Serum Biomarkers of Iron Status and Risk of Hepatocellular Carcinoma Development in Patients with Nonalcoholic Fatty Liver Disease.
Serum Biomarkers of Iron Status and Risk of Hepatocellular Carcinoma Development in Patients with Nonalcoholic Fatty Liver Disease.
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DOI：
10.1158/1055-9965.epi-21-0754
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发表时间：
2022-01
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非酒精性脂肪性肝病（NAFLD）已成为美国和其他发达国家肝细胞癌（HCC）发病率上升的主要原因。铁是一种主要储存在肝细胞中的必需金属，可能在NAFLD相关HCC的发展中发挥作用。没有血色病的铁超负荷与HCC相关的流行病学数据很少。本研究旨在研究血清铁生物标志物与NAFLD患者HCC风险之间的关系。我们使用匹兹堡大学医学中心电子健康记录从2004年到2018年确定了18，569名NAFLD患者。经过平均4.34年的随访，244例患者发生了HCC。采用考克斯比例风险回归计算与铁生物标志物水平升高相关的HCC发病率的风险比（HR）和95%置信区间（CI），并调整年龄、性别、种族、体重指数、糖尿病史和吸烟史。血清铁和转铁蛋白饱和度升高的HR（95% CI）分别为2.91（1.34-6.30）和2.02（1.22-3.32）。未观察到总铁结合力或血清铁蛋白与HCC风险的统计学显著相关性。血清铁和转铁蛋白饱和度水平升高与无血色素沉着症或其他慢性肝病主要潜在原因的NAFLD患者发生HCC的风险增加显著相关。血清铁水平的临床监测可能是一个潜在的策略，以确定谁是肝癌的高风险与NAFLD患者。
Non-alcoholic fatty liver disease (NAFLD) has become a major contributor to the rising incidence of hepatocellular carcinoma (HCC) in the US and other developed countries. Iron, an essential metal primarily stored in hepatocytes, may play a role in the development of NAFLD-related HCC. Epidemiological data on iron overload without hemochromatosis in relation to HCC are sparse. This study aimed to examine the associations between serum biomarkers of iron and the risk of HCC in NAFLD patients. We identified 18,569 patients with NAFLD using the University of Pittsburgh Medical Center electronic health records from 2004 through 2018. After an average 4.34 years of follow-up, 244 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence associated with elevated levels of iron biomarkers with adjustment for age, sex, race, body mass index, history of diabetes and tobacco smoking. The HRs (95% CIs) of HCC for clinically defined elevation of serum iron and transferrin saturation were 2.91 (1.34–6.30) and 2.02 (1.22–3.32), respectively, compared with their respective normal range. No statistically significant association was observed for total iron-binding capacity or serum ferritin with HCC risk. Elevated levels of serum iron and transferrin saturation were significantly associated with increased risk of HCC among patients with NAFLD without hemochromatosis or other major underlying causes of chronic liver diseases. Clinical surveillance of serum iron level may be a potential strategy to identify patients with NAFLD who are at high risk for HCC.