Nonalcoholic fatty liver disease and cholesterol gallstones: which comes first?

Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) are both highly prevalent in the general population and are associated with obesity, insulin resistance, dyslipidemia, and high dietary cholesterol intake. Insulin resistance is a key feature of both NAFLD and GD. Hepatic insulin resistance provides a crucial link between the metabolic syndrome, NAFLD, and increased cholesterol gallstone susceptibility. Hepatic insulin resistance is not only associated with accumulation of hepatic fat but also has a crucial role in supersaturation and excessive production of bile salts. It is not yet clear whether NAFLD is a precursor of GD or whether the presence of GD possibly indicates the presence of long-standing features of metabolic syndrome that accelerates the progression of NAFLD. Recent reports suggested the association between gallstones and nonalcoholic steatohepatitis and liver fibrosis. Importantly, both NAFLD and GD are both associated with high incidence of cardiovascular disease (CVD) and mortality. Emerging evidence suggests a potential benefit of statin therapy in NAFLD and GD. Further research is needed to determine (i) how the presence of NAFLD and GD is associated with CVD (ii) and whether the presence of GD in association with NAFLD increases the risk of liver fibrosis, and (iii) the impact of therapy of NAFLD in the incidence of GD.