Supplementary Material for: Transient Elastography and Serum-based Tests for Diagnosis of Fatty Liver and Advanced Fibrosis in a Community Cohort- a Cross Sectional Analysis

Background: Non-invasive tests (NITs) are necessary for knowing the true prevalence of fatty liver (FL) and advanced fibrosis (AF). Noninvasive tests (NITs) for diagnosis of FL and fibrosis were compared. Methods: Data were obtained from the National Health and Examination Survey (NHANES; 2017-2018). Participants were excluded with other liver diseases, missing data for NIT calculation and/or excessive alcohol use. Area under the receiver operating characteristic (AUROC) compared the accuracy of 4 FL NITs (CAP, HIS, FLI, USFLI) among themselves and to CAP value of 285 dB/m and 5 fibrosis NITs (transient elastography, APRI, NFS, FIB-4, HEPAmet) among themselves and to LSM ≥ 8.7 kPa. Results: Among 2051 participants (average age 47 (±17.7), 48% males, 62% white, 73% overweight/obese, 39% metabolic syndrome), demographics were similar among NIT groups (CAP=812; HSI=1,234; FLI=935; USFLI-824). FL prevalence by NIT: 39% CAP, 58% HSI, 47% FLI, 37% USFLI. AF prevalence by test- LSM (≥ 8.7 kPa) 10%-14%; FIB-4 (≥2.67) and APRI (≥0.7) 1.3%- 2.7%; HEPAmet (>0.47) 14%-21%. Compared to CAP ≥285, FLI (AUROC= 0.823) and USFLI (AUROC=0.833) performed better than HSI (AUROC: 0.798). Compared to LSM ≥8.7kPa, only NFS (AUROC= 0.722) performed well (Fib-4 AUROC=0.606; APRI=0.647; HEPAmet=0.629). Among the CAP cohort, the strongest FL predictor was obesity (OR 15.2, 95%CI 7.97-28.9, P<0.001); the only fibrosis predictor was elevated AST (OR: 1.06, 95%CI 1.00-1.12, P=0.04). The addition of CAP or LSM as a second NIT reduced the number of indeterminate patients especially for FL. Conclusions: Regardless of diagnostic method in 2017-2018, the prevalence of NAFLD was >35%. NITs for FL performed well but not for AF. CAP and LSM as a second NIT reduced those considered indeterminate.

研究背景：明确脂肪肝（Fatty Liver, FL）与进展期肝纤维化（Advanced Fibrosis, AF）的真实患病率，需依托无创检测（Non-invasive Tests, NITs）。本研究对用于诊断脂肪肝及肝纤维化的各类无创检测方法进行了对比分析。
研究方法：本研究数据取自2017-2018年美国国家健康与营养检查调查（National Health and Examination Survey, NHANES）。排除标准包括合并其他肝脏疾病、无创检测计算所需数据缺失，以及过量饮酒的受试者。采用受试者工作特征曲线下面积（Area under the Receiver Operating Characteristic, AUROC）对比4种脂肪肝无创检测方法[受控衰减参数（Controlled Attenuation Parameter, CAP）、肝脂肪变指数（Hepatic Steatosis Index, HIS）、脂肪肝指数（Fatty Liver Index, FLI）、超声脂肪肝指数（Ultrasound-based Fatty Liver Index, USFLI）]的诊断效能，并以CAP值285 dB/m为截点；同时对比5种肝纤维化无创检测方法[瞬时弹性成像（Transient Elastography）、天冬氨酸氨基转移酶与血小板比率指数（Aspartate Aminotransferase to Platelet Ratio Index, APRI）、非酒精性脂肪肝纤维化评分（NAFLD Fibrosis Score, NFS）、FIB-4指数、HEPAmet评分]的诊断效能，并以肝脏硬度值（Liver Stiffness Measurement, LSM）≥8.7 kPa为截点。
研究结果：本研究共纳入2051名受试者，平均年龄47岁（±17.7），其中男性占48%，白人占62%，超重/肥胖者占73%，合并代谢综合征者占39%。不同无创检测分组的人口学特征无显著差异[CAP组812例、HIS组1234例、FLI组935例、USFLI组824例]。不同无创检测方法对应的脂肪肝患病率分别为：CAP组39%、HIS组58%、FLI组47%、USFLI组37%。不同检测方法对应的进展期肝纤维化患病率分别为：以LSM≥8.7 kPa为标准时为10%~14%；以FIB-4≥2.67、APRI≥0.7为标准时为1.3%~2.7%；以HEPAmet>0.47为标准时为14%~21%。以CAP≥285 dB/m为金标准时，FLI（AUROC=0.823）与USFLI（AUROC=0.833）的诊断效能均优于HIS（AUROC=0.798）。以LSM≥8.7 kPa为金标准时，仅NFS（AUROC=0.722）表现出良好的诊断效能（FIB-4的AUROC为0.606、APRI为0.647、HEPAmet为0.629）。在CAP亚组中，预测脂肪肝最强的危险因素为肥胖（比值比OR=15.2，95%置信区间CI：7.97~28.9，P<0.001）；唯一可预测肝纤维化的危险因素为天冬氨酸氨基转移酶（Aspartate Aminotransferase, AST）升高（OR=1.06，95%CI：1.00~1.12，P=0.04）。将CAP或LSM作为第二种无创检测方法补充入检测流程，可减少无法明确诊断的受试者数量，尤其针对脂肪肝的诊断。
研究结论：2017-2018年美国人群中，无论采用何种诊断方法，非酒精性脂肪性肝病（Non-Alcoholic Fatty Liver Disease, NAFLD）的患病率均超过35%。脂肪肝无创检测方法具有良好的诊断效能，但肝纤维化无创检测方法的诊断效能欠佳。将CAP或LSM作为第二种无创检测方法补充入检测流程，可减少无法明确诊断的受试者数量。