The relationship between hepatitis C and the metabolic syndrome is arguably one of the hottest topics in the field of hepatology. For example, hepatitis C virus (HCV) exerts the following significant interactions with both lipid and glucose metabolism:

• Blockade of the lipoprotein assembly and secretion
• Activation of neolipogenesis
• Interference with the insulin-signaling transduction pathway, via several direct and indirect mechanisms

These interactions have been repeatedly proven to occur both in experimental systems and in the liver of infected individuals.
The clinical correlates of such interactions are known: hepatic steatosis, frequently occurring in patients infected with genotype 3a; and insulin resistance, progressing to type 2 diabetes in patients at risk. If virally induced steatosis may have limited consequences from a clinical standpoint, the insulin resistance associated with HCV impacts negatively on both liver disease progression, with accelerated fibrogenesis, and rate of virological response to antiviral therapy. Knowledge of the molecular mechanisms underlying these interactions is paramount to a rational pharmacological management.
In addition to the metabolic alterations induced by HCV, patients with hepatitis C may face the consequences of the growing spread of metabolic syndrome worldwide. The latter is today one of the most formidable factors of comorbidity in patients with liver disease, irrespective of etiology. Despite the growing knowledge of the molecular events occurring in patients with metabolic syndrome, the single most effective measure that has been proved to thwart its ominous effects is collectively referred to as lifestyle changes. Overweight control and increased physical activity are significantly more efficacious than drugs, and chronic hepatitis C patients with metabolic syndrome should not be spared such simple measures. Appropriate tools can be used to optimize their quantification and delivery in patients with chronic hepatitis C to reduce the risk of cardiovascular, oncological, and hepatological sequelae.