From the Guidelines
Elevated bilirubin in adults is most commonly caused by hepatitis, alcoholic liver disease, blockage of the common bile duct by a gallstone or tumor, and toxic reaction to a drug or medicinal herb, as supported by the most recent study 1.
Causes of Elevated Bilirubin
The causes of elevated bilirubin in adults can be categorized into several groups, including:
- Liver diseases such as hepatitis, cirrhosis, and alcoholic liver disease, which impair the liver's ability to process bilirubin
- Biliary obstruction from gallstones, tumors, or strictures, which can block bilirubin excretion
- Hemolytic disorders like sickle cell anemia or autoimmune hemolytic anemia, which increase bilirubin production by accelerating red blood cell breakdown
- Certain medications, including antibiotics, anti-seizure drugs, and anti-tuberculosis medications, which can cause drug-induced liver injury
- Genetic conditions such as Gilbert's syndrome, which cause mild, intermittent elevations due to reduced activity of the enzyme that processes bilirubin
- Sepsis and severe infections, which can impair liver function
Evaluation and Management
When evaluating elevated bilirubin, it's essential to distinguish between direct (conjugated) and indirect (unconjugated) bilirubin, as this helps narrow down potential causes 1. Management depends on treating the underlying condition, which may involve stopping hepatotoxic medications, addressing alcohol use, treating infections, or surgical intervention for obstructions. According to the American Gastroenterological Association, patients with significant elevations of their ALT or AST, with an abnormal albumin or prothrombin time, or with evidence of chronic liver disease and/or hepatic decompensation should typically have more expeditious evaluations 1.
Diagnostic Approach
The diagnostic approach to elevated bilirubin involves a combination of clinical findings, presentation, and laboratory values, including a hepatic profile, conjugated versus unconjugated bilirubinemia, complete blood count, and imaging studies such as abdominal ultrasound, CT, or MRCP 1. The choice of imaging study depends on the clinical scenario and the suspected cause of the elevated bilirubin. For example, MRCP is a safe option to explore the biliary tree and can detect biliary tract obstruction with an accuracy approaching that of ERCP 1.
From the Research
Causes of Elevated Bilirubin in Adults
- Elevated serum bilirubin levels can be caused by various factors, including increased bilirubin production, impaired liver uptake, impaired conjugation, and bile clearance defects 2
- Unconjugated hyperbilirubinemia can occur due to increased bilirubin production caused by red blood cell destruction, such as hemolytic disorders, and disorders of impaired bilirubin conjugation, such as Gilbert syndrome 3
- Conjugated hyperbilirubinemia can occur in disorders of hepatocellular damage, such as viral and alcoholic hepatitis, and cholestatic disorders, such as choledocholithiasis and neoplastic obstruction of the biliary tree 3
- Hemolysis is observed in more than 50% of patients with cirrhosis, and primary biliary cirrhosis can coexist with autoimmune hemolytic anemia or hereditary spherocytosis, leading to confusing serum bilirubin levels 4
Diagnostic Evaluation
- The evaluation of jaundice relies on the history and physical examination, followed by initial laboratory evaluation, including fractionated bilirubin, complete blood count, liver function tests, and imaging studies such as ultrasonography or computed tomography 3, 5, 6
- Measuring fractionated bilirubin allows for determination of whether the hyperbilirubinemia is conjugated or unconjugated, which can help guide further diagnostic evaluation and management 6
- Liver biopsy may be required to establish the diagnosis, prognosis, and management of the disease if the etiology of jaundice is unclear despite laboratory testing and imaging 6
Clinical Significance
- Elevated plasma bilirubin levels are a frequent clinical finding and can be secondary to alterations in any stage of bilirubin metabolism 2
- Jaundice is an indication of hyperbilirubinemia and can indicate serious underlying disease of the liver or biliary tract 6
- Bilirubin is a well-established marker of liver function, but it does not always identify a lesion in this organ, and alterations in bilirubin concentrations should be assessed in relation to patient anamnesis, the degree of the alteration, and the pattern of concurrent biochemical alterations 2