Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis

Abstract

NAFLD is a spectrum of progressive liver disease that encompasses simple steatosis, NASH, fibrosis and, ultimately, cirrhosis. NAFLD is recognized as the hepatic component of the metabolic syndrome, as these conditions have insulin resistance as a common pathophysiological mechanism. Therefore, NAFLD is strongly associated with type 2 diabetes mellitus and abdominal obesity. As lifestyles have become increasingly sedentary and dietary patterns have changed, the worldwide prevalence of NAFLD has increased dramatically and is projected to be the principal aetiology for liver transplantation within the next decade. Importantly, a growing body of clinical and epidemiological evidence suggests that NAFLD is associated not only with liver-related morbidity and mortality, but also with an increased risk of developing both cardiovascular disease and type 2 diabetes mellitus. This article reviews the evidence that suggests NAFLD is a multisystem disease and the factors that might determine interindividual variation in the development and progression of its major hepatic and extrahepatic manifestations (principally type 2 diabetes mellitus and cardiovascular disease).

Time to Replace Assessment of Liver Histology With MR-Based Imaging Tests to Assess Efficacy of Interventions for Nonalcoholic Fatty Liver Disease

“…Recent discoveries of genetic variants [e.g., patatin-like phospholipase domain-containing 3 (PNPLA3 148MM variant)], that influence NAFLD progression by influencing the hepatic lipid droplet, also adds credence to the importance of assessing liver fat accumulation per se in NAFLD. The PNPLA3 148MM variant impairs modification of the lipid droplet in hepatocytes, and this genetic variant plays a major role in the development and progression of NAFLD (triggering inflammation, fibrogenesis, and carcinogenesis) 6 . In addition, PNPLA3 148MM may not only modify liver lipid droplet accumulation, but may also influence the effect of potential treatments to decrease liver fat in NAFLD, such as high-dose long chain omega-3 polyunsaturated fatty acids 7,8 .…”

“…We believe that such an approach has diminished dramatically a focus on finding treatments that decrease liver fat content per se as an early marker of disease, and thereby diminished attention on treating the liver condition in its early stages. Furthermore, since patients with NAFLD die two-fold more frequently due to CVD than to liver disease itself 1,6 , it is also important to ensure that any new treatments for NAFLD do not cause harm beyond the liver. In particular, it is crucial that new treatments for liver disease in NAFLD do not increase the incidence of CVD and/or T2DM.…”

Nonalcoholic fatty liver disease as trigger of cardiovascular and metabolic complication in metabolic syndrome

“…Interestingly, cardiovascular complications are the leading cause of morbidity and mortality in NAFLD subjects [5][6][7]. Moreover, the presence of MS leads to an increased risk of T2DM and cardiovascular disease (CVD), leading these subjects to be a high-risk group for increased morbidity and allcause mortality with a shortened lifespan compared with the general population.…”

From Nonalcoholic Fatty Liver Disease to Hepatocellular Carcinoma: A Systems Understanding

“…NAFLD was initially considered as the hepatic component of the metabolic syndrome due to its strong associations with insulin resistance and links to visceral obesity. NAFLD is now considered as a multifactorial condition that leads not only to increased liver-related mortality but also to increased risk of the development of type 2 diabetes mellitus and cardiovascular diseases (CVD) [4]. Abnormalities in lipid and lipoprotein metabolism accompanied by chronic inflammation are crucial for development of metabolic syndromerelated diseases where cholesterol as the lipid component lies at the crossroad of NAFLD and atherogenesis.…”

“…Abnormalities in lipid and lipoprotein metabolism accompanied by chronic inflammation are crucial for development of metabolic syndromerelated diseases where cholesterol as the lipid component lies at the crossroad of NAFLD and atherogenesis. NA-FLD-associated pathologies can thus on the one hand be triggered by altered metabolism, such as is associated with insulin resistance or dyslipidemia, while on the other hand NAFLD can itself increase the risk for the development of diabetes mellitus and cardiovascular diseases [4]. This complex network of interactions has common roots in the primary metabolic pathways of the liver and of other tissues.…”