Abstract
Background
Poorly performing diagnostic tests can impact patient safety. Clinical investigations must have good precision and diagnostic accuracy before widespread use in clinical practice. Transient elastography (TE) measures liver stiffness, a surrogate marker of liver fibrosis in adults and children. Studies to evaluate its repeatability and reproducibility (precision) in children are limited. Our aim was to determine (i) the normal range of TE measurements and (ii) the repeatability and reproducibility of TE in healthy children.
Methods
TE was performed in 257 healthy children, of whom 235 (91%, mean age 11.7 years, standard deviation (SD) 2.51, 107 were males (45.5%)) had two valid TE measurements performed, at least 24 h apart, by two operators under similar circumstances. High-quality TE images were obtained for each examination.
Results
The normal range of TE was 2.88–6.52 kPa. The mean difference between paired measurements was 0.044 (SD 0.4). The 95% limits of agreement ranged from −0.8 to +0.76 kPa for repeat measurements. There was a difference of >1 kPa between measurements in 61/235 (25.9%) children. The lack of precision was similar across all age groups.
Conclusions
This study demonstrates that TE does not have acceptable precision in healthy children, because random measurement variation results in the lack of agreement between paired measurements.
Impact
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The precision and diagnostic accuracy of a new technology must be determined before it is deployed in children in order to ensure that appropriate clinical decisions are made, and healthcare resources are not wasted.
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TE is widely used to diagnose liver disease in children without adequate evaluation of the precision (repeatability) of TE either in healthy children or children with liver disease.
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This study demonstrates that TE does not have adequate precision in children.
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This study was performed in accordance with methods previously published for children. Refinements to the test protocol, such as duration of fasting or probe size, will have to be evaluated for their impact on precision and accuracy before the test is deployed in research studies or clinical practice.
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Acknowledgements
We thank all those who participated in this study, in particular our healthy volunteers without whom this study would not have been possible. This research was funded by The Health Research Board (HRA-PHS-662). The Health Research Board had no role in the study. There was no industry support for this study. The corresponding author had full access to all the data and has final responsibility for the decision to submit for publication.
Cystic Fibrosis Liver Disease Research Group
B. Casserly11, D. Cox3, A. Das12, C. Gallagher7, P. Greally13, C. Gunaratnam14, F. Healy15, M. Herzig16, S. Javadpour3, G. Lean13, N. G. McElvaney14, E. McKone7, D. Mullane17, M. Ni Chroinin17, M. O’ Mahony16, M. O’ Neil18, B. Plant17, M. Rogan12 and C. Short17
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Contributions
Study concept: M.R., B.B. and P.A.McC. Study design: M.R. and L.E.D. Acquisition of data: A.McG., J.D. and L.R. Data analysis: A.McG., L.E.D. and M.R. Data interpretation: B.L., L.R., E.F., B.B., J.D., P.McN., A.McG. and M.R. First draft manuscript: M.R. and A.McG. Critical revision of manuscript: B.B., B.D., A.McG. and M.R. Final appraisal of manuscript: B.B., B.D., P.A.McC., B.L., E.F., L.R., A.B., J.D., L.C., P.McN., Cystic Fibrosis Registry of Ireland and Cystic Fibrosis Liver Disease Research Group
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The authors declare no competing interests.
Ethical approval
The study was approved by the Ethics Committees of Our Lady’s Children’s Hospital Crumlin (for both healthy volunteers and children with cystic fibrosis) and by the National Children’s Hospital Tallaght, Children’s University Hospital and St Vincent’s University Hospital Dublin for participants with cystic fibrosis. Written informed consent was obtained from parents or guardians of children under 18 years of age for their child’s participation in the study with assent from the children. Participants over 18 years of age provided written informed consent for the study.
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Rowland, M., McGee, A., Broderick, A. et al. Repeatability of transient elastography in children. Pediatr Res 88, 587–592 (2020). https://doi.org/10.1038/s41390-020-0916-4
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DOI: https://doi.org/10.1038/s41390-020-0916-4
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