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 impaired TPO gene expression in the pathogenesis of thrombocytopenia in pediatric patients suffering from liver failure, we measured hepatic TPO mRNA in children with acute or chronic end-stage liver disease undergoing orthotopic liver transplantation. Tissue samples for RNA extraction were obtained from 12 children with compensated cirrhosis (CC), 22 children with decompensated cirrhosis (DC), and 9 children with acute liver failure (ALF). TPO mRNA was quantitated by competitive polymerase chain reaction (PCR), following reverse transcription (RT). Furthermore, in 9 children with ALF, serum TPO levels were measured by enzyme-linked immunosorbent assay before and 10 to 14 days after liver transplantation. The hepatic TPO mRNA concentration was highest in children with CC (median, 50.9 amol/micrograms RNA). This value was significantly reduced in children with DC (30.2 amol/micrograms RNA) or ALF (13.8 amol/micrograms RNA). Children with ALF (139 cells/nL) or DC (200 cells/nL) had lower platelet counts than children with CC (368 cells/nL). The serum TPO concentration increased from a median of 156 pg/mL in patients with ALF to 547 pg/mL after liver transplantation. These results show that the thrombocytopenia 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 serve as a prognostic indicator.