Evaluation of Inter-System Variability in Liver Stiffness Measurements

Abstract

Aim The primary aim of this study was to determine the inter-system variability of liver stiffness measurements (LSMs) in patients with varying degrees of liver stiffness. The secondary aim was to determine the inter-observer variability of measurements.

Materials and Methods 21 individuals affected by chronic hepatitis C and 5 healthy individuals were prospectively enrolled. The assessment of LSMs was performed using six ultrasound (US) systems, four of which with point shear wave elastography (p-SWE) and two with 2 D shear wave elastography (2D-SWE) systems. The Fibroscan (Echosens, France) was used as the reference standard. Four observers performed the measurements in pairs (A-B, C-D). The agreement between different observers or methods was calculated using Lin’s concordance correlation coefficient. The Bland-Altman limits of agreement (LOA) were calculated as well.

Results There was agreement above 0.80 for all pairs of systems. The mean difference between the values of the systems with 2D-SWE technique was 1.54 kPa, whereas the maximum mean difference between the values of three out of four systems with the pSWE technique was 0.79 kPa. The intra-patient concordance for all systems was 0.89 (95 % CI: 0.83 – 0.94). Inter-observer agreement was 0.96 (95 % CI: 0.94 – 0.98) for the pair of observers A-B and 0.93 (95 % CI: 0.89 – 0.96) for the pair of observers C-D.

Conclusion The results of this study show that the agreement between LSMs performed with different US systems is good to excellent and the overall inter-observer agreement in “ideal conditions” is above 0.90 in expert hands.

Zusammenfassung

Ziel Das Primärziel dieser Studie war es, die Intersystem-Variabilität von Lebersteifigkeitsmessungen (LSM) bei Patienten mit unterschiedlichen Lebersteifigkeiten zu bestimmen. Das Sekundärziel bestand in der Bestimmung der Inter-Beobachter-Variabilität der Messungen.

Material und Methoden Einundzwanzig Personen mit chronischer Hepatitis C und fünf gesunde Personen wurden prospektiv aufgenommen. Die Bewertung der LSM erfolgte mit sechs Ultraschallsystemen (US), vier davon verwendeten Punkt-Scherwellen-Elastografie (p-SWE) und zwei 2D-Scherwellen-Elastografie (2D-SWE). Der Fibroscan (Echosens, Frankreich) wurde als Referenzstandard verwendet. Vier Beobachter führten jeweils in Paaren die Messungen durch (A-B, C-D). Die Übereinstimmung zwischen verschiedenen Beobachtern oder Methoden wurde unter Verwendung des Konkordanz-Korrelationskoeffizienten nach Lin berechnet. Die Bland-Altman Übereinstimmungsgrenzen (LOA) wurden ebenfalls bestimmt.

Ergebnisse Die Übereinstimmung betrug mehr als 0,80 für alle Systempaare. Der mittlere Unterschied zwischen den Werten der Systeme mit 2D-SWE-Technik betrug 1,54 kPa, während der maximale mittlere Unterschied zwischen den Werten von drei der vier Systeme mit pSWE-Technik 0,79 kPa betrug. Die Intra-Patienten-Konkordanz für alle Systeme war 0,89 (95 % CI: 0,83 – 0,94). Die Interobserver-Übereinstimmung betrug 0,96 (95 % CI: 0,94 – 0,98) für das Paar der Beobachter A-B und 0,93 (95 % CI: 0,89 – 0,96) für das Paar der Beobachter C-D.

Schlussfolgerung Die Ergebnisse dieser Studie zeigen, dass die Übereinstimmung zwischen LSMs, die mit unterschiedlichen US-Systemen durchgeführt wurden, gut bis hervorragend ist und die globale Übereinstimmung zwischen den Beobachtern, sofern diese Expertise besitzen, unter „idealen Bedingungen“ über 0,90 liegt.

Key words

liver stiffness - shear wave elastography - variability studies - cirrhosis - liver fibrosis

• References

• 1 Perepelyuk M, Terajima M, Wang AY. et al. Hepatic stellate cells and portal fibroblasts are the major cellular sources of collagens and lysyl oxidases in normal liver and early after injury. Am J Physiol Gastrointest Liver Physiol 2013; 304: G605-G614
• 2 Ferraioli G, Parekh P, Levitov AB. et al. Shear wave elastography for evaluation of liver fibrosis. J Ultrasound Med 2014; 33: 197-203
• 3 Barr RG, Ferraioli G, Palmeri ML. et al. Elastography Assessment of Liver Fibrosis: Society of Radiologists in Ultrasound Consensus Conference Statement. Radiology 2015; 276: 845-861
• 4 Hepatitis B (chronic): diagnosis and management | Guidance and guidelines | NICE [Internet]. [cited 2017 Feb 2]. Available from: https://www.nice.org.uk/guidance/cg165
• 5 Dietrich CF, Bamber J, Berzigotti A. et al. EFSUMB Guidelines and recommendations on the clinical use of liver ultrasound elastography, Update 2017 (short version). Ultraschall in Med 2017; 38: 377-394 . doi:10.1055/s-0043-103955
• 6 Ferraioli G, Filice C, Castera L. et al. “WFUMB Guidelines and Recommendations for Clinical Use of Ultrasound Elastography:Part 3: Liver”. Ultrasound Med Biol 2015; 41: 1161-1179
• 7 Hall TJ, Milkowski A, Garra B. et al. RSNA/QIBA: shear wave speed as a biomarker for liver fibrosis staging. In: Ultrasonics Symposium (IUS) I.E. International; 2013: 397-400
• 8 Palmeri M, Nightingale K, Fielding S. et al. RSNA QIBA ultrasound shear wave speed Phase II phantom study in viscoelastic media. Proceedings of the 2015 IEEE Ultrasonics Symposium. 2015: 397-400
• 9 Tsochatzis EA, Gurusamy KS, Ntaoula S. et al. Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy. J Hepatol 2011; 54: 650-659
• 10 Lin LI. A concordance correlation coefficient to evaluate reproducibility. Biometrics 1989; 45: 255-268
• 11 Altman DG. Practical Statistics for Medical Research. London: Chapman & Hall; 1997
• 12 Piscaglia F, Salvatore V, Mulazzani L. et al. Differences in liver stiffness values obtained with new ultrasound elastography machines and Fibroscan: A comparative study. Dig Liver Dis 2017; 49: 802-808 . doi:10.1016/j.dld.2017.03.001
• 13 Ferraioli G, Tinelli C, Zicchetti M. et al. Reproducibility of real-time shear wave elastography in the evaluation of liver elasticity. Eur J Radiol 2012; 81: 3102-3106
• 14 Boursier J, Isselin G, Fouchard-Hubert I. et al. Acoustic radiation force impulse: a new ultrasonographic technology for the widespread noninvasive diagnosis of liver fibrosis. Eur J Gastroenterol Hepatol 2010; 22: 1074-1084
• 15 D’Onofrio M, Gallotti A, Mucelli RP. Tissue quantification with acoustic radiation force impulse imaging: Measurement repeatability and normal values in the healthy liver. Am J Roentgenol 2010; 195: 132-136
• 16 Friedrich-Rust M, Wunder K, Kriener S. et al. Liver fibrosis in viral hepatitis: noninvasive assessment with acoustic radiation force impulse imaging versus transient elastography. Radiology 2009; 252: 595-604
• 17 Ferraioli G, Tinelli C, Lissandrin R. et al. Point shear wave elastography method for assessing liver stiffness. World J Gastroenterol 2014; 20: 4787-4796
• 18 Bota S, Sporea I, Sirli R. et al. Intra- and interoperator reproducibility of acoustic radiation force impulse (ARFI) elastography--preliminary results. Ultrasound Med Biol 2012; 38: 1103-1108
• 19 Yoon JH, Lee JM, Han JK. et al. Shear wave elastography for liver stiffness measurement in clinical sonographic examinations: evaluation of intraobserver reproducibility, technical failure, and unreliable stiffness measurements. J Ultrasound Med 2014; 33: 437-447
• 20 Hudson JM, Milot L, Parry C. et al. Inter- and intra-operator reliability and repeatability of shear wave elastography in the liver: a study in healthy volunteers. Ultrasound Med Biol 2013; 39: 950-955
• 21 Fraquelli M, Rigamonti C, Casazza G. et al. Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut 2007; 56: 968-973