B54-15 Hepatic Clearance of Gut-derived Microbial Products: A Human Model Using the Transjugular Intrahepatic Portosystemic Shunt Procedure

Rationale Translocation of microbial products across the gut barrier contributes to systemic inflammation and organ failure in sepsis and critical illness. Circulating microbial DNA has recently been shown to predict outcomes and correlate with sepsis subphenotypes, yet existing studies rely solely on peripheral blood. The liver is the first and primary anatomic filter between the gut and systemic circulation and likely plays a key role in modulating this systemic exposure. However, its function in clearing microbial products has never been directly measured in humans. The transjugular intrahepatic portosystemic shunt (TIPS) procedure provides a rare opportunity to compare pre- and post-hepatic blood in vivo, enabling direct study of hepatic clearance of microbial products in human subjects. Methods We conducted a prospective observational cohort study to assess the feasibility and safety of collecting paired pre- and post-hepatic blood samples during elective TIPS procedures. Patients scheduled for TIPS were prospectively approached for participation, and informed consent was obtained prior to the procedure. During the procedure and prior to TIPS placement, the interventional radiology team collected 8-mL samples from the portal vein (pre-liver), hepatic vein (post-liver), and right atrium using catheters already in place for clinical care (Figure 1). After TIPS placement, a follow-up right atrial sample was collected to represent systemic venous return. Samples were divided into EDTA and sodium-heparin tubes for plasma and whole blood, processed within two hours, and flash frozen. Clinical data were recorded in REDCap. Results Over a 12-week period, 11 patients scheduled for elective TIPS were approached, and 10 (91%) provided informed consent. Blood sampling was successfully completed in all ten participants. The median age was 60 years, 70% were women, and 80% of procedures were performed in outpatients. In all cases, paired portal, hepatic, and right atrial blood samples were obtained without complication. No adverse events occurred, and there was no interference with clinical workflow, demonstrating that collection of pre- and post-hepatic blood during TIPS is both feasible and safe. There was no participant drop out. Conclusions Collection of time-matched pre- and post-hepatic blood during TIPS placement is feasible and safe. Leveraging this rare clinical opportunity establishes a novel human platform to study hepatic clearance of circulating microbial products in humans.