INTRODUCTION: Pre-transplant screening and therapy of latent tuberculosis infection (LTBI) is recommended. However, there are limited data on the tolerability of LTBI therapy pre- and post-transplant, especially for patients with underlying liver disease. We studied the tolerability of LTBI therapy and effectiveness of a centralized LTBI treatment program in a low risk population.

METHODS: We retrospectively reviewed provincial TB and transplant databases for all pre- and post-transplant referrals for LTBI therapy over a 10 year period. All eligible patients received therapy with isoniazid or rifampin-based regimens. We examined factors associated with failure to complete therapy and followed patients for active TB.

RESULTS: From 2001-2010, 461 transplant candidates were referred to the TB program for consideration of LTBI screening or therapy. Of these, 200 (43.4%) were eligible for therapy. LTBI was diagnosed based on a positive tuberculin skin test (TST) (n=182), positive QFT-TB (n=1), abnormal CXR (n=13), and clinical assessment (n=4). Both TST and QFT-TB were performed in 23 patients, with concordant results in 16/23. Eleven patients refused therapy. The remaining patients (n=189) were initially prescribed isoniazid (73%), rifampin (12.7%), or another regimen (14.3%). Adequate LTBI therapy occurred in 122 (64.6%). The most common reasons for early discontinuation of therapy were liver enzyme elevation (9.5%), other drug toxicity (13.2%), and death (6.3%). Completion of LTBI therapy was less likely in patients with underlying liver disease (36.9% vs 73.4%; p<0.001) and in patients that started therapy post-transplant (51.1% vs 69.0%; p=0.034). Liver enzyme elevation was also more likely to occur in those with underlying liver disease (28.3% vs 3.5%; p<0.001) and patients that started therapy post-transplant (19.1% vs 6.3%; p=0.019). During followup, 123/200 patients underwent transplant including kidney (n=66), liver (n=32), lung (n=10), heart (n=10), and other (n=5). In the subset treated post-transplant (n=47), therapy completion was similar in all organ groups. In 599.4 patient-years of followup post-transplant (mean 4.9 yrs/patient), there were no cases of active TB.

CONCLUSIONS: A centralized referral program for LTBI therapy in transplant candidates is effective to prevent TB reactivation post-transplant. However, a significant proportion of patients with liver disease do not tolerate standard LTBI therapy. Alternative therapies for these patients should be evaluated.

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