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 (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.

The non‐invasive evaluation of liver involvement in patients with cystic fibrosis: A prospective study

“…The classical clinical diagnosis of CFLD 14 is based on the presence of abnormal physical examination (i.e. hepatomegaly), abnormal liver tests and abnormal ultrasound findings and has been recently challenged by the introduction of non‐invasive tests that can accurately assess the presence of fibrosis in patients with chronic liver disease, 16 including the specific context of CF 2,24,33–36 . More importantly, reports showed that NCPH and not biliary cirrhosis is the underlying histological cause of PH in the overwhelming majority (80%–90%) of CF patients undergoing LT 6–8 …”

“…hepatomegaly), abnormal liver tests and abnormal ultrasound findings and has been recently challenged by the introduction of non-invasive tests that can accurately assess the presence of fibrosis in patients with chronic liver disease, 16 including the specific context of CF. 2,24,[33][34][35][36] More importantly, reports showed that NCPH and not biliary cirrhosis is the underlying histological cause of PH in the overwhelming majority (80%-90%) of CF patients undergoing LT. [6][7][8] Noncirrhotic portal hypertension has consistently been recognized as a possible manifestation of liver involvement in CF. 8,13,37 However, its clinical relevance has been greatly underestimated by (i) the lack of unique diagnostic criteria, (ii) difficulty to distinguish between NCPH and ACLD with PH based solely on ultrasound and biochemical data and (iii) paucity of studies on liver biopsy evaluation that could rule-out advanced fibrosis/cirrhosis in such patients.…”

The Diagnostic Performance of Laboratory Tests of Neurosyphilis: A Systematic Review and Network Meta-Analysis

“…Evidence of the superiority of these tests is scarce. DTA-NMA is a novel meta-analysis technique that allows multiple diagnostic tests to be interpreted in a single analysis and compares numerous screening techniques without headto-head comparisons [35][36][37]. It gives access to compare both direct and indirect evidence [38].…”