Causes of High Bilirubin Levels (AKA Hyperbilirubinemia)

Hyperbilirubinemia occurs when bilirubin builds up in the bloodstream, often signaling that the liver, bile ducts, or gallbladder may not be functioning as they should. This condition should be considered a sign of underlying issues, such as liver inflammation or blockages in bile flow.

While some cases cause visible symptoms like jaundice, others may go unnoticed without routine blood tests. Identifying elevated bilirubin early helps pinpoint the root cause and ensures timely care to prevent complications.

Doctors measure bilirubin levels through a blood test, which checks for two forms of bilirubin: indirect and direct. Indirect bilirubin is created when red blood cells break down and is carried in the blood attached to a protein called albumin. The liver processes this into direct bilirubin, a form the body can excrete through bile.

Blood tests can measure indirect, direct, or total bilirubin levels (a combination of both types). Normal total bilirubin levels are typically around 1.2 milligrams per deciliter (mg/dL) for adults and 1 mg/dL for children.

While low bilirubin levels are usually harmless, elevated levels can signal issues in the liver, bile ducts, or gallbladder. These tests help healthcare providers decide if additional testing or treatment is necessary.

Liver-related causes of high bilirubin include the following:

• Liver infections, like hepatitis: Viral hepatitis comes in several forms. Hepatitis A and E typically cause short-term infections, while hepatitis B, C, and D can sometimes lead to chronic conditions. These infections inflame and damage liver cells, hindering the liver’s ability to process bilirubin.
• Liver cirrhosis: Cirrhosis replaces healthy liver tissue with scar tissue, often resulting from hepatitis B or C, or long-term alcohol use. This scarring disrupts liver function, causing bilirubin to accumulate in the blood.
• Alcoholic liver disease: This condition progresses through stages, including fatty liver disease, alcohol-induced hepatitis, and cirrhosis. At any stage, the liver’s ability to process bilirubin can be impaired, leading to elevated levels.

Bile duct obstruction or biliary obstruction occurs when something blocks the bile ducts, preventing bile from flowing into the small intestine. One common reason for this may be gallstones, which affect between 10 to 15 percent of the U.S. population or almost 25 million people. Gallstones themselves can block the bile duct and cause inflammation, making it even more difficult for bile to pass, leading to buildup. Other forms of gallbladder disease that can cause an increase in bilirubin include:

• Cholecystitis, an inflammation of the gallbladder
• Acalculous gallbladder disease is when someone has symptoms of gallstones with no stones present that may be caused by inflammation or a lack of blood flow.
• Sclerosing cholangitis, a liver disease that damages the bile ducts

Liver and bile duct cancer can also cause tumor growth and inflammation that can press on the bile ducts and prevent bilirubin from being processed properly.

Certain genetic and blood disorders can lead to elevated bilirubin levels, impacting how the body processes or breaks down red blood cells. One common genetic condition, Gilbert’s syndrome, hinders the liver’s ability to process bilirubin efficiently. While typically benign, it can cause periodic episodes of jaundice triggered by factors like dehydration, illness, fasting, or menstruation. Though it rarely leads to serious liver disease, Gilbert’s syndrome may increase sensitivity to certain medications.

Another rare genetic condition, Dubin-Johnson syndrome, results from changes in the gene that helps transport bilirubin out of liver cells. While this condition is benign and often asymptomatic, it can be difficult to diagnose due to its rarity and subtle presentation.

Blood disorders such as hemolytic anemia and sickle cell anemia can also raise bilirubin levels by accelerating the breakdown of red blood cells. This rapid turnover releases more bilirubin than the liver can process, leading to noticeable symptoms like jaundice in some cases.

Several conditions beyond liver or bile duct disorders can lead to elevated bilirubin. Autoimmune hepatitis, a chronic disease where the immune system attacks the liver, causes inflammation and damage that can disrupt bilirubin processing. Without treatment, this condition may progress to cirrhosis or liver failure.

Certain medications can also impair liver function, raising bilirubin levels. Prescription antibiotics like erythromycin, tetracyclines, and amoxicillin, as well as over-the-counter pain relievers such as ibuprofen, naproxen, and acetaminophen, are common culprits. Reviewing medication use with a healthcare provider can help identify and manage these risks.

Newborn jaundice occurs when a baby’s blood contains excess bilirubin, a condition common in infants whose livers are not yet mature enough to process it effectively. It is more likely to affect babies born between 38 weeks gestation and some breast-fed infants. For most newborns born after 35 weeks, jaundice resolves on its own without treatment. However, doctors often monitor bilirubin levels to ensure the condition normalizes and to rule out underlying issues.

Physical signs of high bilirubin include:

• Jaundice
• Yellowing of the skin and eyes
• Pale stools from a lack of bilirubin in the intestines
• Dark urine from an increase in bilirubin excretion through the kidneys

Depending on the cause, people with high bilirubin levels may also experience general fatigue, itchy skin, or nausea and vomiting.

Persistent jaundice, unexplained abdominal pain, or extreme fatigue can be signs of a serious health condition and may require medical evaluation. When talking to your doctor, preparing a list of symptoms, recent medications, and health history can be beneficial to help your healthcare provider diagnose potential causes or determine what additional testing to suggest.

Understanding the causes of elevated bilirubin can help you learn to pay attention to your body and know when to seek timely medical advice. While some causes of hyperbilirubinemia are benign or manageable, early diagnosis and treatment can help prevent complications.