For Debate


, Volume 51, Issue 11, pp 1947-1953

First online:

Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon?

  • G. TargherAffiliated withSection of Endocrinology, Department of Biomedical and Surgical Sciences, University of Verona Email author 
  • , F. MarraAffiliated withDepartment of Internal Medicine, Center for Research, High Education and Transfer DENOThe, University of Florence
  • , G. MarchesiniAffiliated withClinical Dietetics, Department of Internal Medicine and Gastroenterology, University of Bologna


Non-alcoholic fatty liver disease (NAFLD), comprising a spectrum of conditions ranging from pure steatosis to steatohepatitis and cirrhosis, has reached epidemic proportions and represents the most common cause of chronic liver disease in the community. The prevalence of NAFLD has been estimated to be between 20% and 30% in the general population, but this value is much higher (∼70–80%) in type 2 diabetic patients, who are also at higher risk of developing advanced fibrosis and cirrhosis. Increasing recognition of the importance of NAFLD and its strong relationship with the metabolic syndrome has stimulated an interest in the possible role of NAFLD in the development of cardiovascular disease (CVD). Several epidemiological studies indicate that NAFLD, especially in its more severe forms, is linked to an increased risk of CVD, independently of underlying cardiometabolic risk factors. This suggests that NAFLD is not merely a marker of CVD, but may also be actively involved in its pathogenesis. The possible molecular mediators linking NAFLD and CVD include the release of pro-atherogenic factors from the liver (C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 and other inflammatory cytokines) as well as the contribution of NAFLD per se to whole-body insulin resistance and atherogenic dyslipidemia, in turn favouring CVD progression. The clinical impact of NAFLD on CVD risk deserves particular attention in view of the implications for screening and surveillance strategies in the growing number of patients with NAFLD.


Cardiovascular disease Insulin resistance Liver fat Metabolic syndrome NAFLD Non-alcoholic fatty liver disease Risk factors Type 2 diabetes