Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, Beatrix Children's Hospital - University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
J Hepatol. 2013 Jan;58(1):134-40. doi: 10.1016/j.jhep.2012.08.011. Epub 2012 Aug 21.
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.
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.
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.
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.
严重未结合高胆红素血症，如发生在克里格勒-纳贾尔病和新生儿黄疸中，存在神经毒性风险。这种神经毒性与未结合胆红素（UCB(free)），即未与血浆蛋白结合的胆红素部分，更多地进入大脑有关。我们假设白蛋白治疗会降低 UCB(free)部分，从而减少胆红素在大脑中的积累。
我们用光疗、人血清白蛋白（HSA）或光疗+HSA 治疗慢性（如克里格勒-纳贾尔病模型）和急性溶血性（如新生儿黄疸模型）中度高胆红素血症 Gunn 大鼠。
在慢性模型中，辅助 HSA 增加了光疗的疗效；它分别降低了 88%和 67%的血浆 UCB(free)和脑胆红素（p<0.001）。在急性模型中，辅助 HSA 也增加了光疗的疗效；它降低了 76%的血浆 UCB(free)（p<0.001），并完全防止了胆红素在大脑中因溶血引起的沉积。单独的光疗未能防止急性溶血性黄疸期间胆红素在大脑中的沉积。
我们表明，辅助 HSA 治疗降低了光疗治疗 Gunn 大鼠的脑胆红素水平。我们假设 HSA 通过降低血浆中的 UCB(free)来降低这些水平。我们的结果支持在克里格勒-纳贾尔病或新生儿黄疸患者中辅助白蛋白治疗的可行性。
