Research ArticlePost-transplant eosinophilic gastrointestinal disorders and lymphoproliferative disorder in pediatric liver transplant recipients on tacrolimus
Introduction
Over the past decades, with advances in surgical technique and improvements in immunosuppression, the graft and patient survival for pediatric liver transplants have steadily increased [[1], [2], [3]]. However, as mortality rates decrease, focuses have shifted to improving the quality of life by reducing morbidity in these patients. Immunosuppressants by their nature have significant trade-offs; they are required to maintain the transplanted organ to treat the original morbidities, but they also create new ones such as lymphoproliferative disorder, frequent/opportunistic infections, kidney dysfunction, and diabetes. Tacrolimus has become the preferred immunosuppressant in pediatric liver transplant recipients due to its superior ability to prolong liver graft survival; however, its mechanism of action has also been considered to play a pivotal role in the development of allergic and immunologic diseases along with susceptibility to infection or malignancy [4].
In the general population, eosinophilic gastrointestinal disorders (which include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enteritis, eosinophilic gastroenteritis, and eosinophilic colitis) are a very rare condition. In the United States, the prevalence of eosinophilic esophagitis was reported to be 25.9 per 100,000 persons while the prevalence of eosinophilic colitis was reported to be 2.1 per 100,000 persons with the prevalence of other forms of eosinophilic gastrointestinal disorders being in between [5,6]. While eosinophilic gastrointestinal disorders are not currently known to increase mortality, they can significantly impact morbidity with a symptomology that affect patients' daily well-being such as persistent dysphagia for patients with eosinophilic esophagitis [7].
Post-transplant lymphoproliferative disorder (PTLD) is a serious condition that can occur in solid organ transplant recipients including liver transplant recipients [8]. The incidence of PTLD can be up to 15% in pediatric liver transplant recipients, much greater than in adults which is only up to 2.8% [9]. Additionally, in pediatric patients, PTLD results in high mortality rates of 18–42% [[10], [11], [12]]. Epstein-Barr virus infection is known to be a major risk factor for developing PTLD [8]; however, these studies typically analyze solid organ transplants in general, and rarely focus on or isolate the liver, especially in pediatric studies. The suppression of T cells from tacrolimus therapy can not only impair Epstein-Barr virus-specific T cell-mediated immunity and contribute to the development of PTLD, but also promote allergic diseases [13]. Thus, we aim to investigate the incidence and the risk factors associated with post-transplant immunologic diseases including post-transplant eosinophilic gastrointestinal disorders (PTEGID) and PTLD in pediatric liver transplant recipients on tacrolimus therapy.
Section snippets
Study population
This was a retrospective cohort study of pediatric liver transplant recipients approved by the institutional review board of Johns Hopkins University School of Medicine. Liver transplant recipients who received transplantation between 0 and 18 years of age at the Johns Hopkins Hospital between 1999 and 2019 were included. Only patients who received tacrolimus as their primary immunosuppressant were included. Patients with substantially incomplete or fragmented medical records were excluded.
Results
Ninety-eight children were included in this study. Of those, 50 (51%) were female and 48 (49%) were male. Their median age at transplantation was 3.3 years (IQR: 1.1–9.3). The racial/ethnic distribution was 56 (57%) White, 19 (19%) Black, 10 (10%) Asian or Pacific Islander, 9 (9%) Hispanic, and 4 (4%) other/unknown. The major indication for liver transplantation for this cohort was biliary atresia at 51 (52%) cases (Table 1). Twenty-eight (29%) of the 96 children had live donor liver
Discussion
A recent study by Marcus et al. on solid organ transplant recipients reported Epstein-Barr virus infection as well as female sex to be risk factors for post-transplant allergy, autoimmunity, and immune-mediated disorders in children; however, in our study, we did not find any significant associations with developing PTEGID due to those factors [14]. In our cohort, we also found an association between Epstein-Barr virus infection in the recipient post-transplantation and the development of PTLD;
Conclusion
PTEGID and PTLD are common in this cohort and are associated with certain risk factors. PTEGID is associated with transplantation at a young age, 1 year or less, and PTLD is associated with high maximal peripheral blood eosinophilic count. Food-induced anaphylaxis increases in prevalence after transplantation. Risk factors for PTEGID and PTLD may be helpful as an inexpensive way to screen children with liver transplants for those potentially severe conditions. Parents may potentially benefit
Disclosures
We have no conflicts of interests or funding to disclose.
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