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Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis
  1. Gabriel Mezzano1,2,
  2. Adria Juanola1,3,4,
  3. Andres Cardenas3,4,5,
  4. Esteban Mezey6,
  5. James P Hamilton6,
  6. Elisa Pose1,3,4,
  7. Isabel Graupera1,3,4,7,
  8. Pere Ginès1,3,4,7,
  9. Elsa Solà1,3,4,7,
  10. Ruben Hernaez8,9,10
  1. 1 Liver Unit, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain
  2. 2 Gastroenterología - Hepatología, Hospital del Salvador. Universidad de Chile, Santiago, Chile
  3. 3 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
  4. 4 Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Madrid, Spain
  5. 5 Institute of Digestive Disease and Metabolism, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain
  6. 6 Division of Gastroenterology and Hepatology. Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  7. 7 Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain
  8. 8 Gastroenterology and Hepatology, Depatment of Medicine, Baylor College of Medicine, Houston, Texas, USA
  9. 9 Section of Gastroenterology, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
  10. 10 Center for Innovation in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
  1. Correspondence to Dr Ruben Hernaez, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA; ruben.hernaez{at}


Background and aims Acute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures.

Methods We searched EMBASE and PubMed from 3/1/2013 to 7/3/2020 using the ACLF-EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) criteria. Two investigators independently conducted the abstract selection/abstraction of the aetiology of CLD, triggers, organ failures and prevalence/mortality by presence/grade of ACLF. We grouped countries into Europe, East/South Asia and North/South America. We calculated the pooled proportions, evaluated the methodological quality using the Newcastle-Ottawa Scale and statistical heterogeneity, and performed sensitivity analyses.

Results We identified 2369 studies; 30 cohort studies met our inclusion criteria (43 206 patients with ACLF and 140 835 without ACLF). The global prevalence of ACLF among patients admitted with decompensated cirrhosis was 35% (95% CI 33% to 38%), highest in South Asia at 65%. The global 90-day mortality was 58% (95% CI 51% to 64%), highest in South America at 73%. Alcohol was the most frequently reported aetiology of underlying CLD (45%, 95% CI 41 to 50). Infection was the most frequent trigger (35%) and kidney dysfunction the most common organ failure (49%). Sensitivity analyses showed regional estimates grossly unchanged for high-quality studies. Type of design, country health index, underlying CLD and triggers explained the variation in estimates.

Conclusions The global prevalence and mortality of ACLF are high. Region-specific variations could be explained by the type of triggers/aetiology of CLD or grade. Health systems will need to tailor early recognition and treatment of ACLF based on region-specific data.

  • cirrhosis
  • liver failure

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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  • ES and RH are joint senior authors.

  • Twitter @acv69cardenas

  • GM and AJ contributed equally.

  • Contributors All authors made substantial contributions to the conception or design of the work, drafting the work and revising it critically for important intellectual content, and final approval of the version published. GM, AJ, ES and RH specifically performed the acquisition of data. RH performed the analysis or interpretation of data.

  • Funding AJ is funded by Contratos Río Hortega (CM19/00044) granted by Instituto de Salud Carlos III and by the Award 'Emili Letang' granted by Hospital Clínic de Barcelona. AC is funded by the Instituto de Salud Carlos III and Plan Estatal de Investigación Científica y Técnica y de Innovación (Grant No. PI19/00752) and by 'Fundaciòn Maria Balust'. PG has been funded by grant number PI16/00043 and ES is funded by PI18/00727, both of which are integrated in the Plan Nacional I+D+I and co-funded by ISCIII-Subdirección General de Evaluación and European Regional Development Fund FEDER and also AGAUR SGR-01281 Grant. This work has been funded in part by an EU H2020 grant: LIVERHOPE, grant number 731875. The work is also supported in part by the Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413), Michael E DeBakey VA Medical Center, Houston, Texas.

  • Disclaimer The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government.

  • Competing interests AC is a consultant for Mallinckrodt Pharmaceuticals, Boston Scientific and Shionogi, has participated on advisory boards for Mallinckrodt Pharmaceuticals, and has received grant support from Mallinckrodt and Boston Scientific. PG declares that he has received research funding from Mallinckrodt, Grifols and Gilead. He has participated on advisory boards for Novartis, Promethera, Sequana, Gilead and Martin Pharmaceuticals.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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