Transjugular intrahepatic portosystemic shunt (TIPS) is a key therapeutic intervention for complications of portal hypertension. However, the risk of post-procedural hepatic encephalopathy (HE) limits its broader clinical application. In the management of gastroesophageal variceal bleeding, the primary goal of TIPS is to reduce the portosystemic pressure gradient (PPG) to less than 12 mmHg (16 cmH₂O), which defines the standard TIPS procedure. The investigators hypothesize that, in patients undergoing TIPS for the prevention of variceal rebleeding, stent underdilation using a 6-mm balloon (underdilated TIPS) will not increase the risk of rebleeding but may reduce the incidence of overt HE and attenuate liver injury. To test this hypothesis, the investigators have designed a prospective, multicenter, randomized controlled trial.
High-risk acute esophageal or type 1 gastroesophageal variceal bleeding, including: Child-Pugh grade B with a score > 7 and endoscopic evidence of active bleeding; Child-Pugh grade C with a score < 14.
Hepatic venous pressure gradient (HVPG) > 20 mmHg during bleeding.
Early rebleeding within 5 days.
Bleeding uncontrolled despite pharmacological and endoscopic therapy. 4. History of esophageal or gastric variceal bleeding with failure of standard first-line treatment [endoscopy combined with non-selective beta-blockers (NSBB)]; or first hemorrhage accompanied by grade 2 ascites and/or portal vein thrombosis; GOV2 or IGV1 gastric variceal bleeding; ectopic variceal bleeding; or bleeding from refractory portal hypertensive gastropathy.
Budd-Chiari syndrome or other causes of non-cirrhotic portal hypertension.
Current or prior malignancy, including hepatocellular carcinoma or malignancies of other organs.
Complete thrombosis of the main portal vein.
Severe psychiatric or neurologic disorders (e.g., uncontrolled epilepsy, dementia).
Parallel
Underdilated TIPS
Procedure/SurgeryThe procedure will be performed via a transjugular approach, involving puncture from the hepatic vein or inferior vena cava into the portal venous system. Upon successful cannulation, direct portography will be performed to visualize varices and determine the optimal shunt tract, followed by targeted variceal embolization. A Novel VIATORR® Controlled Expansion (VCX) stent graft (W. L. Gore \& Associates, Arizona, USA) will then be deployed intrahepatically to establish the shunt. Subsequently, a 6-mm balloon will be used for suboptimal expansion of the TIPS stent, and the immediate portosystemic pressure gradient (PPG) will be measured.
Standard TIPS
Procedure/SurgeryThe procedure will be performed via a transjugular approach, with puncture conducted from the hepatic vein or inferior vena cava into the portal venous system. After successful cannulation, direct portography will be performed to visualize gastroesophageal varices and identify the optimal shunt tract, followed by targeted variceal embolization. A novel VIATORR® Controlled Expansion (VCX) stent graft (W. L. Gore \& Associates, Arizona, USA) will then be deployed intrahepatically to establish the transjugular intrahepatic portosystemic shunt (TIPS). Subsequently, the TIPS stent will be progressively dilated (starting at 8 mm of diameter) to the minimum diameter needed to achieve a portosystemic pressure gradient (PSPG) below 12 mm Hg.
Cumulative incidence of gastroesophageal variceal rebleeding.
Clinically significant rebleeding is defined in accordance with the Baveno V consensus criteria and is identified by recurrence of melena or hematemesis accompanied by any of the following: a) requirement for hospitalization; b) need for blood transfusion; c) hemoglobin decrease of ≥3 g/dL; or d) death within 6 weeks.
All-cause rebleeding
Stent dysfunction
Diagnosis of TIPS stent dysfunction follows a stepwise approach utilizing Doppler ultrasound, angiography, and measurement of the portosystemic pressure gradient (PPG). Stent dysfunction is diagnosed if either of the following criteria is met: (1) shunt stenosis ≥50% or complete occlusion; (2) an increase in PPG ≥25% compared to the baseline value measured immediately after stent placement. Angiography is indicated under the following circumstances: (1) recurrence of portal hypertension-related complications-TIPS stent dysfunction should be suspected upon recurrence of symptoms such as rebleeding, new-onset ascites, or persistence of ascites beyond 4-8 weeks; (2) color Doppler ultrasound findings-when flow direction is hepatofugal and mean maximum portal vein flow velocity (mVPmax) \< 28 cm/s; when flow direction is hepatopetal and mVPmax \< 39 cm/s.
New or worsening ascites
Defined as an increase of at least one grade in ascites severity on ultrasound (grading criteria: Grade 0 = none, Grade 1 = mild, Grade 2 = moderate, Grade 3 = large), or persistent ascites requiring paracentesis.
Incidence of overt hepatic encephalopathy
Hepatic encephalopathy is classified according to the 2022 European Association for the Study of the Liver (EASL) Clinical Practice Guidelines using the West-Haven criteria. Overt hepatic encephalopathy is defined as grade II or higher.
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Air Force Military Medical University, China
Lead sponsor
West China Hospital
Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Collaborator
Daping Hospital of Army Medical University
Collaborator
General Hospital of Ningxia Medical University
Collaborator
