Studies of Pediatric Liver Transplantation (SPLIT) is a cooperative research network comprising 38 pediatric liver transplant centers in North America. Data from the 1092 patients who have received a first liver transplant since 1995 were analyzed for factors influencing patient survival, graft survival and acute rejection. The 3, 12, 24 and 36 month Kaplan-Meier estimates of patient/graft survival were 90.9/85.5, 86.3/80.2, 84.3/76.0, and 83.8/75.3% respectively. Univariate analysis identified initial diagnosis, type of graft (whole vs. living and cadaveric technical variant), growth failure and continuous hospitalization or ICU admission prior to transplantation as significantly influencing patient and graft survival. Subsequent multivariate analysis identified as risk factors for death: fulminant liver failure (RR = 3.05, p < 0.05), cadaveric technical variant grafts (RR = 1.95, p < 0.05), continuous hospitalization pre-transplant (RR = 1.79, p < 0.05), height deficit >2 s.d. from mean (RR = 3.22, p < 0.05). Risk factors for graft loss included: fulminant liver failure (RR = 2.27, p < 0.05), cadaveric technical variant grafts, (RR = 1.97, p < 0.05). Eleven percent of the 1092 patients were re-transplanted; vascular complications, particularly hepatic artery thrombosis (8.3% overall; 36.3% of graft failures), were responsible for the majority of re-transplants. Infection was the single most important cause of death (40 of 141, 28.4%) and was a contributing cause in 55 (39%), particularly with bacterial or fungal organisms. The cumulative Kaplan-Meier estimates of first rejection at 3, 12, 24 and 36 months were 44.8, 52.9, 59.1, and 60.3%. Initial immunosuppression with tacrolimus reduced the probability of rejection (RR = 0.62, p < 0.05). Eleven percent of rejections were steroid-resistant; chronic rejection led to 7 of 121 (5.8%) re-transplants. The SPLIT registry, in compiling data from a large number of centers, reflects the current outcomes for pediatric liver transplants in North America.

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Confluent cultures of normal diploid WI-38 human embryonic lung fibroblasts released somatomedin (SM)-like activity into their incubation medium during culture in serum-free medium. This postculture medium (conditioned medium) stimulated cell division in these same cultured WI-38 fibroblasts and 35SO4 uptake by hypophysectomized rat cartilage in vitro. The conditioned medium also contained immunoreactive SM (IRSM) activity which yielded parallel dose-response curves to human serum in a RIA for SM. The IRSM activity measured in conditioned medium was not the artifactual result of effects of possible SM-binding proteins or proteolytic enzymes in conditioned medium. These studies suggest that cultured WI-38 fibroblasts produce and release SM-like activity which has SM-like biological activity and is immunoreactive with a basic SM purified from human plasma Cohn fraction and having similarity with SM-C and insulin-like growth factor-I. Human GH appears to stimulate production and release of IRSM activity by these cells.

Mitochondrial depletion syndrome (MDS) refers to a heterogeneous group of mitochondrial disorders characterized by a reduction of the mtDNA copy number in affected tissues. Mutations in DGUOK encoding deoxyguanosine kinase (MIM 601465) cause the hepatocerebral form of MDS (MIM 251880). Cystathioninuria (MIM 219500) can result from mutations in CTH encoding cystathionine gamma lyase (MIM 607657) or can be a secondary finding in several diverse clinical conditions. We present three patients from two apparently unrelated old colony Mennonite families, each of whom had the hepatocerebral form of MDS together with cystathioninuria. Each affected child was homozygous for the novel DGUOK p.D255Y mutation, but had no CTH mutation, indicating that the hepatocerebral form of MDS might be associated with secondary cystathioninuria.

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Objective. To review the critical care course of children receiving orthotopic liver transplantation (OLT). Methods. A retrospective chart review of patients admitted to the pediatric critical care following OLT performed in our center between 1988 and 2011. Results. A total of 149 transplants in 145 patients with a median age of 2.7 (IQR 0.9–7) years were analyzed. Mortality in the first 28 days was 8%. The median length of stay (LOS) was 7 (4.0–12.0) days. The median length of mechanical ventilation (MV) was 3 (1.0–6.2) days. Open abdomen, age, and oxygenation index on the 2nd day predicted LOS. Open abdomen, age, amount of blood transfused during surgery, and PRISM III predicted length of MV. 28% of patients had infection and 24% developed acute rejection. In recent group (2000–2011) OLT was performed in younger patients; the risk of infection and acute rejection was reduced and patients required longer LOS and MV compared with old group (1988–1999). Conclusion. The postoperative course of children after OLT is associated with multiple complications. In recent years OLT was performed in younger children; living donors were more common; the rate of postoperative infection and suspected rejection was reduced significantly; however patients required longer MV and LOS in the PCCU.

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