Clinicopathological Associations of Plasma Cell-Rich Rejection in Pediatric Liver Transplant Recipients.

INTRODUCTION

Liver transplantation is the standard treatment for pediatric patients with cirrhosis, acute liver failure, metabolic liver disease, and malignancy. Plasma cell-rich rejection is a poorly characterized form of late-onset rejection. We aimed to evaluate the incidence and clinicopathological factors associated with plasma cell-rich rejection in pediatric liver transplant recipients in Johannesburg, South Africa.

METHODS

We conducted a retrospective review of 91 pediatric liver transplant recipients (≤ 18 years) who underwent transplantation between January 1, 2015, and December 31, 2021. Demographics, clinical characteristics, episodes of acute cellular rejection, Banff Rejection Activity Index scores, histopathological findings, medication level variability index, and outcomes were analyzed. Survival outcomes were assessed using the Kaplan-Meier methods and Cox proportional hazards models, with follow-up censored as of 31 December 2023.

RESULTS

Of 91 recipients, 45 (49.5%) developed acute cellular rejection, with a median medication level variability index of 2.05 (1.1-3.3). Late-onset acute cellular rejection occurred in 19 of these 45 patients (42.2%). Plasma cell-rich rejection was identified in 14 patients (15.3%) and was associated with increased frequency and severity of acute cellular rejection episodes (p < 0.001), autoimmune seropositivity (p = 0.008), central perivenulitis (p < 0.001), and chronic rejection (p = 0.006). In multivariable logistic regression, recurrent rejection episodes (OR 22.04, 95% CI 5.08-95.52; p < 0.001) and severe rejection (OR 3.60, 95% CI 1.66-7.78; p = 0.001) were independently associated with PCRR. Plasma cell-rich rejection was not independently associated with mortality in a Cox proportional hazards analysis (HR 0.51, 95% CI 0.15-1.73; p = 0.282). Mortality was independently associated with higher medication level variability index values (HR 1.06, 95% CI 1.03-1.09; p < 0.001), severe rejection Banff Rejection Activity Index score 7-9 (HR 1.42, 95% CI 1.00-1.99; p = 0.049), and cytomegalovirus disease (HR 3.71, 95% CI 1.67-8.25; p = 0.001).

CONCLUSION

Plasma cell-rich rejection is associated with frequent and severe rejection episodes, autoimmune markers, central perivenulitis, and chronic rejection. PCRR was not independently associated with mortality; mortality was associated with higher medication level variability index values, severe rejection, and CMV disease. Early recognition of these clinicopathological associations may support closer monitoring and inform future research into targeted management strategies.