Treatment of Hyperbilirubinemia in Adults

Diagnostic Approach

When hyperbilirubinemia is due to drug-induced liver injury (DILI), the fraction of direct bilirubin should be measured and is usually greater than 35% 1
CT or MRI may be necessary for further evaluation if ultrasonography is inconclusive, as recommended by the American College of Radiology 2

No specific treatment is required for Gilbert's Syndrome, as this is a benign condition, according to the American Gastroenterological Association 3
Diagnosis of Gilbert's Syndrome is confirmed by calculating the amount of conjugated bilirubin, which should be less than 20%-30% of the total bilirubin, in the absence of hemolysis 3
For malignant biliary obstruction, stent placement or surgical intervention may be necessary, depending on the location and nature of the obstruction, as recommended by the American College of Radiology 2
Ursodeoxycholic acid is commonly used for cholestatic liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), as recommended by the American Association for the Study of Liver Diseases 4
Monitor for fat-soluble vitamin deficiencies in patients with chronic cholestasis, as recommended by the American Gastroenterological Association 1
Parenteral vitamin K supplementation should be attempted to correct prolonged INR in cholestatic patients before assigning causality to liver failure, as recommended by the American Gastroenterological Association 1

More vigilant monitoring is required for patients with pre-existing liver disease, as they may not manifest the same degree of ALT elevation expected with DILI, according to the American Association for the Study of Liver Diseases 1
Patients with advanced cirrhosis typically have an altered AST to ALT ratio >1.0, instead of the normal ratio of 0.8, as reported by the American Association for the Study of Liver Diseases 1
Non-adherence to ursodeoxycholic acid in patients with cholestatic liver diseases can lead to abrupt elevations of liver tests that can mimic DILI, as reported by the American Association for the Study of Liver Diseases 4

Repeat liver function tests to monitor response to treatment, as recommended by the American Gastroenterological Association 5
For prolonged INR, repeat testing within 2-5 days to confirm the value and determine trajectory, as recommended by the American Gastroenterological Association 1
If the etiology of prolonged hyperbilirubinemia is uncertain, a breakdown of the direct bilirubin fraction to conjugated and delta bilirubin should be considered, as recommended by the American Association for the Study of Liver Diseases 3