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.
ARFI and transient elastography for characterization of cystic fibrosis related liver disease: First longitudinal follow-up data in adult patients
