The inverse starving test is not a suitable provocation test for Gilbert's syndrome

BACKGROUND: INTRODUCTION: The aim of this study was to evaluate a simple diagnostic test for Gilbert's syndrome (GS), which avoids hospitalization and exposure to toxic test substrates. GS is the most frequent cause of isolated unconjugated hyperbilirubinemia. The nicotinic acid test and the starving test are established approaches to diagnose GS. However, these tests cause considerable side effects or require hospital admission. In single GS patients, we observed rapid serum bilirubin normalization after a standard European lunch (the "inverse starving test"). FINDINGS: At two consecutive days, 18 profoundly characterized GS patients (7 females, 11 males, median age 34.5 years, range 21–58 years) were investigated with the nicotinic acid test and the inverse starving test. Unconjugated serum bilirubin (UCB) levels were measured before and hourly up to four hours after lunch (median 645 kcal), and after the ingestion of 170 milligrams nicotinic acid, respectively. Patients who consulted their physicians with jaundice were significantly more likely to undergo invasive diagnostic procedures than patients with an incidental finding of elevated UCB, despite UCB levels were indifferent in both groups. Two hours after nicotinic acid ingestion, relative UCB exceeded 1.7 fold the fasting levels (median, range 0.9–2.4 fold, sensitivity 83%). In the inverse starving test, UCB remained almost unchanged three hours after lunch (median 1.0; range: 0.8–1.2 fold). Molecular analysis established the genotype of the TATAA box of the UGT1A1 gene; all patients carried an UGT1A1 promotor polymorphism. CONCLUSION: The inverse starving test is not an appropriate provocation test for patients with suspected GS. The 100% prevalence of the UGT1A1 polymorphism in our cohort underlines that the diagnosis of GS may be substantiated with this simple molecular test in patients with an uncertain diagnosis of GS.