Current molecular medicine · 2026
Diagnostic Accuracy of Pleural Fluid Biomarkers and Nucleic Acid Amplification Tests in Tuberculous Pleural Effusion: An Umbrella Review.
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Nurhayati, Shidiq Achmad, Wirasmi Sundari, Despitasari Mieska, Anggraeni Rahmi, Normakristagaluh Pesigrihastamadya, Lestriandoko Nova Hadi, Wibowanto Gembong Satrio, Hindratno Muhammad Nurkhoiri, Purnomo Juli, Novianti Zakiah, Syamsul Hadi Wahid, Lusinta Hesty, Manety Risty, Jayanti Asykar, Widihartono Edy, Hendarwan Harimat
Аннотация
INTRODUCTION/OBJECTIVE: Tuberculous Pleural Effusion (TPE) is a common but diagnostically challenging form of extrapulmonary tuberculosis. Many overlapping systematic reviews have evaluated pleural-fluid biomarkers and Nucleic Acid Amplification Tests (NAATs). This umbrella review aimed to synthesise and compare the diagnostic accuracy of pleural-fluid tests for TPE within a single appraised framework.
METHODS: We conducted an umbrella review (JBI methodology; PRISMA 2020 reporting) of 20 systematic reviews with meta-analysis, appraised them using AMSTAR 2, quantified primary-study overlap with the Corrected Covered Area (CCA), and summarised the certainty of evidence reported by the source reviews (GRADE).
RESULTS: Cytokine markers showed the highest accuracy (IFN-γ sensitivity 0.93, specificity 0.96; IL-27 0.94/0.97). ADA was a robust rule-out test (0.92/0.90). NAATs were highly specific but insensitive (Xpert MTB/RIF 0.52/0.99; Xpert Ultra 0.68/0.97).
DISCUSSION: The overlap among reviews was high to very high, and the apparent hierarchy was found to be influenced by reference-standard heterogeneity, indicating that the observed ranking should not be interpreted as free of methodological bias.
CONCLUSION: No single test is optimal; pleural-fluid biomarkers and NAATs play complementary roles that depend on pre-test probability.
METHODS: We conducted an umbrella review (JBI methodology; PRISMA 2020 reporting) of 20 systematic reviews with meta-analysis, appraised them using AMSTAR 2, quantified primary-study overlap with the Corrected Covered Area (CCA), and summarised the certainty of evidence reported by the source reviews (GRADE).
RESULTS: Cytokine markers showed the highest accuracy (IFN-γ sensitivity 0.93, specificity 0.96; IL-27 0.94/0.97). ADA was a robust rule-out test (0.92/0.90). NAATs were highly specific but insensitive (Xpert MTB/RIF 0.52/0.99; Xpert Ultra 0.68/0.97).
DISCUSSION: The overlap among reviews was high to very high, and the apparent hierarchy was found to be influenced by reference-standard heterogeneity, indicating that the observed ranking should not be interpreted as free of methodological bias.
CONCLUSION: No single test is optimal; pleural-fluid biomarkers and NAATs play complementary roles that depend on pre-test probability.