Hepatic Venous Pressure Gradient Versus Endoscopic Ultrasound-Guided Portal Pressure Gradient - Comparative Analysis (HEPCA)

Portal hypertension is one of the most severe complications of advanced chronic liver disease. Direct measurement of portal vein pressure is challenging and does not reliably reflect liver parenchymal resistance. To address this, the portal pressure gradient (PPG) - the difference between portal vein and hepatic vein pressures - is commonly used. The PPG not only predicts the risk of hepatic decompensation and hepatocellular carcinoma development but also correlates with overall patient survival. Conversely, reducing PPG is associated with an improved prognosis. PPG evaluation plays a crucial role in determining the feasibility of hepatic resection for liver cancer in patients with cirrhosis. Given the shortage of liver donors in developed countries, the need for bridging therapies has grown. Hepatic resection can serve either as a curative or a bridging modality; however, the risk of post-resection liver failure is significantly increased in patients with clinically significant portal hypertension. Therefore, PPG measurement is a valuable tool for stratifying patients who may require primary liver transplantation. Traditionally, PPG is indirectly measured using hepatic vein catheterization with measurement of hepatic venous pressure gradient (HVPG). This minimally invasive procedure involves cannulation of the right internal jugular vein, followed by the insertion of a balloon-occlusion catheter into the right or middle hepatic vein to measure both free hepatic vein pressure and wedged hepatic vein pressure, enabling the calculation of HVPG. Additionally, this method allows for liver biopsy during the same session. HVPG is widely regarded as the gold standard for PPG measurement. Recent advancements in the field of digestive endoscopy have introduced an innovative alternative: endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) measurement. This emerging technique shows promise for further improving the accessibility of portal hypertension assessment and also offers the possibility of liver biopsy in one session.

Despite its potential, EUS-PPG measurement raises concerns regarding its suitability as a full replacement for HVPG. Proponents of EUS-PPG highlight several advantages, including its minimally invasive nature, excellent safety profile, high technical success rate, the possibility of a "one-stop shop" approach (combining EUS-PPG, liver biopsy, and endoscopic treatment of esophageal varices), absence of radiation exposure, and real-time measurement capability. However, these claimed advantages may not significantly surpass those of HVPG. When performed by experienced operators, HVPG offers comparable safety and technical success rates. It also allows liver biopsy during the same session and provides real-time pressure measurements. Additionally, HVPG facilitates the identification of intrahepatic portosystemic shunts that might affect pressure readings, with the immediate option to repeat measurements in alternative locations. Importantly, HVPG remains feasible in patients with significant ascites, a scenario where EUS-PPG might encounter limitations. The primary question is whether EUS-PPG provides measurements really equivalent to HVPG in terms of gradient accuracy. Significant concerns remain regarding the impact of sedation required for EUS-PPG. Sedatives, particularly widely used propofol, have been shown to influence portal pressure measurements, resulting in obtained lower values. This sedation-induced variability could lead to misclassification of portal hypertension severity, particularly in patients with borderline values, potentially altering clinical decision-making. In this study, we propose a novel design to directly compare two methods-HVPG and EUS-PPG- within a single session, with a specific emphasis on quantifying the impact of sedation on pressure measurements and minimizing potential confounding factors. Patients undergoing HVPG will first undergo the procedure while conscious, performed by the first operator. Immediately thereafter, HVPG will be repeated following the induction of anesthesia by a second operator blinded to the initial readings. Subsequently, EUS-PPG will be performed by an endoscopist, who will also be blinded to all previous pressure measurements. This sequential approach will enable a direct comparison of all three measurements under standardized conditions, maximizing the reduction of potential bias from unintended repetition of measurements to align with prior pressure readings. Statistical analysis will be performed to evaluate the consistency between the methods and to assess the specific impact of sedation on pressure gradients. This study design aims to provide robust evidence regarding the accuracy and clinical applicability of EUS-PPG relative to HVPG, while addressing the potential confounding effects of anesthesia.