Diagnosis and treatment of latent tuberculosis infection in liver transplant recipients in an endemic area

Abstract

Background. Treatment of latent tuberculosis infection (LTBI) with isoniazid is recommended for transplant recipients with positive tuberculin skin test (TST). However, TST could be an imperfect identifier of LTBI in this population. In addition, the risk of isoniazid hepatotoxicity could be high in liver transplant recipients (LTR). A retrospective cohort study was performed to evaluate the diagnosis and treatment of LTBI in LTR. Methods. Charts of all 547 patients who received primary liver transplantation at a University Hospital in Spain between 1988 and 1998 were reviewed. Results. TST was performed in 373 patients (71%) before transplantation. The result was positive in 89 (24%). The median follow-up after transplantation was 49 months. None of the TST-positive patients developed tuberculosis (TB), but 5 out of 284 patients with negative TST (1.76%) had active TB (P =0.6). Twenty-three patients received isoniazid as treatment of LTBI according to the decision of the attending physician. None of these patients developed TB, but 4 of them (17%) presented isoniazid hepatotoxicity. Among patients who did not receive isoniazid, 2 out of 21 (9.52%) with radiologic previous TB developed active TB versus 0.44% (2/452) among the remaining patients (relative risk [RR], 27.8, 95% CI, 3.2–147). Conclusions. Treatment of LTBI with isoniazid can not be recommended to LTR on the basis of a positive TST because it is an imperfect identifier of patients at risk of TB. LTR with radiologic features of previous TB are at higher risk of posttransplant active TB. Isoniazid-related hepatotoxicity is more frequent among LTR than in the general population. One of the most controversial issues in the field of infectious diseases in transplant recipients is the approach to tuberculosis (TB), and most especially the treatment of latent tuberculosis infection (LTBI) in liver transplant recipients (LTR). Treatment of LTBI is effective in preventing TB disease in individuals who have a positive tuberculin skin test (TST) and who are at high risk for developing TB (1). Solid organ transplantation is associated with an increased risk of LTBI progression towards active TB. Thus, general recommendations include the administration of isoniazid to TST-positive patients with organ transplants (2,3). However, there is no consensus regarding the appropriate treatment of LTBI in these patients (4,5). On the one hand, TST could be an imperfect identifier of patients with LTBI because up to 80% of transplant candidates may be anergic (6–8). On the other hand, the risk of active disease in liver transplant patients with positive TST remains unknown. Case series and reports suggest that isoniazid treatment of LTBI is effective for transplant recipients, but this has not been demonstrated in a controlled trial (7). In addition, the efficacy of isoniazid treatment of LTBI must be considered against the risk of hepatotoxicity. It has been suggested that the risk of hepatotoxicity could be greater than the benefit of isoniazid therapy in LTR with positive TST and no other risk factors for TB (6,9–14). Nevertheless, the incidence of isoniazid hepatotoxicity in LTR is not well known (14,15). The objective of this study was to evaluate the diagnosis and treatment of LTBI with isoniazid in a large group of LTR from an endemic geographical area.

Description

Fil: Sued O. Fundación Huésped, Buenos Aires; Argentina

Keywords

Latent Tuberculosis, Liver Transplantation, Transplant Recipients

Citation