Abstract
The top three leading causes of death in patients with nonalcoholic fatty liver disease
(NAFLD) in descending order are cardiovascular disease, cancer, and liver disease.
It is clear now that the increased risk of metabolic and macro- and microvascular
complications in NAFLD stems from the associated features of metabolic syndrome. However,
NAFLD itself may contribute to the spectrum of risk factors associated with insulin
resistance. The primary focus of this review is to summarize the main systemic associations
of NAFLD, as well as to discuss the mechanisms that link them to NAFLD. Hepatic lipid
accumulation in NAFLD impairs hepatic glucose and lipid metabolism further increasing
the risk of type 2 diabetes mellitus and of cardiovascular disease, independently
of established risk factors. The incidence, prevalence, and severity of these complications
are proportional to the histological severity of liver damage suggesting that NAFLD,
but particularly nonalcoholic steatohepatitis, can also contribute to the low-grade
inflammatory state through the systemic release of several markers of inflammation,
oxidative stress, and of procoagulant factors. The clinical implication of these findings
is that patients with NAFLD require a multidisciplinary evaluation, with a major focus
on type 2 diabetes mellitus and cardiovascular disease complications and may benefit
from more intensive surveillance and early treatment interventions to decrease the
risk for cardiovascular and kidney complications.
Keywords
nonalcoholic fatty liver disease - metabolic syndrome - cardiovascular disease - type
2 diabetes mellitus - colorectal cancer - chronic kidney disease
