What diseases cause jaundice?

Increased production of bilirubin

There are several uncommon conditions that give rise to over-production of bilirubin. The bilirubin in the blood in these conditions usually is only mildly elevated, and the resultant jaundice usually is mild and difficult to detect. These conditions include: 1) rapid destruction of red blood cells (referred to as hemolysis), 2) a defect in the formation of red blood cells that leads to the over-production of hemoglobin in the bone marrow (called ineffective erythropoiesis), or 3) absorption of large amounts of hemoglobin when there has been much bleeding into tissues (e.g., from hematomas, collections of blood in the tissues).

Acute inflammation of the liver

Any condition in which the liver becomes inflamed can reduce the ability of the liver to conjugate (attach glucuronic acid to) and secrete bilirubin. Common examples include acute viral hepatitis, alcoholic hepatitis, and Tylenol-induced liver toxicity.

Chronic liver diseases

Chronic inflammation of the liver can lead to scarring and cirrhosis, and can ultimately result in jaundice. Common examples include chronic hepatitis B and C, alcoholic liver disease with cirrhosis, and autoimmune hepatitis.

Infiltrative diseases of the liver

Infiltrative diseases of the liver refer to diseases in which the liver is filled with cells or substances that don't belong there. The most common example would be metastatic cancer to the liver, usually from cancers within the abdomen. Uncommon causes include a few diseases in which substances accumulate within the liver cells, for example, iron (hemochromatosis), alpha-one antitrypsin (alpha-one antitrypsin deficiency), and copper (Wilson's disease).

Inflammation of the bile ducts

Diseases causing inflammation of the bile ducts, for example, primary biliary cirrhosis or sclerosing cholangitis and some drugs, can stop the flow of bile and elimination of bilirubin and lead to jaundice.

Blockage of the bile ducts

The most common causes of blockage of the bile ducts are gallstones and pancreatic cancer. Less common causes include cancers of the liver and bile ducts.

Drugs

Many drugs can cause jaundice and/or cholestasis. Some drugs can cause liver inflammation (hepatitis) similar to viral hepatitis. Other drugs can cause inflammation of the bile ducts, resulting in cholestasis and/or jaundice. Drugs also may interfere directly with the chemical processes within the cells of the liver and bile ducts that are responsible for the formation and secretion of bile to the intestine. As a result, the constituents of bile, including bilirubin, are retained in the body. The best example of a drug that causes this latter type of cholestasis and jaundice is estrogen. The primary treatment for jaundice caused by drugs is discontinuation of the drug. Almost always the bilirubin levels will return to normal within a few weeks, though in a few cases it may take several months.

Genetic disorders

There are several rare genetic disorders present from birth that give rise to jaundice. Crigler-Najjar syndrome is caused by a defect in the conjugation of bilirubin in the liver due to a reduction or absence of the enzyme responsible for conjugating the glucuronic acid to bilirubin. Dubin-Johnson and Rotor's syndromes are caused by abnormal secretion of bilirubin into bile.

The only common genetic disorder that may cause jaundice is Gilbert's syndrome which affects approximately 7% of the population. Gilbert's syndrome is caused by a mild reduction in the activity of the enzyme responsible for conjugating the glucuronic acid to bilirubin. The increase in bilirubin in the blood usually is mild and infrequently reaches levels that cause jaundice. Gilbert's syndrome is a benign condition that does not cause health problems.

Developmental abnormalities of bile ducts

There are rare instances in which the bile ducts do not develop normally and the flow of bile is interrupted. Jaundice frequently occurs. These diseases usually are present from birth though some of them may first be recognized in childhood or even adulthood. Cysts of the bile duct (choledochal cysts) are an example of such a developmental abnormality. Another example is Caroli's disease.

Jaundice of pregnancy

Most of the diseases discussed previously can affect women during pregnancy, but there are some additional causes of jaundice that are unique to pregnancy.

Cholestasis of pregnancy. Cholestasis of pregnancy is an uncommon condition that occurs in pregnant women during the third trimester. The cholestasis is often accompanied by itching but infrequently causes jaundice. The itching can be severe, but there is treatment (ursodeoxycholic acid or ursodiol). Pregnant women with cholestasis usually do well although they may be at greater risk for developing gallstones. More importantly, there appears to be an increased risk to the fetus for developmental abnormalities. Cholestasis of pregnancy is more common in certain groups, particularly in Scandinavia and Chile, and tends to occur with each additional pregnancy. There also is an association between cholestasis of pregnancy and cholestasis caused by oral estrogens, and it has been hypothesized that it is the increased estrogens during pregnancy that are responsible for the cholestasis of pregnancy.

Pre-eclampsia. Pre-eclampsia, previously called toxemia of pregnancy, is a disease that occurs during the second half of pregnancy and involves several systems within the body, including the liver. It may result in high blood pressure, fluid retention, and damage to the kidneys as well as anemia and reduced numbers of platelets due to destruction of red blood cells and platelets. It often causes problems for the fetus. Although the bilirubin level in the blood is elevated in pre-eclampsia, it usually is mildly elevated, and jaundice is uncommon. Treatment of pre-eclampsia usually involves delivery of the fetus as soon as possible if the fetus is mature.

Acute fatty liver of pregnancy. Acute fatty liver of pregnancy (AFLP) is a very serious complication of pregnancy of unclear cause that often is associated with pre-eclampsia. It occurs late in pregnancy and results in failure of the liver. It can almost always be reversed by immediate delivery of the fetus. There is an increased risk of infant death. Jaundice is common, but not always present in AFLP. Treatment usually involves delivery of the fetus as soon as possible.