非酒精性脂肪性肝病（NAFLD）和相关合并症的人群筛查仍然是一个尚未解决的临床需求。我们的目的是利用英国生物银行评估脂肪肝指数 (FLI) 对 NAFLD 和相关合并症风险分层的效用。电子健康记录和肝脏 MRI 质子密度脂肪分数 (PDFF) 用于定义 NAFLD 病例。计算 FLI 并排除酒精摄入量高和其他肝脏疾病的个体。使用列表删除分析，确定了 NAFLD 风险 FLI 的受试者工作特征曲线下面积 (AUROC)。此后，使用时间依赖性协变量调整 Cox 回归模型来估计 FLI 对感兴趣的合并症的风险分层潜力。FLI 是针对 327,800 名中位年龄为 58 岁（IQR 51.5-64.5）的个体得出的，其中 59.8% 是女性。使用 Perspectum Diagnostics 和 AMRA 方案作为参考，FLI 确定 AUROC（95% CI，n）的 NAFLD 风险分别为 0.858（0.848-0.867，n = 7,566）和 0.851（0.844-0.856，n = 10,777）。中危和高危 FLI 与心脏代谢和恶性疾病的增加有关。在前 3 年中，高风险 FLI 导致缺血性心脏病 (2.14, 1.94-2.36)、高血压 (2.84, 2.70-2.98)、2 型糖尿病 (4.55) 的风险增加（调整后风险比，95% CI）。 ，4.04-5.12），血脂异常（2.48，2.32-2.64），缺血性中风（1.31，1.20-1.42）和肝脏恶性肿瘤（1.69，1.23-2.30）。 FLI 与肝外恶性肿瘤的风险无关，但与特定癌症（结肠癌、上消化道癌和乳腺癌）的较高风险相关。 FLI 也对全因死亡率进行了类似的分层，独立于非侵入性纤维化评分。FLI 可识别 NAFLD，并具有对心脏代谢和恶性疾病结果（包括一些肝外恶性肿瘤）以及全因死亡率进行风险分层的潜力。应考虑将其用于 NAFLD 一级和二级预防的人群筛查。我们使用英国生物银行研究进行的分析表明，脂肪肝指数作为风险分层工具的潜力，可用于识别发生 NAFLD、缺血性心脏病、缺血性中风的风险、2型糖尿病、高血压、高脂血症、肝脏恶性肿瘤、特定代谢相关恶性肿瘤和全因死亡率。这些结果表明，脂肪肝指数应被视为一种非侵入性脂肪变性评分，可能有助于指导 NAFLD 和相关结果的一级预防策略。© 2023 作者。

Population screening for non-alcoholic fatty liver disease (NAFLD) and associated comorbidities remains an unaddressed clinical need. We aimed to assess the utility of the fatty liver index (FLI) for risk stratification of NAFLD and related comorbidities using the UK Biobank.Electronic health records and liver MRI-proton density fat fraction (PDFF) were used to define NAFLD cases. FLI was calculated and individuals with high alcohol intake and other liver diseases were excluded. Using listwise deletion analysis, the area under receiver-operating characteristic curve (AUROC) of FLI for NAFLD risk was determined. Thereafter, time-dependent covariate-adjusted Cox regression models were used to estimate FLI's risk stratification potential for comorbidities of interest.FLI was derived for 327,800 individuals with a median age of 58 (IQR 51.5-64.5), of whom 59.8% were females. Using Perspectum Diagnostics and AMRA protocols as references, FLI identified the risk of NAFLD with AUROCs (95% CI, n) of 0.858 (0.848-0.867, n = 7,566) and 0.851 (0.844-0.856, n = 10,777), respectively. Intermediate and high-risk FLI was associated with increased cardiometabolic and malignant disease. In the first 3 years, high-risk FLI conferred an increased risk (adjusted hazard ratio, 95% CI) of ischaemic heart disease (2.14, 1.94-2.36), hypertension (2.84, 2.70-2.98), type 2 diabetes mellitus (4.55, 4.04-5.12), dyslipidaemia (2.48, 2.32-2.64), ischaemic stroke (1.31, 1.20-1.42) and hepatic malignancy (1.69, 1.23-2.30). FLI was not associated with risk of extrahepatic malignancy but was associated with a higher risk of specific cancers (colon, upper gastrointestinal and breast). All-cause mortality was similarly stratified by FLI, independently of non-invasive fibrosis scores.FLI identifies NAFLD and holds potential for the risk stratification of cardiometabolic and malignant disease outcomes (including some extrahepatic malignancies), as well as all-cause mortality. Its use in population screening for primary and secondary prevention of NAFLD should be considered.Our analysis using the UK Biobank study shows the potential of the fatty liver index as a risk stratification tool for identifying the risk of developing NAFLD, ischaemic heart disease, ischaemic stroke, type 2 diabetes mellitus, hypertension, hyperlipidaemia, hepatic malignancy, specific metabolism-related malignancies and all-cause mortality. These results suggest that the fatty liver index should be considered as a non-invasive steatosis score that may help guide primary prevention strategies for NAFLD and related outcomes.© 2023 The Authors.