Effective Tuberculosis and Hepatitis Screening Prior to Anti-TNF-α Therapy: Are We There Yet?

Abstract

Anti-tumor necrosis factor-a (anti-TNF-a) drugs are widely used for the management of patients who suffer from Crohn’s disease (CD) and ulcerative colitis (UC). Screening for latent tuberculosis infection (LTBI) and hepatitis B virus (HBV) is mandatory prior to commencing therapy with anti-TNF-a drugs, due to an increased reactivation risk for these diseases. Unfortunately, in the case of LTBI, a consensus has not been reached, highlighted by the heterogeneity of current guidelines, regarding the use of the tuberculin skin test (TST) or an interferon-gamma release assay (IGRA) as parts of the initial screening strategy [1, 2]. Historically, the diagnosis of LTBI has been dependent on the TST whose mechanism relies on a delayed-type T cell mediated hypersensitivity reaction to purified protein derivative (PPD). Regrettably, the TST has well-known limitations including potential sources for false positive results, due to the non-specific nature of PPD leading to cross-reactivity with non-tuberculosis mycobacterium and individuals who have received bacillus Calmette-Guerin vaccination. Moreover, there is intrinsic test subjectivity due to induration interpretation; furthermore, two healthcare visits are required. Alternatively, the IGRAs, which measure the release of interferon-gamma post antigen exposure, have recently gained popularity as an alternative for LTBI diagnosis as their antigens are more specific for Mycobacterium tuberculosis. Nonetheless, IGRA testing is more expensive and requires appropriate infrastructure, potentially limiting its universal implementation. In this issue, van der Have et al. [3] describe a costeffectiveness analysis in patients with CD of screening strategies for LTBI and HBV: (1) traditional LTBI screening (TST and chest X-ray) versus additional IGRA testing; and (2) HBV screening versus no HBV screening. Neither extensive LTBI screening (traditional testing plus IGRA) nor HBV screening were cost-effective. Nevertheless, if LTBI prevalence was[12 % or the TST false positivity rate [20 %, cost-effectiveness of extensive testing was achieved, emphasizing the importance of the varying global prevalence of LTBI and the sensitivity and specificity of LTBI diagnostic tests. Similarly, if HBV reactivity or HBVrelated mortality were[37 and[62 %, respectively, HBV screening was cost-effective, leading the authors to conclude that although extensive LTBI screening and HBV screening are effective, their implementation should be targeted towards high-risk populations. An interesting aspect to this study was how the authors calculated probabilities for the LTBI-component of the model, which appear to be largely derived from a recent meta-analysis which analyzed TST and IGRA performance in patients with inflammatory bowel disease (IBD) [4]. Concerning the perceived false-positivity rate of TST, it appears the authors based this off an estimate of discordance between TST?/IGRAresults, which is simply the discrepancy between these two tests in a patient. IGRAs are not commonly regarded as the ‘gold standard’ in LTBI diagnostics; therefore, the discordance is potentially an inaccurate quantification of false positivity. Moreover, it was unclear how the authors established the advantage that additional IGRA testing would have over traditional LTBI screening. It appears that they may have estimated this from the alternate discordant scenario TST-/IGRA?, which would lend itself to the same limitations as the false positivity risk. N. Shahidi B. Bressler (&) Division of Gastroenterology, Department of Medicine, University of British Columbia, 770-1190 Hornby Street, Vancouver, BC V6Z 2K5, Canada e-mail: brian_bressler@hotmail.com