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Evaluate liver and biliary disease. Increased direct bilirubin occurs with biliary diseases, including both intrahepatic and extrahepatic lesions. 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.