Probiotics Prevent Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt: A Randomised Controlled Trial

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is the most common complication of cirrhosis after transjugular intrahepatic portosystemic shunt (TIPS) and is closely related to intestinal dysbiosis. The efficacy of probiotics in improving minimal HE (MHE) has been well studied, while the role of probiotics for the primary prophylaxis of overt HE (OHE) after TIPS has not been established. We aimed to determine whether Live Combined Bifidobacterium and Lactobacillus Tablets, a commonly used probiotic preparation in China, reduced the risk of post-TIPS HE. METHOD: We conducted an open-label, randomised, blank-controlled trial of 142 patients with cirrhosis receiving TIPS. Patients were randomly assigned to receive probiotics (2 g three times daily) or not. The primary outcome was the incidence of OHE within 24 weeks after TIPS. The secondary outcomes were improvement in cognitive function [defined by the number connection test-A (NCT-A) and digit symbol test (DST)] and the incidence of other cirrhosis-related complications at 24 weeks. RESULTS: The incidence of post-TIPS OHE was 51.4% in the control group (n = 70), which was significantly lower in the probiotics group (n = 72, 36.1%, Fine-Grey p = 0.043). In the subgroup of patients without post-TIPS OHE, liver transplantation or death, there was no significant difference in DST and NCT-A tests at 24 weeks compared with baseline in the control group. By contrast, both DST [31.5 (26.4-39.3) vs. 34.5 (29.8-43.0), p < 0.0001] and NCT-A [53.8 (43.3-71.2) vs. 46.6 (40.2-64.4), p = 0.0045] significantly improved at 24 weeks in the probiotics group. There was no significant difference in other cirrhosis-related complications between the two groups. CONCLUSION: Live Combined Bifidobacterium and Lactobacillus Tablets might reduce the risk of OHE and improve cognitive function in cirrhosis patients receiving TIPS for variceal bleeding without previous OHE. Multicenter studies should be performed to provide further evidence. TRIAL REGISTRATION: Chictr.org: ChiCTR2200062996.