The Inflamed Liver and Atherosclerosis: A Link Between Histologic Severity of Nonalcoholic Fatty Liver Disease and Increased Cardiovascular Risk

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. It encompasses a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Growing evidence links NAFLD to cardiovascular (CV) disease; however, the association between the histologic severity of NAFLD and CV risk remains poorly understood. To assess the relationship between severity of liver injury and CV risk markers in a large, well-characterized group of patients with biopsy-proven NAFLD. Our cohort consisted of 83 consecutive patients undergoing liver biopsy for clinical suspicion of NAFLD. Patients were subsequently divided into three groups: normal biopsy (n = 11) simple steatosis (n = 36), and NASH (n = 36). CV risk markers included: triglyceride/high-density lipoprotein (HDL), total cholesterol/HDL, and low-density lipoprotein/HDL ratios. All lipid ratios were found to be significantly associated with NAFLD (p < 0.05) after adjusting for age and gender. More importantly, there was a stepwise, statistically significant increase in lipid ratios from patients with normal biopsies to patients with simple steatosis to those with NASH (p < 0.05). A positive correlation was found between the lipid ratios and NAFLD activity score (NAS) as well as the individual histological features of the NAS (steatosis, inflammation, and ballooning) with the strongest correlation being with NAS (rho (95% CI) 0.41 (0.21, 0.62), p < 0.001). In patients with NAFLD, the histologic severity of liver injury and inflammation is strongly associated with an increased CV risk and an atherogenic lipid profile.