Evaluation of the Efficacy and Safety of Portal Pressure Gradient (PPG) Measurement Guided by Endoscopic Ultrasound (EUS) in the Therapeutic Algorithm of Patients with Liver Cirrhosis.

Liver cirrhosis is a progressive disease with a continuum of compensated to decompensated stages. The development of portal hypertension (PH) and fibrosis are the primary pathophysiological processes in this clinical course. Clinical significant PH (CSPH) is a major driver of complications such as ascites and variceal bleeding. PPG is the strongest predictor of decompensation with a negative predictive value of 90% for PPG < 10 mmHg. Non-selective beta-blockers (NSBB) have demonstrated efficacy in reducing PH and preventing variceal bleeding. The clinical efficacy of NSBB is based on a significant reduction in PPG, estimated by HVPG measurement. However, this requires a second invasive procedure, and there is high interindividual variability in the hemodynamic response to NSBB. Therefore, the development of tools to identify patients who are likely to benefit from beta-blockers is an unmet clinical need. In this regard, PPG measurement guided by EUS can potentially predict the chronic hemodynamic response, serving as a strategy to guide therapy and identify patients who can benefit from NSBB in a single hemodynamic study, substantially reducing the need for repeated measurements. The aim of this project is to assess the safety and efficacy of EUS-derived GPP measurement (EUS-GPP) in patients diagnosed with cirrhosis, to assess the acute hemodynamic response through EUS-derived GPP to intravenous propranolol administration in order to determine the patients who would benefit from NSBB treatment in primary prophylaxis to prevent decompensation using a strategy guided by EUS-GPP measurement.

The natural history of cirrhosis can be described as a continuum from a compensated phase to decompensation and liver failure, marked by the development of overt ascites (or pleural effusion with a serum ascites albumin gradient [>1.1 g/dl]), encephalopathy (West Haven grade >II), and variceal bleeding, with a rate of 5 to 7% per year. This decompensation results in higher mortality and a median survival of 2 years compared to 12 years in the compensated phase1.

The events defining decompensation are hepatic fibrosis and the development of portal hypertension as the main pathophysiological processes of this clinical course. It has been demonstrated that the hepatic venous pressure gradient (HVPG) is the strongest predictor of decompensation, with a negative predictive value of 90% for HVPG less than 10 mm Hg2.

Compensated cirrhosis can be divided into 2 stages, based on the absence or presence of clinically significant portal hypertension (CSPH). Clinically significant portal hypertension (CSPH) is the main driver of complications3-4 - such as the development of ascites or variceal bleeding. It is important to note that CSPH, diagnosed by a hepatic venous pressure gradient (HVPG) of ≥10 mmHg, may be present before the complications of portal hypertension develop.

In general, CSPH is present in around 50 to 60% of patients with compensated cirrhosis without varices5-6, while patients with varices typically have an HVPG of at least 10 mmHg3-4. Patients with an HVPG >12 mmHg are at risk of variceal bleeding7. The risk of hepatic decompensation and mortality increases at HVPG levels >16 mmHg8, and at >20 mmHg, there is a higher frequency of uncontrolled bleeding, early rebleeding, and bleeding-related death3-9-10.