Purpose: UW, IGL-1, HTK, and Celsior have been the mostly used liver graft preservation solutions in Europe in the last 10 years. Between 2003 and 2010, 37,422 first LT performed by European centers with the use of either UW (N=23342), IGL-1 (N=1096), HTK (N=7070) or Celsior (N=5914) preserved grafts, were selected to evaluate the grafts' outcome. One and 3-year graft survival were compared between groups. Results: While UW solution was for long the gold standard, alternative solutions were used with increasing proportion from 20% in 2003 to 57% in 2010. For Full size livers, graft survival was higher in UW, IGL-1, and Celsior groups (82, 81 and 81% at 1 year - 74, 75 and 71% at 3 years, respectively), compared to the HTK group (76% and 69%, respectively) (p<0.0001). The same trend was observed when considering grafts with long ischemia time (CIT>12 hours) or grafts used for patients with cancer (p<0.0001). For partial grafts, 3-year graft survival was 82% for IGL-1, 69% for UW, 68% for Celsior and 62% for HTK (p=0.032). Multivariate analysis identified HTK as an independent factor of graft loss and confirmed other risk factors.Table: No Caption available.Conclusion: HTK appears to be an independent risk factor of graft loss. Both UW and IGL-1, and Celsior to a lesser extent, provides similar results for full size grafts. For partial liver grafts, IGL-1 seems to offer the best graft outcome.

Background and Aims:The clinical application of a bioartificial liver (BAL) depends on the availability of a human cell source with high hepatic functionality.The human hepatoma cell line HepaRG has a unique high hepatic functionality in monolayer culture.Characteristics of the HepaRG cells cultured in the AMC-BAL over time were compared with those in monolayer cultures.Methods: HepaRG cells were cultured in laboratory-scale AMC-BALs for 21 days.14-Day-old HepaRG-AMC-BALs were studied by immunohistochemistry. Hepatic functionality was studied at 7, 14, and 21 days.Functional parameters included ammonia elimination, urea production, conversion of 15 N-ammonia into 15 N-urea, 6b-hydroxylation of testosterone (cytochrome P450 3A4 activity), lactate metabolism, and apolipoprotein A1 production.Next, 14-day-old HepaRG-AMC-BALs were compared with 28-dayold monolayer HepaRG cultures for the same protein-normalized functional parameters, cell leakage (lactate dehydrogenase and aspartate aminotransferase), transcript levels of various hepatic genes, and amino acid metabolism.Results: Immunohistochemistry of 14-day-old BALs demonstrated functional heterogeneity similar to that of monolayer cultures, Hepatic functionality of the HepaRG-AMC-BALs increased during 2-3 weeks of culture.The majority of the measured proteinnormalized hepatic functions were higher in day 14 BAL cultures compared to monolayer cultures, including ammonia elimination (3.2-fold), urea production (1.5-fold), conversion of 15 N-ammonia into 15 N-urea (1.4-fold), and cytochrome P450 3A4 activity (7.9fold).Lactate production in monolayer cultures switched into lactate elimination in the BALs, which is a hallmark of primary hepatocytes.Cell damage was 4-fold lower in 14-day-old BALs compared to monolayer cultures.In BAL cultures, transcript levels of cytochrome P450 1A2, 2B6, 3A4 and 3A7 genes and of the regulatory genes hepatic nuclear factor 4a and pregnane X receptor increased over time and were markedly higher than in monolayer cultures.In addition amino acid metabolism of HepaRG-AMC-BALs more resembled that of primary hepatocytes than monolayer HepaRG cultures.Conclusions: BAL culture of HepaRG cells increases its hepatic functionality both over time as well as compared to monolayer.This is associated with a reduction in cell damage, upregulation of both regulatory and structural hepatic genes, and changes in amino-acid metabolism.These results confirm the high potential of HepaRG cells for BAL application.

L’histoire de l’humanité foisonne en empoisonnements tentés ou réussis, par administration à autrui de substances toxiques ou vénéneuses variées. Cette observation récente est riche en enseignements tant sur le choix du toxique utilisé que sur les limites du diagnostic médical et l’impunité des assassins.Successful or attempted poisonings are abundant in human history. Various toxic or harmful substances were administered to the victims. The interest of this recent case-report regards not only the choice of poison but also the limits of medical diagnosis tools as well as murderers’ persistent impunity.

Mutations in the serine protease inhibitor Kazal type 1 gene (SPINK1) encoding pancreatic secretory trypsin inhibitor (PSTI) have recently been found to be associated with chronic pancreatitis. Nevertheless, knowledge of severe mutations is particularly scarce, both in terms of number and in the extent of clinical information. The aim of this study was to expand the known spectrum of such mutations. 46 unrelated families, each including at least two pancreatitis patients and carrying neither cationic trypsinogen (PRSS1) mutations nor the frequent SPINK1 N34S mutation, participated in this study. The four exons and their flanking sequences of the SPINK1 gene were screened by denaturing high performance liquid chromatography analysis (DHPLC); and mutations were identified by direct sequencing. A heterozygous microdeletion mutation (c.27delC), which occurs within a symmetric element, was identified in two families. In one family, c.27delC showed segregation with the disease across two generations, with a penetrance of up to 75%. But in the other family, however, the same mutation manifested as a low‐penetrance susceptibility factor. In addition, a novel heterozygous splicing mutation, c.87+1G>A (G>A substitution at nucleotide +1 of intron 2) was found in one family with familial pancreatitis. Our results also helped to resolve the sharply differing views about PSTI's role in pancreatitis. © 2003 Wiley‐Liss, Inc.