Association Between Non-alcoholic Fatty Liver Disease and Risk of Atrial Fibrillation in Adult Individuals

An Updated Meta-analysis

Alessandro Mantovani; Marco Dauriz; Damiano Sandri; Stefano Bonapace; Giacomo Zoppini; Herbert Tilg; Christopher D. Byrne; Giovanni Targher


Liver International. 2019;39(4):758-769. 

In This Article

Abstract and Introduction


Background & Aims: Recent studies examined the association between non-alcoholic fatty liver disease (NAFLD) and risk of atrial fibrillation (AF) in adults, but the findings have been inconsistent. We provided a quantitative estimate of the magnitude of the association between NAFLD and risk of AF.

Methods: We searched publication databases using predefined keywords to identify observational studies (published up to December 14, 2018), in which NAFLD was diagnosed by biopsy, imaging or biochemistry and AF was diagnosed by medical history and electrocardiograms. Data from selected studies were extracted and meta-analysis was performed using random-effects modelling.

Results: Nine cross-sectional and longitudinal studies were included in the final analysis (n = 364 919 individuals). Meta-analysis of data from 5 cross-sectional studies showed that NAFLD was associated with an increased risk of prevalent AF (random-effects odds ratio 2.07, 95% CI 1.38-3.10; I 2 = 54.7%), independent of age, sex, body mass index, hypertension and other common AF risk factors. This risk was particularly high among patients with established diabetes (n = 1 study; random-effects odds ratio 5.17, 95% CI 2.05-13.02). Meta-analysis of data from 4 longitudinal studies showed that NAFLD was independently associated with a 10-year increased risk of incident AF only in type 2 diabetic patients (n = 1 study; random-effects hazard ratio 4.96, 95% CI 1.42-17.28). Sensitivity analyses did not modify these findings. Funnel plots did not reveal significant publication bias.

Conclusions: NAFLD is associated with an increased risk of AF in middle-aged and elderly individuals (especially in those with type 2 diabetes). However, the observational design of the eligible studies does not allow for proving causality.


Non-alcoholic fatty liver disease (NAFLD) is a global health problem, affecting up to one-quarter of the world's population. In parallel with the rise in obesity rates, the worldwide prevalence of NAFLD is expected to increase markedly.[1]

Over the past 10 years, it has become increasingly clear that NAFLD is just 1 facet of a multisystem disease that confers substantially increased morbidity and mortality to those patients who are affected and where the most common causes of death are cardiovascular disease (~40-45% of the total deaths), followed by extra-hepatic malignancies and liver-related complications.[2–5] This concept implies that patients with NAFLD should undergo careful cardiovascular surveillance, as recommended by the most recent European, Italian and United States clinical practice guidelines for the management of NAFLD.[6–8]

Recently, it has also become increasingly clear that NAFLD adversely affects not only coronary arteries, but also all other anatomical structures of the heart, including the cardiac electrical system.[9] Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice and is a major health problem worldwide, owing to its associated morbidity and increased mortality.[10] As it will be discussed in greater detail below, a number of observational studies have recently examined the association between NAFLD and risk of both prevalent and incident AF in middle-aged and elderly individuals, but these have produced conflicting results.[11–18]

We therefore carried out a comprehensive systematic review and meta-analysis of observational studies examining the association between NAFLD and risk of permanent (chronic) AF in middle-aged and elderly individuals. Our aim was to determine whether, and to what extent, NAFLD is associated with the risk of both prevalent and incident AF. Given the growing clinical burden of NAFLD worldwide, we believe that quantitative estimation of the magnitude of the association between NAFLD and risk of AF might also have relevant clinical implications for the prevention and treatment of this common and burdensome arrhythmic disorder.