7042 From NAFLD to MASLD: Assessing the Impact of Changing the Definition of Fatty Liver Disease

Abstract Disclosure: M.J. McPhaul: Consulting Fee; Self; Quest Diagnostics. J.Z. Louie: Employee; Self; Quest Diagnostics. D. Shiffman: Consulting Fee; Self; Quest Diagnostics. F. Bril: None. Nonalcoholic fatty liver disease (NAFLD) has been renamed metabolic dysfunction-associated steatotic liver disease (MASLD), and its definition has also been updated to include the presence of at least one cardiometabolic (CM) risk factor. The aim of this study was to assess the demographic and biochemical characteristics of patients with NAFLD, who do not meet criteria for MASLD, and to assess the effect of cumulative number of CM risk factors on liver disease severity. Methods: The study population included 33,674 participants in the 2020 annual wellness program of a nation-wide employer that included laboratory tests and anthropometric measurements, after excluding those with incomplete data and BMI <18.5 kg/m2. Hepatic steatosis was defined as intact insulin (II)*ALT ≥290 (Bril et al, JCEM 2021). CM risk factors were defined according to MASLD definition. Differences between groups were assessed using t-tests or Chi-square tests. The association between number of CM risk factors and hepatic steatosis was assessed by a trend test. Association with II, AST, and ALT was assessed by linear regression models. Results: A total of 7,059 (27%) participants had hepatic steatosis. However, 61 (1%) of these participants did not have any CM risk factors, and thus had NAFLD, but not MASLD. Compared with participants with no steatosis, they were younger (-8 [95% CI: -10 to -5] years), had a lower fraction of women (54 vs. 67%, p=0.04), higher fraction of Hispanic patients (28 vs. 13%, p=0.0007). Despite absence of CM risk factors, 39% were insulin resistant (II>10.5 uIU/mL). This group of patients with no CM risk factors had plasma AST and ALT levels that were higher than MASLD patients (p <0.002). Among patients with hepatic steatosis and only 1 CM risk factor, the most common CM risk factors were overweight, obesity, or increased waist circumference. Less than 15% had any glucose, lipid, or BP abnormality. Higher number of CM risk factors was associated with a higher prevalence of hepatic steatosis (p<0.0001). Among patients with MASLD, higher number of CM risk factors was associated with higher levels of II (p<0.0001), but not with higher AST or ALT (both p>0.15). Conclusion: Changes in NAFLD definition resulted in a new subgroup of patients that were previously defined as NAFLD, but do not have MASLD. Our results showed that this group of patients are likely to have insulin resistance and may be at risk of liver fibrosis, despite their lack of CM risk factors. Presentation: 6/2/2024