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

NCT02653846 | Unknown

• 1 other identifier: KBD-IG-LS/SSvsHVPG
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Liver Diseases

Outcome Measures

Primary Outcomes (2)

• 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

• HVPG

  severity of portal hypertension assessed by hepatic venous pressure gradient (HVPG) measurements

  within one week of enrollment

Secondary Outcomes (3)

• development of hepatic decompensation

  during follow-up period of 5 years

• Hepatocellular carcinoma (HCC) development

  during follow-up period of 5 years

• mortality

  during follow-up period of 5 years

Interventions

RT-2D-SWE measurement PROCEDURE

measurement of liver and spleen stiffness by ultrasound real-time 2D shear wave elastography (SWE™)

HVPG measurement PROCEDURE

assessment of portal hypertension assessed by hepatic venous pressure gradient measurement

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

outpatients and inpatients in a tertiary care hospital 1) with suspicion of having compensated advanced chronic liver disease (cACLD) as assessed by transabdominal ultrasound, laboratory findings, FIB-4 and/or APRI score, and/or LS measurements by TE; 2) 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; 3) 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Dubrava: lead

Study Sites (1)

University Hospital Dubrava

Zagreb, 10040, Croatia

RECRUITING

Related Publications (7)

• Berzigotti A, Seijo S, Arena U, Abraldes JG, Vizzutti F, Garcia-Pagan 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.

  PMID: 23058320 BACKGROUND

• Augustin S, Millan L, Gonzalez A, Martell M, Gelabert A, Segarra A, Serres X, Esteban R, Genesca 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.

  PMID: 24211744 BACKGROUND

• 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.

  PMID: 21376047 BACKGROUND

• 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):646-654. doi: 10.1053/j.gastro.2012.05.035. Epub 2012 May 27.

  PMID: 22643348 BACKGROUND

• 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.

  PMID: 24607624 BACKGROUND

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

  PMID: 23729981 BACKGROUND

• 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.

  PMID: 24007769 BACKGROUND

Study Officials

• Ivica Grgurevic, MD, PhD

  University Hospital Dubrava

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ivica Grgurevic, MD, PhD

CONTACT

ivica.grgurevic@zg.htnet.hr

Tomislav Bokun, MD

CONTACT

tbokun@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assist. prof. Ivica Grgurevic, MD, PhD, FEBGH

Study Record Dates

• First Submitted: December 31, 2015
• First Posted: January 12, 2016
• Study Start: June 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2022
• Last Updated: September 8, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)