What are the bilirubin levels in Gilbert's syndrome (a benign condition characterized by elevated unconjugated bilirubin)?

From the Guidelines

Gilbert syndrome typically presents as mild, intermittent unconjugated hyperbilirubinemia, with total bilirubin levels usually between 1-3 mg/dL (17-51 μmol/L), though they can occasionally rise to 5-6 mg/dL during periods of stress, fasting, or illness. The key laboratory finding is an elevated unconjugated (indirect) bilirubin with normal conjugated (direct) bilirubin levels, as noted in the study by 1. Liver function tests, including ALT, AST, and alkaline phosphatase, remain normal, which helps distinguish Gilbert syndrome from other liver disorders. Complete blood count is also typically normal, with no evidence of hemolysis. This benign genetic condition results from reduced activity of the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is responsible for conjugating bilirubin in the liver. The reduced enzyme activity (about 30% of normal) leads to decreased bilirubin processing and subsequent mild elevation in the bloodstream. Some key points to consider in the diagnosis of Gilbert syndrome include:

• Total bilirubin levels are usually mildly elevated, but rarely greater than 4-5 mg/dL, as mentioned in the study by 1.
• The proportion of conjugated bilirubin should be less than 20%-30% of the total bilirubin, as recommended by 1.
• Genetic testing for DNA mutations of uridine 5'-diphospho-glucuronyl-transferase may be considered for definitive confirmation, especially when total bilirubin elevations occur in combination with elevated ALP and aminotransferases, as suggested by 1. Gilbert syndrome requires no treatment and has an excellent prognosis with no progression to liver disease, though patients should be aware that fasting, illness, or physical exertion may temporarily increase bilirubin levels and cause mild jaundice.

From the Research

Presentation of Gilbert Syndrome

Gilbert syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation 2. The syndrome presents with:

• Mildly elevated total bilirubin with normal serum activities of liver transaminases, biliary damage markers, and red blood cell counts 3
• Unconjugated hyperbilirubinemia, with total plasma bilirubin levels that can be as high as 80 mumol/l 4
• Bilirubin levels that can rise under certain physiologic or pathologic events, but typically do not exceed 3 mg/dl 2
• In some rare cases, bilirubin levels can be higher than 6 mg/dl without any trigger or coexisting condition 2

Bilirubin Results

The bilirubin results in Gilbert syndrome are characterized by:

• Mildly elevated unconjugated bilirubin, which is strongly associated with reduced prevalence of chronic diseases, particularly cardiovascular diseases and type 2 diabetes mellitus 3
• Elevated unconjugated bilirubin (UCB) is negatively associated with multiple thrombotic risk factors, including platelet activity, hemostatic function, and inflammation 5
• Reduced platelet activation-dependent degranulation and platelet aggregation, which may contribute to protection from platelet hyperactivation-induced thrombosis and cardiovascular mortality 5