High Bilirubin (Hyperbilirubinemia) and How to Treat It

A high bilirubin level, or hyperbilirubinemia, occurs when bilirubin has accumulated in your body in excessive amounts. Bilirubin forms when red blood cells break down at the end of their life cycle, in a normal process called hemolysis. It's usually processed in the liver and gallbladder, and leaves the body in urine and stool.

Symptoms of bilirubin include jaundice—a condition that causes skin, mucous membranes, and white parts of the eyes to take on a yellow hue. That's because bilirubin is a brownish-yellow color. It's common in healthy newborns (about 80% experience jaundice) and typically resolves, but it can be a sign of a health concern in adults.

Symptoms

The excessive buildup of bilirubin can cause jaundice. Signs of jaundice include:

• Yellowing of the skin and whites of the eyes
• Darkening of urine, sometimes to a brownish tone
• Pale, clay-colored stools if the liver is the source of the issue

In addition to jaundice, you may have other symptoms related to the underlying cause of hyperbilirubinemia, such as anemia, liver disease, or pancreatic cancer. These include:

• Fever
• Extreme fatigue
• Unexplained weight loss
• Abdominal or back pain
• Indigestion, nausea, and vomiting
• Constipation or diarrhea

Having high bilirubin levels can be dangerous and can lead to complications, especially in newborns. This can result in a condition known as kernicterus, in which seizures, irreversible brain damage, and death can occur.

Causes

Certain health conditions can lead to high bilirubin levels. Some people can have both, but there are two main forms or types of hyperbilirubinemia:

• Conjugated hyperbilirubinemia: Bilirubin that has been altered by the liver and is more readily passed in urine and bile. It's sometimes called direct.
• Unconjugated hyperbilirubinemia: Bilirubin that is formed by the breakdown of red blood cells and can't be excreted in urine. It binds to albumin, a protein in the blood. It's sometimes called indirect.

Causes of unconjugated high bilirubin levels include:

• Hemolytic anemia: When red blood cells are rapidly destroyed, often as a result of cancer (such as leukemia or lymphoma), autoimmune diseases (like lupus), or medications (such as acetaminophen, ibuprofen, interferon, and penicillin), it can cause high bilirubin levels.
• A lack of digestive bacteria in newborns: This can cause jaundice in newborns due to impaired breakdown of bilirubin.
• Gilbert syndrome: This is a genetic disorder that causes the liver to process bilirubin slowly.
• Liver disease: This can occur if the liver is not functioning as it should due to hepatitis, alcohol-related liver disease, or another diagnosis.

Causes of conjugated high bilirubin levels include:

• Liver disease: This can occur when blood flow through the liver is impaired.
• Bile duct obstruction: Bilirubin cannot be delivered to the small intestine in bile, often as a result of cirrhosis, gallstones, pancreatitis, or tumors.
• Rotor syndrome: A rare hereditary disorder that limits bilirubin uptake in the body.

Medications and Bilirubin

Some drugs can impair liver function and cause high bilirubin levels. Certain protease inhibitors used to treat human immunodeficiency virus (HIV) and targeted therapies like Nexavar (sorafenib), used to treat liver and kidney cancers, can do so. Others include:

• Cyclosporine, used as an anti-rejection drug after organ transplant and for psoriasis
• Rifampin, a drug used to treat tuberculosis
• Certain antibiotics (like amoxicillin and ciprofloxacin)
• Seizure medications (like valproic acid)
• Antifungals (like fluconazole)
• Oral contraceptives
• Statin drugs
• Over-the-counter Tylenol (acetaminophen)

Certain herbs and herbal remedies also can be toxic to the liver. Talk with your healthcare provider if you are using medications or supplements that may affect liver health.

High Bilirubin in Newborns

In a newborn, a high bilirubin level is normal and usually resolves during the first month of life. This happens because the placenta no longer removes bilirubin and the newborn's body takes over but needs time to become efficient. 

Premature babies, babies who are small for gestational age, and twins are more likely to have high bilirubin levels. It’s also more common in breastfed babies. Severe jaundice in babies can also be a sign of an underlying health condition, such as: 

• Bleeding under the scalp from a difficult delivery
• Cystic fibrosis
• Enzyme deficiencies
• A genetic or inherited disorder
• Hepatitis
• Higher levels of red blood cells
• An infection, such as rubella, syphilis, or sepsis
• Low oxygen levels
• Mismatched blood type between the pregnant person and fetus, such as Rh incompatibility or ABO incompatibility
• Sickle cell anemia
  

Diagnosis

Hyperbilirubinemia can be diagnosed with a blood test. The test measures the level of total bilirubin (both conjugated and unconjugated) and direct (conjugated) bilirubin levels in the blood.

The indirect (unconjugated) bilirubin levels can be inferred from the total and direct bilirubin values. Although labs may use different reference ranges, there are generally accepted normal levels.

Bilirubin is often included as part of a panel of tests that evaluate liver function and enzymes, including:

• Alanine transaminase (ALT)
• Aspartate aminotransferase (AST)
• Alkaline phosphatase (ALP)
• Gamma-glutamyl transpeptidase (GGT) bilirubin

Normal Bilirubin Levels

Normal bilirubin level ranges in adults and children older than seven days old are as follows:

• Total bilirubin: 0.3–1.9 mg dL
• Conjugated bilirubin: 0.1–0.4 mg dL
• Unconjugated bilirubin: 0.2–0.7 mg dL

In newborns, a conjugated bilirubin level is normal at 0.3 mg/dL or less. A direct blood sample for bilirubin concentration should be 1.0 mg/dL or less. Low bilirubin levels are usually nothing to be concerned about.

Other Tests for High Bilirubin Levels

Additional tests may be ordered to pinpoint the underlying cause of the dysfunction, particularly in the presence of jaundice.

• Urinalysis: This test may be ordered to evaluate the amount of bilirubin excreted in the urine.
• Imaging tests: Ultrasound and computed tomography (CT) can help distinguish between biliary obstruction and liver disease, including cancer.
• Liver biopsy: This would be considered if there is a concern about possible liver cancer.

Bilirubin testing would typically be repeated to monitor your response to treatment or to track the progression or resolution of the disease. If your bilirubin levels are high, your healthcare provider will need to identify the underlying cause.

Treatment

In adults, treatment for high bilirubin levels depends on the underlying cause. Treatment can include different strategies:

• If high bilirubin levels are caused by drugs, a change of medication can resolve the effects.
• In cases of obstructive hyperbilirubinemia, surgery (usually laparoscopic) may be needed to remove gallstones or other sources of obstruction.
• Severe liver or pancreatic diseases would require the care of a qualified hepatologist, with treatment options ranging from drug therapies to organ transplants.
• While there are no home treatments that bring bilirubin levels down, you can avoid placing additional stress on the liver by cutting out alcohol, red meat, processed foods, and refined sugar.

Sometimes, hyperbilirubinemia may not require specific treatment. For example, symptoms of acute viral hepatitis typically go away on their own as the infection resolves. The same applies to Gilbert's syndrome, which is not considered harmful and does not require treatment.

Treatment for Hyperbilirubinemia in Newborns

Neonatal hyperbilirubinemia may not require treatment if the jaundice is mild. For moderate to severe cases, treatment may involve:

• Light therapy, which changes the structure of bilirubin molecules in newborns
• Intravenous immunoglobulin, which prevents the rapid breakdown of red blood cells
• A blood transfusion
• Hydration and improved feeding

Treatment for any underlying cause also is needed.

Summary

Bilirubin, a brownish-yellow substance that forms when red blood cells break down, is normally metabolized by the liver and gallbladder. Too much bilirubin causes jaundice—a yellowing of the skin and whites of the eyes. High bilirubin occurs in newborns because their body is not yet efficient at removing bilirubin. Treatments include light therapy, IV immunoglobulin, or a blood transfusion.

In older children and adults, high bilirubin can indicate a problem with the liver or gallbladder. It can also be caused by medication. Treatment focuses on addressing the underlying cause and may include stopping medications, surgery, and, in severe cases, an organ transplant.