학술논문
Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving β-blockers+ligation to prevent re-bleeding.
Document Type
Academic Journal
Author
Balcar L; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Austria.; Mandorfer M; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Austria; Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Universitat de Barcelona, Spain.; Hernández-Gea V; Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Universitat de Barcelona, Spain; Fundació Clinic Recerca Biomèdica-Institut d'Investigacions Biomèdiques August Pi I Sunyer (FCRB-IDIBAPS), Spain; Centro De Investigación Biomédica Red De Enfermedades Hepáticas y Digestivas (CIBERehd)), Spain.; Procopet B; Hepatology Department and 3rd Medical Clinic, Regional Institute of Gastroenterology and Hepatology 'Octavian Fodor' and 'Iuliu Hatieganu' University of Medicine and Pharmacy, Romania.; Meyer EL; Section for Medical Statistics, Center for Medical Data Science, Medical University of Vienna, Vienna, Austria; Berry Consultants, Vienna, Austria.; Giráldez Á; Clinical Management Unit of Digestive Diseases, University Hospital Virgen Del Rocio, Spain.; Amitrano L; Gastroenterology Unit, Ospedale a Cardarelli, Italy.; Villanueva C; Centro De Investigación Biomédica Red De Enfermedades Hepáticas y Digestivas (CIBERehd)), Spain; Servei De Patologia Digestiva, Hospital De La Santa Creu I Sant Pau, Spain.; Thabut D; Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, France.; Samaniego LI; Centro De Investigación Biomédica Red De Enfermedades Hepáticas y Digestivas (CIBERehd)), Spain; Servicio De Medicina De Aparato Digestivo Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Lisgm, Spain.; Silva-Junior G; Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Universitat de Barcelona, Spain.; Martinez J; Department of Gastroenterology and Instituto Ramón y Cajal De Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal and University of Alcalá, Spain.; Genescà J; Centro De Investigación Biomédica Red De Enfermedades Hepáticas y Digestivas (CIBERehd)), Spain; Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Spain.; Bureau C; Department of Hepato-Gastroenterology, Purpan Hospital, University of Toulouse, France.; Trebicka J; Department of Internal Medicine B, University of Münster, Germany; Department of Gastroenterology and Hepatology, Odense University Hospital, Denmark; Department of Internal Medicine I, University of Bonn, Germany.; Herrera EL; Centro De Investigación Biomédica Red De Enfermedades Hepáticas y Digestivas (CIBERehd)), Spain; Liver Unit, Hospital Universitario Puerta De Hierro Majadahonda, Universidad Autònoma de Madrid, Spain.; Laleman W; Department of Liver and Biliopancreatic Disorders, KU Leuven, Belgium.; Palazón Azorín JM; Hepatology, Hospital General Universitario de Alicante, Spain.; Alonso JC; Gastroenterology Department, Hepatology Unit, Hospital Universitari de Bellvitge, Idibell, Universitat de Barcelona, Spain.; Gluud LL; Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre and Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark.; Ferreira CN; Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria - Centro Hospitalar Universitário Lisboa Norte, Portugal.; Cañete N; Liver Section, Gastroenterology Department and Imim (Hospital del Mar Medical Research Institute), Gastroenterology Department, Spain.; Rodríguez M; Department of Gastroenterology, Hospital Universitario Central de Asturias, Spain.; Ferlitsch A; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Austria; Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Universitat de Barcelona, Spain; Department of Internal Medicine I, Gastroenterology and Nephrology, St. John of God Hospital, Vienna, Austria.; Mundi JL; Department of Gastroenterology, University Hospital San Cecilio, Spain.; Grønbæk H; Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark.; Hernandez Guerra MN; Gastroenterology Department, University Hospital of the Canary Islands, Spain.; Sassatelli R; Unit of Gastroenterology and Digestive Endoscopy, Arcispedale Santa Maria Nuova-IRRCS, Italy.; Dell'Era A; Gastroenterology Unit, Asst Fatebenefratelli Sacco, Department of Clinical and Biomedical Sciences, Università Degli Studi Di Milano, Italy.; Senzolo M; Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Italy.; Abraldes JG; Cirrhosis Care Clinic, Division of Gastroenterology (Liver Unit), CEGIIR, University of Alberta, Canada.; Romero-Gómez M; Centro De Investigación Biomédica Red De Enfermedades Hepáticas y Digestivas (CIBERehd)), Spain; Unidad De Hepatología, Hospital Universitario De Valme, Spain.; Zipprich A; First Department of Internal Medicine, Martin Luther University Halle-Wittenberg, Germany.; Casas M; Hepatology Unit, Digestive Disease Department, Hospital De Sabadell, Universitat Autónoma de Barcelona, Spain.; Masnou H; Hospital Universitari Germans Trias I Pujol, Universitat Autònoma Barcelona, Spain.; Primignani M; CRC 'a.M. and a. Migliavacca' Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università Degli Studi Di Milano, Italy.; Krag A; Department of Gastroenterology and Hepatology, Odense University Hospital, Denmark.; Nevens F; Department of Liver and Biliopancreatic Disorders, KU Leuven, Belgium.; Calleja JL; Centro De Investigación Biomédica Red De Enfermedades Hepáticas y Digestivas (CIBERehd)), Spain; Liver Unit, Hospital Universitario Puerta De Hierro Majadahonda, Universidad Autònoma de Madrid, Spain.; Jansen C; Department of Internal Medicine I, University of Bonn, Germany.; Catalina MV; Servicio De Medicina De Aparato Digestivo Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Lisgm, Spain.; Albillos A; Department of Gastroenterology and Instituto Ramón y Cajal De Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal and University of Alcalá, Spain.; Rudler M; Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, France.; Tapias EA; Centro De Investigación Biomédica Red De Enfermedades Hepáticas y Digestivas (CIBERehd)), Spain; Servei De Patologia Digestiva, Hospital De La Santa Creu I Sant Pau, Spain.; Guardascione MA; Gastroenterology Unit, Ospedale a Cardarelli, Italy.; Tantau M; Hepatology Department and 3rd Medical Clinic, Regional Institute of Gastroenterology and Hepatology 'Octavian Fodor' and 'Iuliu Hatieganu' University of Medicine and Pharmacy, Romania.; Schwarzer R; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Austria.; Reiberger T; Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Austria.; Laursen SB; Department of Gastroenterology and Hepatology, Odense University Hospital, Denmark.; Lopez-Gomez M; Liver Unit, Hospital Universitario Puerta De Hierro Majadahonda, Universidad Autònoma de Madrid, Spain; Liver Unit, Hospital Universitario Puerta De Hierro Majadahonda, Spain.; Cachero A; Gastroenterology Department, Hepatology Unit, Hospital Universitari de Bellvitge, Idibell, Universitat de Barcelona, Spain.; Ferrarese A; Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Italy.; Ripoll C; First Department of Internal Medicine, Martin Luther University Halle-Wittenberg, Germany; Internal Medicine IV, Universitätsklinikum Jena, Friedrich Schiller University, Jena, Germany.; La Mura V; Hospital Universitari Germans Trias I Pujol, Universitat Autònoma Barcelona, Spain; Uoc Medicina Generale - Emostasi e Trombosi, Fondazione IRRCS, Cà Granda, Ospedale Maggiore Policlinico, Italy.; Bosch J; Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Universitat de Barcelona, Spain; Fundació Clinic Recerca Biomèdica-Institut d'Investigacions Biomèdiques August Pi I Sunyer (FCRB-IDIBAPS), Spain; Centro De Investigación Biomédica Red De Enfermedades Hepáticas y Digestivas (CIBERehd)), Spain; Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.; García-Pagán JC; Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clínic, Universitat de Barcelona, Spain; Fundació Clinic Recerca Biomèdica-Institut d'Investigacions Biomèdiques August Pi I Sunyer (FCRB-IDIBAPS), Spain; Centro De Investigación Biomédica Red De Enfermedades Hepáticas y Digestivas (CIBERehd)), Spain. Electronic address: jcgarcia@clinic.cat.
Source
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8503886 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-0641 (Electronic) Linking ISSN: 01688278 NLM ISO Abbreviation: J Hepatol Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
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.
(Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)