Hepatocellular causes of elevation include hepatitis, cirrhosis, and advanced neoplastic states. Increased with cholestatic drug reactions, Dubin-Johnson syndrome, and Rotor syndrome. In the latter two syndromes, the level is usually <5 mg/dL.Theoretically, direct bilirubin should not be increased in hemolytic anemias, in which bilirubin increase should be in the indirect bilirubin fraction in the absence of complications. In practice, some increase in the direct fraction may be encountered in patients with hemolytic anemia in whom complications have not been proven. Some methods have shown the direct bilirubin to be spuriously high. This may be due to different concentrations of sodium nitrite, which may convert some of the unconjugated bilirubin to conjugated bilirubin.Direct bilirubin is the water soluble fraction. When increased in serum, bilirubin should become positive in the urine. Physiologic jaundice, occurring two to four days after birth, is due to lack of liver glucuronyl transferase.

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