Pre-emptive TIPS for the treatment of bleeding from gastric fundal varices: Results of a randomised controlled trial

Abstract

Background & aims: Bleeding from gastric fundal varices (isolated gastric varices type 1/gastroesophageal varices type 2) represents a major problem because of a high incidence of rebleeding and death with standard-of-care therapy (endoscopic obliteration with tissue adhesives plus pharmacological therapy). Transjugular intrahepatic portosystemic shunts (TIPSs) are recommended as a rescue therapy. Pre-emptive 'early' TIPS (pTIPS) significantly improves control of bleeding and survival in patients at high-risk of dying or rebleeding from esophageal varices.

Methods: This randomised controlled trial investigate whether the use of pTIPS improves rebleeding-free survival in patients with gastric fundal varices (isolated gastric varices type 1 and/or gastroesophageal varices type 2) compared with standard therapy.

Results: The study did not achieve the predefined sample size because of low recruitment. Nevertheless, pTIPS (n = 11) was more effective compared with combined endoscopic and pharmacological therapy (n = 10) in improving rebleeding-free survival (per protocol analysis: 100 vs. 28%; p = 0.017). This was mainly because of a better outcome in patients with Child-Pugh B or C scores. There were no differences in serious adverse events or in the incidence of hepatic encephalopathy among the different cohorts.

Conclusion: The use of pTIPS should be considered in patients with Child-Pugh B or C scores bleeding from gastric fundal varices.

Impact and implications: The first-line treatment of gastric fundal varices (GOV2 and/or IGV1) is the combination of pharmacological therapy and endoscopic obliteration with glue. TIPS is considered the main rescue therapy. Recent data suggest that, in patients at high-risk of dying or rebleeding (Child-Pugh C or B scores + active bleeding at endoscopy) from esophageal varices, the use of pTIPS, performed during the first 72 h from admission, results in an increased rate of control of bleeding and survival compared with combined endoscopic and pharmacological therapy. Herein, we present a randomised controlled trial comparing pTIPS with combined endoscopic (injection of glue) and pharmacological therapy (first, somatostatin or terlipressin; carvedilol after discharge) in the treatment of patients bleeding from GOV2 and/or IGV1. Although we were not able to include the calculated sample size because of the scarcity of these patients, our results show that the use of pTIPS is associated with a significantly higher actuarial rebleeding-free survival when analysed as per protocol. This is because of the greater efficacy of this treatment in patients with Child-Pugh B or C scores.

Keywords: Cirrhosis; Non-selective beta-blockers; Portal hypertension; Tissue adhesive injection.

Conflict of interest statement

AE/CV: travel grant from Gore. JCGP: Cook advisory board member, travel grants from Gore and Mallinkrodt; JB: consultant/advisory board member for Astra Zeneca, BioVie, 10.13039/100001003Boehringer Ingelheim, NovoNordisk, and Resolution Therapeutics. Please refer to the accompanying ICMJE disclosure forms for further details.

© 2023 The Authors.

Figures

Graphical abstract

Figure 1

Actuarial probability of survival free of rebleeding (A) according to intention to treat (curves constructed with the Kaplan-Meier method and compared with the Mantel-Cox test), (B) according to per protocol analysis (curves constructed with the Kaplan-Meier method and compared with the Mantel-Cox test).