Prevention of variceal rebleeding in cirrhotic patients with advanced hepatocellular carcinoma receiving molecularly targeted therapy: a randomized pilot study of transjugular intrahepatic portosystemic shunt versus endoscopic plus β-blocker

Although transjugular intrahepatic portosystemic shunt (TIPS) is recommended for secondary prophylaxis of variceal bleeding if standard therapy fails and for patients with high risk of recurrent bleeding, no guidelines for the treatment of symptomatic portal hypertension in HCC patients are available. This study aimed to compare the efficacy and safety of TIPS with endoscopic + β-blocker for prevention of the rebleeding in such patients. 106 consecutive advanced HCC patients receiving tyrosine kinase inhibitor (TKI) who had been treated with vasoactive drugs plus endoscopic therapy for variceal bleeding were randomly assigned to receive either TIPS (n = 52) or endoscopic + β-blocker therapy (n = 54) for the prevention of rebleeding. The primary endpoint was variceal rebleeding after randomization. During a median follow-up of 16 months, rebleeding occurred in 14 patients in the endoscopic + β-blocker group and 3 patients in the TIPS group (p < 0.001). Forty-nine patients died (38 in endoscopic + β-blocker group and 11 in TIPS group, p < 0.001). The 6-, 12-, and 18-month overall survival rates were 95, 81, and 73% for TIPS group and 35, 21, and 15% for endoscopic + β-blocker group, respectively (p < 0.001). Eight patients in endoscopic + β-blocker group received TIPS as rescue therapy, but two died. TKIs was discontinued in 32 patients, including 24 in the endoscopic + β-blocker group and 8 in the TIPS group (p < 0.001). No significant differences were observed between the two groups with respect to serious adverse events. In advanced HCC patients receiving TKIs and presented with variceal bleeding, the use of TIPS was associated with significant reduction in rebleeding, improved a higher adherence to TKIs therapy, and prolonged survival.