ABSTRACT: Background and Aims: 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. Methods: 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. Results: 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. Conclusion: 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.
