Fibrotic Burden Determines Cardiovascular Risk among Subjects with Metabolic Dysfunction-Associated Fatty Liver Disease

Abstract

Background/Aims: Metabolic dysfunction associated fatty liver disease (MAFLD) has recently been introduced to compensate for the conventional concept of nonalcoholic fatty liver disease (NAFLD). We explored whether fibrotic burden determines the risk of atherosclerotic cardiovascular disease (ASCVD) among subjects with MAFLD.Methods: We recruited 9,444 participants from the Korea National Health and Nutrition Examination Survey (2008 to 2011. Liver fibrosis was identified using the fibrosis-4 (FIB-4) index and NAFLD fibrosis score. The 10-year ASCVD risk score (>10%) was used to determine a high probability ASCVD risk. For sensitivity analysis, propensity score matching was assessed to subjects with aged 40 to 75 years free from ASCVD. Results:The prevalence of MAFLD was 38.0% (n=3,592). The ASCVD risk scores stratified in quartile were positively correlated to MAFLD and FIB-4 defined-significant liver fibrosis (p for trend <0.001). Individuals with both MAFLD and FIB-4 defined-significant liver fibrosis had a greater chance of high probability ASCVD risk (odds ratio [OR]=2.40; p<0.001) than those without MAFLD. The impact of MAFLD on high probability ASCVD risk was greater than that of significant liver fibrosis (OR=4.72 for MAFLD vs OR=1.88 for FIB-4 defined-significant liver fibrosis; all p<0.001). Among participants with MAFLD, low muscle mass enhanced the risk of significant liver fibrosis (OR=1.56 to 2.43; p<0.001). When NAFLD fibrosis score was applied to define significant liver fibrosis, similar findings were observed.Conclusions: Individuals with MAFLD had a substantial ASCVD risk compared to those without MAFLD. Accompanying significant liver fibrosis further enhanced the risk of ASCVD among subjects with MAFLD.

Fibrotic Burden in the Liver Differs Across Metabolic Dysfunction-Associated Fatty Liver Disease Subtypes

“…High fibrotic burden in patients with FLD is a major risk factor for developing HCC and liver-related mortality, 27,28 and other studies have shown that a high fibrotic burden in liver is independently associated with an increased CVD risk in patients with FLD. 16,17,19 Based on these findings, it might be suggested that no MAFLD group with the lowest fibrotic burden in our study might have the lowest risk of HCC, liver-related mortality, and CVD, although additional longitudinal or mechanistic analyses were not performed. Second, in our study, DM-MAFLD had the highest risk of advanced liver fibrosis.…”

Heterogeneity of non-alcoholic fatty liver disease (NAFLD): Implication for cardiovascular risk stratification

“…Given the metabolic hallmark of the new definition of MAFLD, it could be speculated that an increased risk of cardiovascular complications should be expected in this subtype of NAFLD [37]. Indeed, despite data about cardiovascular abnormalities in MAFLD are limited, it has been showed that individuals with MAFLD phenotype had a substantially increased ASCVD risk compared to those without MAFLD [38]. However, while the new MAFLD definition better outlines the syndromic of NAFLD and encloses the large majority of fatty liver patients, it excludes those with metabolic-healthy NAFLD, that could be probably considered as the "pure" genetic ones [39].…”

Association between Triglyceride-glucose index and carotid artery plaque in young and middle-aged occupational population

“…Furthermore, the TyG index was associated with a higher risk of CAP among those with MAFLD, suggesting that MAFLD may enhance the effect of TyG index on the risk of CAP. A recent study indicated that individuals with MAFLD had a substantial ASCVD risk compared to those without MALFD [37]. Thus, our ndings might provide clinical implications for applying identi cation and intervention for subjects with higher TyG index and MAFLD, which may prevent the risk of CAP.…”

“…Previous studies indicated that railway workers were more likely to have a high incidence of the metabolic disease due to their association with poor lifestyle behaviors and irregular work schedules. As one of the metabolic diseases, MAFLD, a novel concept proposed by an international consensus in 2020, was mainly related to insulin resistance and as a risk factor for ASCVD, and the TyG index was a potential risk factor for MAFLD [34][35][36][37][38]. Moreover, scienti c evidence has shown that lifestyle including physical activity, dietary pattern, salt intake, etc., improved cardiovascular disease markers effectively [39,40].…”