Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: An update

Abstract

Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.

Keywords: Arterial stiffness; Cardiovascular disease; Chronic kidney disease; Inflammation; Liver fibrosis; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Statins.

Figure 1

Factors that contribute to the pathogenesis of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; TNF-α: Tumor necrosis factor-alpha; CYP2E1: Cytochrome P450 2E1; FFA: Free fatty acid; NF-κB: Nuclear factor kappa-light-chain-enhancer.

Figure 2

Liver biopsy of a patients with non-alcoholic steatohepatitis at baseline (A) and one year after 10 mg/d of rosuvastatin monotherapy (B) [unpublished data from personal archive].