Supplementary Material for: Incidence and predictors of esophagogastric varices bleeding in patients with hepatocellular carcinoma in lenvatinib

Introduction: Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use maybe limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib. Methods: In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC, were enrolled if upper-gastrointestinal endoscopy (UGE) available within 6 months before treatment. Primary endpoint was the incidence of EGV bleeding during lenvatinib therapy; secondary endpoints were predictors for EGV bleeding, prevalence and risk factors for the presence of EGV and high risk EGV at baseline, impact of EGV bleeding on patients’ survival. Results: 535 patients were enrolled in the study [median age 72 years, 78% male, 63% viral aetiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis (nPVT), 56% BCLC-C]: 234 had EGV (44%): 70 (30%) at high-risk and 59 on primary prophylaxis. During lenvatinib treatment, 17 patients bled from EGV (3 grade 5), the 12-month cumulative incidence being 3%. The only baseline independent predictor of EGV bleeding was the presence of baseline high risk EGV (HR 6.94, 95% CI 2.23-21.57, p=0.001). In these patients the 12-month risk was 17%. High risk varices were independently associated with Child-Pugh B score (OR 2.12; 95%CI 1.08-4.17, p=0.03), nPVT (OR 2.54; 95%CI 1.40-4.61, p=0.002) and platelets <150.000/uL (OR 2.47; 95%CI 1.35-4.50, p=0.003. Conclusion: In HCC patients treated with lenvatinib, the risk of EGV bleeding was mostly low but significant only in patients with high-risk EGV at baseline.