Cirrhosis

Cirrhosis is a clinical entity characterized by a spectrum of diffused hepatic pathologic features that underpin a number of characteristic clinical signs and symptoms. It represents an irreversible state of chronic liver failure resulting from a wide variety of chronic liver diseases. The word cirrhosis derives from the Greek scirrhus, which means “tawny” (the color of the orange or tawny surface of the liver seen at autopsy). The term was coined by René Laënnec in 1826, through his work in which he also discusses the stethoscope. Chronic liver disease and cirrhosis are responsible for about 35,000 deaths per year in the United States, where it is the ninth leading cause of death, accounting for 1.2 percent of total deaths.

The pathologic features that define cirrhosis are extensive fibrosis (deposition of the components of the extracellular matrix), along with regenerative, structurally abnormal nodules. They are a consequence of events such as destruction of liver cells (hepatocytes), collapse of the supporting fibrous network with ulterior deposition of connective tissue, distortion of the normal vascular architecture, and nodular regeneration of the remaining liver parenchyma.

Hepatic fibrosis is the result of the activation of hepatic stellate cells (quiescent liver cells that store vitamin A) through the release of factors from hepatocytes and Kupffer cells (specialized liver cells of the immune system), thus producing collagen. These pathologic features imply the presence of irreversible chronic injury to the hepatic parenchyma.

Cirrhosis can be classified using etiologic or morphologic criteria. However, it is more accurate to devise a classification by combining both types of criteria. The same pathological pattern can be caused by different types of injury, whereas the same type of injury may result in a variety of morphologic patterns. Thus, cirrhosis can be classified as alcoholic, cryptogenic and posthepatitic, biliary, cardiac, metabolic, inherited, and drug related. Alcoholic cirrhosis is a consequence of chronic alcohol consumption and is one of the most common types of cirrhosis in North America and many areas in western Europe and South America. Posthepatitic cirrhosis refers to the final stage of diverse types of chronic liver disease. Cryptogenic cirrhosis pertains to the cases where the etiology of cirrhosis is unknown (around 10 percent of all patients with cirrhosis). Biliary cirrhosis (either primary biliary cirrhosis or secondary biliary cirrhosis) is caused by the protracted obstruction of the biliary system. Cardiac cirrhosis is a consequence of severe right-sided congestive heart failure.

Cirrhosis can also result from infectious diseases (e.g., brucellosis, toxoplasmosis, viral hepatitis), drugs and toxins (e.g., alcohol, amiodarone, oral contraceptives), inherited and metabolic disorders (e.g., α1-antitrypsin deficiency, hemochromatosis, Wilson's disease), and other causes (e.g., cystic fibrosis, nonalcoholic fatty liver disease, sarcoidosis). Hepatitis C has [Page 415]replaced alcoholic liver disease as the main cause of cirrhosis, accounting for around 26 percent of cases, with alcoholic liver disease comprising 21 percent.

The clinical manifestations of cirrhosis are often suggestive of the degree of liver damage and not of the liver disease causing it. While some patients are completely asymptomatic and have a reasonable life expectancy, others have severe symptoms and a short life expectancy.

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