Noninvasive Serum Fibrosis Markers are Associated with Coronary Artery Calcification in Patients with Nonalcoholic Fatty Liver Disease

Background/Aims: Advanced hepatic fibrosis is associated with cardiovascular disease (CVD) in patients with nonalcoholic fatty liver disease (NAFLD). We investigated the association between noninvasive serum fibrosis markers and the coronary artery calcium score (CACS) in subjects with NAFLD. Methods: We analyzed 665 NAFLD subjects without chronic liver disease or heart disease between 2011 and 2015. The noninvasive fibrosis markers that were used to evaluate the severity of hepatic fibrosis included the NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4) score, Forn's index, and the aspartate aminotransferase to platelet ratio index (APRI). Results: The areas under the receiver operating characteristics curves for the NFS, FIB-4 score, Forn's index and APRI for predicting CACS >100 were 0.689, 0.683, 0.659, and 0.595, respectively. According to the multivariate analysis, older age, increased body mass index (BMI), and decreased estimated glomerular filtration rate (eGFR) were significant factors associated with CACS >100. The NFS, FIB-4 score and APRI were significantly associated with CACS >100 after adjusting for age and gender (p=0.006, p=0.012, and p=0.012, respectively) and after adjusting for age, gender, BMI and eGFR (p=0.013, p=0.022, and p=0.027, respectively). Scores integrating noninvasive fibrosis markers and other risk factors improved the predictive accuracy. Conclusions: The NFS and FIB-4 score were associated with coronary atherosclerosis in subjects with NAFLD. Furthermore, scores integrating these noninvasive scores and risk factors for CVD showed good discriminatory power in predicting CACS >100. Therefore, noninvasive serum fibrosis markers may be useful tools for identifying NAFLD subjects at a high risk for CVD.