Unstimulated Pleural Fluid Interferon Gamma for Diagnosis of Tuberculous Pleural Effusion: a Systematic Review and Meta-analysis.

Unstimulated interferon gamma may be a useful pleural fluid biomarker in the diagnosis of tuberculous pleural effusion (TPE). However, the exact threshold of pleural fluid interferon gamma and its accuracy during routine clinical decision-making is not clear. We assessed the performance of pleural fluid interferon gamma in diagnosing TPE and tried to identify a useful assay threshold. We queried the PubMed and Embase databases for publications indexed until May 2020 that provided both sensitivity and specificity data on unstimulated pleural fluid interferon gamma for diagnosis of TPE. A bivariate random effects model was employed to compute summary estimates for diagnostic accuracy parameters, both overall as well as at threshold ranges of <2, 2 to 5, and >5 IU/ml. We retrieved 2,048 citations, of which 67 publications (7,153 patients) were assessed in our review. The summary estimates for sensitivity, specificity, and diagnostic odds ratio were 0.93 (95% confidence interval [CI], 0.91 to 0.95), 0.96 (95% CI, 0.94 to 0.97), and 310.72 (95% CI, 185.24 to 521.18), respectively. Increasing interferon gamma thresholds did not translate into any substantial change in diagnostic performance; however, eight studies using thresholds of >5 IU/ml showed poorer diagnostic accuracy estimates than other studies with lower thresholds. None of the prespecified subgroup variables significantly influenced relative diagnostic odds ratios in a multivariate meta-regression model. All publications demonstrated a high risk of bias. Unstimulated pleural fluid interferon gamma level provides excellent accuracy for diagnosing TPE and has the potential of becoming a first-line test for this purpose.