Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood

The liver is the main production site of the hormone thrombopoietin (TPO), the major regulator of megakaryopoiesis. To investigate the role of an impa ired TPO gene expression in the pathogenesis of thrombocytopenia in pediatr ic patients suffering from liver failure, we measured hepatic TPO mRNA in c hildren with acute or chronic end-stage liver disease undergoing orthotopic liver transplantation. Tissue samples for RNA extraction were obtained fro m 12 children with compensated cirrhosis (CC), 22 children with decompensat ed cirrhosis (DC), and 9 children with acute liver failure (ALF). TPO mRNA was quantitated by competitive polymerase chain reaction (PCR), following r everse transcription (RT). Furthermore, in 9 children with ALF, serum TPO l evels were measured by enzyme-linked immunosorbent assay before and 10 to 1 4 days after liver transplantation. The hepatic TPO mRNA concentration was highest in children with CC (median, 50.9 amol/mu g RNA). This value was si gnificantly reduced in children with DC (30.2 amol/mu g RNA) or ALF (13.8 a mol/mu g RNA). Children with ALF (139 cells/nL) or DC (200 cells/nL) had lo wer platelet counts than children with CC (368 cells/nL). The serum TPO con centration increased from a median of 156 pg/mL in patients with ALF to 547 pg/mL after liver transplantation. These results show that the thrombocyto penia in children with liver failure is associated with reduced hepatic TPO mRNA levels. It remains to be investigated whether the serum TPO level and platelet counts are markers for the severity of liver damage that may serv e as a prognostic indicator.