Non-invasive Diagnostic Tests in Cystic Fibrosis-Related Liver Disease: A Diagnostic Test Accuracy Network Meta-Analysis.

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 (Se94%[CI58-100], Sp72%[CI52-84]); while transient elastography (Se65%[CI56-74], Sp88%[CI84-91]) and a combination of it with a tissue inhibitor of metalloproteinase-4 measurement (Se78%[CI30-100], Sp64%[CI18-95%]) proved to be the second and third best options, respectively. In the imaging techniques subgroup, transient elastography (Se66%[CI57-72], Sp88%[CI85-91%]), acoustic radiation force impulse in the right lobe (Se54%[CI33-74], Sp88%[CI66-96]) and that in the left lobe (Se55%[CI23-81], Sp82%[CI50-95]) were ranked the highest. Comparing biochemical markers/fibrosis indices, the measurement of the Forns index (Se72%[CI25-99], Sp63%[CI16-94]), the aspartate aminotransferase-to-platelet ratio (Se55%[CI41-68], Sp83%[CI66-89]) and alkaline phosphatase (Se63%[CI18-93], Sp64%[CI19-95]) 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.