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

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.