Impaired intention-to-treat survival after listing for liver transplantation in children with biliary atresia compared to other chronic liver diseases: 20 years' experience from the Nordic countries.

Biliary atresia (BA) is the most common indication for LT in children. We investigated whether this diagnosis per se, compared to other chronic liver diseases (OCLD), had an influence on patient survival. Data from 421 Scandinavian children, 194 with BA and 227 with OCLD, listed for LT between 1990 and 2010 were analyzed. The intention-to-treat survival and influencing risk factors were studied. Patients with BA had higher risk of death after listing than patients with OCLD. The youngest (<1 year) and smallest (<10 kg) children with the highest bilirubin (>510 µmol/L), highest INR (>1.6), and highest PELD score (>20) listed during 1990s had the worst outcome. Given the same PELD score, patients with BA had higher risk of death than patients with OCLD. For adolescents, low weight/BMI was the only prognostic marker. Impaired intention-to-treat survival in patients with BA was mainly explained by more advanced liver disease in younger ages and higher proportion of young children in the BA group rather than diagnosis per se. PELD score predicted death, but seemed to underestimate the severity of liver disease in patients with BA. Poor nutritional status and severe cholestasis had negative impact on survival, supporting the "sickest children first" allocation policy and correction of malnutrition before surgery.

Variations in erythropoiesis throughout a lifetime. Studies in a high-leukaemic mouse strain, the AKR/O strain, and a non-leukaemic strain, the WLO strain.

We have studied the development of some haematological variables: erythropoiesis stimulating factor(s) (ESF), investigated with an in vitro cell culture assay; and the content of bone marrow and spleen erythroid colony forming unit(s) (CFU-E) and erythroid burst forming unit(s) (BFU-E) throughout the lifetime of 2 different mouse strains: the high-leukaemic, retrovirus infected AKR/O strain, and the non-leukaemic WLO strain. During the recovery phase of the postnatal anaemia, a peak in plasma ESF occurs in both strains. In young adult mice of both strains another peak in plasma ESF occurs at 70-110 days of age, associated with an increased number of bone marrow CFU-E, in a period when packed cell volume (PCV) remains stable. As the animals grow older PCV decreases, whereas plasma ESF and bone marrow CFU-E concentration increase. These results, together with in vitro dose-response studies, suggest reduced sensitivity to erythropoietin (Epo) of the ageing erythron. Throughout, the AKR/O strain has higher levels of plasma ESF and bone marrow CFU-E concentrations than the WLO strain, indicating both a reduced Epo responsiveness and some degree of ineffective erythropoiesis in the AKR/O strain. At all ages the AKR/O strain has a high concentration of Epo independent bone marrow CFU-E, possibly caused by the virus infection of precursor cells.

Immunoreactive erythropoietin and erythropoiesis stimulating factor(s) in plasma from hypertransfused neonatal and adult mice. Studies with a radioimmunoassay and a cell culture assay for erythropoietin.

The objective was to study whether the high erythropoietic stimulatory activity found in plasma from neonatal mice during the growth period is erythropoietin (Ep) alone, or Ep in combination with other factors. Plasma from hypertransfused neonatal (20 d) and adult (13-20 weeks) mice were compared with a radioimmunoassay (RIA) and a cell culture assay for Ep. The RIA determines immunoreactive Ep (iEp) while the cell culture assay reflects erythropoiesis stimulating factor(s) (ESF). Compared to control values, hypertransfusion resulting in PCVs of 55% and higher reduced the mean iEp levels in neonatal and adult mice by 82% and 38%, respectively (P less than 0.01). There was no detectable difference between the mean iEp levels of hypertransfused neonatal and adult animals (P greater than 0.3). The parallel ESF data showed a reduction in mean plasma ESF levels by 68% in hypertransfused neonatal and 72% in hypertransfused adult animals (P less than 0.001). And notably, in contrast to the iEp data, the mean ESF level found in hypertransfused neonatal mice with PCVs of 55% and higher was significantly above that of hypertransfused adult animals (P less than 0.001). No correlation was found between PCV and iEp (r less than 0.4, P greater than 0.1) or ESF (r less than 0.2, P greater than 0.2) in hypertransfused animals. The parallel data from the two Ep assays show that plasma from hypertransfused 20-d-old mice contain one or more erythropoietic stimulatory factors not detected by the RIA. It is concluded that part of the high erythropoietic stimulatory activity found in plasma from neonatal mice is due to non-Ep factors.

Regulation of erythropoiesis in suckling rabbits with and without postnatal anemia: partial suppression of production/release of erythropoiesis stimulating factor(s) by iron supplements.

The postnatal anemia in rabbits is accompanied by a marked rise in the plasma erythropoiesis stimulating factor(s) (ESF). The purpose of this study was to establish whether the increase in plasma ESF is only related to the anemia, or whether other mechanisms also are involved. Two matched groups of rabbits were studied from the 15th to the 36th day after birth. One group received iron parenterally and had no postnatal fall in hemoglobin concentration (Hb), the other developed the usual anemia. In both groups plasma ESF was undetectable on the 15th day, and also on the 22nd day, despite a marked fall in Hb in the untreated group and rise in the iron-treated group. Thereafter plasma ESF showed a slight, continuous rise in the nonanemic rabbits, in contrast to a marked, transient rise with maximum on the 29th day in the untreated group. On the 36th day there was no difference between the groups. In the iron-treated group the reticulocyte production rate remained unchanged, while the Hb mass rose continuously. In the untreated animals there was an initial decline in reticulocyte production rate, while Hb mass showed a slight increase. From the 29th day, however, reticulocyte production rate rose to the same level as in the iron-treated group and Hb mass rose markedly. In conclusion, the rise in plasma ESF during the postnatal anemia in rabbits is only in part related to the low Hb. Hypoxia-independent mechanisms, probably related to the growth and maturation per se also are involved. The lack of erythropoietic response to the rise in plasma ESF is due to lack of available iron.

Erythropoietin and uremic toxicity during continuous ambulatory peritoneal dialysis.

This study examined the effect of continuous ambulatory peritoneal dialysis (CAPD) on erythropoiesis and macrophage function. The parameters evaluated were hemoglobin, erythropoiesis-stimulating factor(s) (ESF), and the inhibitory effect of patients' plasma and peritoneal dialysate on erythropoiesis in vitro and on the function of macrophages from normal humans cultured in vitro. ESF was determined by a cell culture assay using hepatic erythroid colony forming cells (CFUE) from newborn mice. The uremic inhibitory effect on macrophages cultured in vitro was expressed as macrophage survival in percentage of controls. Five patients were studied, one of whom was anephric. Hemoglobin increased, without blood transfusions during CAPD treatment, suggesting improved erythropoiesis. Plasma ESF increased in all patients; dialysate ESF increased in all but one patient. Survival of macrophage in vitro, incubated with plasma or dialysate, also improved. In two patients, the inhibitory effect of plasma samples on erythropoiesis in vitro decreased during CAPD treatment. These observations indicate that CAPD removes inhibitors of erythropoiesis and human macrophage function in vitro, and are consistent with transport of inhibitory substances of high molecular weight into the peritoneal cavity. The anephric patient showed improvement of erythropoiesis similar to that of the nephric patients, indicating that the kidney may not be the main producer of erythropoietin (Ep) in patients undergoing CAPD. Peritoneal macrophages may be a site of extrarenal Ep production in this situation. With regard to the parameters studied, CAPD treatment is superior to conventional hemodialysis.