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NCT Number: NCT07554183

4D-Flow MRI Assessment of Portal Hypertension and TIPS Outcomes in Cirrhosis

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.

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.

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Key information

Conditions

Cirrhosis Brain Diseases Brain Diseases, Metabolic Central Nervous System Diseases Digestive System Diseases Fibrosis Hepatic Encephalopathy Hepatic Insufficiency Hypertension, Portal Liver Diseases Liver Failure Metabolic Diseases Nervous System Diseases Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Portal Hypertension

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

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

Exclusion criteria

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.

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

Treatment and study plan

4D-Flow Liver and heart MRI with Gadolinium injection

Other

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 DNA

Biological

Portal, hepatic and systemic veins blood collection

Primary outcomes

  1. Correlation between invasive hepatic venous pressure gradient (HVPG) and quantitative hepatic 4D-flow MRI hemodynamic parameters

    Time frame: Baseline (4D-flow MRI performed within 3 days before or after invasive measurements)

    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

Secondary outcomes

  1. : Correlation between 4D Flow MRI measured flows and the percentage of shunt with the incidence of events related to portal hypertension

    Time frame: 6 months

    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.

  2. Correlation between proteomic signatures and the occurrence of hepatic encephalopathy

    Time frame: Occurrence of hepatic encephalopathy will be monitored for 6 months following the TIPS procedure

    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).

  3. Correlation between transcriptomic signatures and the occurrence of hepatic encephalopathy

    Time frame: Occurrence of hepatic encephalopathy will be monitored for 6 months following the TIPS procedure

    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).

  4. Correlation between metabolomic signatures and the occurrence of hepatic encephalopathy.

    Time frame: Occurrence of hepatic encephalopathy will be monitored for 6 months following the TIPS procedure

    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).

  5. Correlation between viromic signatures and the occurrence of hepatic encephalopathy

    Time frame: Occurrence of hepatic encephalopathy will be monitored for 6 months following the TIPS procedure

    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).

  6. Correlation between bacteriomic signatures and the occurrence of hepatic encephalopathy

    Time frame: Occurrence of hepatic encephalopathy will be monitored for 6 months following the TIPS procedure

    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).

  7. Correlation between TIPS diameter and hemodynamic measurements and 4D Flow MRI results before and after TIPS

    Time frame: TIPS diameter measured immediately after the procedure

    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.

  8. Correlation between 4D Flow MRI results and hemodynamic measurements before and after TIPS

    Time frame: 4D Flow MRI performed within 3 days before and 3 days 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.

  9. 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

    Time frame: Complications will be monitored for 6 months following the TIPS procedure

    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.

  10. 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

    Time frame: Complications will be monitored for 6 months following the TIPS procedure.

    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 (%)

  11. Evaluation of the variation in 4D Flow MRI-measured flow rates and percentage of shunt before and after TIPS, according to TIPS diameter

    Time frame: Flow measurements and shunt percentage will be assessed before and after TIPS (within 3 days before and 3 days after TIPS).

    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).

  12. Correlation between changes in ammonia levels before and after TIPS with changes in percentage of shunt before and after TIPS

    Time frame: Ammonia levels and shunt percentage will be measured within 3 days before and 3 days 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

  13. Correlation between proteomic signatures (before TIPS and the occurrence of hepatic encephalopathy within 6 months following TIPS

    Time frame: before TIPS, with follow-up for the occurrence of hepatic encephalopathy during the 6 months after 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).

  14. Correlation between transcriptomic signatures (before TIPS and the occurrence of hepatic encephalopathy within 6 months following TIPS

    Time frame: before TIPS, with follow-up for the occurrence of hepatic encephalopathy during the 6 months after 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).

  15. Correlation between metabolomic signatures (before TIPS and the occurrence of hepatic encephalopathy within 6 months following TIPS

    Time frame: before TIPS, with follow-up for the occurrence of hepatic encephalopathy during the 6 months after 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)

  16. Correlation between bacteriomic signatures (before TIPS and the occurrence of hepatic encephalopathy within 6 months following TIPS

    Time frame: before TIPS, with follow-up for the occurrence of hepatic encephalopathy during the 6 months after 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).

  17. Correlation between viromic signatures (before TIPS and the occurrence of hepatic encephalopathy within 6 months following TIPS

    Time frame: before TIPS, with follow-up for the occurrence of hepatic encephalopathy during the 6 months after 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).

Study contacts

Contact information is provided by the study sponsor or research team.

Charles ROUX, MD

CONTACT

[email protected]

+33 1 42 16 27 70

Louis MEYBLUM, MD

CONTACT

[email protected]

+331 84 82 82 68

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

  • Institute of Cardiometabolism and Nutrition, France
  • Sorbonne University

Registry information

Official study title

Predicting Outcomes and Risk of Complications Related to Portal hyperTension by Non-invasive Assessment of Liver Flow With 4D MRI

Acronym: PORTAL-4D

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
Apr 28, 2026
Registry last updated
Jun 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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