Hyperbilirubin in Adults and Babies

High bilirubin levels, or hyperbilirubinemia, means you have an excessive accumulation of bilirubin.

Bilirubin is a brownish-yellow substance that forms as red blood cells break down at the end of their normal life cycle. It is processed by the liver and gallbladder and excreted in stool and urine.

A build-up of excess bilirubin causes jaundice—a condition that causes the skin, mucous membranes, and white part of the eyes to take on a yellow hue.

High bilirubin is common in newborns because their liver is still learning how to efficiently clear bilirubin. In adults, high bilirubin may indicate an underlying health condition, such as gallstones or liver problems.

This article discusses high bilirubin levels. It explains the symptoms and causes of hyperbilirubinemia and how it is diagnosed and treated.

Symptoms of High Bilirubin

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 or liver disease. These include:

• Fever
• Extreme fatigue
• Loss of appetite
• Abdominal pain
• Constipation
• Bloating
• Vomiting

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.

What Causes High Bilirubin Levels?

Many conditions can lead to high bilirubin levels. There are two different types of hyperbilirubinemia comes in two main forms:

• Conjugated hyperbilirubinemia: Bilirubin that has been altered by the liver and is more readily passed in urine and bile
• Unconjugated hyperbilirubinemia: Bilirubin that is formed by the breakdown of red blood cells and can't be excreted in urine

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.

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.

What Medications Cause High Bilirubin?

Some drugs can impair liver function and cause high bilirubin levels. This can be due to underlying liver problems or the result of prolonged use or overuse.

These include:

• Certain antibiotics (like amoxicillin and ciprofloxacin)
• Anticonvulsives (like valproic acid)
• Antifungals (like fluconazole)
• Oral contraceptives
• Statin drugs
• Over-the-counter Tylenol (acetaminophen)

Certain herbs and herbal remedies are known to be highly toxic to the liver. These include Chinese ginseng, comfrey, Jin Bu Huan, kava, kombucha tea, and sassafras.

What Causes 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 baby's body is just learning how to regulate itself.

Prior to birth, the placenta—the organ shared by the mother and baby—works to remove bilirubin from the baby’s body. Once born, the baby’s liver takes over the job of clearing excess bilirubin. It can take some time for the liver to become efficient at it. 

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, resulting in hemolytic disease of the fetus and newborn
• 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:

• Total bilirubin: 0.3 to 1 milligrams per deciliter (mg/dL)
• Direct (conjugated) bilirubin: 0.1 to 0.3 mg/dL

In newborns, an indirect (unconjugated) bilirubin level below 8.7 mg/dL within the first 48 hours of birth is considered normal.

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.

Differential Diagnoses

If your bilirubin levels are high, your healthcare provider will need to identify the underlying cause. It is important to remember that hyperbilirubinemia is not a disease, but rather a characteristic of a disease.

To this end, your healthcare provider will classify the cause as follows:

• Pre-hepatic: The underlying process is due to a problem occurring before the liver processes bilirubin, as the result of the rapid breakdown of red blood cells.
• Hepatic: The problem involves the liver.
• Post-hepatic: The problem is the result of something occurring after the liver processes bilirubin, as the result of bile duct obstruction.

Pre-Hepatic Causes

Pre-hepatic causes are differentiated by the lack of bilirubin in the urine since unconjugated bilirubin cannot be excreted in the urine.

In addition to a panel of red blood cell tests, your healthcare provider may request a bone marrow biopsy if cancer or other serious diseases are suspected.

Hepatic Causes

Hepatic causes are characterized by elevated liver enzymes and evidence of bilirubin in the urine. A full liver function panel and imaging tests might help with identifying the problem.

A liver biopsy may be recommended if there is a possibility of liver cancer. Genetic testing may be used to distinguish between the different types of viral hepatitis or to confirm genetic disorders like hemochromatosis or Gilbert's syndrome.

Post-Hepatic Causes

Post-hepatic causes are characterized by normal unconjugated bilirubin levels and a normal spleen. A computed tomography (CT) scan, bile tract MRI, or endoscopic ultrasonography may be done if there is concern about possible gallstones. An ultrasound and stool tests may be done if there is concern about abnormalities of the pancreas.

Hyperbilirubinemia Treatment

In adults, treatment for high bilirubin levels depends on the underlying cause. Treatment can include approaches such as stopping the use of a toxic drug, surgery, or long-term therapy.

These are a few treatment approaches:

• 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.

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.

If you are experiencing any symptoms of liver impairment, speak with your healthcare provider before taking any medications.

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

Summary

High bilirubin levels are common in newborns but can signal an underlying health problem in adults and children. 

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.