The Clinical Importance of a Protein-Bound Fraction of Serum Bilirubin in Patients with Hyperbilirubinemia

A directly reacting fraction of bilirubin that is probably covalently bound to albumin (albumin-bound bilirubin) has recently been described. To determine its clinical importance we used a new high-performance liquid—chromatography technique to measure it in the serum of 200 patients with hyperbilirubinemia from various causes. Albumin-bound bilirubin was an important fraction (8 to 90 per cent) of total bilirubin in patients with hepatocellular and cholestatic jaundice as well as in patients with the Dubin–Johnson syndrome. It was not detected in normal volunteers, neonates with physiologic jaundice, or patients with Gilbert's disease or hemolysis. Thus, albumin-bound bilirubin appears in serum when hepatic excretion of conjugated bilirubin is impaired. It becomes a larger component of serum bilirubin as jaundice subsides, delaying resolution of this disorder and causing bilirubin to persist in plasma after it has disappeared from the urine. (N Engl J Med 1983; 309:147–50.) Bilirubin is generally thought to exist in three major forms in serum: as unconjugated bilirubin, as the monoglucuronide, or as the diglucuronide. The latter two subfractions give a "direct" reaction with standard diazo reagents, whereas unconjugated bilirubin gives an "indirect" reaction. A fourth fraction, albumin-bound bilirubin, has recently been identified by use of a new reversed-phase high-performance liquid-chromatography procedure. 1 , 2 This fraction reacts directly with diazo reagents and appears to be covalently bound to albumin. 3 The new technique retains albumin during sample preparation and thus separates all bilirubin fractions accurately and reliably; previously described techniques for bilirubin subfractionation require extensive deproteination . . .