Investigating the Effect of Metabolic Phenotypes on Health Events in Alcoholic and Nonalcoholic Fatty Liver Disease

BACKGROUND AND AIMS: Metabolic dysfunction and obesity commonly coexist with both alcoholic and nonalcoholic fatty liver disease (AFLD and NAFLD). The association of AFLD and NAFLD with incident diseases in individuals with different metabolic phenotypes are unclear. METHODS: UK Biobank study participants were screened for the presence of fatty liver at baseline. Body mass index and metabolic dysfunction were used to define metabolic phenotypes. Cox regression model was performed to examine the associations of AFLD and NAFLD with incident significant liver diseases (SLDs), cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), and cancers, respectively. RESULTS: A total of 43,974 AFLD and 103,248 NAFLD cases were identified. Both AFLD and NAFLD were associated with an increased risk of diseases of interest. The effects were amplified by obesity and metabolic abnormalities and modified by metabolic phenotypes. Compared to individuals free of fatty liver and with phenotype of metabolically healthy-normal weight, AFLD [hazard ratio (HR) 3.27; 95% CI: 1.95–5.47)] and NAFLD (HR 2.25; 95% CI: 1.28–3.94) cases with phenotype of metabolically obese-normal weight had the greatest risk of SLDs. For CVDs, CKDs, and cancer, the greatest risks were detected in AFLD and NAFLD cases with phenotype of metabolically obese-overweight/obesity. In this subpopulation, AFLD and NAFLD conferred a 2.75-fold (95% CI: 2.32–3.25) and 4.02-fold 95% CI: (3.64–4.43) increased risk of CVDs, 4.37-fold 95% CI: (3.38–5.64) and 6.55-fold 95% CI: (5.73–7.48) increased risk of CKDs, and 1.19-fold 95% CI: (1.08–1.27) and 1.21-fold 95% CI: (1.14–1.28) increased risk of cancers, respectively. CONCLUSIONS: Metabolic phenotypes modified the association of AFLD and NAFLD with intrahepatic and extrahepatic diseases.