title: Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis.
abstract: There have been many studies of the effects of non-alcoholic fatty liver disease (NAFLD) and the risk of cardiovascular disease (CVD), but these have produced conflicting results. We performed a meta-analysis of these studies to quantify the magnitude of the association between NAFLD (and NAFLD severity) and risk of CVD events.
  
  
  
  We searched PubMed, Google scholar, and Web of Science databases using terms "NAFLD", "cardiovascular events", "cardiovascular mortality", "prognosis" and their combinations to identify observational studies published through January 2016. We included only observational studies conducted in adults >18years and in which NAFLD was diagnosed on imaging or histology. Data from selected studies were extracted and meta-analysis was then performed using random effects modelling.
  
  
  
  A total of 16 unique, observational prospective and retrospective studies with 34,043 adult individuals (36.3% with NAFLD) and approximately 2,600 CVD outcomes (>70% CVD deaths) over a median period of 6.9years were included in the final analysis. Patients with NAFLD had a higher risk of fatal and/or non-fatal CVD events than those without NAFLD (random effect odds ratio [OR] 1.64, 95% CI 1.26-2.13). Patients with more 'severe' NAFLD were also more likely to develop fatal and non-fatal CVD events (OR 2.58; 1.78-3.75). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias.
  
  
  
  NAFLD is associated with an increased risk of fatal and non-fatal CVD events. However, the observational design of the studies included does not allow to draw definitive causal inferences.
  
  
  
  The data on whether NAFLD by itself is associated with increased cardiovascular events and death remains an issue of debate. The findings of this updated and large meta-analysis of observational studies indicate that NAFLD is significantly associated with an increased risk of fatal and non-fatal cardiovascular events. However, the observational design of the studies included does not allow us to prove that NAFLD causes cardiovascular disease. Clinicians who manage patients with NAFLD should not focus only on liver disease but should also consider the increased risk of cardiovascular disease and undertake early, aggressive risk factor modification.
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. Electronic address: giovanni.targher@univr.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Targher
authors.affiliation: Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, UK.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Byrne
authors.affiliation: Outpatient Liver Clinic and Division of Internal Medicine, Department of Biomedical, Metabolic and Neural Sciences, NOCSAE, Azienda USL and University of Modena and Reggio Emilia, Baggiovara, Modena, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Lonardo
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Zoppini
authors.affiliation: WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, University of Verona, Verona, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Barbui
mesh_terms: D002318:Cardiovascular Diseases; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors
keywords: CVD events; Cardiovascular disease; Meta-analysis; Mortality; NAFLD