Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Cancer Epidemiol Biomarkers Prev. 2022 Jan;31(1):230-235. doi: 10.1158/1055-9965.EPI-21-0754. Epub 2021 Oct 14.
Nonalcoholic fatty liver disease (NAFLD) has become a major contributor to the rising incidence of hepatocellular carcinoma (HCC) in the United States and other developed countries. Iron, an essential metal primarily stored in hepatocytes, may play a role in the development of NAFLD-related HCC. Epidemiologic 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 patients with NAFLD.
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 (HR) and 95% confidence intervals (CI) 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.
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 的发展中起作用。关于无血色病的铁过载与 HCC 之间的流行病学数据很少。本研究旨在研究 NAFLD 患者血清铁生物标志物与 HCC 风险之间的关系。
我们使用匹兹堡大学医学中心的电子病历，从 2004 年到 2018 年，确定了 18569 例 NAFLD 患者。在平均 4.34 年的随访后，244 例患者发生 HCC。使用 Cox 比例风险回归计算与升高的铁生物标志物相关的 HCC 发生率的危险比（HR）和 95%置信区间（CI），并调整年龄、性别、种族、体重指数、糖尿病史和吸烟情况。
与正常范围相比，临床定义的血清铁和转铁蛋白饱和度升高的 HCC 的 HR（95%CI）分别为 2.91（1.34-6.30）和 2.02（1.22-3.32）。总铁结合能力或血清铁蛋白与 HCC 风险之间没有观察到统计学显著关联。
在无血色病或其他慢性肝病主要潜在原因的 NAFLD 患者中，血清铁和转铁蛋白饱和度升高与 HCC 风险增加显著相关。
对血清铁水平的临床监测可能是识别 HCC 风险较高的 NAFLD 患者的潜在策略。
