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

详细信息    查看全文

• 作者：Frans J.C. Cuperus¹ ; ^&dagger ; ; Andrea B. Schreuder¹ ; ^&dagger ; ; Deirdre E. van Imhoff² ; Libor Vitek³ ; ⁴ ; Jana Vanikova³ ; Renata Konickova³ ; Charles E. Ahlfors⁵ ; Christian V. Hulzebos² ; Henkjan J. Verkade¹ ; ^{h.j.verkade@umcg.nl}
• 关键词：Unconjugated hyperbilirubinemia ; Phototherapy ; Albumin ; Brain ; Gunn rat
• 刊名：Journal of Hepatology
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：58
• 期：1
• 页码：134-140
• 全文大小：667 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

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.