Author:
Iavarone Massimo,Alimenti Eleonora,Tada Toshifumi,Shimose Shigeo,Suda Goki,Yoo Changhoon,Soldà Caterina,Piscaglia Fabio,Tosetti Giulia,Marra Fabio,Vivaldi Caterina,Conti Fabio,Schirripa Marta,Iwamoto Hideki,Sho Takuya,Lee So Heun,Rizzato Mario Domenico,Tonnini Matteo,Rimini Margherita,Campani Claudia,Masi Gianluca,Foschi Francesco,Bruccoleri Mariangela,Kawaguchi Takumi,Kumada Takashi,Hiraoka Atsushi,Atsukawa Masanori,Fukunishi Shinya,Ishikawa Toru,Tajiri Kazuto,Ochi Hironori,Yasuda Satoshi,Toyoda Hidenori,Hatanaka Takeshi,Kakizaki Satoru,Kawata Kazuhito,Tada Fujimasa,Ohama Hideko,Itokawa Norio,Okubo Tomomi,Arai Taeang,Imai Michitaka,Naganuma Atsushi,Casadei-Gardini Andrea,Lampertico Pietro
Abstract
Introduction: Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be 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 was 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, as well as impact of EGV bleeding on patients’ survival. Results: 535 patients were enrolled in the study (median age: 72 years, 78% male, 63% viral etiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis [nPVT], 56% Barcelona Clinic Liver Cancer-C): 234 had EGV (44%), 70 (30%) were at high risk and 59 were 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 (hazard ratio: 6.94, 95% confidence interval [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 (odds ratio [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/μL (OR: 2.47; 95% CI: 1.35–4.50, p = 0.003). Conclusion: In hepatocellular carcinoma patients treated with lenvatinib, the risk of EGV bleeding was mostly low but significant only in patients with high-risk EGV at baseline.