Systematic review with meta-analysis: risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients

Background: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is closely associated with the co-occurrence of multiple pathological conditions characterising the metabolic syndrome (MetS), obesity in particular. However, NAFLD also develops in lean subjects, whose risk factors remain poorly defined. Methods: We performed a meta-analysis of 15 studies, along with the data pertaining to our own population (n=336 patients). Data from lean (n=1966) and obese (n=5938) patients with NAFLD were analysed; lean (n=9946) and obese (n=6027) subjects without NAFLD served as controls. Results: Relative to the lean non-NAFLD controls, lean patients with NAFLD were older (3.79 +/- 0.72 years, P=1.36910(-6)) and exhibited the entire spectrum of the MetS risk factors. Specifically, they had a significant (P=10(-10)) increase in plasma glucose levels (6.44 +/- 1.12 mg/dL) and HOMA-IR (0.52 +/- 0.094-unit increment), blood lipids (triglycerides: 48.37 +/- 3.6, P=10(-10) and total cholesterol: 7.04 +/- 3.8, mg/dL, P=4.2910(-7)), systolic (5.64 +/- 0.7) and diastolic (3.37 +/- 0.9) blood pressure (mm Hg), P=10(-10), and waist circumference (5.88 +/- 0.4 cm, P= 10(-10)); values denote difference in means +/- SE. Nevertheless, the overall alterations in the obese group were much more severe when compared to lean subjects, regardless of the presence of NAFLD. Meta-regression suggested that NAFLD is a modifier of the level of blood lipids. Conclusion: Lean and obese patients with NAFLD share a common altered metabolic and cardiovascular profile. The former, while having normal body weight, showed excess of abdominal adipose tissue as well as other MetS features.