Hepatology International

, Volume 10, Issue 2, pp 267–276 | Cite as

Non-invasive assessment of portal hypertension and liver fibrosis using contrast-enhanced ultrasonography

  • Hitoshi MaruyamaEmail author
  • Gamal Shiha
  • Osamu Yokosuka
  • Ashish Kumar
  • Barjesh Chander Sharma
  • Alaa Ibrahim
  • Vivek Saraswat
  • Cosmas Rinaldi A. Lesmana
  • Masao Omata
Review Article


Portal hypertension and hepatic fibrosis are key pathophysiologies with major manifestations in cirrhosis. Although the degree of portal pressure and hepatic fibrosis are pivotal parameters, both are determined using invasive procedures. Ultrasound (US) is a simple and non-invasive technique that is available for use worldwide in the abdominal field. Because of its safety and easy of use, contrast-enhanced US is one of the most frequently used tools in the management of liver tumors for the detection and characterization of lesions, assessment of malignancy grade, and evaluation of therapeutic effects. This wide range of applications drives the practical use of contrast-enhanced US for evaluation of the severity of portal hypertension and hepatic fibrosis. The present article reviews the recent progress in contrast-enhanced US for the assessment of portal hypertension and hepatic fibrosis.


Ultrasound Contrast agent Liver Portal hemodynamics Fibrosis Cirrhosis 


Compliance with ethical standards

Conflict of interest

No potential conflict of interest relevant to this article was reported.


  1. 1.
    Goyal N, Jain N, Rachapalli V, Cochlin DL, Robinson M. Non-invasive evaluation of liver cirrhosis using ultrasound. Clin Radiol 2009;64:1056–1066.CrossRefPubMedGoogle Scholar
  2. 2.
    Baik SK. Haemodynamic evaluation by Doppler ultrasonography in patients with portal hypertension: a review. Liver Int 2010;30:1403–1413.CrossRefPubMedGoogle Scholar
  3. 3.
    Soresi M, Giannitrapani L, Cervello M, Licata A, Montalto G. Non invasive tools for the diagnosis of liver cirrhosis. World J Gastroenterol 2014;28(20):18131–18150.CrossRefGoogle Scholar
  4. 4.
    Gerstenmaier JF, Gibson RN. Ultrasound in chronic liver disease. Insights Imaging 2014;5:441–455.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Van Beers BE, Daire JL, Garteiser P. New imaging techniques for liver diseases. J Hepatol 2015;62:690–700.CrossRefPubMedGoogle Scholar
  6. 6.
    Quaia E. Microbubble ultrasound contrast agents: an update. Eur Radiol 2007;17:1995–2008.CrossRefPubMedGoogle Scholar
  7. 7.
    Claudon M, Dietrich CF, Choi BI, Cosgrove DO, Kudo M, Nolsøe CP, Piscaglia F, et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver—update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultrasound Med Biol 2013;39:187–210.CrossRefPubMedGoogle Scholar
  8. 8.
    Bouakaz A, de Jong N. WFUMB safety symposium on echo-contrast agents: nature and types of ultrasound contrast agents. Ultrasound Med Biol 2007;33:187–196.CrossRefPubMedGoogle Scholar
  9. 9.
    Lencioni R, Piscaglia F, Bolondi L. Contrast-enhanced ultrasound in the diagnosis of hepatocellular carcinoma. J Hepatol 2008;48:848–857.CrossRefPubMedGoogle Scholar
  10. 10.
    Maruyama H, Ishibashi H, Takahashi M, et al. Effect of signal intensity from the accumulated microbubbles in the liver for differentiation of idiopathic portal hypertension from liver cirrhosis. Radiology 2009;252:587–594.CrossRefPubMedGoogle Scholar
  11. 11.
    Kim MY, Jeong WK, Baik SK. Invasive and non-invasive diagnosis of cirrhosis and portal hypertension. World J Gastroenterol 2014;20:4300–4315.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Cobbold JF, Patel D, Fitzpatrick JA, Patel N, Crossey MM, Abdalla MS, Goldin RD, Vennart W, Thomas HC, Taylor-Robinson SD. Accuracy and reliability of microbubble ultrasound measurements for the non-invasive assessment of hepatic fibrosis in chronic hepatitis C. Hepatol Res 2012;42:515–522.CrossRefPubMedGoogle Scholar
  13. 13.
    Albrecht T, Blomley MJ, Cosgrove DO, Taylor-Robinson SD, Jayaram V, Eckersley R, Urbank A, Butler-Barnes J, Patel N. Non-invasive diagnosis of hepatic cirrhosis by transit-time analysis of an ultrasound contrast agent. Lancet 1999;353:1579–1583.CrossRefPubMedGoogle Scholar
  14. 14.
    Sugimoto H, Kaneko T, Hirota M, Tezel E, Nakao A. Earlier hepatic vein transit-time measured by contrast ultrasonography reflects intrahepatic hemodynamic changes accompanying cirrhosis. J Hepatol 2002;37:578–583.CrossRefPubMedGoogle Scholar
  15. 15.
    Staub F, Tournoux-Facon C, Roumy J, Chaigneau C, Morichaut-Beauchant M, Levillain P, et al. Liver fibrosis staging with contrast-enhanced ultrasonography: prospective multicenter study compared with METAVIR scoring. Eur Radiol 2009;19:1991–1997.CrossRefPubMedGoogle Scholar
  16. 16.
    Li N, Ding H, Fan P, et al. Intrahepatic transit time predicts liver fibrosis in patients with chronic hepatitis B: quantitative assessment with contrast-enhanced ultrasonography. Ultrasound Med Biol 2010;36:1066–1075.CrossRefPubMedGoogle Scholar
  17. 17.
    Tang A, Kim TK, Heathcote J, et al. Does hepatic vein transit time performed with contrast-enhanced ultrasound predict the severity of hepatic fibrosis? Ultrasound Med Biol 2011;37:1963–1969.CrossRefPubMedGoogle Scholar
  18. 18.
    Cobbold JF, Crossey MME, Colman P, et al. Optimal combinations of ultrasound-based and serum markers of disease severity in patients with chronic hepatitis C. J Viral Hepat 2010;17:537–545.CrossRefPubMedGoogle Scholar
  19. 19.
    Ridolfi F, Abbattista T, Marini F, et al. Contrast-enhanced ultrasound to evaluate the severity of chronic hepatitis C. Dig Liver Dis 2007;39:929–935.CrossRefPubMedGoogle Scholar
  20. 20.
    Lim AK, Patel N, Eckersley RJ, Goldin RD, Thomas HC, Cosgrove DO, et al. Hepatic vein transit time of SonoVue: a comparative study with Levovist. Radiology 2006;240:130–135.CrossRefPubMedGoogle Scholar
  21. 21.
    Orlacchio A, Bolacchi F, Petrella MC, et al. Liver contrast enhanced ultrasound perfusion imaging in the evaluation of chronic hepatitis C fibrosis: preliminary results. Ultrasound Med Biol 2011;37:1–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Ishibashi H, Maruyama H, Takahashi M, et al. Assessment of hepatic fibrosis by analysis of the dynamic behavior of microbubbles during contrast ultrasonography. Liver Int 2010;30:1355–1363.CrossRefPubMedGoogle Scholar
  23. 23.
    Tawada A, Maruyama H, Kamezaki H, et al. Magnitude of contrast-enhanced ultrasonography as a noninvasive predictor for hepatic fibrosis: comparison with liver stiffness measurement and serum-based models. Hepatol Int 2013;7:749–757.CrossRefPubMedGoogle Scholar
  24. 24.
    Ishibashi H, Maruyama H, Takahashi M, et al. Demonstration of intrahepatic accumulated microbubble on ultrasound represents the grade of hepatic fibrosis. Eur Radiol 2012;22:1083–1090.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Maruyama H, Shimada T, Ishibashi H, Takahashi M, Kamesaki H, Yokosuka O. Delayed periportal enhancement: a characteristic finding on contrast ultrasound in idiopathic portal hypertension. Hepatol Int 2012;6:511–519.CrossRefPubMedGoogle Scholar
  26. 26.
    Maruyama H, Okugawa H, Kobayashi S, Yoshizumi H, Takahashi M, Ishibashi H, Yokosuka O. Non-invasive portography: a microbubble-induced three-dimensional sonogram for discriminating idiopathic portal hypertension from cirrhosis. Br J Radiol 2012;85:587–595.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Zhang CX, Hu J, Hu KW, Zhang C, Wang L, Xu JM. Noninvasive analysis of portal pressure by contrast-enhanced sonography in patients with cirrhosis. J Ultrasound Med 2011;30:205–211.PubMedGoogle Scholar
  28. 28.
    Kim MY, Suk KT, Baik SK, Kim HA, Kim YJ, Cha SH, Kwak HR, 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.CrossRefPubMedGoogle Scholar
  29. 29.
    Jeong WK, Kim TY, Sohn JH, Kim Y, Kim J. Severe portal hypertension in cirrhosis: evaluation of perfusion parameters with contrast-enhanced ultrasonography. PLoS ONE 2015;10:e0121601.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Furuichi Y, Moriyasu F, Sugimoto K, Taira J, Sano T, Miyata Y, Sofuni A, Itoi T, Nakamura I, Imai Y. Obliteration of gastric varices improves the arrival time of ultrasound contrast agents in hepatic artery and vein. J Gastroenterol Hepatol 2013;28:1526–1531.CrossRefPubMedGoogle Scholar
  31. 31.
    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.CrossRefPubMedGoogle Scholar
  32. 32.
    Qu EZ, Zhang YC, Li ZY, Liu Y, Wang JR. Contrast-enhanced sonography for quantitative assessment of portal hypertension in patients with liver cirrhosis. J Ultrasound Med 2014;33:1971–1977.CrossRefPubMedGoogle Scholar
  33. 33.
    Shimada T, Maruyama H, Kondo T, Sekimoto T, Takahashi M, Yokosuka O. Impact of splenic circulation: non-invasive microbubble-based assessment of portal hemodynamics. Eur Radiol 2015;25:812–820.CrossRefPubMedGoogle Scholar
  34. 34.
    Dave JK, Halldorsdottir VG, Eisenbrey JR, Merton DA, Liu JB, Zhou JH, Wang HK, Park S, Dianis S, Chalek CL, Lin F, Thomenius KE, Brown DB, Forsberg F. Investigating the efficacy of subharmonic aided pressure estimation for portal vein pressures and portal hypertension monitoring. Ultrasound Med Biol 2012;38:1784–1798.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Eisenbrey JR, Dave JK, Halldorsdottir VG, et al. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology 2013;268:581–588.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Micol C, Marsot J, Boublay N, et al. Contrast-enhanced ultrasound: a new method for TIPS follow-up. Abdom Imaging 2012;37:252–260.CrossRefPubMedGoogle Scholar
  37. 37.
    Maruyama H, Ishibashi H, Takahashi M, Shimada T, Kamesaki H, Yokosuka O. Prediction of the therapeutic effects of anticoagulation for recent portal vein thrombosis: a novel approach with contrast-enhanced ultrasound. Abdom Imaging 2012;37:431–438.CrossRefPubMedGoogle Scholar
  38. 38.
    Maruyama H, Takahashi M, Shimada T, Yokosuka O. Emergency anticoagulation treatment for cirrhosis patients with portal vein thrombosis and acute variceal bleeding. Scand J Gastroenterol 2012;47:686–691.CrossRefPubMedGoogle Scholar
  39. 39.
    Kuroda T, Hirooka M, Koizumi M, et al. Pancreatic congestion in liver cirrhosis correlates with impaired insulin secretion. J Gastroenterol 2015;50:683–693.CrossRefPubMedGoogle Scholar
  40. 40.
    Sekimoto T, Maruyama H, Kondo T, Shimada T, Kiyono S, Yokosuka O. Potential stagnation in the splanchnic hemodynamics demonstrated by the dynamic microbubble in chronic liver disease. J Gastroenterol Hepatol 2015;30:1001–1008.CrossRefPubMedGoogle Scholar
  41. 41.
    Sekimoto T, Maruyama H, Kiyono S, Kondo T, Shimada T, Ishibashi H, Takahashi M, Yokosuka O, Yamaguchi T. Hepatic filling rate by a microbubble agent: a novel predictor of long-term outcomes in patients with cirrhosis. Ultrasound Med Biol 2014;40:2082–2088.CrossRefPubMedGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2015

Authors and Affiliations

  • Hitoshi Maruyama
    • 1
    Email author
  • Gamal Shiha
    • 2
  • Osamu Yokosuka
    • 1
  • Ashish Kumar
    • 3
  • Barjesh Chander Sharma
    • 4
  • Alaa Ibrahim
    • 5
  • Vivek Saraswat
    • 6
  • Cosmas Rinaldi A. Lesmana
    • 7
  • Masao Omata
    • 8
  1. 1.Department of Gastroenterology and NephrologyChiba University Graduate School of MedicineChibaJapan
  2. 2.Egyptian Liver Research Institute and Hospital (ELRIAH)MansouraEgypt
  3. 3.Department of Gastroenterology & HepatologyGanga Ram Institute for Postgraduate Medical Education & Research (GRIPMER), Sir Ganga Ram HospitalNew DelhiIndia
  4. 4.Department of GastroenterologyGB Pant HospitalNew DelhiIndia
  5. 5.GI/Liver divisionGIT Endoscopy Unit, University of BenhaBanhaEgypt
  6. 6.Department of GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
  7. 7.Department of Internal Medicine, Hepatobiliary DivisionCipto Mangunkusumo Hospital, University of IndonesiaJawa BaratIndonesia
  8. 8.Yamanashi Hospitals (Central and Kita) OrganizationKofu-shiJapan

Personalised recommendations