BACKGROUND & AIMS: Severe unconjugated hyperbilirubinemia, as occurs in Crigler-Najjar disease and neonatal jaundice, carries the risk of neurotoxicity. This neurotoxicity is related to the increased passage of free bilirubin (UCB(free)), the fraction of bilirubin that is not bound to plasma proteins, into the brain. We hypothesized that albumin treatment would lower the UCB(free) fraction, and thus decrease bilirubin accumulation in the brain. METHODS: We treated chronic (e.g., as a model for Crigler-Najjar disease) and acute hemolytic (e.g., as a model for neonatal jaundice) moderate hyperbilirubinemic Gunn rats with phototherapy, human serum albumin (HSA) or phototherapy+HSA. RESULTS: In the chronic model, adjunct HSA increased the efficacy of phototherapy; it decreased plasma UCB(free) and brain bilirubin by 88% and 67%, respectively (p<0.001). In the acute model, adjunct HSA also increased the efficacy of phototherapy; it decreased plasma UCB(free) by 76% (p<0.001) and completely prevented the hemolysis-induced deposition of bilirubin in the brain. Phototherapy alone failed to prevent the deposition of bilirubin in the brain during acute hemolytic jaundice. CONCLUSIONS: We showed that adjunct HSA treatment decreases brain bilirubin levels in phototherapy-treated Gunn rats. We hypothesize that HSA decreases these levels by lowering UCB(free) in the plasma. Our results support the feasibility of adjunct albumin treatment in patients with Crigler-Najjar disease or neonatal jaundice.
BACKGROUND & AIMS: Severe unconjugated hyperbilirubinemia, as occurs in Crigler-Najjar disease and neonatal jaundice, carries the risk of neurotoxicity. This neurotoxicity is related to the increased passage of free bilirubin (UCB(free)), the fraction of bilirubin that is not bound to plasma proteins, into the brain. We hypothesized that albumin treatment would lower the UCB(free) fraction, and thus decrease bilirubin accumulation in the brain. METHODS: We treated chronic (e.g., as a model for Crigler-Najjar disease) and acute hemolytic (e.g., as a model for neonatal jaundice) moderate hyperbilirubinemicGunn rats with phototherapy, humanserum albumin (HSA) or phototherapy+HSA. RESULTS: In the chronic model, adjunct HSA increased the efficacy of phototherapy; it decreased plasma UCB(free) and brain bilirubin by 88% and 67%, respectively (p<0.001). In the acute model, adjunct HSA also increased the efficacy of phototherapy; it decreased plasma UCB(free) by 76% (p<0.001) and completely prevented the hemolysis-induced deposition of bilirubin in the brain. Phototherapy alone failed to prevent the deposition of bilirubin in the brain during acute hemolytic jaundice. CONCLUSIONS: We showed that adjunct HSA treatment decreases brain bilirubin levels in phototherapy-treated Gunn rats. We hypothesize that HSA decreases these levels by lowering UCB(free) in the plasma. Our results support the feasibility of adjunct albumin treatment in patients with Crigler-Najjar disease or neonatal jaundice.
Authors: John M Lahmann; Ryan A Faase; Hsuan Yu Leu; Steven L Jacques; Brian Scottoline; Kate F Schilke; Joe E Baio; Adam Z Higgins Journal: Biomicrofluidics Date: 2021-11-24 Impact factor: 2.800
Authors: Christian V Hulzebos; Libor Vitek; Carlos D Coda Zabetta; Aleš Dvořák; Paul Schenk; Eline A E van der Hagen; Christa Cobbaert; Claudio Tiribelli Journal: Pediatr Res Date: 2021-05-04 Impact factor: 3.756
Authors: Andrea B Schreuder; Jana Vanikova; Libor Vitek; Rick Havinga; Charles E Ahlfors; Christian V Hulzebos; Henkjan J Verkade Journal: PLoS One Date: 2013-10-15 Impact factor: 3.240