INTRODUCTION: Although a milder metabolic phenotype of nonalcoholic fatty liver disease (NAFLD) in lean patients (body mass index [BMI] <25 kg/m 2 ) 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/m 2 ), and obese NAFLD (BMI >30 kg/m 2 ). 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.

Background: Many patients with non-alcoholic fatty liver disease (NAFLD) simultaneously suffer from cardiovascular (CV) disease and often carry multiple CV risk factors. Several CV risk factors are known to drive the progression of fibrosis in patients with NAFLD. Objectives: To investigate whether an established CV risk score, the Framingham risk score (FRS), is associated with the diagnosis of NAFLD and the degree of fibrosis in an Austrian screening cohort for colorectal cancer. Material and Methods: In total, 1965 asymptomatic subjects (59 ± 10 years, 52% females, BMI 27.2 ± 4.9 kg/m 2 ) were included in this study. The diagnosis of NAFLD was present if (1) significantly increased echogenicity in relation to the renal parenchyma was present in ultrasound and (2) viral, autoimmune or hereditary liver disease and excess alcohol consumption were excluded. The FRS (ten-year risk of coronary heart disease) and NAFLD Fibrosis Score (NFS) were calculated for all patients. High CV risk was defined as the highest FRS quartile (>10%). Both univariable and multivariable logistic regression models were used to calculate associations of FRS with NAFLD and NFS. Results: Compared to patients without NAFLD (n = 990), patients with NAFLD (n = 975) were older (60 ± 9 vs. 58 ± 10 years; p < 0.001), had higher BMI (29.6 ± 4.9 vs. 24.9 ± 3.6 kg/m 2 ; p < 0.001) and suffered from metabolic syndrome more frequently (33% vs. 7%; p < 0.001). Cardiovascular risk as assessed by FRS was higher in the NAFLD-group (8.7 ± 6.4 vs. 5.4 ± 5.2%; p < 0.001). A one-percentage-point increase of FRS was independently associated with NAFLD (OR 1.04, 95%CI 1.02-1.07; p < 0.001) after correction for relevant confounders in multivariable logistic regression. In patients with NAFLD, NFS correlated with FRS (r = 0.29; p < 0.001), and FRS was highest in patients with significant fibrosis (F3-4; 11.7 ± 5.4) compared to patients with intermediate results (10.9 ± 6.3) and those in which advanced fibrosis could be ruled-out (F0-2, 7.8 ± 5.9, p < 0.001). A one-point-increase of NFS was an independent predictor of high-risk FRS after correction for sex, age, and concomitant diagnosis of metabolic syndrome (OR 1.30, 95%CI 1.09-1.54; p = 0.003). Conclusion: The presence of NAFLD might independently improve prediction of long-term risk for CV disease and the diagnosis of NAFLD might be a clinically relevant piece in the puzzle of predicting long-term CV outcomes. Due to the significant overlap

Context Recently, the novel “metabolic dysfunction-associated fatty liver disease” (MAFLD) definition has been introduced. Objective To assess the relevance of MAFLD for mortality. Design Single-center cohort-study. Setting Colorectal cancer screening program. Patients 4718 subjects aged 45-80 were grouped according to their BMI and the presence or absence of MAFLD. Main Outcome Measures Mortality was compared among these groups by performing a systematic read-out of the national health insurance system, fatty liver (FL) was diagnosed using ultrasound. Results Overall prevalence of FL was 47.9%. 1200 (25.4%) were lean (BMI&lt;25kg/m2) and did not have MAFLD, 73 (1.5%) patients were lean and had non-alcoholic fatty liver disease (NAFLD), but did not fulfill criteria for MAFLD, 221 (4.7%) were lean and fulfilled criteria for MAFLD. Additionally, 1043 (22.1%) and 925 (19.6%) subjects had MAFLD with overweight (BMI 25-30kg/m²) and obesity (BMI≥30kg/m²) while 1041 (22.1%) and 215 (4.6%) had overweight and obesity without FL. During a median follow-up of 7.5 (IQR: 4.0-9.6) years, 278 deaths (5.9%) occurred. Of these, 98 (2.1%) were cancer-related, 65 (1.4%) were cardiovascular, and 17 (0.4%) were liver-related. Overall survival was similar between patient strata (after 5 years: 93.9%-98.2%) with lean MAFLD having the numerically worst survival. Although lean and overweight patients with MAFLD had a numerically worse outcome compared to their non-MAFLD counterparts, this association was driven by age and metabolic comorbidities (predominantly diabetes) rather than the presence of MAFLD. Conclusions Presence of MAFLD does not increase mortality in a cohort of individuals aged 45-80 years.