Posttransplant Mycobacterium Tuberculosis Disease Following Liver
Transplantation and the Need for Cautious Evaluation of Quantiferon
TB GOLD Results in the Transplant Setting: A Case Report
M. Codeluppi, S. Cocchi, G. Guaraldi, F. Di Benedetto, N. De Ruvo, M. Meacci, B. Meccugni,
R. Esposito, and G.E. Gerunda
ABSTRACT
This report describes a case of pulmonary tuberculosis in a liver transplant patient without
a history of previous exposure to Mycobacterium tuberculosis (MTB) complex. Prior to
transplantation, the tuberculin skin test was negative and the QuantiFERON–TB Gold
(QFT Gold), an interferon gamma– based blood test, was negative before and after
transplant including a period beginning on postoperative day 55 when the patient
developed a febrile illness with an interstitial infiltrate and pleural effusion that was
unresponsive to broad-spectrum antibiotic therapy. Empiric treatment with isoniazid,
ethambutol, and levofloxacin resulted in resolution of the clinical symptoms. A sputum
culture grew MTB on postoperative day 87. This case illustrates the need for caution when
QFT Gold is used as diagnostic tool for latent tuberculosis during the pretransplant
assessment. Further studies evaluating the usefulness of QFT Gold and other interferon
gamma tests in posttransplantation active infection are warranted.
D
IAGNOSIS OF LATENT and active infection due to
Mycobacterium tubercolosis (MTB) complex is diffi-
cult to assess, both in patient candidates and recipients of
liver transplantation, because of the frequent loss of tuber-
culin skin test reactivity during end-stage liver disease and
the atypical clinical presentations during active infections.
1
This justifies the attempt to use new diagnostic tests as an
adjunctive tool confirm a diagnosis of latent or active MTB.
QuantiFERON–TB Gold (QFT Gold) is an enzyme-
linked immunosorbent assay that effectively evaluates the
interferon gamma response to MTB-specific antigens early
secreted antigenic target-6 (ESAT-6) and culture filtrate
protein-10 (CFP-10). The test has recently become com-
mercially available.
The test consists of a negative control (nil well, ie, whole
blood without antigens or mitogen), a positive control (mito-
gen well, ie, whole blood stimulated with the mitogen phyto-
hemagglutinin [PHA]) and two sample wells (ie, whole blood
stimulated with either ESAT-6 or CFP-10).
The response to PHA is used as positive control, and the
test is considered positive if the concentration of interferon
gamma in the sample, after stimulation with ESAT-6 and
CFP-10, is greater than or equal to 0.35 IU/mL (regardless
of the result of the positive control). The result of the test is
considered indeterminate if both antigen-stimulated samples
are negative and if the value of the positive control is less than
0.5 IU/mL.
2
The concentration of interferon gamma is
calculated after subtraction of the value of the nil well,
which is considered the background. A negative response to
PHA can reflect immune defects.
In previous studies, QFT Gold and the tuberculin skin
test (TST) showed variable agreement, and generally QFT
Gold was found to be more sensitive for diagnosing latent
infection
1
; more recently, in one single-center study, the use
of QFT Gold was found to be feasible in routine hospital
use even though immunosuppression affects the test’s per-
formance.
3
From the Department of Internal Medicine and Medical Spe-
cialties (M.C., S.C., G.G., R.E.), Infectious Diseases Clinic, Uni-
versity of Modena and Reggio Emilia, Modena, Italy; Microbio-
logic and Virologic Laboratory Services (M.M., B.M.), Azienda
Policlinico di Modena, Modena, Italy; and Division of Liver and
Multivisceral Transplant Center (F.D.B., N.D.R., G.E.G.), Univer-
sity of Modena and Reggio Emilia, Modena, Italy.
Address reprint requests to Mauro Codeluppi, MD, Depart-
ment of Internal Medicine and Medical Specialties, Infectious
Diseases Clinic, University of Modena and Reggio Emilia School
of Medicine, Via del Pozzo 71, 41100 Modena, Italy. E-mail:
codeluppi.mauro@unimo.it
© 2006 by Elsevier Inc. All rights reserved. 0041-1345/06/$–see front matter
360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2006.02.012
Transplantation Proceedings, 38, 1083–1085 (2006) 1083