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Cardiovascular disease risk in paediatric and young adult non-alcoholic fatty liver disease
  1. Tracey G Simon1,
  2. Bjorn Roelstraete2,
  3. Naim Alkhouri3,
  4. Hannes Hagström2,4,
  5. Johan Sundström5,
  6. Jonas F Ludvigsson6,7
  1. 1Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
  2. 2Karolinska Institute, Stockholm, Sweden
  3. 3Hepatology, Arizona Liver Health, Chandler, Arizona, USA
  4. 4Division of Hepatology, Department of Upper GI Diseases, Karolinska Hospital, Stockholm, Sweden
  5. 5Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  6. 6Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
  7. 7Department of Pediatrics, Örebro University, Örebro, Sweden
  1. Correspondence to Dr Tracey G Simon, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA; tgsimon{at}mgh.harvard.edu

Abstract

Objective Longitudinal evidence is lacking regarding the long-term risk of major adverse cardiovascular events (MACE) in children and young adults with non-alcoholic fatty liver disease (NAFLD).

Design This nationwide cohort study included all Swedish children and young adults ≤25 years old with histologically confirmed NAFLD and without underlying cardiovascular disease (CVD) at baseline (1966–2016; n=699). NAFLD was defined from prospectively recorded histopathology, and further categorised as simple steatosis or non-alcoholic steatohepatitis (NASH). NAFLD patients were matched to ≤5 population controls without NAFLD or CVD (n=3353). Using Cox proportional hazards modelling, we calculated multivariable-adjusted HRs (aHRs) and 95% CIs for incident MACE (ie, ischaemic heart disease, stroke, congestive heart failure or cardiovascular mortality). In secondary analyses, we also explored rates of incident cardiac arrhythmias.

Results Over a median follow-up of 16.6 years, incident MACE was confirmed in 33 NAFLD patients and 52 controls. NAFLD patients had significantly higher rates of MACE than controls (3.1 vs 0.9/1000 person-years (PY); difference=2.1/1000 PY; aHR=2.33, 95% CI=1.43 to 3.78), including higher rates of ischaemic heart disease (difference=1.4/1000 PY; aHR=3.07, 95% CI 1.62 to 5.83) and congestive heart failure (difference=0.5/1000 PY; aHR=3.89, 95% CI=1.20 to 12.64). Rates of incident MACE outcomes appeared to be further augmented with NASH (aHR=5.27, 95% CI=1.96 to 14.19). In secondary analyses, NAFLD patients also had significantly higher rates of cardiac arrythmias (aHR=3.16, 95% CI=1.49 to 6.68).

Conclusion Compared with matched population controls, children and young adults with biopsy-proven NAFLD had significantly higher rates of incident MACE, including ischaemic heart disease and congestive heart failure. Research to better characterise cardiovascular risk in children and young adults with NAFLD should be prioritised.

  • FATTY LIVER
  • HEPATIC FIBROSIS
  • CARDIOVASCULAR DISEASE
  • CARDIOVASCULAR COMPLICATIONS

Data availability statement

No data are available. No additional data are available due to Swedish regulations.

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Data availability statement

No data are available. No additional data are available due to Swedish regulations.

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Footnotes

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  • Contributors The corresponding author (TGS) had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Study concept and design: all coauthors. Acquisition of data: JFL. Analysis: BR. Interpretation of data: all coauthors. Writing first draft of the manuscript: TGS and JFL. Critical revision of the manuscript for important intellectual content and approval of final version: all coauthors. Guarantor: TGS.

  • Funding TGS was supported by NIH K23 DK122104. HH was supported by grants from Region Stockholm (postdoctoral appointment).

  • Disclaimer No funding organisation had any role in the design and conduct of the study; in the collection, management, and analysis of the data; or in the preparation, review, and approval of the manuscript.

  • Competing interests TGS has received research funding from Amgen and has received consulting fees from Aetion, for work unrelated to this manuscript. HH reports research grants to his institution from Astra Zeneca, Pfizer, Merck, EchoSens, Intercept, and board advisory for Bristol-Myers Squibb and Gilead. JS reports ownership in companies providing services to Itrim, Amgen, Janssen, Novo Nordisk, Eli Lilly, Boehringer, Bayer, Pfizer and AstraZeneca, outside the submitted work. JFL coordinates an unrelated study on behalf of the Swedish IBD quality register (SWIBREG), that has received funding from Janssen corporation. The remaining authors have no disclosures and no conflicts of interest to disclose.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or 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.