Brest, France.
Paris, France.
Aliment Pharmacol Ther. 2022 Apr;55(8):1016-1027. doi: 10.1111/apt.16775. Epub 2022 Feb 4.
Venesection is the key therapy in haemochromatosis, but it remains controversial in hyperferritinaemia with moderate iron accumulation. There is substantial evidence that the results of HFE genotyping are routinely misinterpreted, while elevated serum ferritin has become more frequent in recent years in white adult populations following the increase of obesity and metabolic traits.
To examine the reasons for prescribing venesection in 1,059 French patients during the period 2012-2015, determine the true prevalence of HFE-related haemochromatosis, and compare iron overload profiles between haemochromatosis and non-haemochromatosis patients.
Only 258 of the 488 patients referred for haemochromatosis had the p.[Cys282Tyr];[Cys282Tyr] disease causative genotype (adjusted prevalence: 24.4%). Of the 801 remaining patients, 112 (14.0%) had the debated p.[Cys282Tyr];[His63Asp] compound heterozygote genotype, 643 (80.3%) had central obesity, 475 (59.3%) had metabolic syndrome (MetS) and 93 (11.6%) were heavy drinkers. The non-haemochromatosis patients started therapeutic venesection 9 years later than haemochromatosis patients (P < 0.001). Despite similar serum ferritin values, they had lower transferrin saturation (41.1% vs 74.3%; P < 0.001), lower amounts of iron removed by venesection (1.7 vs 3.2 g; P < 0.001) and lower hepatic iron concentrations (107 vs 237 µmol/g; P < 0.001).
Haemochromatosis is over-diagnosed and is no longer the main reason for therapeutic venesection in France. Obesity and other metabolic abnormalities are frequently associated with mild elevation of serum ferritin, the MetS is confirmed in ~50% of treated patients. There is a minimal relationship between serum ferritin and iron overload in non-p.Cys282Tyr homozygotes. Our observations raise questions about venesection indications in non-haemochromatosis patients.
放血疗法是血色素沉着症的关键治疗方法，但在铁蓄积量中等的高血铁蛋白症中仍存在争议。有大量证据表明，HFE 基因分型的结果通常被误解，而近年来，随着肥胖和代谢特征的增加，白种成年人的血清铁蛋白水平升高更为常见。
检查 2012 年至 2015 年间法国 1059 例患者放血治疗的原因，确定与 HFE 相关的血色素沉着症的真实患病率，并比较血色素沉着症和非血色素沉着症患者的铁过载情况。
在 488 例被转诊为血色素沉着症的患者中，只有 258 例患者携带 p.[Cys282Tyr];[Cys282Tyr]疾病致病基因型（调整后的患病率：24.4%）。在其余 801 名患者中，有 112 名（14.0%）携带有争议的 p.[Cys282Tyr];[His63Asp]复合杂合基因型，643 名（80.3%）患有中心性肥胖，475 名（59.3%）患有代谢综合征（MetS），93 名（11.6%）为重度饮酒者。非血色素沉着症患者开始接受治疗性放血的时间比血色素沉着症患者晚 9 年（P<0.001）。尽管血清铁蛋白值相似，但他们的转铁蛋白饱和度较低（41.1%比 74.3%；P<0.001），放血去除的铁量较少（1.7 克比 3.2 克；P<0.001），肝脏铁浓度较低（107 微摩尔/克比 237 微摩尔/克；P<0.001）。
血色素沉着症被过度诊断，不再是法国治疗性放血的主要原因。肥胖和其他代谢异常常与血清铁蛋白轻度升高有关，在接受治疗的患者中，约有 50%被确诊患有代谢综合征。在非 p.Cys282Tyr 纯合子患者中，血清铁蛋白与铁过载之间的关系极小。我们的观察结果对非血色素沉着症患者的放血治疗指征提出了质疑。
