Liver Stiffness Assessed by Ultrasound Shear Wave Elastography from General Electric Accurately Predicts Clinically Significant Portal Hypertension in Patients with Advanced Chronic Liver Disease

Abstract

Purpose Clinically significant portal hypertension (CSPH) is responsible for most of the complications in patients with cirrhosis. Liver stiffness (LS) measurement by vibration-controlled transient elastography (VCTE) is currently used to evaluate CSPH. Bi-dimensional shear wave elastography from General Electric (2D-SWE.GE) has not yet been validated for the diagnosis of PHT. Our aims were to test whether 2D-SWE.GE-LS is able to evaluate CSPH, to determine the reliability criteria of the method and to compare its accuracy with that of VCTE-LS in this clinical setting.

Materials and Methods Patients with chronic liver disease referred to hepatic catheterization (HVPG) were consecutively enrolled. HVPG and LS by both VCTE and 2D-SWE.GE were performed on the same day. The diagnostic performance of each LS method was compared against HVPG and between each other.

Results 2D-SWE.GE-LS was possible in 123/127 (96.90 %) patients. The ability to record at least 5 LS measurements by 2D-SWE.GE and IQR < 30 % were the only features associated with reliable results. 2D-SWE.GE-LS was highly correlated with HVPG (r = 0.704; p < 0.0001), especially if HVPG < 10 mmHg and was significantly higher in patients with CSPH (15.52 vs. 8.14 kPa; p < 0.0001). For a cut-off value of 11.3 kPa, the AUROC of 2D-SWE.GE-LS to detect CSPH was 0.91, which was not inferior to VCTE-LS (0.92; p = 0.79). The diagnostic accuracy of LS by 2D-SWE.GE-LS to detect CSPH was similar with the one of VCTE-LS (83.74 % vs. 85.37 %; p = 0.238). The diagnostic accuracy was not enhanced by using different cut-off values which enhanced the sensitivity or the specificity. However, in the subgroup of compensated patients with alcoholic liver disease, 2D-SWE.GE-LS classified CSPH better than VCTE-LS (93.33 % vs. 85.71 %, p = 0.039).

Conclusion 2D-SWE.GE-LS has good accuracy, not inferior to VCTE-LS, for the diagnosis of CSPH.

Zusammenfassung

Ziel Klinisch signifikante portale Hypertonie (CSPH) ist für die meisten Komplikationen bei Patienten mit Zirrhose verantwortlich. Die Messung der Lebersteifigkeit (LS) mittels vibrationsgesteuerter transienter Elastografie (VCTE) wird derzeit zur Abschätzung einer CSPH verwendet. Die 2-dimensionale Scherwellenelastografie von General Electric (2D-SWE.GE) wurde für die Diagnose der PHT noch nicht validiert. Unser Ziel war es zu untersuchen, ob die LS mittels 2D-SWE.GE in der Lage ist, eine CSPH abzuschätzen, die Zuverlässigkeitskriterien der Methode zu bestimmen und ihre Treffsicherheit in diesem klinischen Anwendungsbereich mit der VCTE-LS zu vergleichen.

Material und Methoden Patienten mit chronischer Lebererkrankung, die für einen Lebervenendruckgradienten (HVPG) mittels Lebervenenkatheter vorgesehen wurden, wurden nacheinander eingeschlossen. HVPG und LS wurden sowohl mittels VCTE als auch 2D-SWE.GE am selben Tag durchgeführt. Die diagnostische Leistung jeder LS-Methode wurde mit dem HVPG sowie untereinander verglichen.

Ergebnisse 2D-SWE.GE-LS war bei 123/127 (96,90 %) Patienten durchführbar. Die Fähigkeit, mindestens 5 LS-Messungen mit 2D-SWE.GE und einer IQR < 30 % aufzuzeichnen, waren die einzigen Parameter, die zu zuverlässigen Ergebnissen führten. Die 2D-SWE.GE-LS korrelierte stark mit dem HVPG (r = 0,704; p < 0,0001), insbesondere bei HVPG < 1 mmHg, und war bei Patienten mit CSPH signifikant höher (15,52 vs. 8,14 kPa; p < 0,0001). Bei einen Cut-off von 11,3 kPa betrug die AUROC der 2D-SWE.GE-LS zum Nachweis einer CSPH 0,91, was der VCTE-LS nicht unterlegen war (0,92; p = 0,79). Die diagnostische Genauigkeit der LS mittels 2D-SWE.GE-LS zur Erkennung von einer CSPH war ähnlich wie bei VCTE-LS (83,74 % gegenüber 85,37 %; p = 0,238). Die diagnostische Genauigkeit wurde durch den Einsatz unterschiedlicher Cut-offs, die die Sensitivität oder Spezifität erhöhten, nicht verbessert. In der Untergruppe der kompensierten Patienten mit alkoholbedingter Lebererkrankung klassifizierte die 2D-SWE.GE-LS eine CSPH jedoch besser als die VCTE-LS (93,33 % gegenüber 85,71 %, p = 0,039).

Schlussfolgerung Für die Diagnose der CSPH zeigt die 2D-SWE.GE-LS eine gute Treffsicherheit – diese ist nicht schlechter als die der VCTE-LS.

Key words

liver stiffness - ultrasound elastography - portal hypertension - noninvasive

Publication History

Received: 26 September 2018

Accepted: 12 June 2019

Article published online:
02 September 2019

• References

• 1 Bosch J, Berzigotti A, Garcia-Pagan JC. et al. The management of portal hypertension: Rational basis, available treatments and future options. J Hepatol 2008; 48: 68-92
• 2 Targownik LE, Spiegel BMR, Dulai GS. et al. The Cost-Effectiveness of Hepatic Venous Pressure Gradient Monitoring in the Prevention of Recurrent Variceal Hemorrhage. Am J Gastroenterol 2004; 99: 1306-1315
• 3 Bosch J, Abraldes JG, Berzigotti A. et al. The clinical use of HVPG measurements in chronic liver disease. Nat Rev Gastroenterol Hepatol Nature Publishing Group 2009; 6: 573-582
• 4 Castera L, Yuen Chan HL, Arrese M. et al. EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015; 63: 237-264
• 5 Franchis RD, Abraldes JG, Bajaj J. et al. Expanding consensus in portal hypertension Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol European Association for the Study of the Liver 2015; 63: 743-752
• 6 Bureau C, Metivier S, Peron JM. et al. Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease. Aliment Pharmacol Ther 2008; 27: 1261-1268
• 7 Robic MA, Procopet B, Métivier S. et al. Liver stiffness accurately predicts portal hypertension related complications in patients with chronic liver disease: a prospective study. J Hepatol 2011; 55: 1017-1024
• 8 Singh S, Fujii LL, Murad MH. et al. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: A systematic review and meta-analysis. Clin Gastroenterol Hepatol Elsevier, Inc 2013; 11: 1573-1584
• 9 Castéra L, Foucher J, Bernard P-H. et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13369 examinations. Hepatology 2010; 51: 828-835
• 10 Bende F, Sporea I, Sirli R. et al. Performance of 2D-SWE.GE for predicting different stages of liver fibrosis, using Transient Elastography as the reference method. Med Ultrason 2017; 19: 143
• 11 Boursier J, de Ledinghen V, Poynard T. et al. An extension of STARD statements for reporting diagnostic accuracy studies on liver fibrosis tests: The Liver-FibroSTARD standards. J Hepatol European Association for the Study of the Liver 2015; 62: 807-815
• 12 Arena U, Lupsor Platon M, Stasi C. et al. Liver stiffness is influenced by a standardized meal in patients with chronic hepatitis C virus at different stages of fibrotic evolution. Hepatology 2013; 58: 65-72
• 13 Berzigotti A, de Gottardi A, Vukotic R. et al. Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension. PLoS One 2013; 8: e58742
• 14 Simkin P, Rattansingh A, Liu K. et al. Reproducibility of 2 Liver 2‐Dimensional Shear Wave Elastographic Techniques in the Fasting and Postprandial States. J Ultrasound Med 2018; 38: 1739-1745
• 15 Ziol M, Handra-Luca A, Kettaneh A. et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 2005; 41: 48-54
• 16 Boursier J, Zarski JP, de Ledinghen V. et al. Determination of reliability criteria for liver stiffness evaluation by transient elastography. Hepatology 2013; 57: 1182-1191
• 17 Fluss R, Faraggi D, Reiser B. Estimation of the Youden Index and its Associated Cutoff Point. Biometrical J 2005; 47: 458-472
• 18 Vizzutti F, Arena U, Romanelli RG. et al. Liver stiffness measurement predicts severe portal hypertension in patients with HCV-related cirrhosis. Hepatology 2007; 45: 1290-1297
• 19 Augustin S, Pons M, Maurice JB. et al. Expanding the Baveno VI criteria for the screening of varices in patients with compensated advanced chronic liver disease. Hepatology 2017; 66: 1980-1988
• 20 Elkrief L, Rautou PE, Ronot M. et al. Prospective Comparison of Spleen and Liver Stiffness by Using Shear-Wave and Transient Elastography for Detection of Portal Hypertension in Cirrhosis. Radiology 2015; 275: 589-598
• 21 Procopet B, Berzigotti A, Abraldes JG. et al. Real-time shear-wave elastography: Applicability, reliability and accuracy for clinically significant portal hypertension. J Hepatol 2015; 62: 1068-1075
• 22 Bende F, Mulabecirovic A, Sporea I. et al. Assessing Liver Stiffness by 2-D Shear Wave Elastography in a Healthy Cohort. Ultrasound Med Biol 2018; 44: 332-341
• 23 Schellhaas B, Strobel D, Wildner D. et al. Two-dimensional shear-wave elastography. Eur J Gastroenterol Hepatol 2017; 29: 723-729
• 24 Attia D, Schoenemeier B, Rodt T. et al. Evaluation of liver and spleen stiffness with acoustic radiation force impulse quantification elastography for diagnosing clinically significant portal hypertension. Ultraschall der Medizin 2015; 36: 603-610
• 25 Jansen C, Bogs C, Verlinden W. et al. Shear-wave elastography of the liver and spleen identifies clinically significant portal hypertension: A prospective multicentre study. Liver Int 2017; 37: 396-405
• 26 Berzigotti A. Non-invasive evaluation of portal hypertension using ultrasound elastography. In: Journal of Hepatology 2017; 67: 399-411
• 27 Abraldes JG, Bureau C, Stefanescu H. et al. Noninvasive tools and risk of clinically significant portal hypertension and varices in compensated cirrhosis: The “Anticipate” study. Hepatology 2016; 64: 2173-2184
• 28 Christoph Dietrich AF, Bamber J, Berzigotti A. et al EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version) EFSUMB-Leitlinien und Empfehlungen zur klinischen Anwendung der Leberelastographie, Update 2017 (Langversion).. EFSUMB Guidel and … Ultraschall in Med 2017; 38: 16-47
• 29 Mulazzani L, Salvatore V, Ravaioli F. et al. Point shear wave ultrasound elastography with Esaote compared to real-time 2D shear wave elastography with supersonic imagine for the quantification of liver stiffness. J Ultrasound 2017; 20: 213-225
• 30 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
• 31 Gress V, Glawion E, Schmidberger J. et al. Comparison of Liver Shear Wave Elastography Measurements using Siemens Acuson S3000, GE LOGIQ E9, Philips EPIQ7 and Toshiba Aplio 500 (Software Versions 5.0 and 6.0) in Healthy Volunteers. Ultraschall der Medizin – Eur J Ultrasound 2018;