Powell Lawrie W, Dixon Jeannette L, Ramm Grant A, Purdie David M, Lincoln Douglas J, Anderson Gregory J, Subramaniam V Nathan, Hewett David G, Searle Jeffrey W, Fletcher Linda M, Crawford Darrell H, Rodgers Helen, Allen Katrina J, Cavanaugh Juleen A, Bassett Mark L
Centre for the Advancement of Clinical Research, Royal Brisbane & Women's Hospital, Brisbane, Queensland 4029, Australia.
Arch Intern Med. 2006 Feb 13;166(3):294-301. doi: 10.1001/archinte.166.3.294.
Hemochromatosis in white subjects is mostly due to homozygosity for the common C282Y substitution in HFE. Although clinical symptoms are preventable by early detection of the genetic predisposition and prophylactic treatment, population screening is not currently advocated because of the discrepancy between the common mutation prevalence and apparently lower frequency of clinical disease. This study compared screening for hemochromatosis in subjects with or without a family history.
We assessed disease expression by clinical evaluation and liver biopsy in 672 essentially asymptomatic C282Y homozygous subjects identified by either family screening or health checks. We also observed a subgroup of untreated homozygotes with normal serum ferritin levels for up to 24 years.
Prevalence of hepatic iron overload and fibrosis were comparable between the 2 groups. Disease-related conditions were more common in male subjects identified by health checks, but they were older. Hepatic iron overload (grades 2-4) was present in 56% and 34.5% of male and female subjects, respectively; hepatic fibrosis (stages 2-4) in 18.4% and 5.4%; and cirrhosis in 5.6% and 1.9%. Hepatic fibrosis and cirrhosis correlated significantly with the hepatic iron concentration, and except in cases of cirrhosis, there was a 7.5-fold reduction in the mean fibrosis score after phlebotomy. All subjects with cirrhosis were asymptomatic.
Screening for hemochromatosis in apparently healthy subjects homozygous for the C282Y mutation with or without a family history reveals comparable levels of hepatic iron overload and disease. Significant hepatic fibrosis is frequently found in asymptomatic subjects with hemochromatosis and, except when cirrhosis is present, is reversed by iron removal.
白种人中的血色素沉着症主要是由于HFE基因常见的C282Y替换纯合子所致。尽管通过早期发现遗传易感性和预防性治疗可预防临床症状，但由于常见突变患病率与明显较低的临床疾病发生率之间存在差异，目前不主张进行人群筛查。本研究比较了有或无家族史的受试者血色素沉着症的筛查情况。
我们通过临床评估和肝活检，对672名通过家族筛查或健康检查确定的基本无症状的C282Y纯合子受试者进行了疾病表现评估。我们还观察了一组血清铁蛋白水平正常的未经治疗的纯合子亚组长达24年。
两组之间肝铁过载和纤维化的患病率相当。与疾病相关的情况在通过健康检查确定的男性受试者中更常见，但他们年龄更大。肝铁过载（2 - 4级）在男性和女性受试者中分别为56%和34.5%；肝纤维化（2 - 4期）分别为18.4%和5.4%；肝硬化分别为5.6%和1.9%。肝纤维化和肝硬化与肝铁浓度显著相关，除肝硬化病例外，放血后平均纤维化评分降低了7.5倍。所有肝硬化患者均无症状。
对有或无家族史的C282Y突变纯合子的明显健康受试者进行血色素沉着症筛查，发现肝铁过载和疾病水平相当。血色素沉着症的无症状受试者中经常发现明显的肝纤维化，除存在肝硬化外，通过去除铁可使其逆转。
