Department of Gastroenterology and Hepatology and OPEN, Odense Patient data Explorative Network, Odense University Hospital, Odense C, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark.
Department of Gastroenterology and Hepatology and OPEN, Odense Patient data Explorative Network, Odense University Hospital, Odense C, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark.
Gastroenterology. 2018 Apr;154(5):1369-1379. doi: 10.1053/j.gastro.2018.01.005. Epub 2018 Jan 6.
BACKGROUND & AIMS: Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3).
We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield.
The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P = .521 and .004 for comparison with ELF). Adding a serum marker to transient elastography analysis did not increase accuracy. For patients in primary care, ELF values below 10.5 and FibroTest values below 0.58 had negative predictive values for advanced liver fibrosis of 98% and 94%, respectively.
In a prospective, direct comparison of tests, ELF and FibroTest identified advanced liver fibrosis in alcoholic patients from primary and secondary care with high diagnostic accuracy (AUROC values of 0.90 or higher using biopsy as reference). Advanced fibrosis can be ruled out in primary health care patients based on an ELF value below 10.5 or a FibroTest value below 0.58.
酒精是肝硬化和与肝脏相关死亡率的主要原因，但我们缺乏用于检测代偿性疾病的血清标志物。我们比较了增强型肝脏纤维化检测（ELF）、FibroTest、肝硬度测量（通过瞬时弹性成像和二维剪切波弹性成像进行）以及 6 种间接标志物检测在检测晚期纤维化（Kleiner 分期≥F3）方面的准确性。
我们进行了一项前瞻性研究，共纳入了 10 种肝纤维化标志物（已获得专利和未获得专利的标志物），均在同一天进行检测。研究对象来自丹麦南部地区的初级医疗中心（市政酒精康复中心，n=128；6%的患者存在晚期纤维化）和二级医疗机构（医院门诊，n=161；36%的患者存在晚期纤维化）。肝活检证实的纤维化分期作为参考标准。主要目的是使用文献中基于 10.5 的截断值，验证 ELF 在检测来自初级和二级医疗保健中心的酒精性肝病患者中晚期纤维化的准确性。次要目的是评估 ELF 对显著纤维化和肝硬化的诊断准确性，并确定是否可以组合使用纤维化标志物来提高诊断效果。
ELF 检测晚期肝纤维化的曲线下面积（AUROC）为 0.92（95%置信区间为 0.89-0.96）；初级和二级保健患者之间的检测结果无显著差异（P=0.917）。ELF 比间接标志物检测更准确地识别出晚期肝纤维化患者，但 ELF 和 FibroTest 的诊断准确性相当（FibroTest 的 AUROC 为 0.90）（与 ELF 比较，P=0.209）。ELF 和 FibroTest 的检测结果在意向诊断分析中与肝硬度测量无显著差异（瞬时弹性成像的 AUROC 为 0.90），但在方案分析中有所不同（瞬时弹性成像的 AUROC 为 0.97）（与 ELF 比较，P=0.521 和 P=0.004）。在瞬时弹性成像分析中添加血清标志物并未提高准确性。对于初级保健患者，ELF 值<10.5 和 FibroTest 值<0.58 时，对晚期肝纤维化的阴性预测值分别为 98%和 94%。
在一项前瞻性的直接测试比较中，ELF 和 FibroTest 以高诊断准确性（使用肝活检作为参考，AUROC 值为 0.90 或更高）在来自初级和二级保健的酒精性肝病患者中识别出晚期肝纤维化。基于 ELF 值<10.5 或 FibroTest 值<0.58，可排除初级保健患者的晚期纤维化。
