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Safety of BCG Vaccination in Pediatric Liver Transplant Recipients

Kinoshita, Noriko, MD1; Shoji, Kensuke, MD1; Funaki, Takanori, MD1; Fukuda, Akinari, MD, PhD2; Sakamoto, Seisuke, MD, PhD2; Kasahara, Mureo, MD, PhD2; Miyairi, Isao, MD1,3

doi: 10.1097/TP.0000000000002103
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1 Division of Infectious Diseases, Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo, Japan.

2 Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.

3 Department of Microbiology, Immunology, Biochemistry, University of Tennessee Health Science Center, Memphis, TN.

Received 1 September 2017. Revision received 27 November 2017.

Accepted 12 December 2017.

This study was supported by NCCHD grants 27-1 and 27-6 awarded to M.K. and I.M., respectively.

The authors declare no conflict of interests.

N.K. contributed to conceptualizing and designing the study, drafted the article, and performed the data and statistical analyses. K.S. and T.F. also contributed to conceptualizing and designing the study and helped to revise the article. A.F., S.S., and M.K. contributed to data collection and helped to revise the article. I.M. contributed to conceptualizing and designing the study, helped to revise manuscript, and supervised the study as the corresponding author.

This study was approved by the Institutional Review Board at the NCCHD (NCCHD-1057).

Correspondence: Isao Miyairi, MD, Division of Infectious Diseases, Department of Medical Subspecialties, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. (miyairi-i@ncchd.go.jp).

Bacille de Calmette et Guérin (BCG) vaccination is recommended for patients awaiting solid organ transplantation who are at risk of exposure to tuberculosis.1 However, avoidance of live vaccines within 4 weeks before transplantation is recommended.2 This situation is complicated by the fact that it is often difficult to avoid liver transplantation (LT) within this period because rapid deterioration of liver function may occur in infants, and the risk of BCG disease in these patients is still unknown. Moreover, the appropriateness of this time interval may not be applicable for BCG, given that Mycobacterium bovis may remain dormant and complications of BCG occur on average 13.9 months after vaccination.3

We identified 5 pediatric living donor LT recipients who received BCG vaccine within 4 weeks before LT (median, 22 days; 7-28) and 2 patients who received it after LT between January 2006 and October 2015. The reasons for requiring LT were to avoid crisis in patients with biliary atresia with severe liver failure (n = 3) or metabolic diseases (n = 2). No abnormal reaction at the site of BCG inoculation was observed at the time of LT. Initial immunosuppression after LT consisted of tacrolimus (TAC) and low-dose corticosteroids. The corticosteroids were tapered over 3 months. The average blood concentration of TAC in these patients was 4.5 and 3.8 after 6 months and 1 year, respectively. Two patients received high-dose methylprednisolone therapy to treat acute rejection, and 2 received mycophenolate mofetil and prednisolone. None of these patients required antithymocyte globulin therapy. Two patients received BCG vaccination inadvertently after LT at 28 and 29 months after LT from their primary care physician. No BCG disease was observed in any of these cases during the median (range) follow-up period of 80 (42-122) months. In addition, no BCG disease was observed in 144 patients who received BCG vaccination within 4 years to 4 weeks before LT, with an interval between BCG inoculation and LT of less than 3 months in 50 patients, 4 to 12 months in 54 patients, 13 to 24 months in 22 patients, and more than 25 months in 21 patients. One patient developed a BCG site subcutaneous abscess 1 month before LT but had an uneventful course after LT.

There are several potential explanations for the absence of BCG disease in these patients. The BCG Tokyo 172 strain used in Japan and some other Asian countries is associated with fewer side effects compared with other vaccine strains.4 Living donor LT, which is common in Japan, usually requires lower levels of immunosuppression to suppress rejection compared with deceased donor LT.5 The small number of subjects evaluated in our report limits the generalizability of our results, particularly outside Japan. However, we were able to document the lack of occurrence of BCG complications in a larger number of patients who received BCG vaccination within several years before LT. Our results suggest that prior receipt of BCG vaccination may not be a contraindication for LT.

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