From the Guidelines
Increased urine bilirubin is a significant indicator of liver dysfunction or biliary obstruction, necessitating prompt medical evaluation to prevent morbidity and mortality. The presence of bilirubin in urine often precedes clinical jaundice and may be accompanied by dark urine, pale stools, fatigue, abdominal pain, or nausea. According to the most recent guidelines 1, total bilirubin should be fractionated to determine the percentage derived from direct bilirubin, and elevations of alkaline phosphatase should be confirmed to be of hepatobiliary origin with gamma glutamyl transferase and/or alkaline phosphatase isoenzyme fractionation.
Causes and Diagnosis
Common causes of increased urine bilirubin include hepatitis, cirrhosis, gallstones, pancreatic cancer, or medication-induced liver injury. Patients should seek prompt medical attention for proper diagnosis, which typically involves:
- Blood tests (liver function tests, complete blood count)
- Imaging studies (ultrasound, CT scan)
- Possibly liver biopsy While awaiting medical care, patients should avoid alcohol and hepatotoxic medications. The underlying mechanism involves impaired bilirubin conjugation or excretion in the liver, allowing water-soluble conjugated bilirubin to appear in urine.
Treatment and Management
Treatment depends on identifying and addressing the specific cause of the liver or biliary dysfunction. As recommended by recent consensus guidelines 1, evaluation for a dominant stricture by magnetic resonance cholangiography or endoscopic retrograde cholangiography should be performed when elevations in liver tests abruptly occur. Additionally, the presence of fever, right upper quadrant pain, and jaundice coupled with elevated inflammatory blood tests (white blood cell count and C-reactive protein) will assist in assigning causality to cholangitis 1.
Key Considerations
It is essential to note that the natural course of primary sclerosing cholangitis (PSC) characteristically includes episodes of cholangitis, which may mimic drug-induced liver injury (DILI) biochemically, making detection and assignment of causality challenging 1. Therefore, a thorough evaluation and consideration of the patient's medical history and underlying conditions are crucial in determining the cause of increased urine bilirubin. Prompt medical attention and proper diagnosis are critical to preventing morbidity and mortality associated with liver dysfunction or biliary obstruction.
From the Research
Interpreting Increased Urine Bilirubin
- Increased urine bilirubin can be an indicator of liver disease or dysfunction, as bilirubin is a byproduct of the liver's processing of old red blood cells 2.
- However, urine bilirubin tests can also yield false positive results, with one study finding that 40% of positive results were deemed "unexpected positives" and did not correlate with abnormal liver function tests (LFTs) in the previous 2 weeks 3.
- In patients with unexpected positive urine bilirubin test results, 85% had abnormal LFT results after their positive urine bilirubin result, suggesting that the test may still have some utility in identifying liver dysfunction 3.
Differentiating Between Hepatocellular and Cholestatic Injury
- Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels, while cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 4.
- Elevated conjugated bilirubin implies hepatocellular disease or cholestasis, and total bilirubin elevation can occur in either cholestatic or hepatocellular diseases 4.
- The evaluation of hepatocellular injury includes testing for viral hepatitis, nonalcoholic fatty liver disease, and other conditions, while the evaluation of cholestatic injury includes testing for primary biliary cholangitis and primary sclerosing cholangitis 4.
Clinical Significance of Urine Bilirubin
- One study found that urine bilirubin does not appear to add significant information toward the diagnosis of most patients, with unexpected positives amounting to only 0.13% of all test results 3.
- However, another study found that patients with higher urinary bilirubin levels had greater numbers of granular casts and renal tubular epithelial cells in their urine, suggesting an association between hyperbilirubinemia/hyperbilirubinuria and tubular injury independent of acute kidney injury or non-acute kidney injury 5.
- The clinical significance of increased urine bilirubin should be interpreted in the context of other laboratory tests and clinical findings, including LFTs, imaging studies, and medical history 6, 4.