Incidence and Predictors of Esophagogastric Varices Bleeding in Patients with Hepatocellular Carcinoma in Lenvatinib

Massimo Iavarone; Eleonora Alimenti; Toshifumi Tada; Shigeo Shimose; Goki Suda; Changhoon Yoo; Caterina Soldà; Fabio Piscaglia; Giulia Tosetti; Fabio Marra; Caterina Vivaldi; Fabio Conti; Marta Schirripa; Hideki Iwamoto; Takuya Sho; So Heun Lee; Mario Domenico Rizzato; Matteo Tonnini; Margherita Rimini; Claudia Campani; Gianluca Masi; Francesco Foschi; Mariangela Bruccoleri; Takumi Kawaguchi; Takashi Kumada; Atsushi Hiraoka; Masanori Atsukawa; Shinya Fukunishi; Toru Ishikawa; Kazuto Tajiri; Hironori Ochi; Satoshi Yasuda; Hidenori Toyoda; Takeshi Hatanaka; Satoru Kakizaki; Kazuhito Kawata; Fujimasa Tada; Hideko Ohama; Norio Itokawa; Tomomi Okubo; Taeang Arai; Michitaka Imai; Atsushi Naganuma; Andrea Casadei-Gardini; Pietro Lampertico

doi:10.1159/000534127

Incidence and Predictors of Esophagogastric Varices Bleeding in Patients with Hepatocellular Carcinoma in Lenvatinib

Massimo Iavarone^*, Eleonora Alimenti, Toshifumi Tada, Shigeo Shimose, Goki Suda, Changhoon Yoo, Caterina Soldà, Fabio Piscaglia, Giulia Tosetti, Fabio Marra, Caterina Vivaldi, Fabio Conti, Marta Schirripa, Hideki Iwamoto, Takuya Sho, So Heun Lee, Mario Domenico Rizzato, Matteo Tonnini, Margherita Rimini, Claudia CampaniGianluca Masi, Francesco Foschi, Mariangela Bruccoleri, Takumi Kawaguchi, Takashi Kumada, Atsushi Hiraoka, Masanori Atsukawa, Shinya Fukunishi, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Atsushi Naganuma, Andrea Casadei-Gardini, Pietro Lampertico

^*Corresponding author for this work

Internal Medicine （3）

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English
Pages (from-to)	215-226
Number of pages	12
Journal	Liver Cancer
Volume	13
Issue number	2
DOIs	https://doi.org/10.1159/000534127
State	Published - 2023/09/14

Keywords

Bevacizumab
Cirrhosis
Neoplastic portal vein thrombosis
Portal hypertension
Varices

ASJC Scopus subject areas

Hepatology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1159/000534127

Cite this

Iavarone, M., Alimenti, E., Tada, T., Shimose, S., Suda, G., Yoo, C., Soldà, C., Piscaglia, F., Tosetti, G., Marra, F., Vivaldi, C., Conti, F., Schirripa, M., Iwamoto, H., Sho, T., Lee, S. H., Rizzato, M. D., Tonnini, M., Rimini, M., ... Lampertico, P. (2023). Incidence and Predictors of Esophagogastric Varices Bleeding in Patients with Hepatocellular Carcinoma in Lenvatinib. Liver Cancer, 13(2), 215-226. https://doi.org/10.1159/000534127

@article{6c6d946396834b1ab6cc8db6d374e0ad,

title = "Incidence and Predictors of Esophagogastric Varices Bleeding in Patients with Hepatocellular Carcinoma in Lenvatinib",

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.",

keywords = "Bevacizumab, Cirrhosis, Neoplastic portal vein thrombosis, Portal hypertension, Varices",

author = "Massimo Iavarone and Eleonora Alimenti and Toshifumi Tada and Shigeo Shimose and Goki Suda and Changhoon Yoo and Caterina Sold{\`a} and Fabio Piscaglia and Giulia Tosetti and Fabio Marra and Caterina Vivaldi and Fabio Conti and Marta Schirripa and Hideki Iwamoto and Takuya Sho and Lee, {So Heun} and Rizzato, {Mario Domenico} and Matteo Tonnini and Margherita Rimini and Claudia Campani and Gianluca Masi and Francesco Foschi and Mariangela Bruccoleri and Takumi Kawaguchi and Takashi Kumada and Atsushi Hiraoka and Masanori Atsukawa and Shinya Fukunishi and Toru Ishikawa and Kazuto Tajiri and Hironori Ochi and Satoshi Yasuda and Hidenori Toyoda and Takeshi Hatanaka and Satoru Kakizaki and Kazuhito Kawata and Fujimasa Tada and Hideko Ohama and Norio Itokawa and Tomomi Okubo and Taeang Arai and Michitaka Imai and Atsushi Naganuma and Andrea Casadei-Gardini and Pietro Lampertico",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s).",

year = "2023",

month = sep,

day = "14",

doi = "10.1159/000534127",

language = "英語",

volume = "13",

pages = "215--226",

journal = "Liver Cancer",

issn = "2235-1795",

publisher = "S. Karger AG",

number = "2",

}

Iavarone, M, Alimenti, E, Tada, T, Shimose, S, Suda, G, Yoo, C, Soldà, C, Piscaglia, F, Tosetti, G, Marra, F, Vivaldi, C, Conti, F, Schirripa, M, Iwamoto, H, Sho, T, Lee, SH, Rizzato, MD, Tonnini, M, Rimini, M, Campani, C, Masi, G, Foschi, F, Bruccoleri, M, Kawaguchi, T, Kumada, T, Hiraoka, A, Atsukawa, M, Fukunishi, S, Ishikawa, T, Tajiri, K, Ochi, H, Yasuda, S, Toyoda, H, Hatanaka, T, Kakizaki, S, Kawata, K, Tada, F, Ohama, H, Itokawa, N, Okubo, T, Arai, T, Imai, M, Naganuma, A, Casadei-Gardini, A & Lampertico, P 2023, 'Incidence and Predictors of Esophagogastric Varices Bleeding in Patients with Hepatocellular Carcinoma in Lenvatinib', Liver Cancer, vol. 13, no. 2, pp. 215-226. https://doi.org/10.1159/000534127

TY - JOUR

T1 - Incidence and Predictors of Esophagogastric Varices Bleeding in Patients with Hepatocellular Carcinoma in Lenvatinib

AU - Iavarone, Massimo

AU - Alimenti, Eleonora

AU - Tada, Toshifumi

AU - Shimose, Shigeo

AU - Suda, Goki

AU - Yoo, Changhoon

AU - Soldà, Caterina

AU - Piscaglia, Fabio

AU - Tosetti, Giulia

AU - Marra, Fabio

AU - Vivaldi, Caterina

AU - Conti, Fabio

AU - Schirripa, Marta

AU - Iwamoto, Hideki

AU - Sho, Takuya

AU - Lee, So Heun

AU - Rizzato, Mario Domenico

AU - Tonnini, Matteo

AU - Rimini, Margherita

AU - Campani, Claudia

AU - Masi, Gianluca

AU - Foschi, Francesco

AU - Bruccoleri, Mariangela

AU - Kawaguchi, Takumi

AU - Kumada, Takashi

AU - Hiraoka, Atsushi

AU - Atsukawa, Masanori

AU - Fukunishi, Shinya

AU - Ishikawa, Toru

AU - Tajiri, Kazuto

AU - Ochi, Hironori

AU - Yasuda, Satoshi

AU - Toyoda, Hidenori

AU - Hatanaka, Takeshi

AU - Kakizaki, Satoru

AU - Kawata, Kazuhito

AU - Tada, Fujimasa

AU - Ohama, Hideko

AU - Itokawa, Norio

AU - Okubo, Tomomi

AU - Arai, Taeang

AU - Imai, Michitaka

AU - Naganuma, Atsushi

AU - Casadei-Gardini, Andrea

AU - Lampertico, Pietro

PY - 2023/9/14

Y1 - 2023/9/14

N2 - 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.

AB - 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.

KW - Bevacizumab

KW - Cirrhosis

KW - Neoplastic portal vein thrombosis

KW - Portal hypertension

KW - Varices

UR - http://www.scopus.com/inward/record.url?scp=85190884178&partnerID=8YFLogxK

U2 - 10.1159/000534127

DO - 10.1159/000534127

M3 - 学術論文

C2 - 38751557

AN - SCOPUS:85190884178

SN - 2235-1795

VL - 13

SP - 215

EP - 226

JO - Liver Cancer

JF - Liver Cancer

IS - 2

ER -

Incidence and Predictors of Esophagogastric Varices Bleeding in Patients with Hepatocellular Carcinoma in Lenvatinib

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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