Jérémie Gras

Steroid-free liver transplantation in children.

Although corticosteroids have been part of immunosuppressive regimens since the early days of transplantation, steroid avoidance could be beneficial. To test this hypothesis in paediatric liver transplantation, we compared liver-transplantation under steroid-free immunosuppression in 20 children, who received combined tacrolimus and basiliximab, with that under tacrolimus and steroids in 20 matched historical recipients as a historical control group. 12-month rejection-free survival was 75% in the tacrolimus-basiliximab group compared with 50% in the steroid group (p=0.05). Growth in the first year after transplantation was significantly better in the tacrolimus-basiliximab group than in the steroid group. Steroid avoidance was, therefore, not harmful to our patients, and combining tacrolimus with basiliximab as a steroid substitution seems a safe alternative to tacrolimus and steroid immunosuppression.

Steroid-free, tacrolimus-basiliximab immunosuppression in pediatric liver transplantation: Clinical and pharmacoeconomic study in 50 children†

Corticosteroid‐free immunosuppression (IS) may be potentially beneficial for transplanted patients, particularly children. The purpose of this study was to evaluate the efficacy and cost of such strategy in primary pediatric liver transplantation (LT). Fifty pediatric LT recipients were prospectively treated with a steroid‐free, tacrolimus‐basiliximab–based IS (group TB). A group of 34 children transplanted under a conventional tacrolimus‐steroids regimen served as control series (group TS). Groups TB and TS were compared regarding patient and graft survival, rejection incidence, infectious complications, and growth, as well as cost of the transplant procedure. Patient and graft survivals at 3 years were 96% and 94% in group TB, versus 91% and 88% in group TS (P = 0.380 and P = 0.370, respectively). Rejection‐free graft survival at 3 years was 72% in group TB, versus 41% in group TS (P = 0.007). Patients in group TB had significantly less viral infections than patients in group TS (P = 0.045). Height standard deviation score was significantly enhanced in children from group TB, when compared to group TS. Medical care costs were similar in both groups. Steroid avoidance together with basiliximab immunoprophylaxis was not harmful in terms of allograft acceptance, and even seemed to be beneficial in the long term. Liver Transpl, 2008.

Iron storage is significantly increased in peritoneal macrophages of endometriosis patients and correlates with iron overload in peritoneal fluid

OBJECTIVE To further investigate peritoneal iron disruption in endometriosis by studying iron storage in peritoneal macrophages of patients with endometriosis compared with controls. DESIGN Cross-sectional study. SETTING Academic gynecology research unit in a university hospital. PATIENT(S) Fifty patients undergoing laparoscopy. INTERVENTION(S) Collection of peritoneal fluid samples (N = 50) from patients with (n = 27) and without (n = 23) endometriosis undergoing laparoscopy. MAIN OUTCOME MEASURE(S) Quantification of peritoneal macrophage ferritin by immunocytochemical staining and immunodensitometry and measurement of peritoneal iron, transferrin, ferritin, and prohepcidin concentrations. RESULT(S) The optical density of peritoneal macrophage ferritin staining was statistically significantly higher in endometriosis patients than in controls. Higher iron concentrations, transferrin saturations, and ferritin concentrations were also detected in case of endometriosis. A statistically significant positive correlation was found between the optical density of macrophage ferritin staining and peritoneal iron concentrations in endometriosis and control patients. CONCLUSION(S) Iron storage is statistically significantly increased in peritoneal macrophages of patients with endometriosis and correlates with iron overload in peritoneal fluid. The potential implications of iron accumulation in peritoneal macrophages in case of endometriosis are discussed.

Early immunological monitoring after pediatric liver transplantation: cytokine immune deviation and graft acceptance in 40 recipients.

Cytokine deviation may be a factor contributing to graft acceptance. We analyze, in the context of liver transplantation, circulating cytokine levels and their mRNA precursors in liver biopsy samples to study a putative correlation with early immunologic outcome. Forty primary pediatric liver recipients were submitted to a prospective immune monitoring protocol, including 8 of 40 patients with an early, biopsy‐proven acute rejection episode. The 32 patients with graft acceptance showed markedly increased interleukin (IL)‐10 blood levels at 2 hours after reperfusion on days 1 and 4 after transplantation as compared with baseline, whereas patients with graft rejection only exhibited increased IL‐10 levels at 2 hours. A good correlation was observed between IL‐10 peripheral levels and levels ascertained by IL‐10 reverse transcriptase–polymerase chain reaction at 2 hours and on day 7. Patients with graft acceptance also showed a decrease in interferon gamma (IFN‐γ) at 1 and 2 hours after reperfusion on days 1, 4, 7, 14, and 28 after transplantation. One patient with graft tolerance who had subsequent immunosuppression withdrawal after posttransplantation lymphoproliferative disease showed a similar intraoperative IL‐10 pattern, whereas posttransplantation tumor necrosis factor alpha and IFN‐γ levels greatly decreased. The occurrence of cytokine immune deviation may therefore be related to early graft acceptance in children who receive liver transplants. Liver Transpl 13:426–433, 2007.

PELD score and posttransplant outcome in pediatric liver transplantation: a retrospective study of 100 recipients.

Background. Pediatric End-stage Liver Disease (PELD) score is proposed as an objective tool to prioritize children awaiting liver transplantation (LT), higher PELD being associated with increased pre-LT mortality. This study investigated whether PELD may also impact on post-LT results. Methods. PELD was retrospectively analyzed in 100 pediatric recipients of a primary LT from living-related (n = 49) or postmortem donors (PMD, n = 51). The main pre-LT diagnosis was biliary atresia (n = 64), hepatic malignancy and fulminant hepatitis cases being excluded. PELD was calculated in all patients at the time of pre-LT assessment. Considering the median delay of 117 days between listing and LT in the PMD subgroup, a second PELD was calculated at the time of LT, allowing the determination of a &Dgr;PELD during the waiting period. PMD grafts were allocated using an allocation system taking into account waiting times as well as medical urgency, operative at EuroTransplant. Results. Overall 5-year actuarial patient and graft survivals were 96% and 91%, respectively. PELD at listing (13.3 ± 9.7) showed a normal statistical distribution. PELD scores at listing and at LT were not found to significantly impact on post-LT outcome (NS). In contrast, higher &Dgr;PELD might be associated with lower posttransplant patient survival (p = 0.094). Conclusions. The results of this retrospective analysis suggest that giving priority to high PELD recipients may not result in worsening post-LT outcome. Accordingly, these data support such “sickest children first” allocation policy, which should contribute to reduce pre-LT mortality without worsening post-LT results and increasing organ waste.

The immunological monitoring of alloreactive responses in liver transplant recipients: a review.

The aim of this work is to review the current knowledge in the field of immunological monitoring of allogenic responsiveness in clinical liver transplantation. When compared to other solid‐organ transplants, liver allografts are considered as immunologically privileged, and, accordingly, constitute a favorable setting to develop experimental as well as clinical strategies for minimization of immunosuppression and even induction of operational tolerance. The validation of simple, reliable, noninvasive assays exploring antidonor alloreactivity will constitute a crucial step toward implementing such approaches in the clinic. In contrast to research in rodents claiming the development of donor‐specific tolerance in case of graft survivals of over 100 days without immunosuppression, it is impractical to confirm tolerance induction in this way in humans. Promising candidate assays include the detection of post‐transplant immune deviation, of circulating precursors of dendritic cells subtypes, and of regulatory T cells. A conceptual framework for the development of tolerance assays in clinical liver transplantation is also proposed. Liver Transpl 12:373–383, 2006.

Liver transplantation in children with fulminant hepatic failure : The UCL experience

Abstract:  The outcome of pediatric LT for FHF was shown to be poor in our center. To better understand such results, recipient and transplant parameters with a putative impact on post‐transplant outcome were analyzed in LT for FHF. Between March 1984 and June 2002, 33 children with FHF received a primary liver allograft. The overall results in this series were studied with respect to pre‐operative demographic and metabolic variables, peri‐operative events, and outcome. Five‐yr patient and graft survivals were 71% and 66%, respectively, with a retransplantation rate at 18%. Incidences of perioperative hemorrhage, of HAT and PVT were 14%, 8%, and 4%, respectively. Five‐yr acute rejection‐free survival rate was 55%. These data confirm the worse outcome following LT for FHF when compared with LT in elective, non‐malignant indications such as BA; results in FHF could not be related to surgical or immunological complications in the post‐transplant period and it is hypothesized that the MOF associated with FHF contributes to early post‐transplant mortality which would justify special management, including aggressive renal and hepatic support.