Nonalcoholic Fatty Liver Disease-Associated Liver Fibrosis Is Linked with the Severity of Coronary Artery Disease Mediated by Systemic Inflammation

Abstract

Background and Aim. Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease. Hepatic fibrosis is the most significant determinant of all-cause- and liver -related mortality in NAFLD. However, the relationship between NAFLD fibrosis and severe coronary artery disease (CAD) remains unclear. Methods and Results. We conducted a retrospective study of 531 patients with ultrasonogram-confirmed NAFLD who underwent percutaneous coronary intervention (PCI). Then, all patients were separated into four categories by Gensini score (0, 0-9, 9-48, and ≥48) for use in ordinal logistic regression analysis to determine whether NAFLD fibrosis was associated with increased Gensini scores. Mediation analysis was used to investigate whether systemic inflammation is a mediating factor in the association between NAFLD fibrosis and CAD severity. $\text{FIB}-4>2.67$ ( $\text{OR}=5.67$ , 95% CI 2.59-12.38) and $\text{APRI}>1.5$ ( $\text{OR}=14.8$ , 95% CI 3.24-67.60) remained to be independent risk factors for the severity of CAD after adjusting for conventional risk factors, whereas among the inflammation markers, only neutrophils and neutrophil-to-lymphocyte ratio (NLR) were independently associated with CAD. Multivariable ordinal regression analysis suggested that increasing Gensini score (0, 0-9, 9-48, and ≥48) was associated with advanced NAFLD fibrosis. ROC curve showed that either fibrosis markers or inflammation markers, integrating with traditional risk factors, could increase the predictive capacity for determining CAD. Inflammation markers, especially neutrophils and NLR, were mediators of the relationship between NAFLD fibrosis and CAD severity. Conclusions. NAFLD patients with advanced fibrosis are at a high risk of severe coronary artery stenosis, and inflammation might mediate the association between NAFLD fibrosis and CAD severity.