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

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.

Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease.

OBJECTIVE: Various lines of evidence suggest that malfunctioning of the gut-liver axis contributes to hepatic damage of rodents and humans with nonalcoholic fatty liver disease. We evaluated the effects of short-term probiotic treatment in children with obesity-related liver disease who were noncompliant with lifestyle interventions. PATIENTS AND METHODS: Twenty obese children (age 10.7 ± 2.1 years) with persisting hypertransaminasemia and ultrasonographic (US) bright liver were enrolled in this double-blind, placebo-controlled pilot study. At baseline, patients underwent clinical and laboratory anthropometric evaluation, measurement of the US hepatorenal ratio, standard liver function tests, oral glucose tolerance test, serum tumor necrosis factor-alpha, the glucose hydrogen breath test, and evaluation of serum antibodies to antipeptidoglycan-polysaccharide polymers. After exclusion of causes of liver disease other than obesity, patients received either probiotic Lactobacillus rhamnosus strain GG (12 billion CFU/day) or placebo for 8 weeks. RESULTS: Multivariate analysis after probiotic treatment revealed a significant decrease in alanine aminotransferase (average variation vs placebo P = 0.03) and in antipeptidoglycan-polysaccharide antibodies (average variation vs placebo P = 0.03) irrespective of changes in BMI z score and visceral fat. Tumor necrosis factor-alpha, and US bright liver parameters remained fairly stable. CONCLUSIONS: Probiotic L rhamnosus strain GG warrants consideration as a therapeutic tool to treat hypertransaminasemia in hepatopathic obese children noncompliant with lifestyle interventions.

Prevalence and long-term course of macro-aspartate aminotransferase in children.

OBJECTIVES: To investigate the prevalence, association with clinical conditions, and long-term course of macro-aspartate aminotransferase (macro-AST). STUDY DESIGN: Forty-four children with an isolated elevation of serum AST were screened for macro-AST with electrophoresis and % polyethylene glycol (PEG) precipitable activity (PPA). RESULTS: All children were healthy, except they had elevated AST values. Seventeen children (38.6%) were macro-AST-positive. They had higher AST values than the 27 children who were macro-AST-negative (P = .001). Values <67.1% PPA and >82.2% PPA were associated with a very low probability of being macro-AST-positive and macro-AST-negative, respectively. Thirty-eight children underwent clinical and laboratory follow-up (mean, 4.7 +/- 3.8; range, 1-16 years). All remained symptom-free. AST levels decreased significantly only in children who were macro-AST-negative (P = .006). Macroenzyme persisted in 6 of the 9 children who were macro-AST-positive after 6.0 +/- 4.1 years. CONCLUSIONS: Macro-AST was present in more than one-third of children with an isolated increase of AST levels. The lack of pathological correlates in a long period argues for the benign nature of this phenomenon in childhood. We suggest that our %PPA thresholds can be used as a screening test and that electrophoresis be reserved for confirming positive screen test results and cases in which %PPA levels are of intermediate discriminant accuracy.