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).

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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酒精性肝病患者中增强肝纤维化测试与FibroTest，弹性成像和间接标记物检测晚期纤维化的准确性

背景与目标

酒精是肝硬化和与肝脏相关的死亡率的主要原因，但是我们缺乏血清标记物来检测代偿性疾病。我们比较了增强型肝纤维化测试（ELF），FibroTest，肝硬度测量值（通过瞬时弹性成像和二维剪切波弹性成像）和6种间接标记测试在检测晚期肝纤维化（Kleiner≥阶段）中的准确性。 F3）。

方法

我们对10种肝纤维化标记物（已获得专利和未获得专利）进行了前瞻性研究，所有这些均在同一天进行。从2013年到2014年，患者来自丹麦南部地区的主要中心（市政酒精康复，n = 128； 6％患有晚期纤维化）和二级保健中心（医院门诊，n = 161； 36％患有晚期纤维化）。 2016年。经活检验证的纤维化阶段被用作参考标准。其主要目的是使用基于文献的临界值为10.5，对从一级和二级医疗保健中心招募的酒精性肝病患者的晚期纤维化进行检测以验证ELF。次要目的是评估ELF对严重纤维化和肝硬化的诊断准确性，并确定纤维化标记物的组合是否可提高诊断率。

结果

ELF识别出患有晚期肝纤维化的患者，其接受者工作特征曲线（AUROC）下的面积为0.92（95％置信区间为0.89-0.96）。初级保健与二级保健之间的发现无显着差异（P  = .917）。与间接标记试验相比，ELF更准确地鉴定了晚期肝纤维化患者，但ELF和FibroTest具有可比的诊断准确性（FibroTest的AUROC，0.90）（ 与ELF相比，P = .209）。ELF和FibroTest的结果与意图诊断分析中的肝硬度测量结果没有显着差异（瞬态弹性成像的AUROC为0.90），但按协议分析的差异（瞬态弹性成像的AUROC为0.97）（P = .521和.004（与ELF进行比较）。在瞬时弹性成像分析中添加血清标记物不会提高准确性。对于初级保健患者，低于10.5的ELF值和低于0.58的FibroTest值对晚期肝纤维化的阴性预测值分别为98％和94％。

结论

在一项前瞻性，直接的测试比较中，ELF和FibroTest在一级和二级保健中对酒精中毒患者进行了晚期肝纤维化诊断，具有较高的诊断准确性（以活检为参考，AUROC值为0.90或更高）。基于低于10.5的ELF值或低于0.58的FibroTest值，可以排除初级保健患者的晚期纤维化。