What is ADA in Tuberculous Peritonitis?
ADA (adenosine deaminase) is an enzyme measured in ascitic fluid that serves as a highly sensitive and specific biomarker for diagnosing tuberculous peritonitis, with diagnostic thresholds of ≥32-40 U/L in non-cirrhotic patients and ≥27-32 U/L in cirrhotic patients. 1, 2
Diagnostic Performance
In non-cirrhotic patients:
- ADA ≥32-40 U/L demonstrates 100% sensitivity and 96.6-100% specificity for tuberculous peritonitis 2, 3
- A meta-analysis of 16 studies showed pooled sensitivity of 93% and specificity of 96% 4
- The area under the ROC curve is 0.98, indicating excellent diagnostic accuracy 3, 4
In cirrhotic patients:
- Use a lower threshold of 27-32 U/L to maintain 91.7-100% sensitivity and 92-93.3% specificity 1, 2, 3
- This lower threshold is necessary because cirrhotic ascites has reduced total protein content 5
- One U.S. study found only 30% sensitivity in cirrhotic patients, highlighting the importance of using appropriate thresholds 6
Clinical Interpretation Algorithm
When ADA is elevated (≥32-40 U/L):
- First suspect tuberculous peritonitis, not malignancy 3
- Consider patient risk factors: recent immigration from endemic areas, HIV/AIDS, immunosuppression 1
- Do not delay treatment while awaiting culture results, as mycobacterial culture sensitivity from ascitic fluid is only 20-83% and AFB smear sensitivity is 0-86% 2
When ADA is <40 U/L:
- Effectively excludes tuberculosis with 100% negative predictive value 7
- Consider alternative diagnoses 3, 5
Important Caveats and Pitfalls
False positives can occur in:
- Lymphoma-related ascites (the most important mimic of tuberculous peritonitis with similar clinical manifestations) 7
- Bacterial peritonitis (5.8% false-positive rate) 6
- Malignancy-related ascites (13% false-positive rate) 6
- Empyema, rheumatoid arthritis, and other neoplasias 5
False negatives can occur in:
- HIV-positive patients, where ADA levels may not be elevated even with confirmed tuberculosis 5
- Cirrhotic patients when using inappropriately high thresholds 1, 6
Geographic considerations:
- In endemic areas, empiric antituberculosis treatment is recommended for exudative ascites with elevated ADA after excluding malignancy, uremia, trauma, and bacterial peritonitis 2
- In non-endemic areas (like the United States), do not start empiric treatment without stronger diagnostic evidence, as the positive predictive value drops to 53.3% when disease prevalence is low 7
- One U.S. study showed overall sensitivity of only 58.8% due to low tuberculosis prevalence and high cirrhosis prevalence 6
Complementary Diagnostic Tests
ADA does not provide definitive diagnosis—it must be interpreted in clinical context: 1, 5
- Combine with differential cell count, microbiological cultures, and acid-fast staining 5
- Polymerase chain reaction testing for mycobacteria or laparoscopy with biopsy and mycobacterial culture of tubercles are the most rapid and accurate definitive diagnostic methods 1
- Free IFN-γ levels in peritoneal fluid show 93% sensitivity and 99% specificity (threshold 0.35-9 U/L or 20-112 pg/mL) 1
Do NOT use CA-125: