Measurement and clinical usefulness of bilirubin in liver disease

Elevated plasma bilirubin levels are a frequent clinical finding. It can be secondary to alterations in any stage of its metabolism: (a) excess bilirubin production (i.e., pathologic hemolysis); (b) impaired liver uptake, with elevation of indirect bilirubin; (c) impaired conjugation, prompted by a defect in the UDP-glucuronosyltransferase; and (d) bile clearance defect, with elevation of direct bilirubin secondary to defects in clearance proteins, or inability of the bile to reach the small bowel through bile ducts. A liver lesion of any cause reduces hepatocyte cell number and may impair the uptake of indirect bilirubin from plasma and diminish direct bilirubin transport and clearance through the bile ducts. Various analytical methods are currently available for measuring bilirubin and its metabolites in serum, urine and feces. Serum bilirubin is determined by (1) diazo transfer reaction, currently, the gold-standard; (2) high-performance liquid chromatography (HPLC); (3) oxidative, enzymatic, and chemical methods; (4) direct spectrophotometry; and (5) transcutaneous methods. Although bilirubin is a well-established marker of liver function, it does not always identify a lesion in this organ. Therefore, for accurate diagnosis, alterations in bilirubin concentrations should be assessed in relation to patient anamnesis, the degree of the alteration, and the pattern of concurrent biochemical alterations.