Binding of bilirubin and bromosulphthalein to albumin: Implications for understanding the pathophysiology of liver failure and its management

The binding/transporting functions of albumin provide the rationale for using albumin dialysis (e.g., molecular adsorbents recirculating system [MARS]) in liver failure. This study investigates these properties in vitro , validating the findings in vivo . In vitro bromosulphthalein (BSP) and bilirubin‐spiked plasma were dialyzed against albumin and sampled. In vivo serum biochemistry was analyzed in: 7 MARS‐treated liver failure patients; 98 MARS‐treated patients from the MARS Registry; and 8 patients receiving albumin infusion. In vitro BSP concentrations did not equilibrate, but the molar ratio of BSP to albumin (C BSP /C alb ) did, with no subsequent transmembrane transport, suggesting that the C BSP /C alb gradient (rather than simple diffusion) drives BSP transport. Bilirubin was transported similarly. In vivo serum bilirubin reduction during MARS sessions (n = 26) correlated with pre‐treatment bilirubin (r = 0.42), but better (r = 0.85) with pre‐treatment molar ratio of bilirubin to albumin (C bilirubin /C alb ). The strongest correlation was between C bilirubin /C alb reduction and pre‐treatment C bilirubin /C alb (r = 0.9). A similar pattern was observed in the MARS Registry patients. After albumin infusion (n = 8), both serum albumin and bilirubin increased, while C bilirubin /C alb remained unchanged. C bilirubin /C alb appears to be important in albumin dialysis, and generally in liver disease patients, reinforcing the importance of the toxin‐binding functions of albumin in liver disease. (Liver Transpl 2004;10:1531–1538.)