• It forms in serum when the liver can't excrete bilirubin glucuronides, so conjugated bilirubin builds up in the blood (cholestasis, biliary obstruction, hepatocellular injury).
• It appears when conjugated hyperbilirubinemia is prolonged and severe. - Harrison's Principles of Internal Medicine 22E; Sleisenger and Fordtran's Gastrointestinal and Liver Disease

• Long half-life. Ordinary conjugated bilirubin has a half-life of about 4 hours (Harrison's) to under 24 hours (Henry's). Delta bilirubin is cleared at about the rate of albumin, a half-life of roughly 17 to 20 days. - Harrison's Principles of Internal Medicine 22E; Henry's Clinical Diagnosis and Management by Laboratory Methods
• Jaundice persists after recovery. Serum bilirubin can stay high for weeks after the underlying cause has resolved. The patient looks jaundiced even though the liver or bile duct problem is improving. - Henry's Clinical Diagnosis and Management by Laboratory Methods
• No bilirubin in the urine. Because it is bound to albumin, it isn't filtered by the glomeruli. Patients with conjugated hyperbilirubinemia can therefore have a negative urine bilirubin dipstick, particularly in prolonged cholestasis or during recovery. - Harrison's Principles of Internal Medicine 22E
• Direct bilirubin assays. It reacts in the direct (diazo) assay. Roughly 70 to 80% of conjugated and delta bilirubin is measured as "direct" bilirubin. - Henry's Clinical Diagnosis and Management by Laboratory Methods
• Different methods disagree. Dry-slide (differential spectrophotometry) methods measure conjugated and unconjugated bilirubin separately. Their sum was found to be less than total bilirubin, and the gap is the delta fraction. - Henry's Clinical Diagnosis and Management by Laboratory Methods
• Enzymatic assays. Bilirubin oxidase at pH 10 doesn't oxidize delta bilirubin at all. - Tietz Textbook of Laboratory Medicine, 7th Edition

• A 2025 case report (PMID 41362196) describes delta bilirubin and lipoprotein-X interfering with lab results in primary biliary cholangitis.
• A 2026 paper (PMID 41568404) examines how elevated direct bilirubin affects unbound bilirubin measurement in neonates.
• A 2025 study (PMID 39181293) uses machine learning to predict delta bilirubin levels.

Summary table by source

Comparison of bilirubin fractions

Key points

• Delta bilirubin is conjugated bilirubin covalently bound to albumin. It forms when conjugated bilirubin stays high in the blood for a long time.
• It takes on albumin's long half-life of about 2-3 weeks, so jaundice and a raised bilirubin can outlast the actual recovery.
• It is not filtered by the kidney, so the urine bilirubin dipstick can be falsely negative.
• It counts as "direct" bilirubin in diazo assays. Some automated and enzymatic methods under-detect it, so assay type affects the reported conjugated fraction.

Background

False positives (high ADA, not TB)

False negatives (normal ADA, but TB)

How to reduce the errors

• Check the cell type. Look for lymphocyte predominance. A raised ADA with a neutrophilic effusion points to empyema or parapneumonic effusion.
• Use the ADA1/ADA(p) ratio. A ratio below 0.42 correctly classified all 7 raised-ADA non-TB lymphocytic effusions as non-TB. - Jimenez Castro 2003
• Use a low ADA to rule out. ADA below 40 IU/L virtually excluded TB in lymphocytic effusions (negative predictive value 99%). - Jimenez Castro 2003
• Add other tests. Interferon-gamma has about 89% sensitivity and 97% specificity. - Symptom to Diagnosis. Also use culture, cytology, pleural biopsy and PCR.
• Don't rely on ADA alone if suspicion persists. Pleural biopsy is still advised when clinical suspicion of TB remains.

Other sites

Recent evidence check

Absolute (firm) indications

Relative or conditional indication (primary prophylaxis, no prior SBP)

• Symptom to Diagnosis calls primary prophylaxis outside GI bleeding "controversial".
• Ascitic protein below 1.5 g/dL is the main risk marker, usually with advanced liver or kidney dysfunction.
  • AASLD criteria: ascitic protein below 1.5 g/dL plus either Child-Pugh score of 9 or more with bilirubin of 3 mg/dL or more, or creatinine of 1.2 mg/dL or more, BUN of 25 mg/dL or more, or sodium below 130 mmol/L (web source: AASLD Liver Fellow Network).
  • EASL and NICE use ascitic protein below 1.5 g/dL alone. The British Society of Gastroenterology makes no recommendation (same source).
  • Goldman-Cecil uses a threshold of below 1 g/L (1 g/dL) with jaundice, hyponatremia or renal dysfunction.
  • Rosen's Emergency Medicine lists norfloxacin, ciprofloxacin or TMP-SMX as options for these high-risk patients. It says the recommendations are not graded.

Regimen and caveats

• Norfloxacin 400 mg once daily for long-term prophylaxis. Alternatives are ciprofloxacin 500 mg daily or TMP-SMX 800/160 mg daily. - Rosen's Emergency Medicine
• Norfloxacin availability. It was withdrawn from the US market in 2014. Goldman-Cecil suggests oral ciprofloxacin 500 mg daily or rifaximin 600 mg twice daily instead.
• GI bleeding. Rosen's recommends IV ceftriaxone 1 g daily, then oral TMP-SMX once the patient is eating. Ceftriaxone is generally preferred over norfloxacin in advanced cirrhosis. This is from general guideline knowledge, not the library passages I read.
• Rate of SBP. Prophylaxis can cut SBP incidence by 60 to 80% in high-risk patients. - Rosen's
• Concerns about routine use. AASLD now cites worries about resistance and wider consequences of routine prophylaxis.

Recent evidence

Indications

• Child-Pugh score of 9 or more with bilirubin of 3 mg/dL or more.
• Creatinine of 1.2 mg/dL or more, or BUN of 25 mg/dL or more.
• Sodium below 130 mmol/L.

• In patients with low-protein ascites and impaired liver or renal function, norfloxacin cut the 1-year probability of SBP from 61% to 7%. It also improved 1-year survival (60% vs 48%, p=0.05). - AASLD Liver Fellow Network (web source), describing the Fernandez 2007 RCT.

Not lifelong

• Cirrhosis with GI bleeding: short course only, about 7 days. - AASLD (web source)
• Ascitic protein below 1.5 g/dL alone: only EASL and NICE would treat this. AASLD requires added liver or kidney dysfunction. The British Society of Gastroenterology makes no recommendation (web source).

Regimen and caveats

• Dose: norfloxacin 400 mg once daily. Alternatives are ciprofloxacin 500 mg daily or TMP-SMX once daily. - Rosen's Emergency Medicine; AASLD
• US availability: norfloxacin was withdrawn from the US market in 2014. Ciprofloxacin or rifaximin 600 mg twice daily are suggested instead. - Goldman-Cecil
• Resistance: long-term use has raised quinolone-resistant and Gram-positive SBP (web source on a rifaximin vs norfloxacin trial).
• Primary prophylaxis may be dropping out of guidelines. A 2026 Hepatology Communications review says primary SBP prophylaxis is no longer recommended in refractory ascites. It cites lack of efficacy and rising multidrug-resistant organisms. It says secondary prophylaxis with norfloxacin or TMP-SMX remains recommended, though resistance is also a concern there (Hepatology Communications). This conflicts with the AASLD page above, so check the current local guideline before starting primary prophylaxis.

Bottom line