Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute.
Department of Internal Medicine, Cleveland Clinic.
J Clin Gastroenterol. 2020 Nov/Dec;54(10):891-897. doi: 10.1097/MCG.0000000000001339.
Recent guidelines have recommended screening for nonalcoholic fatty liver disease (NAFLD) and case finding of advanced disease with fibrosis in patients with type-2 diabetes (T2D). The aim of this study is to assess the accuracy of commonly used noninvasive scores to predict the presence of advanced fibrosis (AF) in a large cohort of diabetics in real-life settings.
Using International Classification of Diseases, Ninth Revision (ICD-9) codes, all patients with the diagnosis of T2D who had a liver biopsy for suspected NAFLD between January 2000 and December 2015, were identified and analyzed. Patients with secondary causes of hepatic steatosis were excluded. AST/ALT ratio, aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4) index, and Nonalcoholic fatty liver disease Fibrosis Score (NFS) were calculated to predict advanced disease. Sensitivity, specificity, and area under the receiver operator curve were calculated and compared with liver biopsies to predict the overall accuracy of each score.
A total of 1319 patients with T2D underwent liver biopsy for suspected NAFLD. After exclusions, 1,157 subjects were included in the final analysis. Our cohort consisted of 64.6% females and 88.4% were whites. Overall, 85% of the population was overweight or obese (body mass index>25 kg/m). Liver biopsy showed 31.7% with AF [Nonalcoholic Steatohepatitis Clinical Research Network (NASH-CRN) stage 3 to 4]. In comparison to liver biopsy, for the diagnosis of AF, AST/ALT>1.4, APRI>1.5, FIB-4>2.67, and NFS>0.676 had reasonable specificities of 84.2%, 97.4%, 69.9%, and 93% but poor sensitivities of 27.4%, 16.5%, 6.7%, and 44.1%, respectively. Even at lower cutoff values of AST/ALT≥1, APRI≥1, and FIB-4≥1.45 sensitivities remained low at 60.7%, 27.9%, and 72.6%, respectively, except for NFS ≥-1.455 with sensitivity of 94.6%, but at this cutoff, its specificity decreased to 16.9%. The area under the receiver operator curve to detect AF was 0.62, 0.74, 0.77, and 0.72, respectively.
In this large cohort of adult patients with T2D and NAFLD, commonly used fibrosis scores had reasonable specificity, but poor sensitivity for detecting AF in diabetics. The development of reliable biomarkers for NAFLD/NASH in diabetics is urgently needed.
最近的指南建议对 2 型糖尿病（T2D）患者进行非酒精性脂肪性肝病（NAFLD）筛查，并通过纤维化对进展性疾病进行病例发现。本研究旨在评估常用无创评分在真实环境中对大量糖尿病患者中存在进展性纤维化（AF）的预测准确性。
使用国际疾病分类，第九修订版（ICD-9）代码，确定并分析了 2000 年 1 月至 2015 年 12 月间因疑似 NAFLD 而接受肝活检的所有 T2D 患者。排除了继发性肝脂肪变性的患者。计算天冬氨酸氨基转移酶/丙氨酸氨基转移酶比值、天门冬氨酸氨基转移酶血小板比值指数（APRI）、纤维化-4（FIB-4）指数和非酒精性脂肪性肝病纤维化评分（NFS）以预测进展性疾病。计算敏感性、特异性和接收者操作特征曲线下面积，并与肝活检进行比较，以预测每个评分的总体准确性。
共有 1319 名 T2D 患者因疑似 NAFLD 接受肝活检。排除后，共有 1157 例患者纳入最终分析。我们的队列由 64.6%的女性和 88.4%的白人组成。总体而言，85%的人群超重或肥胖（体重指数>25kg/m）。肝活检显示 31.7%存在 AF[非酒精性脂肪性肝炎临床研究网络（NASH-CRN）3 至 4 期]。与肝活检相比，AST/ALT>1.4、APRI>1.5、FIB-4>2.67 和 NFS>0.676 对 AF 的诊断具有合理的特异性（分别为 84.2%、97.4%、69.9%和 93%），但敏感性较低（分别为 27.4%、16.5%、6.7%和 44.1%）。即使在 AST/ALT≥1、APRI≥1 和 FIB-4≥1.45 的较低临界值下，敏感性仍分别为 60.7%、27.9%和 72.6%，除 NFS≥-1.455 外，敏感性为 94.6%，但在此临界值下，特异性降至 16.9%。检测 AF 的接收者操作特征曲线下面积分别为 0.62、0.74、0.77 和 0.72。
在这一大群患有 T2D 和 NAFLD 的成年患者中，常用的纤维化评分对糖尿病患者的 AF 具有合理的特异性，但敏感性较低。迫切需要开发用于糖尿病患者的 NAFLD/NASH 的可靠生物标志物。
