TY - JOUR

T1 - Predicting survival in patients with ‘non-high-risk’ acute variceal bleeding receiving β-blockers+ligation to prevent re-bleeding

AU - Balcar, Lorenz

AU - Mandorfer, Mattias

AU - Hernández-Gea, Virginia

AU - Procopet, Bogdan

AU - Meyer, Elias Laurin

AU - Giráldez, Álvaro

AU - Amitrano, Lucio

AU - Villanueva, Candid

AU - Thabut, Dominique

AU - Samaniego, Luis Ibáñez

AU - Silva-Junior, Gilberto

AU - Martinez, Javier

AU - Genescà, Joan

AU - Bureau, Christophe

AU - Trebicka, Jonel

AU - Herrera, Elba Llop

AU - Laleman, Wim

AU - Palazón Azorín, José María

AU - Alonso, Jose Castellote

AU - Gluud, Lise Lotte

AU - Ferreira, Carlos Noronha

AU - Cañete, Nuria

AU - Rodríguez, Manuel

AU - Ferlitsch, Arnulf

AU - Mundi, Jose Luis

AU - Grønbæk, Henning

AU - Hernandez Guerra, Manuel Nicolas

AU - Sassatelli, Romano

AU - Dell'Era, Alessandra

AU - Senzolo, Marco

AU - Abraldes, Juan Gonzalez

AU - Romero-Gómez, Manuel

AU - Zipprich, Alexander

AU - Casas, Meritxell

AU - Masnou, Helena

AU - Primignani, Massimo

AU - Krag, Aleksander

AU - Nevens, Frederik

AU - Calleja, Jose Luis

AU - Jansen, Christian

AU - Catalina, María Vega

AU - Albillos, Agustín

AU - Rudler, Marika

AU - Tapias, Edilmar Alvarado

AU - Guardascione, Maria Anna

AU - Tantau, Marcel

AU - Schwarzer, Rémy

AU - Reiberger, Thomas

AU - Laursen, Stig Borbjerg

AU - Lopez-Gomez, Marta

AU - International Variceal Bleeding Observational Study Group by the Baveno Cooperation: an EASL consortium

N1 - Publisher Copyright: © 2023 European Association for the Study of the Liver

PY - 2024

Y1 - 2024

N2 - Background & Aims: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some ‘non-high-risk’ patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in ‘non-high-risk’ AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. Methods: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. Results: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. Conclusion: The majority of ‘non-high-risk’ patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. Impact and implications: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some ‘non-high-risk’ patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in ‘non-high-risk’ acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably ‘non-high-risk’ patients who are identified as being at increased risk of death.

AB - Background & Aims: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some ‘non-high-risk’ patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in ‘non-high-risk’ AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. Methods: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. Results: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. Conclusion: The majority of ‘non-high-risk’ patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. Impact and implications: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some ‘non-high-risk’ patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in ‘non-high-risk’ acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably ‘non-high-risk’ patients who are identified as being at increased risk of death.

KW - Cirrhosis

KW - decompensation

KW - endoscopic variceal ligation

KW - non-selective betablocker

KW - TIPS

U2 - 10.1016/j.jhep.2023.10.007

DO - 10.1016/j.jhep.2023.10.007

M3 - Journal article

C2 - 37852414

AN - SCOPUS:85176385705

VL - 80

SP - 73

EP - 81

JO - Journal of Hepatology, Supplement

JF - Journal of Hepatology, Supplement

SN - 0169-5185

IS - 1

ER -