Elsevier

Transplant Immunology

Volume 68, October 2021, 101438
Transplant Immunology

Research Article
Post-transplant eosinophilic gastrointestinal disorders and lymphoproliferative disorder in pediatric liver transplant recipients on tacrolimus

https://doi.org/10.1016/j.trim.2021.101438Get rights and content

Highlights

  • Liver transplantation in children ≤1 year was associated with PTEGID.

  • Eosinophilic count of ≥500/μL was associated with having PTLD.

  • The frequency of food-induced anaphylaxis increased post-transplantation.

  • PTEGID and PTLD are common in children with liver transplant.

Abstract

Aim

To examine and characterize post-transplant eosinophilic gastrointestinal disorders (PTEGID) and post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients.

Methods

This is a single center retrospective study of all liver transplant recipients aged 0–18 years from 1999 to 2019 who received tacrolimus as their primary immunosuppressant. Demographic data and clinical/laboratory data including PTEGID, PTLD, liver transplant types, Epstein-Barr virus status, and blood eosinophil count were reviewed. Analysis was done with logistic regression and Mann-Whitney U test.

Results

Ninety-eight pediatric liver transplant recipients were included with median age at transplantation of 3.3 years (IQR: 1.1–9.3). The major indication for transplantation was biliary atresia, 51 (52%) cases. Eight (8%) children had PTLD and 14 (14%) had PTEGID. Receiving liver transplantation at an age of ≤1 year was associated with developing PTEGID (OR = 11.9, 95% CI = 3.5–45.6, p < 0.001). Additionally, eosinophilic count of ≥500/μL was associated with having PTLD (OR = 10.7, 95% CI = 1.8–206.0, p = 0.030) as well as having at least one liver rejection (OR = 2.8, 95% CI = 1.2–7.0, p = 0.024). The frequency of food-induced anaphylaxis significantly increased post-transplantation (p = 0.023).

Conclusions

PTEGID and PTLD are common in this cohort and are associated with certain risk factors that help screen children to improve recipient survival. Further studies are needed to evaluate the clinical benefits of these findings.

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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