Histological severity of nonalcoholic fatty liver disease is associated with 10-year risk for atherosclerotic cardiovascular disease

Abstract

Background and aim: Nonalcoholic fatty liver disease (NAFLD) is associated with atherosclerotic cardiovascular disease (ASCVD). However, few studies have investigated the association between the histological severity of NAFLD and ASCVD. Therefore, we investigated whether the histological severity of NAFLD is associated with ASCVD risk.

Methods: We performed cross-sectional analysis of prospectively enrolled, biopsy-proven NAFLD patients. The 10-year ASCVD risk was assessed using the Korean Risk Prediction Model. The histological spectrum of NAFLD was classified by the nonalcoholic steatohepatitis (NASH) clinical research network histological scoring system. The association between each histological subgroup and ASCVD risk was analyzed using logistic regression analysis.

Results: This study included 398 Korean subjects (mean age, 57.9 years; male, 44.2%) with biopsy-proven NAFLD and 102 no-NALFD controls. Subjects with ASCVD risk ≥ 10% showed more severe grades of hepatocellular ballooning and more advanced stages of fibrosis when compared with subjects with ASCVD risk < 10% (p < 0.05 for each). The presence of NASH (odds ratio [OR] 4.07; 95% confidence interval [CI] 1.40-11.88) or advanced fibrosis (OR 8.11; 95% CI 1.83-35.98) was independently associated with a higher risk of ASCVD even after adjustment for age, sex, body mass index, blood pressure, lipids, liver enzymes, systemic inflammation, and insulin resistance.

Conclusions: Patients with NASH or advanced fibrosis are at an increased risk of developing ASCVD compared with no-NAFLD controls or subjects with NAFL, independent of conventional metabolic risk factors for CVD. Histological information on NAFLD may be helpful to promote our understanding of extrahepatic complications, such as ASCVD, resulting from NAFLD progression.

Keywords: Atherosclerotic cardiovascular disease; Ballooning; Fibrosis; Histology; Liver biopsy; Lobular inflammation; NAFLD activity score; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Steatosis.