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Non-alcoholic fatty liver disease and risk of new-onset heart failure: an updated meta-analysis of about 11 million individuals
  1. Alessandro Mantovani1,
  2. Graziana Petracca1,
  3. Alessandro Csermely1,
  4. Giorgia Beatrice1,
  5. Stefano Bonapace2,
  6. Andrea Rossi3,
  7. Herbert Tilg4,
  8. Christopher D Byrne5,
  9. Giovanni Targher1
  1. 1 Endocrinology and Metabolism, Department of Medicine, University of Verona, Verona, Italy
  2. 2 Division of Cardiology, IRCSS Sacro Cuore - Don Calabria Hospital, Negrar (VR), Italy
  3. 3 Section of Cardiology, Department of Medicine, University of Verona, Verona, Italy
  4. 4 Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria
  5. 5 Faculty of Medicine, University of Southampton, Southampton, UK
  1. Correspondence to Professor Giovanni Targher, Endocrinology and Metabolism, University of Verona Department of Medicine, Verona 37129, Italy; giovanni.targher{at}


Objective Recent studies reported an association between non-alcoholic fatty liver disease (NAFLD) and increased risk of new-onset heart failure (HF). However, the magnitude of the risk and whether this risk changes with severity of liver disease remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of new-onset HF.

Design We systematically searched Scopus, Web of Science and PubMed from database inception to March 2022 to identify eligible observational studies, in which NAFLD was diagnosed by serum biomarkers/scores, International Classification of Diseases (ICD) codes, imaging techniques or liver histology. The primary outcome was new-onset HF, as assessed mainly by ICD codes. Data from selected studies were extracted, and meta-analysis was performed using random-effects models to obtain summary hazard ratios (HRs) with 95% CIs.

Results We identified 11 longitudinal cohort studies with aggregate data on 11 242 231 middle-aged individuals from different countries and 97 716 cases of incident HF over a median of 10 years. NAFLD was associated with a moderately higher risk of new-onset HF (pooled random-effects hazard ratio 1.50, 95% CI 1.34 to 1.67, p<0.0001; I 2=94.8%). This risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension and other common cardiovascular risk factors. Sensitivity analyses did not change these results. The funnel plot did not show any significant publication bias.

Conclusion NAFLD is associated with a 1.5-fold higher long-term risk of new-onset HF, regardless of the presence of diabetes, hypertension and other common cardiovascular risk factors. However, the observational design of the studies does not allow for proving causality.


Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Contributors AM and GT designed the study, analysed the data and did the figures. AM, GP, AC and GT did the literature search, with arbitration by AC. GB, AR, SB, HT and CDB interpreted the data. GT and CDB wrote the manuscript. All authors reviewed and approved the final version of the manuscript. GT is the guarantor and accepts full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to publish.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • 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.