Kowdley Kris V, Brandhagen David J, Gish Robert G, Bass Nathan M, Weinstein Jeffrey, Schilsky Michael L, Fontana Robert J, McCashland Timothy, Cotler Scott J, Bacon Bruce R, Keeffe Emmet B, Gordon Fredric, Polissar Nayak
University of Washington, Seattle, 98195, USA.
Gastroenterology. 2005 Aug;129(2):494-503. doi: 10.1016/j.gastro.2005.05.004.
BACKGROUND & AIMS: Previous uncontrolled studies have suggested that patients with hepatic iron overload have a poor outcome after liver transplantation. We examined the effect of HFE mutations on posttransplantation survival in patients with hepatic iron overload.
Two hundred sixty patients with end-stage liver disease and hepatic iron overload were enrolled from 12 liver transplantation centers. Hepatic iron concentration (HIC), hepatic iron index (HII), HFE mutation status, and survival after liver transplantation were recorded.
HFE-associated hemochromatosis (HH) defined as homozygosity for the C282Y (n = 14, 7.2%) mutation or compound heterozygosity for the C282Y/H63D (n = 11, 5.6%) mutation was identified in 12.8% of patients. Survival postliver transplantation was significantly lower among patients with HH (1-, 3-, and 5-year survival rates of 64%, 48%, 34%, respectively) compared with simple heterozygotes (C282Y/wt or H63D/wt) or wild-type patients. Patients with HH had a hazard ratio for death of 2.6 (P = .002) after adjustment for age, United Network for Organ Sharing status, year of transplantation, and either elevated HII or HIC. Non-HH patients with hepatic iron overload also had significantly decreased survival when compared with the overall population undergoing liver transplantation (OR = 1.4, 95% CI: 1.15-1.61, P < .001).
One- and 5-year survivals after liver transplantation are significantly lower among patients with HFE-associated HH. Our data also suggest that hepatic iron overload may be associated with decreased survival after liver transplantation, even in patients without HH. Early diagnosis of hepatic iron overload using HFE gene testing and iron depletion prior to liver transplantation may improve posttransplantation survival, particularly among patients with HH.
既往非对照研究提示,肝铁过载患者肝移植后预后较差。我们研究了HFE突变对肝铁过载患者移植后生存的影响。
从12个肝移植中心纳入260例终末期肝病合并肝铁过载患者。记录肝铁浓度(HIC)、肝铁指数(HII)、HFE突变状态及肝移植后的生存情况。
12.8%的患者被鉴定为HFE相关性血色素沉着症(HH),定义为C282Y突变纯合子(n = 14,7.2%)或C282Y/H63D突变复合杂合子(n = 11,5.6%)。与单纯杂合子(C282Y/wt或H63D/wt)或野生型患者相比,HH患者肝移植后的生存率显著降低(1年、3年和5年生存率分别为64%、48%、34%)。校正年龄、器官共享联合网络状态、移植年份以及HII或HIC升高后,HH患者的死亡风险比为2.6(P = 0.002)。与接受肝移植的总体人群相比,非HH的肝铁过载患者生存率也显著降低(OR = 1.4,95%CI:1.15 - 1.61,P < 0.001)。
HFE相关性HH患者肝移植后1年和5年生存率显著降低。我们的数据还提示,即使在无HH的患者中,肝铁过载也可能与肝移植后生存率降低有关。使用HFE基因检测早期诊断肝铁过载并在肝移植前进行铁耗竭可能改善移植后生存,尤其是HH患者。