Overlap prevalence and interaction effect of cardiometabolic risk factors for metabolic dysfunction-associated steatotic liver disease.

Background: Cardiometabolic risk factors (CMRFs) related to metabolic dysfunction-associated steatotic liver disease (MASLD) comprised overweight/obesity, impaired glucose metabolism, hypertension, hypertriglyceridemia and low high-density lipoprotein cholesterol. We aimed to describe the overlap prevalence and synergistic interaction of the five CMRFs on MASLD and liver fibrosis.

Methods: Using data of 2017-2020 National Health and Nutrition Examination Survey, we included non-pregnant participants aged ≥ 20 years who completed vibration-controlled transient elastography examinations and had sufficient information to determine their metabolic status. Logistic and generalized linear regression models were performed to assess synergistic interaction between CMRFs on MASLD and identify the contributions to liver fibrosis.

Results: The overall estimated prevalence of MASLD was about 33.1%. More than 80% of patients had three or more CMRFs. For MASLD, synergistic interaction between pairs of overweight/obesity and other four CMRFs were higher than it between other CMRFs' pairs [attributable proportion(AP): 40-50% vs 20-30%]. For liver fibrosis, overweight/obesity and impaired glucose metabolism or hypertension had significant synergistic interactions (AP: 50% or 30%, respectively). We identified 27 out of 31 possible CMRF combinations. Combinations including dyslipidemia were more frequent in men than women (77% vs 59%). Combinations including hypertension were less in Mexican Americans than other ethnicities (25% vs 45-57%). Most combinations with three or more CMRFs, regardless of overlap type, had significant associations with elevated liver stiffness value.

Conclusions: CMRF overlap was quite common and had additive interaction in patients with MASLD. Overlapping number may be more important than combination type in liver fibrosis development.