Juvenile erythrocytosis in children after liver transplantation: prevalence, risk factors and outcome

Abstract

Most reports of post-transplant erythrocytosis have involved kidney recipients and, so far, there have been no large studies of onset of erythrocytosis after orthotopic liver transplantation (oLt) in children. We present a long-term survey of pediatric liver recipients, evaluating prevalence, outcome and the main potential causes of erythrocytosis, including a comprehensive mutational analysis of commonly related genes (mutations of HBB and HBA, JAK2, EPOR, VHL, EPAS1 and EGLN1). Between 2000 and 2015, 90 pediatric OLT recipients were observed for a median period of 8.7 years (range 1-20.4 [IQR 4.9-13.6] years). Five percent of the study population (4 males and 1 female) developed erythrocytosis at 8.5 years post OLT (range 4.1-14.9 [IQR 4.7-14.7]) at a median age of 16.6 years (range 8.2-18.8 [IQR 11.7-17.7]). Erythrocytosis-free survival after OLT was 98.6% at 5 years, 95% at 10 years, and 85% at 15 years, with an incidence rate of 6/1000 person-years. No cardiovascular events or thrombosis were reported. no germinal mutation could be clearly related to the development of erythrocytosis. one patient, with high erythropoietin levels and acquired multiple bilateral renal cysts, developed clinical hyper-viscosity symptoms, and was treated with serial phlebotomies. in conclusion, this prospective longitudinal study showed that erythrocytosis is a rare complication occurring several years after oLt, typically during adolescence. erythrocytosis was non-progressive and manageable. its pathogenesis is still not completely understood, although male gender, pubertal age, and renal cysts probably play a role. Erythrocytosis is defined by an increase in red-cell mass to >125% of the predicted valued according to sex and body mass 1. In adults, hematocrit (Hct) >56% in females and 60% in males has been considered sufficient to define the condition of absolute erythrocytosis 2 , although the World Health Organization has now proposed lower levels among the criteria for Polycythemia Vera (i.e. Hct > 49% or >48% and Hemoglobin [Hb] > 16.5 g/ dL or >16 g/dL, respectively, for males and females) 3. In children, diagnosis can be challenging as it relies on Hb and Hct percentiles and cutoff values that vary according to age and sex, even though fixed cut off criteria are used for adults. Furthermore, some diagnostic tests for erythrocytosis may require specific procedures for use in pediatric populations, making them more complex and expensive than those used in adults 4. The main concern related to erythrocytosis in the general population, and especially in patients undergoing organ transplantation, is the risk for cardiovascular events and death, as erythrocytosis can affect transplant outcome and lead to long-term complications 5. Erythrocytosis is quite a common complication after renal transplants with a prevalence of 10-15% 5 , varying from as low as 3.2% in children 6 to as high as 20.2% in adults 5-7. Erythropoietin (EPO), renin-angiotensin system, insulin-like growth factor, male gender and renal cysts are some of the fac...