CirrhosisPORTAL-4DNCT07554183
4D-Flow MRI Assessment of Portal Hypertension and TIPS Outcomes in Cirrhosis
A study testing 4D-Flow Liver and heart MRI with Gadolinium injection and Samples Without DNA in people with Cirrhosis and Portal Hypertension, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial summary
PORTAL-4D is a prospective, interventional, non-randomized, parallel-group diagnostic study conducted at Pitié-Salpêtrière Hospital (Paris, France). Portal hypertension is the main driver of hepatic decompensation and is associated with ascites, variceal bleeding, hepatic encephalopathy, and reduced survival. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis, Portal Hypertension
- What is being tested?
- 4D-Flow Liver and heart MRI with Gadolinium injection and Samples Without DNA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesFrance
- Study dates
- 25 Aug 2026to 1 May 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Applicable to both groups :
- Age ≥ 18 years
- Eligible to undergo MRI examination
- Prior clinical evaluation completed
- Covered by a national health insurance scheme or beneficiary thereof (excluding State Medical Aid AME)
- Patient informed and written informed consent obtained
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- Specific to the MASLD group :
- Indication for TIPS validated during a multidisciplinary team meeting and documented in the patient's medical record, including one of the following:
- Refractory ascites
- Hepatic hydrothorax
- Failure of secondary prophylaxis of variceal gastrointestinal bleeding
- Preemptive TIPS
- Preoperative TIPS
- Specific to the MASLD group :
- Past or current exposure to metabolic risk factors (overweight, obesity, type 2 diabetes mellitus, arterial hypertension, dyslipidemia)
- Liver stiffness > 15 kPa measured by transient elastography
- Liver biopsy documenting steatosis with stage 3 fibrosis or cirrhosis
- Alcohol consumption < 20 g/day for women and < 30 g/day for men, assessed using validated routine clinical questionnaires
Who cannot join
- Applicable to both groups :
- Any contraindication to MRI (cardiac pacemaker, implantable cardioverter-defibrillator, cochlear implants, intraocular metallic foreign bodies, intracranial vascular clips).
- Prior liver transplantation.
- Pregnancy, breastfeeding, or women of childbearing potential not using effective contraception.
- Individual under legal guardianship or trusteeship, or unable to provide informed consent.
- Participation in another interventional clinical study or currently within the exclusion period following a previous ongoing study.
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- Specific to the TIPS group
- Patients undergoing salvage TIPS placement in the setting of hemorrhagic shock. Specific to the MASLD group
- Other etiologies of chronic liver disease, including viral hepatitis, autoimmune liver disease, or hemochromatosis
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France2 sites, 2 recruiting
- Recruiting
Hôpital Pitié Salpêtrière
Paris, 75013
Louis MEYBLUM, MD, 01 84 82 82 68, louis.meyblum@aphp.fr
Charles ROUX, MD, +33 1 42 16 27 70, charles.roux@aphp.fr
- Recruiting
Service d'hépato-gastroentérologie
Paris, 75013
Marika RUDLER, Prof, marika.rudler@aphp.fr
About this study
Official title: Predicting Outcomes and Risk of Complications Related to Portal hyperTension by Non-invasive Assessment of Liver Flow With 4D MRI
PORTAL-4D is a prospective, interventional, non-randomized, parallel-group diagnostic study conducted at Pitié-Salpêtrière Hospital (Paris, France).
Portal hypertension is the main driver of hepatic decompensation and is associated with ascites, variceal bleeding, hepatic encephalopathy, and reduced survival. The current gold standard for assessing portal hypertension is the invasive hepatic venous pressure gradient (HVPG) measurement performed via the transjugular route. However, HVPG is invasive, operator-dependent, and limited to specialized centers. A reliable non-invasive alternative is therefore highly needed.
Read more
60 adults patients with cirrhosis will be enrolled and divided into two parallel groups: MASLD group (n=24): Patients with compensated cirrhosis related to metabolic dysfunction-associated steatotic liver disease (MASLD).
TIPS group (n=36): Patients with decompensated cirrhosis referred for transjugular intrahepatic portosystemic shunt (TIPS) placement.
The primary objective is to assess the correlation between invasive HVPG values and 4D-flow MRI parameters. Secondary objectives include evaluating the prognostic value of 4D-flow MRI in predicting portal hypertension-related complications and post-TIPS outcomes within 6 months.
The study is expected to validate 4D-flow MRI as an non-invasive diagnostic and prognostic tool for portal hypertension, potentially improving patient selection for TIPS and reducing reliance on invasive procedures.
Read the detailed description
Portal hypertension is the main determinant of hepatic decompensation in cirrhotic patients and is associated with major complications such as variceal gastrointestinal bleeding, refractory ascites, hepatic encephalopathy, and liver-related mortality. The reference standard for assessing clinically significant portal hypertension is the invasive hepatic venous pressure gradient (HVPG), measured via the transjugular route. HVPG reflects the hemodynamic consequences of increased intrahepatic resistance and portal inflow and has strong prognostic value. An HVPG ≥10 mmHg defines clinically significant portal hypertension and is associated with a higher risk of decompensation and mortality. In patients treated with TIPS, achieving a post-procedural gradient <12 mmHg or a reduction of at least 50% from baseline is associated with a decreased risk of rebleeding and other complications.
Despite its clinical relevance, HVPG measurement is invasive, requires specialized expertise, and is not widely available. Moreover, it may not capture the full complexity of portal and systemic hemodynamics. Consequently, there is a critical unmet need for non-invasive, reproducible, and operator-independent techniques capable of assessing portal hypertension and guiding clinical decision-making.
4D-flow MRI is an advanced imaging technique that enables time-resolved, three-dimensional quantification of blood flow in multiple vascular territories within a single acquisition. In the hepatic and splanchnic circulation, it allows comprehensive measurement of portal vein, splenic vein, superior mesenteric vein, hepatic veins, and inferior vena cava flow, including velocities, flow volumes, and shunt fractions. Preliminary studies have demonstrated the feasibility and reproducibility of 4D-flow MRI in evaluating portal hemodynamics, but robust validation against invasive HVPG and prospective prognostic evaluation remain limited.
The study will enroll 60 adult patients with confirmed cirrhosis, divided into two parallel groups:
MASLD Group (n=24) participants will undergo transjugular HVPG measurement (performed specifically for research purposes), hepatic 4D-flow MRI with gadolinium contrast, and standardized blood sampling. They will be followed for 6 months to evaluate the occurrence of portal hypertension-related events, including ascites requiring intervention, variceal bleeding, hepatic encephalopathy, and liver-related death.
TIPS Group (n=36) participants will undergo 4D-flow MRI within 3 days prior to TIPS and again 3 days after the procedure. Invasive pressure measurements (including right atrial pressure, free and wedged hepatic venous pressures, and portal pressure when applicable) will be performed before and immediately after TIPS placement, as well as at day 3. Clinical and biological follow-up will continue for 6 months to assess post-TIPS outcomes and complications, including hepatic encephalopathy, cardiac dysfunction, persistent portal hypertension, and liver-related events.
The primary objective is to evaluate the correlation between invasive HVPG measurements and quantitative hemodynamic parameters derived from 4D-flow MRI. Agreement between techniques will be assessed using correlation coefficients and Bland-Altman analysis.
In addition, multi-omics analyses (proteomic, metabolomic, transcriptomic, and metagenomic profiling) will be performed on systemic, suprahepatic, and portal blood samples to identify biological signatures associated with hepatic encephalopathy and clinical decompensation.
By validating 4D-flow MRI as a non-invasive surrogate for HVPG and as a prognostic tool for portal hypertension-related complications, PORTAL-4D aims to improve risk stratification, optimize patient selection for TIPS, and potentially reduce reliance on invasive procedures. The integration of advanced imaging and multi-omics profiling may also provide new insights into the pathophysiology of hepatic encephalopathy and shunt-related complications, contributing to a more personalized and physiology-driven management of cirrhotic patients.
- Conditions
- Cirrhosis, Portal Hypertension
- Being tested
- 4D-Flow Liver and heart MRI with Gadolinium injection, Samples Without DNA
- Keywords
- 4D-Flow MRI, Hepatic Venous Pressure Gradient, Portal Hemodynamics, Noninvasive Liver Imaging, Hepatic Encephalopathy, Portal hypertension complications, TIPS, MASLD
- Medical subject headings
- Fibrosis, Hypertension, Portal, Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4D-Flow Liver and heart MRI with Gadolinium injectionOther
Non-invasive hepatic 4D-flow magnetic resonance imaging performed with gadolinium contrast to quantify portal and systemic venous blood flow, velocities, and shunt fraction. Measurements are compared with invasive hepatic venous pressure gradient (HVPG) values and clinical outcomes to assess diagnostic accuracy and prognostic value for portal hypertension-related complications.
Samples Without DNABiological
Portal, hepatic and systemic veins blood collection
| Study group | Role | What they receive |
|---|---|---|
| TIPS group | Experimental | TIPS group : Adults with decompensated cirrhosis referred for transjugular intrahepatic portosystemic shunt (TIPS). Participants undergo 4D-flow liver MRI before and after TIPS placement, invasive pressure measurements, blood sampling, and 6-month follow-up to assess post-TIPS outcomes. Receives: Other: 4D-Flow Liver and heart MRI with Gadolinium injection; Biological: Samples Without DNA |
| MASLD group | Experimental | MASLD group : Adults with compensated cirrhosis related to metabolic dysfunction-associated steatotic liver disease (MASLD). Participants undergo invasive HVPG measurement and 4D-flow liver MRI, with 6-month follow-up to assess portal hypertension-related complications and prognostic value of imaging parameters. Receives: Other: 4D-Flow Liver and heart MRI with Gadolinium injection; Biological: Samples Without DNA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between invasive hepatic venous pressure gradient (HVPG) and quantitative hepatic 4D-flow MRI hemodynamic parameters
The primary outcome is the association between the invasive hepatic venous pressure gradient (HVPG; wedged hepatic venous pressure minus free hepatic venous pressure) measured during transjugular catheterization and quantitative hepatic 4D-flow MRI-derived parameters, including flow rate and peak velocity in the portal venous system (main portal vein and right/left branches), splenic vein, superior mesenteric vein, hepatic veins, and inferior vena cava. When available, direct portal pressure will be recorded as supportive invasive data
Measured: Baseline (4D-flow MRI performed within 3 days before or after invasive measurements)
Secondary outcomes (17)
: Correlation between 4D Flow MRI measured flows and the percentage of shunt with the incidence of events related to portal hypertension
Evaluation of the correlation between 4D Flow MRI-measured flows and the percentage of shunt (ratio of splenomesenteric inflow to hepatic venous outflow).
Incidence of events related to portal hypertension, including:
- Ascites requiring diagnostic or therapeutic paracentesis.
- Hospitalization for encephalopathy.
- Variceal rupture.
- Liver-related death in patients without prior decompensation. Method of Measurement: 4D Flow MRI to assess the flow rates and calculate the shunt percentage (ratio of splenomesenteric inflow to hepatic venous outflow).
Clinical event documentation (hospitalization, paracentesis, etc.) in the 6-month follow-up period.
Measured: 6 months
Correlation between proteomic signatures and the occurrence of hepatic encephalopathy
Evaluation of the correlation between proteomic signatures (measured using mass spectrometry) and the onset of hepatic encephalopathy in patients with compensated cirrhosis.
Method of Measurement: Mass spectrometry for proteomic analysis. Unit of Measure: Protein concentration (mg/mL).
Measured: Occurrence of hepatic encephalopathy will be monitored for 6 months following the TIPS procedure
Correlation between transcriptomic signatures and the occurrence of hepatic encephalopathy
Evaluation of the correlation between transcriptomic signatures (measured by RNA sequencing) and the onset of hepatic encephalopathy in patients with compensated cirrhosis.
Method of Measurement: RNA sequencing for transcriptomic profiling. Unit of Measure: Gene expression levels (RPKM or TPM).
Measured: Occurrence of hepatic encephalopathy will be monitored for 6 months following the TIPS procedure
Correlation between metabolomic signatures and the occurrence of hepatic encephalopathy.
Evaluation of the correlation between metabolomic profiles (measured by mass spectrometry or NMR) and the occurrence of hepatic encephalopathy in patients with compensated cirrhosis.
Method of Measurement: Mass spectrometry or NMR for metabolite profiling. Unit of Measure: Metabolite concentration (µM, nmol/mL).
Measured: Occurrence of hepatic encephalopathy will be monitored for 6 months following the TIPS procedure
Correlation between viromic signatures and the occurrence of hepatic encephalopathy
Evaluation of the correlation between viromic signatures (measured by high-throughput sequencing) and the onset of hepatic encephalopathy in patients with compensated cirrhosis.
Method of Measurement: High-throughput sequencing for viromic profiling. Unit of Measure: Viral load (copy number of viral genomes per mL) and viral diversity (Shannon diversity index).
Measured: Occurrence of hepatic encephalopathy will be monitored for 6 months following the TIPS procedure
Correlation between bacteriomic signatures and the occurrence of hepatic encephalopathy
Evaluation of the correlation between bacteriomic signatures (measured by 16S rRNA sequencing) and the onset of hepatic encephalopathy in patients with compensated cirrhosis.
Method of Measurement: 16S rRNA sequencing for bacterial diversity and abundance analysis.
Unit of Measure: Relative bacterial abundance (e.g., % of total microbiome).
Measured: Occurrence of hepatic encephalopathy will be monitored for 6 months following the TIPS procedure
Correlation between TIPS diameter and hemodynamic measurements and 4D Flow MRI results before and after TIPS
Evaluation of the correlation between the TIPS diameter and the hemodynamic measurements (right atrium, inferior vena cava, hepatic veins, portal pressure) and 4D Flow MRI results at three time points.
Method of Measurement: TIPS diameter will be measured using imaging techniques such as fluoroscopy or ultrasound.
Unit of Measure: TIPS diameter (mm). Pressure (mmHg) at the specified sites.
Measured: TIPS diameter measured immediately after the procedure
Correlation between 4D Flow MRI results and hemodynamic measurements before and after TIPS
Evaluation of the correlation between 4D Flow MRI results and invasive hemodynamic measurements (right atrium, inferior vena cava, hepatic veins, and portal pressure) before, immediately after, and 72 hours after TIPS creation.
Method of Measurement: 4D Flow MRI to assess blood flow dynamics. Unit of Measure: Flow rate (mL/min) and velocity (cm/s) for blood flow measurements in the hepatic and portal vasculature. Pressure (mmHg) at the specified sites.
Measured: 4D Flow MRI performed within 3 days before and 3 days after TIPS
Correlation between 4D Flow MRI-measured flow rates and the percentage of shunt with the occurrence of TIPS-related and/or portal hypertension-related complications within 6 months following TIPS
Evaluation of the correlation between 4D Flow MRI-measured flow rates and the percentage of shunt (ratio of splenomesenteric inflow to hepatic venous outflow) before the Transjugular Intrahepatic Portosystemic Shunt (TIPS) procedure with the occurrence of complications related to TIPS and/or portal hypertension within 6 months after TIPS.
Complications include: Ascites requiring diagnostic or therapeutic paracentesis,Hospitalization for encephalopathy,Rupture of varices and Liver-related death in patients without a prior history of decompensation.
Method of Measurement: The occurrence of complications will be recorded through clinical follow-up, including hospital records and patient reports.
Unit of Measure:
Complications: Presence/absence of each complication within the 6-month period (binary measure: yes/no).
Flow rate: mL/min and velocity (cm/s) for blood flow measurements. Shunt percentage: Percentage (%) of splenomesenteric inflow to hepatic venous outflow.
Measured: Complications will be monitored for 6 months following the TIPS procedure
Correlation between 4D Flow MRI flow-rate changes and shunt percentage before and after TIPS, and the occurrence of TIPS- or portal hypertension-related complications within 6 months, in relation to these flow-rate and shunt changes
Evaluation of TIPS- and/or portal hypertension-related complications within 6 months after TIPS, in relation to changes in 4D Flow MRI-measured flow rates and shunt percentage (pre- and post-TIPS).
Complications include: Ascites requiring paracentesis ,Hospitalization for encephalopathy, Rupture of varices, Liver-related death in patients without prior decompensation.
Method of Measurement: The occurrence of complications will be recorded through clinical follow-up, including hospital records and patient reports.
4D Flow MRI will assess blood flow rates in the hepatic and splenomesenteric circulation and shunt percentage as the ratio of splenomesenteric inflow to hepatic venous outflow.
Unit of Measure:
Complications: Presence/absence of each complication within the 6-month period (binary measure: yes/no).
Flow rate: mL/min and velocity (cm/s) for blood flow measurements in the hepatic and splenomesenteric vasculature and Shunt percentage (%)
Measured: Complications will be monitored for 6 months following the TIPS procedure.
Evaluation of the variation in 4D Flow MRI-measured flow rates and percentage of shunt before and after TIPS, according to TIPS diameter
Evaluation of the variations in 4D Flow MRI-measured blood flow rates and the percentage of shunt (calculated as the ratio of splenomesenteric inflow to hepatic venous outflow) before and after Transjugular Intrahepatic Portosystemic Shunt (TIPS), in relation to the diameter of the shunt.
Method of Measurement:
4D Flow MRI will be used to measure blood flow dynamics in the hepatic and splenomesenteric circulation before and after TIPS.
Shunt percentage will be calculated as the ratio of splenomesenteric inflow to hepatic venous outflow, before and after TIPS.
TIPS diameter will be measured using imaging techniques such as fluoroscopy or ultrasound.
Unit of Measure:
Flow rate: mL/min and velocity (cm/s) for blood flow measurements in the hepatic and splenomesenteric vasculature.
Shunt percentage: Percentage (%) of splenomesenteric inflow to hepatic venous outflow.
TIPS diameter: Millimeters (mm).
Measured: Flow measurements and shunt percentage will be assessed before and after TIPS (within 3 days before and 3 days after TIPS).
Correlation between changes in ammonia levels before and after TIPS with changes in percentage of shunt before and after TIPS
Evaluation of the changes in ammonia levels before and after Transjugular Intrahepatic Portosystemic Shunt (TIPS) in correlation with the changes in the percentage of shunt (calculated as the ratio of splenomesenteric inflow to hepatic venous outflow) before and after TIPS, as measured by 4D Flow MRI.
Method of Measurement: Blood samples will be taken to measure serum ammonia levels using standard laboratory techniques (e.g., enzymatic assay or ion-selective electrode). 4D Flow MRI will be used to measure blood flow dynamics and calculate the percentage of shunt as the ratio of splenomesenteric inflow to hepatic venous outflow before and after TIPS.
Unit of Measure:
Serum ammonia concentration (µmol/L). Percentage (%) of splenomesenteric inflow to hepatic venous outflow
Measured: Ammonia levels and shunt percentage will be measured within 3 days before and 3 days after TIPS
Correlation between proteomic signatures (before TIPS and the occurrence of hepatic encephalopathy within 6 months following TIPS
Evaluation of the correlation between proteomic signatures (measured using mass spectrometry) measured before TIPS and the subsequent development of hepatic encephalopathy within 6 months following TIPS.
Method of Measurement: Mass spectrometry for proteomic analysis. Unit of Measure: Protein concentration (mg/mL).
Measured: before TIPS, with follow-up for the occurrence of hepatic encephalopathy during the 6 months after TIPS
Correlation between transcriptomic signatures (before TIPS and the occurrence of hepatic encephalopathy within 6 months following TIPS
Evaluation of the correlation between transcriptomic signatures (measured by RNA sequencing) measured before TIPS and the subsequent development of hepatic encephalopathy within 6 months following TIPS.
Method of Measurement: RNA expression levels will be quantified using RNA sequencing or microarrays Unit of Measure: Gene expression levels (RPKM or TPM).
Measured: before TIPS, with follow-up for the occurrence of hepatic encephalopathy during the 6 months after TIPS
Correlation between metabolomic signatures (before TIPS and the occurrence of hepatic encephalopathy within 6 months following TIPS
Evaluation of the correlation between metabolomic profiles (measured by mass spectrometry or NMR) measured before TIPS and the subsequent development of hepatic encephalopathy within 6 months following TIPS.
Method of Measurement : mass spectrometry or nuclear magneticresonance (NMR) spectroscopy Unit of Measure : Concentrations of metabolites (µM or nmol/mL)
Measured: before TIPS, with follow-up for the occurrence of hepatic encephalopathy during the 6 months after TIPS
Correlation between bacteriomic signatures (before TIPS and the occurrence of hepatic encephalopathy within 6 months following TIPS
Evaluation of the correlation between bacteriomic signatures (measured by 16S rRNA sequencing) measured before TIPS and the subsequent development of hepatic encephalopathy within 6 months following TIPS.
Method of Measurement : 16S rRNA sequencing for bacterial diversity and abundance analysis.
Unit of Measure : Relative bacterial abundance (e.g., % of total microbiome).
Measured: before TIPS, with follow-up for the occurrence of hepatic encephalopathy during the 6 months after TIPS
Correlation between viromic signatures (before TIPS and the occurrence of hepatic encephalopathy within 6 months following TIPS
Evaluation of the correlation between viromic signatures (measured by high-throughput sequencing) measured before TIPS and the subsequent development of hepatic encephalopathy within 6 months following TIPS.
Method of Measurement: High-throughput sequencing for viromic profiling. Unit of Measure: Viral load (copy number of viral genomes per mL) and viral diversity (Shannon diversity index).
Measured: before TIPS, with follow-up for the occurrence of hepatic encephalopathy during the 6 months after TIPS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2026
- Study start25 Aug 2026
- Primary completion1 Dec 2027 (estimated)
- Study completion1 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Sorbonne University, Institute of Cardiometabolism and Nutrition, France
- Responsible party
- Sponsor
- Investigators
- Louis MEYBLUM, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07554183
- Sponsor's protocol ID
- APHP251208
- Other IDs
- 2025-A01858-41
- Acronym
- PORTAL-4D
- Status last verified
- Oct 2026
- First submitted
- 18 Mar 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data are available upon reasonable request The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations