From the Guidelines
Elevated bilirubin with normal liver function tests is most commonly due to Gilbert's syndrome, a benign genetic condition affecting about 5-10% of the population. This condition results from a reduced activity of the enzyme UDP-glucuronosyltransferase, which is responsible for conjugating bilirubin for excretion 1. No treatment is typically needed for Gilbert's syndrome as it doesn't cause liver damage or health problems. Patients may notice mild jaundice (yellowing of the skin or eyes) during periods of stress, fasting, illness, or physical exertion. Other potential causes of isolated hyperbilirubinemia include hemolytic disorders (where red blood cells break down prematurely), certain medications, or rare conditions like Crigler-Najjar syndrome.
Key Considerations
- If a patient has persistent elevated bilirubin with normal liver enzymes (ALT, AST, alkaline phosphatase), a healthcare provider should check whether the elevation is primarily in unconjugated (indirect) bilirubin, which supports Gilbert's syndrome, or conjugated (direct) bilirubin, which may indicate other issues like biliary obstruction 1.
- Gilbert's syndrome can be presumed by calculating the amount of conjugated bilirubin, which is normally less than 30% of the total bilirubin, in the absence of haemolysis 1.
- While generally harmless, patients with Gilbert's syndrome should inform healthcare providers about their condition to avoid unnecessary testing when bilirubin levels rise during illness.
Diagnosis and Management
- Diagnosis of Gilbert's syndrome should be determined by calculating the proportion of conjugated bilirubin, which should be less than 20%-30% of the total bilirubin 1.
- Genetic testing for DNA mutations of uridine 5'-diphospho-glucuronyl-transferase should be considered for definitive confirmation, especially when total bilirubin elevations occur in combination with elevated ALP and aminotransferases 1.
- Patients with Gilbert's syndrome should be fully reassured, as it is a benign condition that does not cause liver damage or health problems 1.
From the Research
Elevated Bilirubin with Normal Liver Function Tests
- Elevated plasma bilirubin levels can be secondary to alterations in any stage of its metabolism, including excess bilirubin production, impaired liver uptake, impaired conjugation, and bile clearance defect 2.
- A liver lesion 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.
- Serum bilirubin is determined by various analytical methods, including diazo transfer reaction, high-performance liquid chromatography (HPLC), oxidative, enzymatic, and chemical methods, direct spectrophotometry, and transcutaneous methods 2.
- Although bilirubin is a well-established marker of liver function, 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.
- Ultrasound and liver function tests, including serum bilirubin and serum alkaline phosphatase, are used as screening tests for the diagnosis of common bile duct stones, but their diagnostic accuracy can vary 3.
- The sensitivity and specificity of ultrasound for diagnosing common bile duct stones can range from 0.32 to 1.00 and 0.77 to 0.97, respectively, while the sensitivity and specificity of bilirubin can range from 0.84 to 0.95 and 0.91 to 0.94, respectively 3.
- It is essential to interpret the results of these tests with caution, considering the poor methodological quality of the studies and the possibility of false-positive or false-negative results 3.