Review Article

Non-alcoholic Fatty Liver Disease and Cardiovascular Diseases

Associations and Treatment Considerations

Stergios A. Polyzos; Stergios Kechagias; Emmanuel A. Tsochatzis


Aliment Pharmacol Ther. 2021;54(8):1013-1025. 

In This Article

Abstract and Introduction


Background: There are increasing data on the association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD).

Aim: To summarise evidence on the association between NAFLD and CVD in the clinical setting and provide potential therapeutic implications.

Methods: We searched PubMed. Evidence was primarily derived from meta-analyses. and then, if data were insufficient, from clinical trials, and then from observational studies.

Results: NAFLD has been linked to arterial hypertension, arterial stiffness, atherosclerosis, coronary artery disease, atrial fibrillation and aortic valvular sclerosis. Advanced liver fibrosis is a crucial prognostic factor for end-stage liver disease and for cardiovascular and overall mortality. Weight loss through lifestyle modifications (diet and exercise) remains the cornerstone of the management of both NAFLD and CVD, but is difficult to achieve and possibly more difficult to sustain long term. Therefore, pharmacological management of NAFLD seems to be important, although no licenced medication currently exists. Pioglitazone, proposed for non-alcoholic steatohepatitis (NASH) by most guidelines, increases weight and should be avoided in congestive heart failure. Statins should not be avoided in NAFLD patients at risk for CVD. Glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter-2 inhibitors, two classes of anti-diabetic drugs, have shown promising results in NAFLD and CVD, but more studies with hard end points are needed. Obeticholic acid, a promising medication for NASH under investigation, should be carefully considered, owing to its adverse effect on lipid profile.

Conclusions: NAFLD is associated with CVD, which may have certain clinical and therapeutic implications.


Non-alcoholic fatty liver disease (NAFLD) is closely associated with the epidemics of obesity and type 2 diabetes mellitus (T2DM).[1] NAFLD entails a spectrum of histopathological features that range from simple steatosis via the establishment of inflammation and hepatocellular injury, ie non-alcoholic steatohepatitis (NASH), with or without fibrosis to cirrhosis with risk of developing end-stage liver disease or hepatocellular carcinoma (HCC).[2] NAFLD shares common pathogenetic factors not only with obesity and T2DM but also with other components of insulin resistance (IR) syndrome or metabolic syndrome (MetS), including dyslipidemia and arterial hypertension.[1,2] NAFLD seems to interplay with the components of MetS in a dynamic way, ie it affects them and it is affected by them, and by this way, NAFLD may add to the cardiovascular (CV) risk of affected individuals.[3] In this regards, when obesity, T2DM and/or other components of MetS coexist with NAFLD, there is a higher risk of advanced liver disease and CV diseases.[3] Although most NAFLD patients have a BMI of >25 kg/m2, a subset of individuals has a BMI of <25 kg/m2, which is usually denoted as lean NAFLD. Most patients with lean NAFLD have excess visceral adiposity and IR, despite normal BMI, thus being on high CV risk.[4] Based on these considerations, the recent recommendation to change the nomenclature of NAFLD to metabolic (dysfunction)-associated fatty liver disease (MAFLD) seems to be rational.[5,6] This recommendation does not only refer to a simple change in the name of the disease but also to a novel definition. Thus, although it has provoked a large-scale discussion,[7] it simultaneously brings to the surface the close relationship of NAFLD with CV diseases (CVD), being the key endpoint of MetS. This is immediately evident if considering that CVD is the first cause of mortality in NAFLD patients.[8]

The aim of this review is to summarise evidence on the association between NAFLD and CVD in the clinical setting and provide potential therapeutic implications. Data were primarily derived from meta-analyses; however, when meta-analyses were not available, data from randomised controlled trials (RCTs), cohort, case–control, and cross-sectional studies were hierarchically selected, based on the principles of evidence-based medicine.