From the Guidelines
Bilirubin elevation requires prompt evaluation to determine its cause and severity, with the most recent guidelines suggesting that the majority of measurable bilirubin should be conjugated, even in individuals with significant liver disease 1. For mild unconjugated hyperbilirubinemia (less than 3 mg/dL), observation and follow-up testing in 2-4 weeks is often appropriate. For moderate elevations (3-10 mg/dL), additional testing including liver function tests, complete blood count, and abdominal ultrasound should be performed. Severe elevations (greater than 10 mg/dL) warrant urgent evaluation and possible hospitalization. Treatment depends on the underlying cause: Gilbert's syndrome requires no treatment; hemolysis may require addressing the underlying condition; hepatitis may need antiviral medications; and biliary obstruction might require endoscopic or surgical intervention. Patients should avoid alcohol and hepatotoxic medications during evaluation. Hydration and a balanced diet can support liver function. Bilirubin elevation occurs when there is increased production (as in hemolysis), decreased conjugation in the liver, or impaired excretion of bilirubin. Unconjugated hyperbilirubinemia typically suggests pre-hepatic causes like hemolysis or Gilbert's syndrome, while conjugated hyperbilirubinemia points to hepatic or post-hepatic causes such as hepatitis, cirrhosis, or biliary obstruction, as supported by recent studies 1.
Some key points to consider in the evaluation of bilirubin elevation include:
- The distinction between unconjugated and conjugated hyperbilirubinemia, which can help guide the diagnosis and treatment plan 1
- The importance of a detailed history, targeted physical examination, and pertinent laboratory studies in differentiating between the various potential etiologies of jaundice 1
- The role of imaging methods, such as abdominal ultrasound, CT, MR cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic US, in evaluating the jaundiced patient, although there is a paucity of rigorous evidence directly comparing these methods 1.
Overall, the management of bilirubin elevation should be guided by the most recent and highest quality evidence, with a focus on determining the underlying cause and severity of the elevation, and providing prompt and effective treatment to improve patient outcomes.
From the Research
Causes of Bilirubin Elevation
- Bilirubin elevation can be caused by derangements in bilirubin metabolism, including excess bilirubin production, impaired liver uptake, impaired conjugation, and bile clearance defects 2
- Liver lesions of any cause can reduce hepatocyte cell number and impair the uptake of indirect bilirubin from plasma and diminish direct bilirubin transport and clearance through the bile ducts 2
- Certain medications, such as rifampin, can induce cholestatic liver injury and hyperbilirubinemia 3
Diagnosis of Bilirubin Elevation
- Evaluation of patients with jaundice starts with a careful history and physical examination, followed by directed imaging of the biliary tree and liver 4, 5
- Laboratory evaluation should include assays for bilirubin (total and fractionated), complete blood cell count, aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, alkaline phosphatase, albumin, prothrombin time, and international normalized ratio 5
- Measuring fractionated bilirubin allows for determination of whether the hyperbilirubinemia is conjugated or unconjugated 5
Treatment and Management
- Treatment of bilirubin elevation depends on the underlying cause, and may involve addressing the underlying liver or biliary disease 4, 5
- In cases of autoimmune hemolytic anemia, treatment may involve immunosuppressive therapy or other medications to reduce hemolysis 6
- Certain medications, such as 4-phenylbutyrate, may be used to alleviate liver injury and reduce serum bilirubin levels in cases of cholestatic liver injury 3