A high bilirubin level, known as hyperbilirubinemia, is a common finding in blood tests. Bilirubin is a yellowish waste product produced when old red blood cells break down. The liver processes this substance so it can be removed from the body. An elevated level suggests a disruption in this normal clearance process. While cancer is a possible cause, the elevation is far more frequently due to less serious and manageable conditions.
Understanding Bilirubin and Its Measurement
Bilirubin originates from the breakdown of hemoglobin in red blood cells. When red blood cells break down, they release “unconjugated” (indirect) bilirubin, which is not water-soluble and travels through the bloodstream. Liver cells take up this unconjugated bilirubin and chemically change it, or “conjugate” it, to become water-soluble. This conjugated (direct) bilirubin is then excreted from the liver as a component of bile into the small intestine.
Measuring bilirubin involves testing the total amount in the blood, which is the sum of both unconjugated and conjugated types. For adults, the normal range for total bilirubin is generally between 0.1 and 1.2 milligrams per deciliter (mg/dL). The ratio of unconjugated to conjugated bilirubin is an important clue for doctors. This ratio helps localize the cause of the problem to before the liver (pre-hepatic), within the liver (hepatic), or after the liver in the bile ducts (post-hepatic).
Common Causes of Elevated Bilirubin
The most common reasons for high bilirubin are not related to malignancy and often involve rapid red blood cell breakdown or temporary liver strain. A pre-hepatic cause, where unconjugated bilirubin is high, is typically due to hemolysis (rapid destruction of red blood cells). Blood disorders, such as hemolytic anemia, cause the body to produce bilirubin faster than the liver can process it.
A common, benign genetic condition known as Gilbert’s syndrome affects 5% to 10% of the population and causes mild, intermittent elevations in unconjugated bilirubin. This occurs because an enzyme deficiency reduces the liver’s ability to conjugate bilirubin. Other hepatic causes, where the liver is struggling, include acute inflammation from viral hepatitis (A, B, or C) or mononucleosis. Medication side effects, particularly from certain antibiotics or pain relievers, can also temporarily impair bilirubin clearance.
Post-hepatic causes result in a buildup of conjugated bilirubin due to a blockage in the bile drainage system. The most frequent non-cancerous obstruction is gallstones, which can migrate and block the common bile duct. Pancreatitis (inflammation of the pancreas) can also cause swelling that compresses the bile duct, leading to bilirubin backup.
High Bilirubin and Malignancy
While many non-cancerous causes exist, a high bilirubin level can indicate a serious underlying malignancy. Cancer causes hyperbilirubinemia primarily by obstructing the bile ducts. When a tumor physically blocks the pathway conjugated bilirubin uses to leave the liver and enter the intestine, the bilirubin backs up into the bloodstream.
Cancers that frequently cause this obstructive pattern include pancreatic cancer (especially tumors near the head of the pancreas) and cholangiocarcinoma (cancer of the bile ducts). Liver cancer (hepatocellular carcinoma) and metastatic cancer spread to the liver can also impair liver function enough to cause high bilirubin levels. The resulting obstruction often leads to symptoms like jaundice, dark urine, and pale, clay-colored stools.
In cases of malignancy, bilirubin elevation is often accompanied by specific findings that distinguish it from benign causes. Unexplained weight loss is a common symptom associated with several digestive system cancers, including pancreatic cancer. Blood tests often show a disproportionate rise in other liver enzymes, such as alkaline phosphatase, suggesting a mechanical blockage rather than primary liver cell injury.
Next Steps After a High Bilirubin Result
When a high bilirubin result is found, a doctor begins a systematic diagnostic process to pinpoint the cause. The first step involves determining whether the elevation is predominantly unconjugated or conjugated, which significantly narrows the possibilities. A physical examination and a review of the patient’s medication history and symptoms provide additional context.
Further blood tests, including liver function tests and blood counts, help assess liver health and check for red blood cell breakdown. Imaging studies are often the next step to look for a blocked bile duct or a mass. These studies may include:
- Abdominal ultrasound, typically used first to look for signs of obstruction.
- CT scan or Magnetic Resonance Cholangiopancreatography (MRCP), if an obstruction is suspected but not clearly seen.
- Endoscopic Retrograde Cholangiopancreatography (ERCP), which may be necessary to visualize and potentially relieve a blockage.