OPEN Research Support
head

Postdoc
Maja Thiele
Department of Medical Gastroenterology, Odense University Hospital


Projekt styring
Projekt status    Sampling finished
 
Data indsamlingsdatoer
Start 01.08.2015  
Slut 01.08.2030  
 



Real-Time 2D Shear Wave Elastography To Diagnose Portal Hypertension And Predict Clinical Outcomes In Patients With Cirrhosis

Short summary

The purpose of this cohort is to evaluate the diagnostic accuracy of the non-invasive ultrasound technicque: real-time 2-dimensional shear wave elastography for clinically significant portal hypertension; and to determine whether the technique has prognostic potential in compensated and decompensated patients with cirrhosis.


Rationale

Liver stiffness (LS) measured with transient elastography (Fibroscan, Echosens) can diagnose clinically significant portal hypertension and esophageal varices and predict risk of decompensation in patients with cirrhosis. However, transient elastography is limited by a high failure rate in patients with cirrhosis due to technical reasons (most often ascites).

The new technology real-time 2D shear wave elastography (2D-SWE) combines real-time multiple shear-waves with traditional B-mode ultrasound imaging. This allows the operator to visualise of the liver and spleen during the elastography and thereby target LS and SS measurements. Consequently, the feasibility of 2D-SWE may be superior to transient elastography in patients with cirrhosis.

Five studies have already assessed the use of LS with 2D-SWE for the diagnosis of portal hypertension and cirrhosis severity, and more studies are on the way. The role of 2D-SWE for long-term prognosis of cirrhosis been investigated only once. A complete evaluation of the diagnostic and prognostic accuracy of 2D-SWE in patients with cirrhosis is therefore desirable.Aims:

Our objective is to evaluate: (A) 2D-SWE to diagnose clinically significant portal hypertension, severe portal hypertension and esophageal varices in patients with cirrhosis, (B) 2D-SWE to predict mortality and morbidity in patients with cirrhosis.


Description of the cohort

This study will be conducted as an individual patient data meta-analysis using data from three published studies and one study still to be published.5-7 Participating centers include Odense, Bonn, Antwerp, Bologne, Paris and Barcelona.

The protocol is also registered in PROSPERO (www.crd.york.ac.uk/PROSPERO/). Authors of all published studies have been contacted for individual patient data.

Inclusion criteria are: (i) cirrhosis evidenced by histologic, clinical, ultrasonographic, endoscopic and/or biochemical characteristics, (ii) fasting liver 2D-SWE evaluation, (iii) invasive portal pressure measurement  and/or upper endoscopy within 3 weeks of 2D-SWE examination, (iv) age 18-80 years.

Exclusion criteria are: (i) disseminated cancer disease (hepatic or non-hepatic), (ii) right side cardiac failure, (iii) decompensating event including severe infection in the interval between 2D-SWE and portal pressure measurement, (iv) severe obstructive cholestasis and (v) severe hepatitis.

The primary outcomes are accuracy of 2D-SWE to diagnose clinically significant portal hypertension (HVPG above or equal to 10 mmHg) and to predict mortality. Secondary outcomes are:

  • Diagnostic accuracy of 2D-SWE for severe portal hypertension (HVPG above or equal to 12 mmHg)
  • Diagnostic accuracy of 2D-SWE for esophageal varices
  • Ability of 2D-SWE to predict 1-, 3-, 6-, 12- and 24-month decompensation, both individual events and composite end-point
  • Ability of 2D-SWE to predict 1-, 3-, 6-, 12- and 24-month deterioration in liver function evidenced by increasing HVPG, MELD- and Child-score
  • Ability of 2D-SWE to predict 3-, 6-, 12- and 24-month other adverse events, both individual events and composite end-point

Sensitivity and subgroup analyses will include:

  • Liver disease etiology
  • Patients with compensated disease versus decompensated disease at baseline
  • Patients with Child-score A, B and C
  • Patients with MELD scores of 0-9, 10-19, 20-29, 30-39 and above or equal to 40.
  • Liver inflammation versus no inflammation (assessed by histology and/or serum transaminases)
  • Cholestasis versus no cholestasis (assessed by levels of GGT, bilirubin and alkaline phosphatase)
  • Alcohol overusing versus abstinent patients
  • High- versus low risk of bias studies, assessed using the MOOSE checklist for observational studies.


Data and biological material

We collect baseline data on: (i) patient characteristics, (ii) pressure measurements (HVPG, direct portosystemic pressure gradient), (iii) upper endoscopy findings, (iv) LS and SS elastography measurements with 2D-SWE and transient elastography, (v) liver biopsy characteristics, (vi) liver blood tests within 3 weeks of 2D-SWE, (vi) ultrasonography characteristics including spleen size, portal venous flow and presence of ascites.

We also collect the following outcome data: (i) length of follow-up since 2D-SWE measurement, (ii) continuous outcome data from baseline to maximum follow up: Child-score, MELD, HVPG (iii) date and cause of death, (iv) date and type of decompensation in the form of ascites, refractory ascites, overt or covert hepatic encephalopathy, hepatocellular carcinoma, esophageal varices and variceal bleeding, (v) date and type of other clinical events in the form of hospitalisations, bacterial infections, portal vein thrombosis, thromboembolic events, diabetes, pancreatitis, suicide attempts, other.

Patients are followed from baseline 2D-SWE and untill death, liver transplantation or end of study.

A biobank is established only for the Odense patients who have prospectively collected data and have signed a consent form.


Collaborating researchers and departments

Laboratory for Liver Fibrosis and Portal Hypertension, Department of Internal Medicine, University Hospital Bonn, Bonn, Germany

Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.

Gastrounit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.

Department of Hepatology, Hôpital Beaujon-AP-HP, Université Paris Diderot, and INSERM U1149, Centre de Recherche sur l'Inflammation, Clichy, France

Division of Internal Medicine, University of Bologna, Bologna, Italy.

Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Spain.

Department of Gastroenterology and Hepatology, Inselspital Bern, Bern, Schweiz.