The prevalence of the metabolic syndrome (MetS), a cluster of cardiovascular risk factors associated with obesity and insulin
resistance, is dramatically increasing in Western and developing countries. This disorder is not only associated with a higher risk of appearance
of type 2 diabetes and cardiovascular events, but impacts on the liver in different ways. Nonalcoholic fatty liver disease
(NAFLD) is considered the hepatic manifestation of MetS, and is characterized by triglyceride accumulation and a variable degree of hepatic
injury, inflammation, and repair. In the presence of significant hepatocellular injury and inflammation, the picture is defined ‘nonalcoholic
steatohepatitis’ (NASH), that has the potential to progress to advanced fibrosis and cirrhosis. Diagnosis of NASH is based on a
liver biopsy, and active search for noninvasive tests is ongoing. Progression of steatohepatitis to advanced fibrosis or cirrhosis has been
shown in at least one third of patients followed with paired biopsies. Presence of NASH is associated with lower life expectancy, both
due to liver-related death and to an increase in cardiovascular events. The appearance of NAFLD is mainly dependent on increased flow
of fatty acids derived from an excess of lipolysis from insulin-resistant adipose tissue. Development of NASH is based on lipotoxicity
and is influenced by signals derived from outside the liver and from intrahepatic activation of inflammatory and fibrogenic pathways. The
presence of the MetS is also associated with worse outcomes in patients with cirrhosis due to any causes, and has complex interactions
with hepatitis C virus infection. Moreover, MetS poses a higher risk of development of hepatocellular carcinoma, not necessarily through
the development of NASH-related cirrhosis. In conclusion, the presence of metabolic alterations has a severe and multifaceted impact on
the liver, and is responsible for a higher risk of liver-dependent and –independent mortality.
Metabolic syndrome, hepatic steatosis, cardiovascular risk, inflammasome, hepatocellular carcinoma.
Dipartimento di Medicina Sperimentale e Clinica, Largo Brambilla, 3, I-50134 Florence, Italy.