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for hepatic triglycerides synthesis) and hepatic VLDL secretion, both of which are hence increased in
association with hepatic and adipose tissue insulin resistance. Subsequently, HDL-cholesterol levels fall
and LDL-cholesterol levels rise, both of which are highly atherogenic conditions.
Figure 1. Schematic overview of the mechanisms that may indirectly or directly link the liver
affected by NAFLD to alterations in the cardiovascular system.
Endothelial dysfunction has been shown to be an early event in the development of atherosclerosis.
Several studies have recently highlighted that insulin resistance at the endothelial level occurs early in
the development of NAFLD and is already present after a few days of high fat feeding, when steatosis
develops but inflammation seems still to be absent [1].
Hepatic insulin resistance has been shown to be increased in severe steatosis. This is in part due to
endothelial damage. An imbalance in locally produced vasodilators and vasoconstrictors has also
been documented. Furthermore, steatosis also induces structural abnormalities of liver vasculature,
contributing to the associated increase in intrahepatic resistance. Angiogenic factors have been shown to
play a role in the intrahepatic vascular changes in cirrhosis and are also studied in NASH. Altered levels
of angiogenic factors, well documented in the pathogenesis of atherosclerosis [1], have been observed in
the peripheral blood of patients with NASH.
Prothrombotic factors have also been shown to play a role in the progression of liver disease. Although
the liver is the main source of most of these coagulation factors, the casual role of the liver has not
been proven. In particular, plasminogen activator inhibitor 1 (PAI-1) has been shown to be specifically
increased in NASH.
Adiponectin, which is lower in patients with NAFLD, is another factor that might represent a link
between NAFLD and CVD. Adiponectin has anti-atherogenic properties and directly affects endothelial
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 61
association with hepatic and adipose tissue insulin resistance. Subsequently, HDL-cholesterol levels fall
and LDL-cholesterol levels rise, both of which are highly atherogenic conditions.
Figure 1. Schematic overview of the mechanisms that may indirectly or directly link the liver
affected by NAFLD to alterations in the cardiovascular system.
Endothelial dysfunction has been shown to be an early event in the development of atherosclerosis.
Several studies have recently highlighted that insulin resistance at the endothelial level occurs early in
the development of NAFLD and is already present after a few days of high fat feeding, when steatosis
develops but inflammation seems still to be absent [1].
Hepatic insulin resistance has been shown to be increased in severe steatosis. This is in part due to
endothelial damage. An imbalance in locally produced vasodilators and vasoconstrictors has also
been documented. Furthermore, steatosis also induces structural abnormalities of liver vasculature,
contributing to the associated increase in intrahepatic resistance. Angiogenic factors have been shown to
play a role in the intrahepatic vascular changes in cirrhosis and are also studied in NASH. Altered levels
of angiogenic factors, well documented in the pathogenesis of atherosclerosis [1], have been observed in
the peripheral blood of patients with NASH.
Prothrombotic factors have also been shown to play a role in the progression of liver disease. Although
the liver is the main source of most of these coagulation factors, the casual role of the liver has not
been proven. In particular, plasminogen activator inhibitor 1 (PAI-1) has been shown to be specifically
increased in NASH.
Adiponectin, which is lower in patients with NAFLD, is another factor that might represent a link
between NAFLD and CVD. Adiponectin has anti-atherogenic properties and directly affects endothelial
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 61
