Martonosi Ágnes Rita, Soós Alexandra, Rumbus Zoltán, Hegyi Péter, Izsák Vera, Pázmány Piroska, Imrei Marcell, Váncsa Szilárd, Szakács Zsolt, Párniczky Andrea
Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Heim Pál National Paediatric Institute, Budapest, Hungary.
Front Med (Lausanne). 2021 Jul 27;8:598382. doi: 10.3389/fmed.2021.598382. eCollection 2021.
Cystic fibrosis-related liver disease (CFLD) is one of the leading causes of morbidity and mortality in cystic fibrosis (CF). Several non-invasive diagnostic methods have been proposed as screening tools for CFLD. Our aim was to rank all available non-invasive modalities for diagnostic performance. A systematic search was performed in five medical databases to find studies which reported on any single or composite non-invasive diagnostic test (as an index test) compared to the Debray, the EuroCare or the Colombo criteria (as a reference standard). Ranking was carried out with a Bayesian diagnostic test accuracy network meta-analysis based on superiority indices, calculated for pooled sensitivity (Se) and specificity (Sp) with a 95% confidence interval (CI). The study was registered under CRD42020155846 in PROSPERO. Fifteen studies with 15 index tests and a combination of them were included. The New criteria proposed by Koh et al. - which represent a composite diagnostic definition for CFLD including liver biochemistry, ultrasonography, transient elastography and fibrosis markers-had the best performance for detecting CFLD (Se:94%[CI:58-100], Sp:72%[CI:52-84]); while transient elastography (Se:65%[CI:56-74], Sp:88%[CI:84-91]) and a combination of it with a tissue inhibitor of metalloproteinase-4 measurement (Se:78%[CI:30-100], Sp:64%[CI:18-95%]) proved to be the second and third best options, respectively. In the imaging techniques subgroup, transient elastography (Se:66%[CI:57-72], Sp:88%[CI:85-91%]), acoustic radiation force impulse in the right lobe (Se:54%[CI:33-74], Sp:88%[CI:66-96]) and that in the left lobe (Se:55%[CI:23-81], Sp:82%[CI:50-95]) were ranked the highest. Comparing biochemical markers/fibrosis indices, the measurement of the Forns index (Se:72%[CI:25-99], Sp:63%[CI:16-94]), the aspartate aminotransferase-to-platelet ratio (Se:55%[CI:41-68], Sp:83%[CI:66-89]) and alkaline phosphatase (Se:63%[CI:18-93], Sp:64%[CI:19-95]) were ranked the highest. The New criteria show the best diagnostic performance. In clinical practice, transient elastography seems to be a simple, cheap and non-invasive tool, outperforming imaging, biochemical and fibrosis tests for detecting CFLD. Further studies are needed to validate our findings.
囊性纤维化相关肝病（CFLD）是囊性纤维化（CF）患者发病和死亡的主要原因之一。目前已提出多种非侵入性诊断方法作为CFLD的筛查工具。我们的目的是对所有可用的非侵入性诊断方法的诊断性能进行排名。我们在五个医学数据库中进行了系统检索，以查找报告了任何单一或复合非侵入性诊断试验（作为指标试验）与德布雷标准、欧洲护理标准或科伦坡标准（作为参考标准）对比情况的研究。基于优势指数，采用贝叶斯诊断试验准确性网络荟萃分析进行排名，计算合并敏感度（Se）和特异度（Sp）以及95%置信区间（CI）。该研究已在国际前瞻性系统评价注册库（PROSPERO）中注册，注册号为CRD42020155846。纳入了15项研究，涉及15种指标试验及其组合。 Koh等人提出的新标准——这是一种用于CFLD的复合诊断定义，包括肝脏生化指标、超声检查、瞬时弹性成像和纤维化标志物——在检测CFLD方面表现最佳（Se：94%[CI：58 - 100]，Sp：72%[CI：52 - 84]）；而瞬时弹性成像（Se：65%[CI：56 - 74]，Sp：88%[CI：84 - 91]）及其与金属蛋白酶组织抑制剂 - 4测量值的组合（Se：78%[CI：30 - 100]，Sp：64%[CI：18 - 95%]）分别被证明是第二和第三好的选择。在成像技术亚组中，瞬时弹性成像（Se：66%[CI：57 - 72]，Sp：88%[CI：85 - 91%]）、右叶声辐射力脉冲（Se：54%[CI：33 - 74]，Sp：88%[CI：66 - 96]）和左叶声辐射力脉冲（Se：55%[CI：23 - 81]，Sp：82%[CI：50 - 95]）排名最高。在比较生化标志物/纤维化指标时，Forns指数测量值（Se：72%[CI：25 - 99]，Sp：63%[CI：16 - 94]）、天冬氨酸转氨酶与血小板比值（Se：55%[CI：41 - 68]，Sp：83%[CI：66 - 89]）和碱性磷酸酶（Se：63%[CI：18 - 93]，Sp：64%[CI：19 - 95]）排名最高。新标准显示出最佳的诊断性能。在临床实践中，瞬时弹性成像似乎是一种简单、廉价且非侵入性的工具，在检测CFLD方面优于成像、生化和纤维化检测。需要进一步研究来验证我们的发现。
