Roles of Epstein-Barr virus viral load monitoring in the prediction of posttransplant lymphoproliferative disorder in pediatric liver transplantation

J Formos Med Assoc. 2019 Sep;118(9):1362-1368. doi: 10.1016/j.jfma.2018.12.007. Epub 2019 Jan 3.

Abstract

Background/purpose: This study is aimed to investigate the risk factors and clinical characteristics of posttransplant lymphoproliferative disorder (PTLD) after conducting Epstein-Barr virus (EBV) viral load monitoring in pediatric liver transplant (LT) patients in Taiwan, where EBV infection is endemic.

Methods: From 2007 to 2013, pediatric LT recipients who underwent EBV viral load monitoring within 3 months after LT were recruited in this study. The impact of clinical parameters-including age at LT, sex, peak EBV viral load and immunosuppressant levels after LT-on the risk of PTLD were assessed.

Results: A total 39 patients underwent LT at a median age of 1.3 years (range: 0.6-14.0 years), and 5 patients developed PTLD during follow-up. Cox's proportional-hazards model identified two predictors of PTLD: peak EBV viral load within 3 months of LT >4100 copies/μg peripheral blood mononuclear cells (PBMC) DNA and peak tacrolimus level within 3 months of LT >14.8 ng/mL (Hazard ratio = 17.14 and 11.54, P = 0.02 and 0.03, respectively). Kaplan-Meier survival analysis revealed significant higher cumulative incidence rates of PTLD (27.3% and 41.8% at 0.3 and 1.2 years after LT) in subjects with peak EBV viral load >4100 copies/μg PBMC DNA within 3 months after LT. (P = 0.001, log-rank test).

Conclusion: Close monitoring of EBV viral load within 3 months after LT is helpful to predict a high risk of PTLD. Tapering of immunosuppressants is suggested if the EBV viral load is >4100 copies/μg PBMC DNA in LT children.

Keywords: Epstein–Barr virus infections; Liver transplantation; Lymphoproliferative disorders; Pediatrics; Viral load.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • DNA, Viral / blood
  • Epstein-Barr Virus Infections / diagnosis*
  • Female
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Infant
  • Kaplan-Meier Estimate
  • Leukocytes, Mononuclear / virology
  • Liver Transplantation*
  • Lymphoproliferative Disorders / diagnosis*
  • Lymphoproliferative Disorders / virology
  • Male
  • Postoperative Complications / diagnosis*
  • Postoperative Complications / virology
  • Proportional Hazards Models
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use
  • Taiwan
  • Viral Load*

Substances

  • DNA, Viral
  • Immunosuppressive Agents
  • Tacrolimus