Increased risk of cardiovascular disease in NAFLD: causal effect or epiphenomenon?

Nonalcoholic fatty liver disease (NAFLD), in its whole spectrum ranging from pure steatosis to steatohepatitis and cirrhosis, has reached epidemic proportions and represents the commonest cause of chronic liver disease in the community. NAFLD prevalence has been estimated between 20% and 30% in the general population, but a much higher prevalence (~70-80%) is observed in type 2 diabetic patients, who are also at higher risk of developing advanced fibrosis and cirrhosis. The importance of NAFLD and its strong relationship to the metabolic syndrome is increasingly recognized, and this 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 progressive forms, is linked to an increased risk of CVD, independently of underlying cardiometabolic risk factors. This suggests that NAFLD is not simply 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.