Liver DiseasesA Variety of Conditions

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There are numerous reasons for impairment of the hepatic function. In the western world, chronic alcohol abuse is one of the main causes of liver disease and can cause steatosis, alcohol hepatitis, and cirrhosis.

Steatosis is a condition caused by disturbances in the lipid metabolism and produce an accumulation of triglycerides within the hepatocytes. The condition may appear quickly and is reversible if the cause of the accumulation is removed. The condition is mainly caused by alcohol but may also be caused by malnutrition, hepatotoxic substances, diabetes, and obesity.

Hepatitis is mainly caused by viruses, hepatotoxic substances, and autoimmune diseases. The condition is characterized by cell necrosis and inflammation in the liver. All forms give the same alterations of the liver, including simultaneous necrosis and degeneration of hepatocytes, infiltration of mononuclear cells, degeneration of Kupffer cells, and varying degree of cholestasis.

Cirrhosis is not a disease in itself but a stage in the course of inflammatory liver diseases. Cirrhosis can be caused by liver damage resulting from alcoholism, hepatitis B and hepatitis C, drugs, metabolic disorders, prolonged cholestasis, etc. Cirrhosis is characterized by increased presence of fibrous tissue, destruction of the lobular architecture and sinusoidal network, and nodular degeneration. The hepatic synthesis of proteins such as albumin, prothrombin, and enzymes is decreased. Cirrhosis often gives rise to portal hypertension. In portal hypertension, the blood flow coming from the intestine through the liver via vena porta is reduced while the arterial blood flow is increased relative to the portal flow. Many cirrhotic patients have portacaval shunts, where a substantial fraction of the portal blood bypasses parenchymal tissue in the liver or enters directly into the superior vena cava via esophageal varices. A characteristic late sign of liver disease is ascites, an accumulation of extracellular fluids in the lower abdominal area. Ascites is believed to be caused by a combination of portal hypertension and decreased colloid osmotic pressure in the blood. The degree of portal hypertension, shunting, ascites, and residual metabolic capacity varies between cirrhotic patients.

Usually pharmacokinetic studies are performed in cirrhotic patients. As there is no optimal marker(s) for assessing hepatic function, extrapolation from study results to individual cirrhotic patients as well as to patients not having cirrhosis is problematic.

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