With a normal direct bilirubin in the face of a rising total bilirubin suggests a rise in unconjucated bilirubin. An increase in unconjugated bilirubin in serum results from either overproduction, impairment of uptake, or impaired conjugation of bilirubin.
There are many causes for this. Examples include hemolysis (breaking up of blood cells), congestive heart failure, medications (i.e. rifampin or probenecid), genetic diseases (i.e. Crigler-Najjar syndrome, Gilbert's syndrome), hyperthyroidism, and chronic liver diseases (hepatitis, cirrhosis).
Some of these diseases are benign, some require further evaluation.
Initial laboratory tests include measurements of serum total and unconjugated (indirect) bilirubin, alkaline phosphatase, aminotransferases, prothrombin time, and albumin.
Depending on these results, a physician should be able to use tests to guide future evaluation.
Other tests to consider after interpreting the initial tests include:
- Serologic tests for viral hepatitis
- Measurement of antimitochondrial antibodies (for primary biliary cirrhosis)
- Measurement of antinuclear anti-smooth muscle (sm), and liver-kidney microsomal (LKM) antibodies (for autoimmune hepatitis)
- Serum levels of iron, transferrin, and ferritin (for hemochromatosis)
- Serum levels of ceruloplasmin (for Wilson's disease)
- Measurement of alpha-1-antitrypsin activity (for alpha-1-antitrypsin deficiency)
Imaging studies of the liver and biliary system can then be considered with an ultrasound or ERCP.
As you can see, there are plenty of reasons for an increase in bilirubin. I would suggest having a physician interpret a basic liver panel (ALT, AST, alk phos etc.) to guide future testing.
Followup with your personal physician is essential.
This answer is not intended as and does not substitute for medical advice - the information presented is for patient education only. Please see your personal physician for further evaluation of your individual case.
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