Lean individuals with NAFLD have more severe liver disease and poorer clinical outcomes (NASH-CO Study).

Background And Aims: The severity of liver injury and clinical outcomes in lean individuals with NAFLD is a subject of debate and very few studies have been performed in the general population. The aim of this study was to compare subject characteristics and mortality between lean and nonlean NAFLD in a community setting.

Approach And Results: The study population included 169,303 participants from the nationwide Constances cohort. Subjects with excessive alcohol consumption, viral hepatitis, or other liver diseases were excluded and 137,206 subjects were analyzed. The diagnosis of NAFLD and fibrosis was performed using the Fatty Liver Index and the Forns Index. The median follow-up was 3.58 years. The prevalence of NAFLD was 5.3% (95% CI: 5.2-5.4) in lean subjects, while 16.3% (95% CI: 15.7-16.8) of NAFLD subjects were lean. Despite their better metabolic profile, the prevalence of advanced fibrosis was significantly higher in lean than in nonlean NAFLD (3.7% vs. 1.7%, respectively, p < 0.01). Among NAFLD subjects and after adjustment for demographics, metabolic risk factors and lifestyle, lean status was associated with advanced fibrosis (OR=1.26, 95% CI: 1.20-1.65, p = 0.005), an increased risk of liver-related events (adjusted HR=5.84, 95% CI: 4.03-8.46), chronic kidney disease (adjusted HR=2.49, 95% CI: 1.49-4.16), and overall mortality (adjusted HR=3.01, 95% CI: 2.21-4.11). Liver-related events and overall mortality were related to the severity of fibrosis, both in lean and nonlean NAFLD subjects, whatever the usual risk factors.

Conclusion: This study in a large community-based cohort confirms that NAFLD in lean subjects is more severe for fibrosis, the progression of liver disease, chronic kidney disease, and overall mortality.