Treatment for ascites in adults with decompensated liver cirrhosis: a network meta-analysis

Amine Benmassaoud, Suzanne C Freeman, Davide Roccarina, Maria Corina Plaz Torres, Alex J Sutton, Nicola J Cooper, Laura Iogna Prat, Maxine Cowlin, Elisabeth Jane Milne, Neil Hawkins, Brian R Davidson, Chavdar S Pavlov, Douglas Thorburn, Emmanuel Tsochatzis, Kurinchi Selvan Gurusamy

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    Abstract

    BACKGROUND: Approximately 20% of people with cirrhosis develop ascites. Several different treatments are available; including, among others, paracentesis plus fluid replacement, transjugular intrahepatic portosystemic shunts, aldosterone antagonists, and loop diuretics. However, there is uncertainty surrounding their relative efficacy.

    OBJECTIVES: To compare the benefits and harms of different treatments for ascites in people with decompensated liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for ascites according to their safety and efficacy.

    SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until May 2019 to identify randomised clinical trials in people with cirrhosis and ascites.

    SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and ascites. We excluded randomised clinical trials in which participants had previously undergone liver transplantation.

    DATA COLLECTION AND ANALYSIS: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance.

    MAIN RESULTS: We included a total of 49 randomised clinical trials (3521 participants) in the review. Forty-two trials (2870 participants) were included in one or more outcomes in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies, without other features of decompensation, having mainly grade 3 (severe), recurrent, or refractory ascites. The follow-up in the trials ranged from 0.1 to 84 months. All the trials were at high risk of bias, and the overall certainty of evidence was low or very low. Approximately 36.8% of participants who received paracentesis plus fluid replacement (reference group, the current standard treatment) died within 11 months. There was no evidence of differences in mortality, adverse events, or liver transplantation in people receiving different interventions compared to paracentesis plus fluid replacement (very low-certainty evidence). Resolution of ascites at maximal follow-up was higher with transjugular intrahepatic portosystemic shunt (HR 9.44; 95% CrI 1.93 to 62.68) and adding aldosterone antagonists to paracentesis plus fluid replacement (HR 30.63; 95% CrI 5.06 to 692.98) compared to paracentesis plus fluid replacement (very low-certainty evidence). Aldosterone antagonists plus loop diuretics had a higher rate of other decompensation events such as hepatic encephalopathy, hepatorenal syndrome, and variceal bleeding compared to paracentesis plus fluid replacement (rate ratio 2.04; 95% CrI 1.37 to 3.10) (very low-certainty evidence). None of the trials using paracentesis plus fluid replacement reported health-related quality of life or symptomatic recovery from ascites.

    FUNDING: the source of funding for four trials were industries which would benefit from the results of the study; 24 trials received no additional funding or were funded by neutral organisations; and the source of funding for the remaining 21 trials was unclear.

    AUTHORS' CONCLUSIONS: Based on very low-certainty evidence, there is considerable uncertainty about whether interventions for ascites in people with decompensated liver cirrhosis decrease mortality, adverse events, or liver transplantation compared to paracentesis plus fluid replacement in people with decompensated liver cirrhosis and ascites. Based on very low-certainty evidence, transjugular intrahepatic portosystemic shunt and adding aldosterone antagonists to paracentesis plus fluid replacement may increase the resolution of ascites compared to paracentesis plus fluid replacement. Based on very low-certainty evidence, aldosterone antagonists plus loop diuretics may increase the decompensation rate compared to paracentesis plus fluid replacement.

    Original languageEnglish
    Article numberCD013123
    Pages (from-to)CD013123
    Number of pages134
    JournalCochrane Database of Systematic Reviews
    Volume2020
    Issue number1
    DOIs
    Publication statusPublished - 16 Jan 2020

    Bibliographical note

    Copyright © and Moral Rights are retained by the author(s) and/ or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders.

    Funder

    Supported by a VA merit review grant and National Institutes of Health grants K-24 DK02727 and P-30DK 034989" Trial name/trial registry number: NCT00108355

    This work was funded by the French Ministry of Health, by a grant from the Délégation Régionale à la Recherche Clinique des Hôpitaux de Toulouse, and supported by the Gore company". Trial name/trial registry number: NCT00222014

    Supported by grant RO1 DK 51523 from the National Institutes of Health (to A.J.S.) and MO1-RR-00065" Trial name/trial registry number: NASTRA.

    Sponsored in part by a research grant (#76273) from the John A Hartford Foundation.

    This work was supported by a grant from the National Science Council of the Republic of China (NSC842331-B075-005).

    Supported by grants from the Consiglio Nazionale delle Ricerche, Rome, Ministero Italiano dell’universita e della Ricerca Scientilica e Tecnologica (Progetto Nazionale Epatiti Virali e Cirrosi Epatica), Rome, and the Italian Liver Foundation, Florence, Italy. Supported by grants of the Ministero dell’Universita` Italiana and of the Os-pedale Maggiore Policlinico Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) of Milan.

    Supported by grants from Fondo de Investigaciones Sanitarias de la Se-guridad Social (FISS 93/0610) and Direccion General de Investigacion Cientifica y Tecnica (DGICYT PM 91-0216). A. Gin,s and J. Sal5 were granted by FISS (91/5549 and 93/0610, respectively)".

    This work was supported by grants from Comision Asesora de investigacion Cientffico y Tecnica (CAICYT 2643-83 and 2114-81) and from Fondo de Investigaciones Sanitarias do la Seguridad Social (FISS, 82-410)".

    Supported by grants from the Fondo de Investigacio´n Sanitaria (Spain) (FIS 97/2073 and 00/0616) and the Veterans Administration Merit Review and NIH-1K24-DK 02727(USA)"

    This project was funded by the National Institute for Health Research (NIHR) Systematic Reviews Programme (project number 16/114/17) and was supported by the Complex Reviews Support Unit, also funded by the National Institute for Health Research (project number 14/178/29).

    This study was supported by a grant from SEARLE.

    The trial was funded by the competitive peer-reviewed grant FARM6P824B from the Italian Medicine Agency". Trial name/trial registry number: 2008–000625–19 and NCT01288794.

    Supported by a grant (2018/84) from the Fondo de Investigaciones Sani-tarias de la Seguridad Social and by the Fundació Catalana per a l'Estudi de les Malalties del Fetge.







    ASJC Scopus subject areas

    • Pharmacology (medical)

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