Beyond plasma bilirubin: The effects of phototherapy and albumin on brain bilirubin levels in Gunn rats

• Published in: Journal of hepatology Vol. 58; no. 1; pp. 134 - 140
• Main Authors: Cuperus, Frans J.C., Schreuder, Andrea B., van Imhoff, Deirdre E., Vitek, Libor, Vanikova, Jana, Konickova, Renata, Ahlfors, Charles E., Hulzebos, Christian V., Verkade, Henkjan J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2013
• Subjects: Acute Disease; Albumin; Albumins - pharmacology; Animals; Bilirubin - blood; Bilirubin - metabolism; Brain; Brain - metabolism; Chronic Disease; Crigler-Najjar Syndrome - metabolism; Crigler-Najjar Syndrome - therapy; Disease Models, Animal; Gastroenterology and Hepatology; Gunn rat; Hyperbilirubinemia - metabolism; Hyperbilirubinemia - therapy; Jaundice - metabolism; Jaundice - therapy; Male; Phototherapy; Phototherapy - methods; Random Allocation; Rats; Rats, Gunn; Unconjugated hyperbilirubinemia; Albumin; Brain; Unconjugated hyperbilirubinemia; Gunn rat; Phototherapy
• ISSN: 0168-8278; 1600-0641; 1600-0641
• DOI: 10.1016/j.jhep.2012.08.011

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 (UCBfree), the fraction of bilirubin that is not bound to plasma proteins, into the brain. We hypothesized that albumin treatment would lower the UCBfree 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 UCBfree 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 UCBfree 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 UCBfree in the plasma. Our results support the feasibility of adjunct albumin treatment in patients with Crigler–Najjar disease or neonatal jaundice.