Project
Stratifying risk and individualizing care for patients with clinically significant portal hypertension (CSPH)
Stratifying risk and individualizing care for patients with clinical significant portal hypertension (CSPH) PhD candidate: Emma Vanderschueren, MD PhD promotor: Wim Laleman, MD PhD, CHROMETA Cirrhosis is the eventual and unavoidable consequence of any given protracted active chronic liver disease, like e.g. hepatitis B, hepatitis C, (non) alcoholic fatty liver disease,... When the underlying liver disease is left untreated, (asymptomatic) compensated cirrhosis will evolve to a decompensated state. Patients with decompensated cirrhosis suffer from ascites, oesophageal varices (with/without bleeding), jaundice, recurrent infections and hepatic encephalopathy, and understandably have a very high risk of mortality. One of the main drivers in the transition to decompensation is portal hypertension. Once symptoms of decompensation show, the label of ‘clinically significant portal hypertension’ (CSPH) is used. Portal pressure is classically measured invasively by means of liver vein catheterization. After puncturing the jugular vein, a catheter is advanced into the right hepatic vein to measure the hepatic venous pressure gradient (HVPG). The HVPG is calculated by subtracting the free pressure in the right hepatic vein from the wedged hepatic sinusoidal pressure after inflating a balloon. Portal hypertension is defined by a HVPG of >5mmHg, CSPH is referred to as a HVPG > 10mmHg. Higher pressure correlates with increasingly severe disease and a higher risk of decompensating events. Evolving portal hypertension is a key pathophysiological mechanism in the cirrhogenesis and its progression to (increasing) decompensation. Yet its assessment by means of the considered ‘golden standard’, transjugular liver vein catheterisation, is invasive and limited to specific liver dedicated hospitals. Due to this, the HVPG-method is rarely measured in clinical practice. As a result, treatment of portal hypertension (e.g. non-selective beta-blocker) is mostly empirically initiated when portal hypertension has already led to symptoms and thus decompensation. Moreover, the effect of this treatment is seldom monitored by sequential HVPG measurement. In recent years, clinical research has increasingly focused on the development of other less invasive/non-invasive and more broadly applicable tools to assess portal hypertension and/or predict risk of decompensation (e.g. variceal bleeding). Laboratory variables, serum fibrosis markers, genetic polymorphisms, liver and spleen stiffness measurements, and different imaging methods have gained more and more attention. Arguably, considerable progress has been made in the search for a (non-invasive) tool that could replace HVPG measurement. Nevertheless, many questions remain unanswered and unstudied. In this PhD project, we would like to explore novel tools and validate or optimize existing scoring systems using large available clinical database as well as search for new non-invasive or less invasive ways to quantify portal hypertension by means of liver-spleen stiffness and endoscopy/endoscopic ultrasound. Once validated, these instruments could help stratifying risk and individualizing care for patients with clinical significant portal hypertension.