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Cirrhosis (cont.)

Medical Author:
Dennis Lee, MD

Dr. Lee was born in Shanghai, China, and received his college and medical training in the United States. He is fluent in English and three Chinese dialects. He graduated with chemistry departmental honors from Harvey Mudd College. He was appointed president of AOA society at UCLA School of Medicine. He underwent internal medicine residency and gastroenterology fellowship training at Cedars Sinai Medical Center.

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Medical Editor:
Jay W. Marks, MD
Jay W. Marks, MD
Jay W. Marks, MD

Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.

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What are the common causes of cirrhosis?

  • Alcohol is a very common cause of cirrhosis, particularly in the Western world. The development of cirrhosis depends upon the amount and regularity of alcohol intake. Chronic, high levels of alcohol consumption injure liver cells. Thirty percent of individuals who drink daily at least eight to sixteen ounces of hard liquor or the equivalent for fifteen or more years will develop cirrhosis. Alcohol causes a range of liver diseases; from simple and uncomplicated fatty liver (steatosis), to the more serious fatty liver with inflammation (steatohepatitis or alcoholic hepatitis), to cirrhosis.
  • Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver diseases that, like alcoholic liver disease, ranges from simple steatosis, to nonalcoholic steatohepatitis (NASH), to cirrhosis. All stages of NAFLD have in common the accumulation of fat in liver cells. The term nonalcoholic is used because NAFLD occurs in individuals who do not consume excessive amounts of alcohol, yet, in many respects, the microscopic picture of NAFLD is similar to what can be seen in liver disease that is due to excessive alcohol. NAFLD is associated with a condition called insulin resistance, which, in turn, is associated with the metabolic syndrome and diabetes mellitus type 2. Obesity is the most important cause of insulin resistance, metabolic syndrome, and type 2 diabetes. NAFLD is the most common liver disease in the United States and is responsible for 24% of all liver disease. In fact, the number of livers that are transplanted for NAFLD-related cirrhosis is on the rise. Public health officials are worried that the current epidemic of obesity will dramatically increase the development of NAFLD and cirrhosis in the population.
  • Cryptogenic cirrhosis (cirrhosis due to unidentified causes) is a common reason for liver transplantation. It is termed cryptogenic cirrhosis because for many years doctors have been unable to explain why a proportion of patients developed cirrhosis. Doctors now believe that cryptogenic cirrhosis is due to NASH (nonalcoholic steatohepatitis) caused by long standing obesity, type 2 diabetes, and insulin resistance. The fat in the liver of patients with NASH is believed to disappear with the onset of cirrhosis, and this has made it difficult for doctors to make the connection between NASH and cryptogenic cirrhosis for a long time. One important clue that NASH leads to cryptogenic cirrhosis is the finding of a high occurrence of NASH in the new livers of patients undergoing liver transplant for cryptogenic cirrhosis. Finally, a study from France suggests that patients with NASH have a similar risk of developing cirrhosis as patients with long standing infection with hepatitis C virus. (See discussion that follows.) However, the progression to cirrhosis from NASH is thought to be slow and the diagnosis of cirrhosis typically is made in patients in their sixties.
  • Chronic viral hepatitis is a condition where hepatitis B or hepatitis C virus infects the liver for years. Most patients with viral hepatitis will not develop chronic hepatitis and cirrhosis. For example, the majority of patients infected with hepatitis A recover completely within weeks, without developing chronic infection. In contrast, some patients infected with hepatitis B virus and most patients infected with hepatitis C virus develop chronic hepatitis, which, in turn, causes progressive liver damage and leads to cirrhosis, and, sometimes, liver cancers.
  • Inherited (genetic) disorders result in the accumulation of toxic substances in the liver which lead to tissue damage and cirrhosis. Examples include the abnormal accumulation of iron (hemochromatosis) or copper (Wilson's disease). In hemochromatosis, patients inherit a tendency to absorb an excessive amount of iron from food. Over time, iron accumulation in different organs throughout the body causes cirrhosis, arthritis, heart muscle damage leading to heart failure, and testicular dysfunction causing loss of sexual drive. Treatment is aimed at preventing damage to organs by removing iron from the body through bloodletting (removing blood). In Wilson disease, there is an inherited abnormality in one of the proteins that controls copper in the body. Over time, copper accumulates in the liver, eyes, and brain. Cirrhosis, tremor, psychiatric disturbances and other neurological difficulties occur if the condition is not treated early. Treatment is with oral medication that increases the amount of copper that is eliminated from the body in the urine.
  • Primary biliary cirrhosis (PBC) is a liver disease caused by an abnormality of the immune system that is found predominantly in women. The abnormal immunity in PBC causes chronic inflammation and destruction of the small bile ducts within the liver. The bile ducts are passages within the liver through which bile travels to the intestine. Bile is a fluid produced by the liver that contains substances required for digestion and absorption of fat in the intestine, as well as other compounds that are waste products, such as the pigment bilirubin. (Bilirubin is produced by the breakdown of hemoglobin from old red blood cells.). Along with the gallbladder, the bile ducts make up the biliary tract. In PBC, the destruction of the small bile ducts blocks the normal flow of bile into the intestine. As the inflammation continues to destroy more of the bile ducts, it also spreads to destroy nearby liver cells. As the destruction of the hepatocytes proceeds, scar tissue (fibrosis) forms and spreads throughout the areas of destruction. The combined effects of progressive inflammation, scarring, and the toxic effects of accumulating waste products culminates in cirrhosis.
  • Primary sclerosing cholangitis (PSC) is an uncommon disease found frequently in patients with ulcerative colitis . In PSC, the large bile ducts outside of the liver become inflamed, narrowed, and obstructed. Obstruction to the flow of bile leads to infections of the bile ducts and jaundice and eventually causes cirrhosis. In some patients, injury to the bile ducts (usually as a result of surgery) also can cause obstruction and cirrhosis of the liver.
  • Autoimmune hepatitis is a liver disease caused by an abnormality of the immune system that is found more commonly in women. The abnormal immune activity in autoimmune hepatitis causes progressive inflammation and destruction of liver cells (hepatocytes), leading ultimately to cirrhosis.
  • Infants can be born without bile ducts (biliary atresia) and ultimately develop cirrhosis. Other infants are born lacking vital enzymes for controlling sugars that leads to the accumulation of sugars and cirrhosis. On rare occasions, the absence of a specific enzyme can cause cirrhosis and scarring of the lung (alpha 1 antitrypsin deficiency).
  • Less common causes of cirrhosis include unusual reactions to some drugs and prolonged exposure to toxins, as well as chronic heart failure (cardiac cirrhosis). In certain parts of the world (particularly Northern Africa), infection of the liver with a parasite (schistosomiasis) is the most common cause of liver disease and cirrhosis.

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