Evaluation of ‘Indeterminateʼ Results of QuantiFERON Gold In-tube Assay as Screening Test for Latent Tuberculosis Infection in Liver Transplant Candidates

Abstract

Introduction: Screening of latent tuberculosis (LTB) infection is recommended in solid organ transplant recipient because of high risk of severe reactivation of LTB after immunosuppression. Traditionally, screening for LTBI was done by PPD skin test and recently Interferon release assay QuantiFERON test (QFT) has shown similar rates of detecting LTB in liver transplant (LT) candidates. Due to convenience of its use and recent support by AASLD guidelines, LT centers have started using QFT as the initial test for LTB screening. QFT is found to have intrinsic inability to result adequately in immunocompromised patients and this leads to a moderate rate of “indeterminate” (IND) test results in LT candidates. We evaluated our experience with QFT as screening test for LT candidates in this retrospective study. The aim of the study was to explore the clinical parameters which are associated with IND results. Methods: We reviewed the data from consecutive 100 LT candidates who underwent QFT as initial screening test after the change in the policy for LT evaluation at the two particpating liver transplant centers. Results: Our study consisted of adults (56.7yrs), mostly Caucasian (60%) LT candidates with decompensated cirrhosis (96%) mainly from chronic hepatitis C infection (38%). All 100 subjects underwent initial QFT which resulted as positive in 6, negative in 68 and IND in 26 subjects. Most (87%) of the tests were done at a single laboratory with (78%) in outpatient settings. When compared with subjects without IND results, IND result was significantly associated with: lower sodium, albumin, and zinc levels; higher Ferritin and MELD score. No differences in age, gender, medications and etiology of liver cirrhosis were present among subjects with and without IND results after initial QFT. Screening tests were repeated in 15 of 26 subjects with initial IND results. 9 out of 15 had PPD performed and all resulted in negative test. The remaining 6 had QFT repeated, 3 had negative result and 3 stayed as IND results. 9 of the 26 initially IND resulted subjects underwent LT and after a mean of 10 months follow-up none has reactivation of LTB. Conclusion: The clinical parameters which indicate the severity of liver disease and possibly chronic inflammation are associated with QFT IND results, the rates of such results was higher (26%) in our population. Since, IND result cannot establish the absence of LTB we suggest repeating QFT to challenge inter-individual variability related to the timing of the test.