Crohn's Disease With Latent Tuberculosis Infection or Intestinal Tuberculosis: Rapid Discrimination by Targeted Next-Generation Sequencing

Background: Discriminating Crohn's disease (CD) with latent tuberculosis infection (LTBI) from intestinal tuberculosis (ITB) in tuberculosis-endemic regions remains challenging. Aim: To assess whether targeted next-generation sequencing (tNGS) could be an efficient method for ITB diagnosis and discrimination from CD with LTBI. Methods: The study was conducted prospectively from September 2020 until December 2023. We recruited patients with undetermined intestinal ulcers and positive interferon-gamma release assay. We compared tNGS (using fresh biopsy tissue samples from ulcer bases) to pathological detection of caseous necrotising granuloma, acid-fast bacillus (AFB) staining, tuberculosis polymerase chain reaction (TB-PCR) for diagnostic efficiency. ITB was diagnosed based on cure by anti-tuberculosis therapy and comprehensive clinical evaluation. Results: Of the 100 patients included, 66 had ITB and 34 had CD with LTBI. The sensitivity, specificity, positive predictive value and negative predictive value of tNGS for ITB were 83% (72%-91%), 100% (87%-100%), 100% (92%-100%) and 76% (60%-87%), respectively. TNGS had significantly higher diagnostic sensitivity than AFB staining [15% (4%-39%), p < 0.05], TB-PCR [22% (12%-36%), p < 0.05] and detection of caseous necrotising granulomas [17% (9%-28%), p < 0.05]. The models combining multiclinical factors increased sensitivity (97% vs. 83%) than tNGS alone. No patients with CD and LTBI had positive tNGS. Conclusions: TNGS using fresh biopsy tissue from ulcer bases is highly sensitive and specific, with superiority over other traditional diagnostic methods for ITB detection. TNGS could facilitate rapid diagnosis of ITB and discrimination from CD with LTBI, particularly in high TB-endemic countries.