Endoscopic ultrasound-guided sampling and profiling of portal circulation in human patients for metabolic research studies and biomarker assessment

Abstract

Portal and hepatic circulation can now be safely accessed using endoscopic ultrasound (EUS). EUS-guided needle access of the portal vein is performed clinically at select tertiary centers for measurement of portal pressure gradients in patients with chronic liver disease and sampling of portal venous thrombus to diagnose malignancy. We propose that this novel clinical technique can be applied in research studies to allow blood collection from and profiling of portal and hepatic circulation. In this technical report, we present and highlight the technical aspects, feasibility and safety of EUS - guided portal venous blood collection. As a proof of the concept and the utility of this technique in metabolic research and biomarker assessment and discovery, we present a pilot metabolite profiling study of portal venous blood in a small cohort of patients with cirrhosis and a comparison to a group without cirrhosis. Despite the very small diameter of the endoscopic needle used for the blood collection, the portal samples have the same quality as those collected from systemic circulation, and they can be used for the same downstream applications. Finally, we propose an analytical workflow to screen for promising metabolites that could qualify for further studies to determine their utility as sensitive, early, candidate biomarkers of hepatic fibrosis, portal shunt and hypertension. We hope that this report could stimulate and facilitate the widespread use of EUS-guided techniques for the profiling of portal circulation, which could potentially open a new field of scientific inquiry.

Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy

“…In recent reports the direct puncture of the portal vein using endoscopic ultrasound have been reported for sampling and a direct measurement of portal pressure, which seems to be safe and technically feasible (134)(135)(136). This technique may then ease the management of the patients, especially when varices are present at endoscopy to stratify risk, although more research is needed.…”

Role of endoscopy in hepatology

“…JID: YDLD [m5G; 22:49 ] or main trunk, could offer a less invasive, safe, and reproducible window to the gut-liver axis and solve a long-lasting impediment to this clinically remaining blind spot [142] .…”

Gut Microbiota and Sinusoidal Vasoregulation in MASLD: A Portal Perspective

“…This technique, consisting of transgastric puncture of the portal and hepatic veins to directly measure the portal pressure gradient, was primarily developed to allow for a less invasive and more accurate alternative to the method of HVPG assessment, which has been almost exclusively used in cirrhosis. EUS-PPG can be combined with liver tissue sampling [ 111 ] and blood collection [ 112 ] from the portal and hepatic veins. A particularly promising aspect of EUS-guided portal sampling is that it can provide insight into the pre-cirrhotic stages of MASLD that have been essentially out of reach due to the invasive nature and inherent risks of HVPG.…”

“…A particularly promising aspect of EUS-guided portal sampling is that it can provide insight into the pre-cirrhotic stages of MASLD that have been essentially out of reach due to the invasive nature and inherent risks of HVPG. Using EUS-guided portal sampling may facilitate the identification of pre-hepatic metabolomic signatures associated with MASLD of different severity and correlate metabolite levels with increases in portal pressure [ 112 ]. While EUS is not without potential complications, it is less invasive and may become an acceptable diagnostic approach to the evaluation of patients with noncirrhotic MASLD.…”