Side Effect: Increased Bilirubin (hyperbilirubinemia)

• Bilirubin is a yellow pigment produced by the breakdown and processing of red blood cells in the spleen, liver, and gall bladder.
• Increased bilirubin can result from problems outside of the liver (extra-hepatic), problems with the liver (intra-hepatic), or problems with bile ducts (post-hepatic).
• Extra-hepatic causes are due to increased breakdown of red blood cells, a process known as hemolysis
• A hepatic cause is often due to a liver disease that prevents the liver from processing bilirubin effectively.
  • A post-hepatic cause involves conditions that obstruct the bile ducts which prevent the excretion of bilirubin from the liver and causes it to build up in the bloodstream.

• High levels of bilirubin can lead to a condition known as jaundice, which is characterized by a yellowing of the skin and whites of the eyes, dark colored urine, light colored stool, and itching of the skin.
• Jaundiced is not usually noticed until the bilirubin in the blood increases to 2.5mg/dL, or higher.
• The severity of jaundice can vary depending on the underlying cause and the level of bilirubin elevation.

Common causes of increased bilirubin include:

• viral infections (hepatitis A, B, and C)
• chronic alcohol use
• autoimmune disorders
• medications
• gallstones
• pancreatitis

Patients with cancer can develop increased bilirubin levels due to various reasons:

• Primary liver, gallbladder, or bile duct cancer
• Liver metastases
• Obstruction of bile ducts by the tumor
• Chemotherapy-induced liver damage
• Radiation damage to liver

Prevention of elevated bilirubin levels in patients with cancer may involve:

• treating the malignancy
• adjusting medication dosage when indicated
  • Some patients with a reduced amount of a certain enzyme in their body have trouble breaking down bilirubin and certain medications in these people cause the bilirubin to go up higher than in those with a normal amount of the enzyme
  • The enzyme deficiency is known as Gilbert’s syndrome (pronounced Jeel-bear’s syndrome), and the enzyme of interest is called “UGT1A1”
• avoiding hepatotoxic drugs
• monitoring liver function during treatment.

• Treatment of an increased bilirubin in patients with cancer depends on the underlying cause such as treating the underlying malignancy or infection.
• Some medications may need to be adjusted or stopped completely.
• In some cases where there is an obstruction of the bile ducts, interventions such as stenting or surgery may be necessary to relieve the obstruction and reduce bilirubin levels.
• In very advanced cases, such as end stage liver disease, the only treatment may be supportive care.