Bilirubin

A bilirubin test may be used as part of a comprehensive metabolic panel (CMP) during a routine health exam to evaluate the health of your liver. It may also be used either alone or as part of a liver panel to detect an increased level in the blood to help determine the cause of jaundice and/or help diagnose conditions such as liver disease, hemolytic anemia, and blockage of the bile ducts.

In adults and older children, bilirubin is measured to:

• Help diagnose and/or monitor diseases of the liver and bile duct (e.g., cirrhosis, hepatitis, or gallstones)
• Evaluate people with sickle cell disease or other causes of hemolytic anemia; these people may have episodes called crises when large numbers of red blood cells (RBCs) are destroyed and bilirubin levels increase.

In newborns with jaundice, bilirubin is used to distinguish the causes of jaundice.

• In both physiologic jaundice of the newborn and hemolytic disease of the newborn, only unconjugated (indirect) bilirubin is increased.
• In much less common cases, damage to the newborn’s liver from neonatal hepatitis and biliary atresia will increase conjugated (direct) bilirubin and unconjugated (indirect) bilirubin, often providing the first evidence that one of these less common conditions is present.

It is important that an elevated level of bilirubin in a newborn be identified and quickly treated because excessive unconjugated bilirubin damages developing brain cells. The consequences of this damage include mental retardation, learning and developmental disabilities, hearing loss, eye movement problems, and death.

A healthcare practitioner may order a bilirubin test along with other laboratory tests (e.g., CMP, liver panel) when you have a routine health exam or when you have signs and symptoms of liver damage or disease, such as:

• Jaundice
• Dark, amber-colored urine
• Nausea/vomiting
• Abdominal pain and/or swelling
• Fatigue and general malaise that often accompany chronic liver disease

A bilirubin level may also be ordered when you have:

• A history of drinking excessive amounts of alcohol
• Signs and symptoms of drug toxicity
• Been exposed to a virus that causes hepatitis

Measuring and monitoring bilirubin in newborns with jaundice is considered standard medical care.

Tests for bilirubin may also be ordered when you have or are suspected of having hemolytic anemia. In this case, it is often ordered along with other tests used to evaluate the breakdown of red blood cells, such as complete blood count, reticulocyte count, haptoglobin, direct antiglobulin test (DAT) and lactate dehydrogenase (LD, LDH).

Adults and children

Total bilirubin that is mainly unconjugated (indirect) bilirubin may be increased when:

• There is an unusual number of red blood cells (RBCs) being broken down and destroyed (e.g., hemolytic or pernicious anemia, blood transfusion reaction)
• The liver is unable to process bilirubin (i.e., with liver disease such as cirrhosis or inherited problems)
• You have a relatively common inherited condition called Gilbert syndrome, due to low levels of the enzyme that produces conjugated bilirubin

If conjugated (direct) bilirubin is elevated more than unconjugated (indirect) bilirubin, there typically is a problem associated with decreased elimination of bilirubin by the liver cells. Some conditions that may cause this include:

• Viral hepatitis (hepatitis A, hepatitis B, hepatitis C)
• Drug reactions
• Alcoholic liver disease

Conjugated (direct) bilirubin is also elevated more than unconjugated (indirect) bilirubin when the liver is able to process bilirubin but there is blockage of the bile ducts. This may occur, for example, with:

• Gallstones present in the bile ducts
• Tumors
• Scarring of the bile ducts

Rare inherited disorders that cause abnormal bilirubin metabolism such as Rotor, Dubin-Johnson, and Crigler-Najjar syndromes, may also cause increased levels of bilirubin.

Low levels of bilirubin are generally not a concern and are not monitored.

Newborns

Increased total and unconjugated bilirubin levels are relatively common in newborns in the first few days after birth. This finding is called “physiologic jaundice of the newborn” and occurs because the newborn’s liver is not mature enough to process bilirubin yet. Usually, physiologic jaundice of the newborn is temporary and resolves within a few days to two weeks.

However, if the bilirubin level is critically high or increases rapidly, the healthcare practitioner will diagnose the cause so appropriate treatment can be started as soon as possible.

Increased bilirubin levels may result from the accelerated breakdown of red blood cells due to:

• Blood type incompatibility between the mother and her newborn, causing hemolytic disease of the newborn (HDN)
• Certain congenital infections
• Lack of oxygen (hypoxia)
• Diseases that can affect the liver

In most of these conditions, only unconjugated (indirect) bilirubin is increased.

A rare (about 1 in 12,000 births) but life-threatening congenital condition called biliary atresia can cause increased total and conjugated bilirubin levels in newborns. This condition must be quickly diagnosed and treated, usually with surgery, to prevent serious liver damage that may require liver transplantation within the first few years of life. Some children may require liver transplantation despite early surgical treatment.

Yes. Bilirubin testing is included as part of the common dipstick tests used in a routine urinalysis. Bilirubin is not normally present in the urine. However, conjugated bilirubin is water-soluble and may be eliminated from the body through the urine if it cannot pass into the bile. If bilirubin is detected in the urine, it usually means your liver or bile ducts are blocked or you have hepatitis or some other form of liver damage. In these cases, bilirubin may be detectable in the urine early in the disease.

Yes, several inherited chronic conditions can increase bilirubin levels in the blood. These include:

• Gilbert syndrome
• Dubin-Johnson syndrome
• Rotor syndrome
• Crigler-Najjar syndrome

The first three are usually mild, chronic conditions that can be aggravated under certain conditions but in general cause no significant health problems. For example, Gilbert syndrome is very common; about 1 in every 6 people has this genetic abnormality, but usually people with Gilbert syndrome do not have elevated bilirubin. Crigler-Najjar syndrome is the most serious inherited condition listed; this disorder is relatively rare, and some people with it may die.

Treatment depends on the cause of the jaundice. In newborns, phototherapy (special light therapy), blood exchange transfusion, and/or certain drugs may be used to reduce the bilirubin level. In Gilbert, Rotor, and Dubin-Johnson syndromes, no treatment is usually necessary. Crigler-Najjar syndrome may respond to certain enzyme drug therapy or may require a liver transplant. Jaundice caused by an obstruction is often resolved by surgery. Jaundice due to cirrhosis is a result of long-term liver damage and does not respond well to any type of therapy other than liver transplantation.

Though unconjugated bilirubin may be toxic to brain development in newborns (up to 2-4 weeks of age), it does not pose the same threat to older children and adults. In older children and adults, the “blood-brain barrier” is more developed and prevents bilirubin from moving from the blood into the brain and affecting brain cells. Nevertheless, elevated bilirubin strongly suggests that a medical condition is present that must be evaluated and treated.

Bilirubin concentrations tend to be slightly higher in males than females. African Americans routinely show lower bilirubin concentrations than non-African Americans. Strenuous exercise may increase bilirubin levels.

Drugs that can decrease total bilirubin include barbiturates, caffeine, penicillin, and high doses of salicylates. The drug atazanavir increases unconjugated (indirect) bilirubin.