Cirrhosis

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Cirrhosis

Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which leads to portal hypertension and end-stage liver disease. Fibrosis describes encapsulation or replacement of injured tissue by a collagenous scar. Liver fibrosis results from the perpetuation of the normal wound-healing response, resulting in an abnormal continuation of fibrogenesis (connective tissue production and deposition). Fibrosis progresses at variable rates depending on the cause of liver disease, environmental factors, and host factors.1–3 Cirrhosis is an advanced stage of liver fibrosis that is accompanied by distortion of the hepatic vasculature. The resultant vascular distortion leads to shunting of the portal and arterial blood supply directly into the hepatic outflow (central veins), compromising exchange between hepatic sinusoids and the adjacent liver parenchyma. The general circulatory abnormalities in cirrhosis (splanchnic vasodilation, vasoconstriction and hypoperfusion of kidneys, water and salt retention, increased cardiac output) are intimately linked to the hepatic vascular alterations and resulting portal hypertension. Cirrhosis and its associated vascular distortion are traditionally regarded as irreversible but recent data suggest that cirrhosis regression or even reversal is possible.

Nonalcoholic fatty liver disease (NAFLD) is hepatic steatosis associated with metabolic abnormalities such as overweight/central obesity, insulin resistance, type 2 diabetes (T2D), and dyslipidemia. NAFLD is becoming the most common liver disease in contemporary society, with the highest prevalence in those over 60 years. NAFLD pathology ranges from simple steatosis to a necroinflammatory fibrosing disorder called steatohepatitis (SH), the latter associated with high risk of developing cirrhosis, often occuring in the seventh to ninth decades of life. While the main health implications of NAFLD are increased risk of developing T2D, cardiovascular diseases, and common cancers, there is substantantially increased standardized mortality, and deaths from decompensated cirrhosis and hepatocellular carcinoma (HCC).