Nonalcoholic Fatty Liver Disease in Lean Subjects: Associations with Metabolic Dysregulation and Cardiovascular Risk—A Single-Center Cross-Sectional Study

INTRODUCTION:Although a milder metabolic phenotype of nonalcoholic fatty liver disease (NAFLD) in lean patients (body mass index [BMI] <25 kg/m2) compared to overweight/obese patients with NAFLD is assumed, the relevance of NAFLD among lean subjects remains a matter of debate. We aimed to characterize the metabolic/cardiovascular phenotype of lean patients with NAFLD. METHODS:In total, 3,043 subjects (cohort I) and 1,048 subjects (cohort II) undergoing screening colonoscopy between 2010 and 2020 without chronic liver disease other than NAFLD were assigned to one of the following groups: lean patients without NAFLD, lean NAFLD, overweight NAFLD (BMI 25-30 kg/m2), and obese NAFLD (BMI >30 kg/m2). Diagnosis of NAFLD was established using ultrasound (cohort I) and controlled attenuation parameter (cohort II). RESULTS:The prevalence of lean patients with NAFLD was 6.7%/16.1% in the overall cohort I/II and 19.7%/40.0% in lean subjects of cohort I/II. Compared with lean subjects without NAFLD, lean patients with NAFLD had a higher prevalence of dyslipidemia, dysglycemia, and the metabolic syndrome, together with a higher median Framingham risk score in both cohorts (all P < 0.001). On multivariable analyses, NAFLD in lean subjects was associated with higher odds of metabolic syndrome (adjusted odds ratio cohort I: 4.27 [95% confidence interval (CI): 2.80-6.51], P < 0.001; cohort II: 2.97 [95% CI: 1.40-6.33], P < 0.001), and higher Framingham risk score (regression coefficient B cohort I: 1.93 [95% CI: 0.95-2.92], P < 0.003; cohort II: 1.09 [95% CI: 0.81-2.10], P = 0.034), among others. Only 69.8% of lean patients with NALFD in cohort I and 52.1% in cohort II fulfilled the novel criteria for metabolic associated fatty liver disease. DISCUSSION:NAFLD in lean patients is associated with the metabolic syndrome and increased cardiovascular risk. Novel metabolic associated fatty liver disease criteria leave a considerable proportion of patients unclassified.