断时血清铁蛋白水平大于1000 μ g/L。方法：我们使用来自HFE C282 Y纯合型血色素沉着症先证者的2个队列（一个亚拉巴马队列，n = 294，63.9%男性和一个安大略队列，n = 128，68.8%男性）的数据，比较了诊断时和其他情况下的血清铁蛋白水平与铁超载相关死亡率。我们将铁超载相关的死亡原因定义为铁沉积引起的肝硬化（包括肝衰竭和原发性肝癌）和心肌铁质沉着引起的心肌病。所有先证者均接受静脉切开术和其他适当的治疗。结果：亚拉巴马和安大略先证者诊断后的平均生存时间分别为13.2 +/- 7.3年和12.5 +/- 8.3年。在亚拉巴马和安大略的先证者中，诊断时血清铁蛋白水平大于1000 μ g/L的比例分别为30.1%和47.7%。在Logistic回归分析中，血清铁蛋白大于1000 μ g/L，在亚拉巴马先证者中与男性和肝硬化显著正相关，在安大略先证者中与年龄、男性、丙氨酸和天冬氨酸转氨酶水平升高和肝硬化显著正相关。在诊断时血清铁蛋白水平大于1000 μ g/L的先证者中，来自亚拉巴马的17.9%和来自安大略的14.8%死于铁过载。在血清铁蛋白水平大于1000 μ g/L的先证者中，亚拉巴马组铁超负荷相关死亡的相对风险为5.4（95%可信区间[CI]，2.2-13.1; P = 0.0002），安大略组为4.9（95% CI，1.1-22.0; P = 0.0359）。结论：在HFE C282 Y纯合子血色素沉着症先证者中，诊断时血清铁蛋白水平大于1000 μ g/L与男性和肝硬化呈正相关。即使接受治疗，血清铁蛋白水平大于1000 μ g/L的先证者死于铁过载的相对风险也高5倍。
BACKGROUND & AIMS: We investigated the risk of death from iron overload among treated hemochromatosis probands who were homozygous for HFE C282Y and had serum levels of ferritin greater than 1000 mu g/L at diagnosis. METHODS: We compared serum levels of ferritin at diagnosis and other conditions with the rate of iron overload-associated death using data from 2 cohorts of probands with hemochromatosis who were homozygous for HFE C282Y (an Alabama cohort, n = 294, 63.9% men and an Ontario cohort, n = 128, 68.8% men). We defined iron overload-associated causes of death as cirrhosis (including hepatic failure and primary liver cancer) caused by iron deposition and cardiomyopathy caused by myocardial siderosis. All probands received phlebotomy and other appropriate therapy. RESULTS: The mean survival times after diagnosis were 13.2 +/- 7.3 y and 12.5 +/- 8.3 y in Alabama and Ontario probands, respectively. Serum levels of ferritin greater than 1000 mu g/L at diagnosis were observed in 30.1% and 47.7% of Alabama and Ontario probands, respectively. In logistic regressions of serum ferritin greater than 1000 mu g/L, there were significant positive associations with male sex and cirrhosis in Alabama probands and with age, male sex, increased levels of alanine and aspartate aminotransferases, and cirrhosis in Ontario probands. Of probands with serum levels of ferritin greater than 1000 mu g/L at diagnosis, 17.9% of those from Alabama and 14.8% of those from Ontario died of iron overload. Among probands with serum levels of ferritin greater than 1000 mu g/L, the relative risk of iron overload-associated death was 5.4 for the Alabama group (95% confidence interval [CI], 2.2-13.1; P = .0002) and 4.9 for the Ontario group (95% CI, 1.1-22.0; P = .0359). CONCLUSIONS: In hemochromatosis probands homozygous for HFE C282Y, serum levels of ferritin greater than 1000 mu g/L at diagnosis were positively associated with male sex and cirrhosis. Even with treatment, the relative risk of death from iron overload was 5-fold greater in probands with serum levels of ferritin greater than 1000 mu g/L.