Correlation of Liver and Spleen Stiffness by RT-2D-SWE and Severity of Portal Hypertension by HVPG

Chronic Liver Diseases Clinical Trial

Official title:

Correlation of Liver and Spleen Stifness as Assesed by Real Time 2-Dimensional Shear Wave Elastography With Severity of Portal Hypertension and Clinical Outcomes in Patients With Compensated Advanced Chronic Liver Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02653846
• Other study ID #: KBD-IG-LS/SSvsHVPG
• Status: Recruiting
• Phase: N/A
• First received: December 31, 2015
• Last updated: September 7, 2016
• Start date: June 2015
• Est. completion date: June 2022

Study information

• Verified date: September 2016
• Source: University Hospital Dubrava
• Contact: Ivica Grgurevic, MD, PhD
• Email: ivica.grgurevic[@]zg.htnet.hr
• Is FDA regulated: No
• Health authority: Croatia: Ministry of Health and Social Care
• Study type: Observational

Clinical Trial Summary

Portal hypertension (PH) results from the increase of portal flow resistance in fibrotic tissue of the liver in patients with chronic liver diseases, leading to complications such as varices formation and variceal bleeding, ascites formation, spleenomegaly and hypersplenismus, systemic haemodynamic disorders and porto-systemic shunts formation. Early detection of PH in patients with chronic liver diseases is clinically important as it should change patient management in order to prevent the formation/onset or recurrence of PH complications. Hepatic venous pressure gradient (HVPG) measurement is the gold standard for the assessment of the severity of PH. However, it is an invasive method with its risks, and relatively costly. On the other hand transient elastography (TE) emerged as a non-invasive, easy, safe and low cost method with the potential to assess the severity of PH, as liver stiffness (LS) and spleen stiffens (SS) measured by TE showed very good correlation with HVPG. Real-time 2D shear wave elastography (RT-2D-SWE) is an ultrasound elastography method reliable for non-invasive assessment of fibrosis stage especially in chronic viral hepatitis, but only preliminary data exist on the correlation of RT-2D-SWE measured LS/SS with and HVPG. In this study we hypothesized that LS and SS measured by RT-2D-SWE correlate with HVPG enabling RT-2D-SWE to be used for the assessment of severity of PH. The primary aim of this study is to analyse correlation between LS and SS as assessed by RT-2D-SWE and TE with the grade of portal hypertension as assessed by HVPG. The secondary aims are: 1) to analyse clinical outcomes of these patients in order to determine if LS and/or SS as assessed by RT-2D-SWE might predict adverse outcomes (liver decompensation, death or HCC development), and 2) to compare clinical performance (AUC) of RT-2D-SWE and TE for the assessment of the PH severity as well as for predicting clinical outcomes. Patients with suspicion of having compensated advanced chronic liver disease (cACLD) as assesed by non-invasive methods (transabdominal ultrasound, laboratory findings, FIB-4 and APRI score, and LS measurements by TE), will be included. Since positive predictive value of non-invasive methods for cirrhosis is generally not very reliable, these patients will be offered transjugular liver biopsy and HVPG measurements as gold-standard methods to define the stage of liver disease and severity of PH. These patients will undergo LS and SS measurements by RT-2D-SWE on Aixplorer SuperSonic Imagine ultrasound system and HVPG measurements as well, with transjugular liver biopsy performed during the same session. After SWE™ and HVPG measurement, 5-year follow-up is planned, including standard surveillance: laboratory findings, transabdominal US every six months and upper-GI endoscopy according to relevant guidelines, as well as treatment according to relevant guidelines as indicated: beta blockers, endoscopic variceal ligation, etiologic treatment and dietary measures. Appropriate statistical analysis will be undertaken after the enrollment period, as well as after follow-up period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 2022
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients with suspicion of having cACLD as assessed by transabdominal ultrasound, laboratory findings, FIB-4 and/or APRI score, and/or LS measurements

• patients with chronic liver disease in whom any extrahepatic surgical procedure is planned and in whom it was not possible to exclude cACLD and/or portal hypertension based on non-invasive procedures only

• patients with HCC or other liver tumors on the ground of presumed liver cirrhosis who are under consideration for surgical resection, in whom HVPG is performed in order to reliably exclude clinically significant portal hypertension

• compliance to the study protocol

• signed approval for the diagnostic ultrasound with SWE™ and for transjugular liver biopsy and HVPG measurement

Exclusion Criteria:

• elevated alanine aminotransferase (ALT) values > 5 x upper limit of normal (ULN)

• obstructive jaundice

• congestive heart failure

• sepsis

• thrombosis of right jugular vein

• thrombosis of hepatic veins

• hydatid cyst

• cholangitis

• absence of cooperation

• pregnancy

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Chronic Liver Diseases
• Hypertension
• Hypertension, Portal
• Liver Diseases

Intervention

Procedure:
• RT-2D-SWE measurement
measurement of liver and spleen stiffness by ultrasound real-time 2D shear wave elastography (SWE™)
• HVPG measurement
assessment of portal hypertension assessed by hepatic venous pressure gradient measurement

Locations

Country	Name	City	State
Croatia	University Hospital Dubrava	Zagreb

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Dubrava

Country where clinical trial is conducted

Croatia, 

References & Publications (7)

Augustin S, Millán L, González A, Martell M, Gelabert A, Segarra A, Serres X, Esteban R, Genescà J. Detection of early portal hypertension with routine data and liver stiffness in patients with asymptomatic liver disease: a prospective study. J Hepatol. 2014 Mar;60(3):561-9. doi: 10.1016/j.jhep.2013.10.027. Epub 2013 Nov 6. — View Citation

Behrens G, Ferral H. Transjugular liver biopsy. Semin Intervent Radiol. 2012 Jun;29(2):111-7. doi: 10.1055/s-0032-1312572. — View Citation

Berzigotti A, Seijo S, Arena U, Abraldes JG, Vizzutti F, García-Pagán JC, Pinzani M, Bosch J. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology. 2013 Jan;144(1):102-111.e1. doi: 10.1053/j.gastro.2012.10.001. Epub 2012 Oct 8. — View Citation

Colecchia A, Colli A, Casazza G, Mandolesi D, Schiumerini R, Reggiani LB, Marasco G, Taddia M, Lisotti A, Mazzella G, Di Biase AR, Golfieri R, Pinzani M, Festi D. Spleen stiffness measurement can predict clinical complications in compensated HCV-related cirrhosis: a prospective study. J Hepatol. 2014 Jun;60(6):1158-64. doi: 10.1016/j.jhep.2014.02.024. Epub 2014 Mar 6. — View Citation

Colecchia A, Montrone L, Scaioli E, Bacchi-Reggiani ML, Colli A, Casazza G, Schiumerini R, Turco L, Di Biase AR, Mazzella G, Marzi L, Arena U, Pinzani M, Festi D. Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis. Gastroenterology. 2012 Sep;143(3):646-54. doi: 10.1053/j.gastro.2012.05.035. Epub 2012 May 27. — View Citation

Dohan A, Guerrache Y, Boudiaf M, Gavini JP, Kaci R, Soyer P. Transjugular liver biopsy: indications, technique and results. Diagn Interv Imaging. 2014 Jan;95(1):11-5. doi: 10.1016/j.diii.2013.08.009. Epub 2013 Sep 3. Review. — View Citation

Vergniol J, Foucher J, Terrebonne E, Bernard PH, le Bail B, Merrouche W, Couzigou P, de Ledinghen V. Noninvasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C. Gastroenterology. 2011 Jun;140(7):1970-9, 1979.e1-3. doi: 10.1053/j.gastro.2011.02.058. Epub 2011 Mar 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	liver and spleen stiffness	liver and spleen stiffness expressed in kPa, measured by real-time 2D shear wave elastography (SWE™) on Aixplorer® ultrasound machine from SuperSonic Imagine, Aix-en-Provence, France	at the time of enrollment	No
Primary	HVPG	severity of portal hypertension assessed by hepatic venous pressure gradient (HVPG) measurements	within one week of enrollment	Yes
Secondary	development of hepatic decompensation	hepatic decompensation defined as: onset of icterus, onset of ascites diagnosed by transabdominal ultrasonud or CT scan, onset of portal encephalophaty diagnosed clinically, episode of variceal bleeding confirmed endoscopically	during follow-up period of 5 years	No
Secondary	Hepatocellular carcinoma (HCC) development	conformed by contrast MDCT and/or MRI and/or tumor biopsy	during follow-up period of 5 years	No
Secondary	mortality		during follow-up period of 5 years	No