Ultraschall Med 2023; 44(04): 428-435
DOI: 10.1055/a-1933-2847
Original Article

Noninvasive Evaluation of Clinically Significant Portal Hypertension in Patients with Liver Cirrhosis: The Role of Contrast-Enhanced Ultrasound Perfusion Imaging and Elastography

Nicht invasive Bewertung der klinisch signifikanten portalen Hypertonie bei Patienten mit Leberzirrhose: Die Rolle der kontrastverstärkten Ultraschall-Perfusionsbildgebung und der Elastografie
Maria Assunta Zocco
1   Internal Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
,
Marco Cintoni
3   Clinical Nutrition, University of Rome Tor Vergata, Roma, Italy (Ringgold ID: RIN9318)
,
Maria Elena Ainora
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
,
Matteo Garcovich
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
,
Andrea Lupascu
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
,
Roberto Iezzi
4   Radiology, University Hospital Agostino Gemelli, Rome, Italy (Ringgold ID: RIN18654)
,
Brigida Eleonora Annichiarico
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
,
Massimo Siciliano
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
,
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
,
Gian Ludovico Rapaccini
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
,
Antonio Grieco
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
,
Maurizio Pompili
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
,
Antonio Gasbarrini
2   CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy (Ringgold ID: RIN18654)
› Author Affiliations

Abstract

Background Hepatic venous pressure gradient (HVPG) is the gold standard for assessing the degree of portal hypertension (PH), but it is not suitable for routine clinical use. The recently developed ultrasonography techniques, dynamic contrast-enhanced ultrasound (D-CEUS) and liver stiffness (LS), have expanded the possibilities for noninvasive evaluation.

Aims To investigate the usefulness of D-CEUS and elastographic parameters in assessing the presence and degree of PH.

Methods This is a prospective monocentric study. Patients with liver cirrhosis referred for HVPG measurements underwent hepatic Doppler ultrasound, LS measurement, and D-CEUS with a second-generation contrast agent. Pearson’s correlation and a receiver operating characteristic (ROC) curve analysis were performed to assess the role of noninvasive findings in predicting clinically significant PH (CSPH) and severe PH (SPH).

Results 46 consecutive patients (31 men; mean age±SD: 57±11 years) were enrolled. A significant positive correlation was noted between LS and HVPG (r = 0.809, p<0.0001) with an area under the ROC curve of 0.923. A cut-off value of 24.2 kPa best predicted CSPH with a positive predictive value of 85%. Among the D-CEUS features, the area under the ROC curves of liver parenchyma peak intensity (PI-LP) was greater than the other indices both for CSPH and SPH (1.000 and 0.981, respectively). A PI-LP under 23.3 arbitrary units indicated the presence of CSPH with a sensitivity and a specificity of 100%.

Conclusion A multimodal ultrasound approach based on D-CEUS and LS might become a reliable predictor of CSPH and SPH and a useful alternative to HVPG.

Zusammenfassung

Hintergrund Der hepatische Venendruckgradient (HVPG) ist der Goldstandard zur Beurteilung des Schweregrads der portalen Hypertonie (PH), eignet sich jedoch nicht für den Einsatz in der klinischen Praxis. Die kürzlich entwickelten Ultraschalltechniken, der dynamische kontrastverstärkte Ultraschall (D-CEUS) und die Lebersteifigkeit (LS), haben die Möglichkeiten der nicht invasiven Untersuchung erweitert.

Ziel Untersuchung des Nutzens von D-CEUS und elastografischen Parametern bei der Diagnose einer PH und Beurteilung ihres Schweregrads.

Methoden Dies ist eine prospektive monozentrische Studie. Bei Patienten mit Leberzirrhose, die zur HVPG-Messung überwiesen wurden, wurden hepatischer Doppler-Ultraschall, LS-Messung und D-CEUS mit einem Kontrastmittel der 2. Generation durchgeführt. Es wurden eine Pearson-Korrelation und eine ROC-Kurvenanalyse (Receiver Operating Characteristic) durchgeführt, um die Rolle nicht invasiver Befunde bei der Vorhersage einer klinisch signifikanten PH (CSPH) und der schweren PH (SPH) zu bewerten.

Ergebnisse Es wurden 46 konsekutive Patienten (31 Männer; Durchschnittsalter ±SD: 57 ±11 Jahre) eingeschlossen. Eine signifikante positive Korrelation wurde zwischen LS und HVPG (r = 0,809, p<0,0001) mit einer Fläche unter der ROC-Kurve von 0,923 festgestellt. Ein Cut-Off-Wert von 24,2 kPa erlaubte die beste Vorhersage für CSPH mit einem positiven Vorhersagewert von 85%. Unter den D-CEUS-Merkmalen war die Fläche unter den ROC-Kurven der Peak-Intensität des Leberparenchyms (PI-LP) sowohl für CSPH als auch für SPH größer (1,000 bzw. 0,981) als die anderen Indizes. Eine PI-LP unter 23,3 arbiträren Einheiten sprach für eine CSPH mit einer Sensitivität und einer Spezifität von 100%.

Schlussfolgerung Ein multimodaler Ultraschallansatz, basierend auf D-CEUS und LS, könnte ein zuverlässiger Prädiktor für CSPH und SPH sowie eine nützliche Alternative zum HVPG werden.

Supporting information



Publication History

Received: 01 October 2021

Accepted after revision: 05 August 2022

Article published online:
16 December 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Berzigotti A, Seijo S, Reverter E. et al. Assessing portal hypertension in liver diseases. Exp Rev Gastroenterol Hepatol 2013; 7: 141-155
  • 2 D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006; 44: 217-231
  • 3 De Franchis R, Bosch J, Garcia-Tsa G. et al. Baveno VII – Renewing consensus in portal hypertension. J Hepatol 2022; 76: 959-974
  • 4 Zocco MA, Garcovich M, Lupascu A. et al. Early prediction of response to Sorafenib in patients with advanced hepatocellular carcinoma: the role of dynamic contrast enhanced ultrasound. J Hepatol 2013; 59: 1014-1021
  • 5 Kim MY, Suk KT, Baik SK. et al. Hepatic vein arrival time as assessed by contrast-enhanced ultrasonography is useful for the assessment of portal hypertension in compensated cirrhosis. Hepatology 2012; 56: 1053-1062
  • 6 Zhang CX, Hu J, Hu KW. et al. Noninvasive analysis of portal pressure by contrast-enhanced sonography in patients with cirrhosis. J Ultrasound Med 2011; 30: 205-211
  • 7 Jeong WK, Kim TY, Sohn JH. et al. Severe Portal Hypertension in Cirrhosis: Evaluation of Perfusion Parameters with Contrast-Enhanced Ultrasonography. Plos One 2015; 10: e0121601
  • 8 Li J, Feng JC, Peng XY. et al. Usefulness of Contrast-Enhanced Ultrasonography for Predicting Esophageal Varices in Patients with Hepatitis B Virus (HBV)-Related Cirrhosis. Med Sci Monit 2017; 23: 2241-2249
  • 9 Berzigotti A, Nicolau C, Bellot P. et al. Evaluation of regional hepatic perfusion (RHP) by contrast-enhanced ultrasound in patients with cirrhosis. J Hepatol 2011; 55: 307-314
  • 10 Abraldes JG, Bureau C, Stefanescu H. et al. Noninvasive tools and risk of clinically significant portal hypertension and varice in compensated cirrhosis: The “Anticipate” study. Hepatology 2016; 64: 2173-2184
  • 11 Castera L, Pinzani M, Bosch J. Noninvasive evaluation of portal hypertension using transient elastography. J Hepatol 2012; 56: 696-703
  • 12 Kim G, Kim MY, Baik SK. Transient elastography versus hepatic venous pressure gradient for diagnosing portal hypertension: a sistematic review and meta-analysis. Clin Mol Hepatol 2017; 23: 34-41
  • 13 Wagner M, Hectors S, Bane O. et al. Non-invasive prediction of portal pressure with MR elastography and DCE-MRI of the liver and spleen: preliminary results. J Magn Reson Imaging 2018; 48: 1091-1103
  • 14 Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg 1964; 1: 1-85
  • 15 Kamath PS, Wiesner RH, Malinchoc M. et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001; 33: 464-470
  • 16 Kim MY, Baik SK, Park DH. et al. Damping index of Doppler hepatic vein waveform to assess the severity of portal hypertension and response to propranolol in liver cirrhosis: a prospective nonrandomized study. Liver Int 2007; 27: 1103-1110
  • 17 Sacerdoti D, Gaiani S, Buonamico P. et al. Interobserver and interequipment variability of hepatic, splenic and renal arterial Doppler resistance indices in normal subjects and patients with cirrhosis. J Hepatol 1997; 27: 986-992
  • 18 Vuille-Lessard E, Rodrigues SG, Berzigotti A. Non invasive detection of clinically significant portal hypertension in compensated advanced chronic liver disease. Clin Liv Dis 2021; 25: 253-289
  • 19 Berzigotti A. Noninvasive evalutation of portal hypertension using ultrasound elastography. J Hepatol 2017; 67: 399-411
  • 20 Jindal A, Shaema S, Agarwal S. et al. Liver stiffness can predict decompensation and need for beta-blockers in compensated cirrhosis: a step beyond Baveno-VI criteria. Hepatol Int 2022; 16: 89-98
  • 21 Stefanescu H, Rusu C, Lupsor-Platon M. et al. Liver Stiffness Assessed by Ultrasound ShearWave Elastography from General Electric Accurately Predicts Clinically Significant Portal Hypertension in Patients with Advanced Chronic Liver Disease. Ultraschall in Med 2020; 41: 526-533
  • 22 Grgurevic I, Madir A, Trkulja V. et al. Assessment of clinically significant portal hypertension by two-dimensional shear wave elastography. Eur J Clin Invest 2022; 18: 13750
  • 23 Thiele M, Hugger MB, Kim Y. et al. 2D shear wave liver elastography by Aixplorer to detect portal hypertension in cirrhosis: an individual patient data meta-analysis. Liver Int 2020; 40 (06) 1435-1446
  • 24 Garcovich M, Di Stasio E, Zocco MA. et al. Assessing Baveno VI criteria with liver stiffness measured using a new point-shear wave elastography technique (BAVElastPQ study). Liver Int 2020; 40: 1952-1960
  • 25 Haag K, Rossle M, Ochs A. et al. Correlation of duplex sonography findings and portal pressure in 375 patients with portal hypertension. AJR Am J Roentgenol 1999; 172: 631-635