Gastroenterology

Gastroenterology

Volume 160, Issue 1, January 2021, Pages 193-205.e10
Gastroenterology

Original Research
Full Report: Clinical—Liver
Effects of Early Placement of Transjugular Portosystemic Shunts in Patients With High-Risk Acute Variceal Bleeding: a Meta-analysis of Individual Patient Data

https://doi.org/10.1053/j.gastro.2020.09.026Get rights and content

Background & Aims

Compared with drugs plus endoscopy, placement of transjugular portosystemic shunt within 72 hours of admission to the hospital (early or preventive transjugular intrahepatic portosystemic shunt [TIPS], also called preemptive TIPS) increases the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survive for 1 year. However, the benefit of preemptive TIPS is less clear for patients with a Child-Pugh score of B and active bleeding (CP-B+AB). We performed an individual data meta-analysis to assess the efficacy of preemptive TIPS in these patients and identify factors associated with reduced survival of patients receiving preemptive TIPS.

Methods

We searched publication databases for randomized controlled trials and observational studies comparing the effects of preemptive TIPS versus endoscopy plus nonselective beta-blockers in the specific population of high-risk patients with cirrhosis and acute variceal bleeding (CP-B+AB or Child-Pugh C, below 14 points), through December 31, 2019. We performed a meta-analysis of data from 7 studies (3 randomized controlled trials and 4 observational studies), comprising 1327 patients (310 received preemptive TIPS and 1017 received drugs plus endoscopy). We built adjusted models to evaluate risk using propensity score for baseline covariates. Multivariate Cox regression models were used to assess the factors associated with survival time. The primary endpoint was effects of preemptive TIPS versus drugs plus endoscopy on 1-year survival in the overall population as well as CP-B+AB and Child-Pugh C patients.

Results

Overall, preemptive TIPS significantly increased the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survived for 1 year, compared with drugs plus endoscopy (hazard ratio [HR] 0.443; 95% CI 0.323–0.607; P < .001). This effect was observed in CP-B+AB patients (HR 0.524; 95% CI 0.307–0.896; P = .018) and in patients with Child-Pugh C scores below 14 points (HR 0.374; 95% CI 0.253–0.553; P < .001). Preemptive TIPS significantly improved control of bleeding and ascites without increasing risk of hepatic encephalopathy in Child-Pugh C and CP-B+AB patients, compared with drugs plus endoscopy. Cox analysis of patients who received preemptive TIPS showed that patients could be classified into 3 categories for risk of death, based on age, serum level of creatinine, and Child-Pugh score. In each of these risk categories, preemptive TIPS increased the proportion of patients who survived for 1 year, compared with drugs plus endoscopy.

Conclusions

In a meta-analysis of data from 1327 patients with cirrhosis, acute variceal bleeding, and Child-Pugh score between 10 and 13 points or CP-B+AB, preemptive TIPS increased the proportion who survived for 1 year, in both subgroups separately, compared with drugs plus endoscopy.

Section snippets

Material and Methods

Studies eligible for inclusion in this meta-analysis were those that included patients with cirrhosis and AVB from RCTs and observational studies aimed to compare the use of medical treatment (endoscopy plus nonselective beta-blockers [NSBBs]) vs p-TIPS. All patients included in the studies should have fulfilled the current accepted high-risk criteria (Child-Pugh B + AB or Child-Pugh C < 14 points).

For this, we have manually searched the literature up to December 31, 2019, for prospective

Results

The meta-analysis included individual data of 1327 patients, among which 602 (45.3%) were CP-B+AB and 725 (54.7%) Child-Pugh C (<14 points). A total of 310 patients were treated with p-TIPS (138 CP-B+ AB and 172 CP-C) and 1017 patients (464 CP-B+AB and 553 CP-C) with Drugs + Endo therapy. Available data on 74% of the patients treated with p-TIPS shows that 66% of TIPS were placed in the first 24 hours, 21% were placed in the first 48 hours, and 13% were placed in the first 72 hours. There were

Discussion

AVB is one of the most life-threating complications of cirrhosis. This is especially true for the subgroup of patients with a high risk of treatment failure even when treated with the current standard of care.21 Patients presenting treatment failure have a high mortality rate regardless of finally controlling bleeding using rescue TIPS. This fact justifies the strong need of identifying patients at a high risk of treatment failure in whom early application of more effective treatments to

CRediT Authorship Contributions

Oana Nicoară-Farcău, MD (Data curation: Equal; Methodology: Equal; Writing – original draft: Lead; Writing – review & editing: Equal)

Guohong Han, MD, PhD (Data curation: Equal; Writing – review & editing: Equal) Marika Rudler, MD, PhD (Investigation: Equal)

Debora Angrisani, MD (Data curation: Equal; Writing – original draft: Equal)

Alberto Monescillo, MD, PhD (Investigation: Equal; Visualization: Supporting; Writing – review & editing: Supporting)

Ferran Torres, PhD (Formal analysis: Lead;

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    Conflict of interest Jaime Bosch has received speaker fees from Gore; and served as a consultant for Actelion, Ambys, BioVie, Brudy, BMS, BLB, Chiasma, Exalenz, Lipocine, and Surrozen. Virginia Hernández-Gea has received consultant fees from Gore. Juan Carlos García-Pagán has received consultant fees from Shionogi and research grants from Novartis and Gore. Christophe Bureau has received speaker fees from GORE and is a board member in Alfawassemran/Norgine. Alvaro Giraldez, Agustin Albillos, Dominique Thabut, Jonel Trebicka, and Frederik Nevens have received speaker fees from GORE. The other authors disclose no conflicts.

    Funding Juan Carlos García-Pagán received support in part through grants from the Spanish Ministry of Education and Science (SAF-2016–75767-R and PIE 15/00027) and from the “Commissioner for Universities and Research of the Generalitat de Catalunya” (AGAUR SGR 2017). CIBERehd is funded by the Instituto de Salud Carlos III. Edilmar Alvarado-Tapias and Anna Baiges are recipients of a "Río Hortega" fellowship grant from the Instituto de Salud Carlos III. The study was partially supported by a GORE grant for statistical support.

    The following are members of the Preemptive TIPS Individual Meta-analysis, International Variceal Bleeding and Baveno Cooperation study groups: Christophe Bureau,11 Juan G. Abraldes,2,63 Frederik Nevens,12 Karel Caca,13 Wim Laleman,12 Beate Appenrodt,14 Angelo Luca,15 Jean Pierre Vinel,11 Joachim Mössner,16 Marco Di Pascoli,2 Alexander Zipprich,17 Tilman Sauerbruch,14 Francisco Martinez-Lagares,18 Luis Ruiz-del-Arbol,19 Angel Sierra,5 Clemencia Guevara,5 Elena Jimenez,5 Jose Miguel Marrero,5 Enrique Buceta,18 Juan Sanchez,20 Ana Castellot,5 Monica Penate,5 Ana Cruz,5 Elena Pena,19 Bogdan Procopeț,1 Álvaro Giráldez,21 Lucio Amitrano,22 Candid Villanueva,8,23 Luis Ibañez-Samaniego,24 Gilberto Silva-Junior,2 Javier Martinez,25 Joan Genescà,8,26 Jonel Trebicka,27,28,29,62 Elba Llop,8,30 Jose Maria Palazon,31 Jose Castellote,32 Susana Rodrigues,9,33 Lise L. Gluud,34 Carlos Noronha Ferreira,35 Rafael Barcelo,6 Nuria Cañete,36 Manuel Rodríguez,37 Arnulf Ferlitsch,38 Jose Luis Mundi,39 Henning Gronbaek,40 Manuel Hernández-Guerra,41 Romano Sassatelli,42 Alessandra Dell’Era,43 Marco Senzolo,44 Manuel Romero-Gómez,8,45 Meritxell Casas,46 Helena Masnou,47 Massimo Primignani,48 Aleksander Krag,29 Jose Luis Calleja,8,30 Christian Jansen,14 Marie Angèle Robic,11 Irene Conejo,8,26 Maria-Vega Catalina,8,24 Agustin Albillos,8,25 Edilmar Alvarado,8,23 Maria Anna Guardascione,22 Marcel Tanțău,1 Luo Zuo,3 Xuan Zhu,49 Jianbo Zhao,50 Hui Xue,51 Zaibo Jiang,52 Yuzheng Zhuge,53 Chunqing Zhang,54 Junhui Sun,55 Pengxu Ding,56 Weixin Ren,57 Yingchun Li,58 Kewei Zhang,59 Wenguang Zhang,60 Chuangye He,3 Jiawei Zhong,50 Qifeng Peng,51 Fuquan Ma,52 Junyang Luo,53 Ming Zhang,54 Guangchuan Wang,55 Minhuang Sun,59 Junjiao Dong,60 Wei Bai,3 Wengang Guo,3 Qiuhe Wang,3 Xulong Yuan,3 Zhengyu Wang,3 Tianlei Yu,3 Bohan Luo,3 Xiaomei Li,3 Jie Yuan,3 Na Han,3 Ying Zhu,3 Jing Niu,3 Kai Li,3 Zhanxin Yin,3 Yongzhan Nie,61 Petra Fischer,1 Horia Ştefănescu,1 Andreea Pop,1 Stig B. Laursen,29 Fanny Turon,2 Anna Baiges,2 José Ferrusquía-Acosta,2 Marta Magaz,2 Eira Cerda,2 Luis Tellez,2 Giulia Allegretti,2 Guilherme Macedo,33 David Haldrup,40 Patricia Santos,35 Miguel Moura,35 Daniela Reis,35 Liliane Meireles,35 Patricia Sousa,35 Paula Alexandrino,35 Carmen Navascues,37 Salvador Augustin,8,26 Vincenzo La Mura,48 Rafael Bañares,24 Raquel Diaz,24 Marta López Gómez,30 and Cristina Ripoll17.

    11Service d’Hépatogastro-entérologie, Centre Hospitalier Universitaire Purpan, Université 3 Paul Sabatier Toulouse, France; 12Department of Hepatology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium; 13Medizinische Klinik I, Klinikum Ludwigsburg, Ludwigsburg, Germany; 14Medical Department I, University of Bonn, Bonn, Germany; 15Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Palermo, Italy; 16Medizinische Klinik und Poliklinik für Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Universitätsklinikum Leipzig AöR, Leipzig, Germany; 17First Department of Internal Medicine, Martin Luther Universität Halle-Wittenberg Klinik, Halle, Germany; 18Department of lnterventional Radiology, Hospiral Universitario Insular de Gran Canaria, Canary Islands; 19Liver Hemodynamic Unit, Hospital Ramdn y Cajal, Madrid, Spain; 20Department of lnterventional Radiology, Hospital Ramdn y Cajal, Madrid, Spain; 21Digestive Diseases Department, IbiS, University Hospital Virgen del Rocío, Seville, Spain; 22Gastroenterology Unit, Ospedale A Cardarelli, Naples, Italy; 23Servei de Patologia Digestiva, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 24Servicio de Medicina de Aparato Digestivo Gregorio Marañón, Hospital General Universitario Gregorio Marañón, liSGM, Barcelona, Spain; 25Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University of Alcalá, Madrid, Spain; 26Liver Unit, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; 27European Foundation for the Study of Chronic Liver Failure (EF-Clif), Barcelona, Spain; 28Institute for Bioengineering of Catalonia, Barcelona, Spain; 29Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; 30Liver Unit, Hospital U, Puerta de Hierro. Universidad Autònoma de Madrid, Madrid, Spain; 31Hospital General Universitario de Alicante, Alicante, Spain; 32Gastroenterology Department, Hepatology Unit, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain; 33Gastroenterology and Hepatology Department, Centro Hospitalar São João, Porto, Portugal; 34Gastrounit, Medical Division, University Hospital of Hvidovre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 35Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria - Centro Hospitalar Lisboa Norte, Lisbon, Portugal; 36Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; 37Department of Gastroenterology, Hospital Central de Asturias, Oviedo, Spain; 38St. John of God Hospital, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria; 39Department of Gastroenterology, University Hospital San Cecilio, Granada, Spain; 40Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 41Gastroenterology Department, University Hospital of the Canary Islands, La Laguna, Tenerife, Spain; 42Unit of Gastroenterology and Digestive Endoscopy, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy; 43Gastroenterology Unit, ASST Fatebenefratelli Sacco, Department of Clinical and Biomedical Sciences, University of the Studies of Milan, Milan, Italy; 44Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy; 45Hepatology Unit, Hospital Universitario de Valme, Sevilla, Spain; 46Hepatology Unit, Digestive Disease Department Hospital de Sabadell, Universitat Autónoma de Barcelona, Sabadell, Spain; 47Hospital Universitari Germans Trias i Pujol, Universitat Autònoma Barcelona, Badalona, Spain; 48CRC “A. M. e A. Migliavacca” Center for Liver Disease Division of Gastroenterology and Hepatology IRCCS Ca’ Granda Maggiore Hospital FoundationUniversity of Milan, Milan, Italy; 49Department of gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China; 50Department of Interventional Radiology, Nanfang Hospital, the Southern Medical University, Guangzhou, China; 51Department of Gastroenterology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China; 52Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; 53Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; 54Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; 55Hepatobiliary and Pancreatic Intervention Centre, Division of Hepatobiliary and Pancreatic Surgery, First affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; 56Department of Vascular and Endovascular Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 57Department of Interventional Radiology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China; 58Department of Interventional Radiology, the Second Affiliated Hospital of Kunming Medical University, Kunming, China; 59Department of Vascular Surgery, Henan Provincial People’s Hospital, Zhengzhou, China; 60Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 61State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China; 62Department of Internal Medicine I, University Hospital, Goethe University, Frankfurt, Germany; and 63Cirrhosis Care Clinic, Division of Gastroenterology (Liver Unit), CEGIIR, University of Alberta, Edmonton, AB, Canada.

    Author names in bold designate shared co-first authorship.

    This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e23. Learning Objective: Upon completion of this CME activity, successful learners will be able to correctly identify the indication for early placement of transjugular intrahepatic portosystemic shunt (TIPS) (preemptive TIPS) in patients with cirrhosis and acute variceal bleeding.

    Authors share co-first authorship.

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