赛尼哌在肝移植中的应用探讨

目的研究赛尼哌在肝移植患者中应用的安全性和有效性 ,探讨其在肝移植中的合理应用方案。方法对 2 0 0 1年 3月到 2 0 0 3年 2月间 5 0例有肾功能不全或有肾功能不全高危因素的肝移植患者应用赛尼哌情况进行回顾性研究。结果与对照组相比以下时期血肌酐水平显著增高 :移植前 (12 6± 5 5 )mmol/L ,P =0 0 0 2 7;术后第 1天 (16 4± 6 0 )mmol/L ,P =0 0 0 14 ;术后第 7天(12 0± 2 8)mmol/L ,P =0 0 179。术后第 14天 (99± 2 6 )mmol/L与对照组比差异无显著意义 ,P =0 4 0 0 7。应用赛尼哌期间未见有其他重要脏器功能损害。急性排斥反应的发生率 :治疗组 6 % (3/5 0 ) ,对照组 2 9% (18/ 6 2 ) ,P =0 0 0 19。感染的发生率 :治疗组 5 6 % (2 8/ 5 0 )。对照组 5 8% (36 / 6 2 ) ;P =0 82 6。结论赛尼哌在肝移植中应用安全有效 ,有利于肾功能不全的恢复 ,不增加感染的发生率 ,不引起重要脏器功能不全。联合应用赛尼哌 ,可减低钙调神经磷酸酶抑制剂 (calcineurininhibitor,CNI)的血药浓度 ,在术后早期推迟CNI的应用时间 ,同时明显减低急性排斥反应的发生率。     

儿童肝移植

Pediatric liver transplantation has long been developed in the western world.Currently,favorable outcomes after liver transplantation have been achieved in pediatric recipients and the postoperative 5-...     

Pediatric liver transplantation

Pediatric liver transplantation is a fast-growing and challenging field. Healthcare providers must stay informed of advancements in the management of liver transplant candidates and recipients. The goal of this paper is to provide nurses who care for pediatric liver transplant candidates and recipients with a review of the basic medical management of these patients, from the preoperative evaluation to postoperative care.     

Pediatric liver transplantation

Liver transplantation, which once was an experimental procedure of no practical interest, has become the preferred treatment for infants and children dying of almost all non-neoplastic end-stage liver diseases. Liver replacement is being provided by many well-trained teams on all of the continents, as is evident from the program today--the first international symposium on pediatric liver transplantation. I have been honored in giving the first paper in the process of introducing the remarkable work of a gifted younger generation of physicians and surgeons.     

Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation

BACKGROUND: Corticosteroid-free maintenance immunosuppression after organ transplantation eliminates the well-known corticosteroid-related side effects and may help to improve long-term outcome. We investigated whether a corticosteroid-free tacrolimus (Tac)/mycophenolate mofetil (MMF) regimen, in combination with daclizumab (Dac) induction therapy, provides adequate immunosuppression after renal transplantation. METHODS: This 6-month, open-label, multicenter, parallel-group study involved 538 renal patients randomized (1:1) to a Dac/Tac/MMF regimen (n = 260) or a Tac/MMF/corticosteroids regimen (n = 278) as a control group. RESULTS: Of the patients who completed the study, 88.8% in the Dac/Tac/MMF group were free from corticosteroid therapy at month 6. The incidence of biopsy-proven acute rejection was 16.5% in both treatment groups; the incidence of biopsy-proven corticosteroid-resistant acute rejection was 4.3% and 5.0% with Tac/MMF/corticosteroids and Dac/Tac/MMF, respectively (P = NS for both comparisons). Renal function was also similar in both groups: median serum creatinine at month 6 was 125.0 micromol/L (Tac/MMF/corticosteroids) and 131.0 microml/L (Dac/Tac/MMF), P = 0.277. The overall safety profile was similar with both regimens. However, compared with the Tac/MMF/steroid regimen, a significantly reduced incidence of new-onset insulin-dependent diabetes mellitus (5.4% vs. 0.4%, P = 0.003) was found with steroid-free immunosuppression. Moreover, mean total cholesterol concentrations increased from baseline in the Tac/MMF/corticosteroids group by 0.19 mmol/L, whereas in the Dac/Tac/MMF group, levels decreased by 0.19 mmol/L, P = 0.005. CONCLUSIONS: Corticosteroid-free immunosuppression with a Dac/Tac/MMF regimen is as effective at preventing acute rejection after renal transplantation as a standard triple regimen of Tac/MMF/corticosteroids. Furthermore, the safety benefits reported with Dac/Tac/MMF treatment may help improve the long-term outcome for renal-transplant patients.     

Outcome of induction immunosuppression for liver transplantation comparing anti‐thymocyte globulin,daclizumab, and corticosteroid

In addition to standard corticosteroid induction, anti‐thymocyte globulin (ATG) or daclizumab as induction immunosuppression has been reported for liver transplantation. However, the effects and long‐term outcomes of antibody induction therapy are not well known, especially for hepatitis C (HCV). The United Network for Organ Sharing (UNOS) database was utilized to analyze 16 898 adult primary liver transplant patients who received ATG alone (n = 452), ATG and steroids (ATG + S) (n = 1758), daclizumab alone (n = 683), or steroid alone (n = 14 005), listed as induction immunosuppression. Graft and patient survival, and donor and recipient factors for survival were analyzed for HCV and all liver diseases. For patients with HCV, ATG + S had significantly inferior graft survival compared with daclizumab (P = 0.01) and steroids (P = 0.03). The Cox proportional hazards model also showed that ATG + S was a marginal risk factor for graft failure (P = 0.05). On the other hand, for patients with all the liver diseases, graft and patient survival were not significantly different between induction regimens. ATG induction appeared to be preferentially used in patients with renal dysfunction, with improvement in renal function after liver transplantation. Thus, ATG induction can be used for patients with renal dysfunction in non‐HCV diseases. Daclizumab induction achieved satisfactory short‐term and long‐term outcomes of liver transplantation in all the liver diseases including HCV disease.     

IL-2 receptor blockers in liver transplantation: initial experience with daclizumab in Chile

Monoclonal antibodies against the interleukin 2 receptor have been developed in an effort to decrease rejection rates and spare calcineurin inhibitors when renal dysfunction occurs after transplant. While success has been reported in kidney transplantation, its effectiveness in liver transplantation is less clear. METHODS: This prospective nonrandomized study including adult patients was performed between October 2000 and April 2003. Two groups of immunosuppressive regimens were compared: group A received 2 g of methylprednisolone intraoperatively followed by a rapid reduction with intention to withdraw by month 4, continuing on Neoral monotherapy. Cellcept was also given for 2 months in the absence or for up to 4 months in the presence of rejection. Group B received the same immunosuppressive regimen but, in addition, daclizumab 1 to 1.5 mg/kg on day 1 and day 5 posttransplant. Rejection diagnosis is made on histology basis. Protocol biopsies were performed in all the patients on day 7 and if indicated by biochemistry thereafter. RESULTS: Both groups were similar in terms of preoperative CHILD score, serum creatinine, incidence of status I, donor and recipient age and ischemia times. The mean follow-up time was 20 months for Group B (n = 24) and 7 months for Group A (n = 10). The 1-month and 1-year rejection rates are 29.1% and 41% in Group A versus 20% and 30% in group B. Rejection severity was similar between both groups. One-year patient and graft survival rates were 96% and 92% in group A and 100% for both in Group B. CONCLUSIONS: In this series, daclizumab induction therapy seems to display a trend toward a lower rejection rate without increasing infectious complications nor affecting graft survival rates.     

Pediatric living donor liver transplantation

AIM: The aim of this study was to analyze the results of living donor in a pediatric liver transplantation program. PATIENTS: Twenty-six living donor liver transplantations were performed in children from 0.5 to 14.8 years of age. The main indication was biliary atresia (72%) followed by tumors (2 hepatoblastomas and 1 hepatocarcinoma). Left lateral segments were used in 23 (1 transformed into a monosegment), 1 left lobe was used in 1, and right lobes were used in 2. Arterial reconstruction employed saphenous venous grafts in the first 3 cases and end-to-end anastomoses with a microsurgical technique in the following 22 cases. RESULTS: There has been no major morbidity in the donors, with a median hospitalization of 6 days. Four grafts have been lost; 2 in the first 3 cases. In only 1 case, the graft loss was related to the procedure saphenous venous graft thrombosis). Early biliary complications were frequent (23%). Six month, 1 year, and 5 year graft and patient survival rates were 91%, 85%, and 85% and 100%, 96%, and 96%, respectively. CONCLUSIONS: Living donor liver transplantation is an excellent option for transplantation in children.     

Pediatric liver transplantation for acute liver failure

The only proven therapy for patients unlikely to recover from acute liver failure (ALF) is liver transplantation. Correct diagnosis of these individuals and rapid referral to a transplant center are crucial. We evaluated 12 pediatric patients with ALF who underwent liver transplantation (LT) at our institution during a 3-year period. The reasons for transplantation were hepatitis A (3 patients); non-A, non-E hepatitis (3); autoimmune hepatitis (1); fulminant Wilson's disease (3); Amanita phalloides (mushroom) poisoning (1); and hepatitis B and toxic hepatitis with leflunomide treatment (1). Seven of the participants were female and five were male (mean age, 9.1 +/- 4.2 years). Three received right liver-lobe grafts, one received a whole liver graft, and the remainder received left or left-lateral liver lobe grafts. All patients recovered from hepatic coma the second postoperative day. Two patients died at postoperative days 57 and 71 due to adult respiratory distress syndrome and sepsis with multiorgan failure, respectively. One patient required retransplantation because of chronic rejection 7 months after the initial transplantation. That patient died 10 days after retransplantation because of sepsis. Nine patients were healthy at follow-up (range, 2-46 months). LT is the only treatment option for ALF in patients in countries with low organ-donation rates. In this scenario, donor preparation in a limited time frame is difficult. We have been able to decrease the duration of donor preparation to approximately 4 hours (including biopsy of the donated liver tissue).     

Two-dose daclizumab induction therapy in 209 liver transplants: a single-center analysis

BACKGROUND: Patient and graft survival after liver transplantation are adversely affected by early posttransplant renal dysfunction. Therefore, our immunosuppressive strategies should be as "renal sparing" as possible. This is the largest published series to date using daclizumab induction therapy in a renal-sparing regimen. METHODS: This is a retrospective, nonrandomized study comparing 209 adult liver transplants with daclizumab induction to 115 transplants with no induction. RESULTS: Patient and graft survival were similar, despite higher pretransplant acuity of illness and older age in the induction group. Acute rejection within the first 6 months occurred less commonly in the induction group (25.4% vs. 39.1%, P=0.01), despite significantly delayed initiation and lower doses of a calcineurin inhibitor. Mycophenolate mofetil was used more commonly in induction patients, but the efficacy of daclizumab in preventing rejection was independent of this. Patients with a pretransplant creatinine concentration 1.5 mg/dL or less had less rejection if they received induction. Renal function worsened in noninduction patients but showed sustained improvement throughout follow-up in induction patients with a pretransplant creatinine concentration greater than 1.5 mg/dL. Induction therapy provided better rejection prophylaxis among those requiring temporary calcineurin inhibitor cessation because of renal dysfunction. The incidences of histologic hepatitis C recurrence and cytomegalovirus infection were similar in each group. CONCLUSIONS: Liver recipients with and without pretransplant renal dysfunction have less acute rejection with daclizumab induction therapy. This is not associated with an increased risk of over-immunosuppression. Sustained renal improvement in recipients with pretransplant renal dysfunction is possible with daclizumab induction.     

Experience with daclizumab in liver transplantation: renal transplant dosing without calcineurin inhibitors is insufficient to prevent acute rejection in liver transplantation

BACKGROUND: Daclizumab is a monoclonal antibody directed against the alpha chain of the interleukin 2 receptor. We review our experience with the use of daclizumab in liver transplant recipients. METHODS: Thirty-two patients were given daclizumab as induction therapy in the setting of hepatic transplantation. Seven of these patients were enrolled in a pilot study to determine the efficacy of daclizumab in conjunction with corticosteroids and mycophenolate mofetil without the initial use of calcineurin inhibitors (CI). The remaining 25 patients received daclizumab, mycophenolate mofetil, and steroids, with the institution of CI generally within the first postoperative week. The majority of these patients (n = 17) had some degree of renal insufficiency. RESULTS: The pilot study was halted after the first seven patients were enrolled because of an unacceptably high rate of rejection (7/7 = 100%). The patients outside of this pilot study, however, had a much lower rate of rejection (36%). The incidence and severity of rejection correlated with the delay in institution of CI. The described dosing schedule resulted in subtherapeutic daclizumab levels in liver transplant recipients. CONCLUSIONS: Daclizumab used in liver transplant recipients without any CI was ineffective and can potentially lead to steroid-resistant rejection. The dosing regimen used in renal transplant recipients is most likely insufficient for liver transplant patients. However, daclizumab can be used safely in patients with preexisting or postoperative renal dysfunction in conjunction with low doses of CI given within the first week postoperatively.     

Pediatric liver transplantation from neonatal donors

Sixteen recipients of neonatal liver grafts were compared with 114 contemporaneous pediatric recipients of grafts from older donors. Graft and patient survival were worse in the neonatal group although the differences were not statistically significant. Patients with neonatal livers who had no technical complications required a longer time postoperatively to correct jaundice and a prolonged prothrombin time. These functional differences were limited to the 1st postoperative month and the end result was the same as with liver transplantation from older donors.     

Acute renal failure following liver transplantation with induction therapy

AIMS: To identify the predictive factors for acute renal failure (ARF) in a retrospective study of 100 orthotopic liver transplantations (OLT) performed in 94 patients between 2000 and 2003. METHODS: Acute renal failure (ARF) was defined using the RIFLE criteria, i.e. injury when creatinine doubles or GFR halves, and failure when creatinine trebles or GFR decreases by > 75%. Patients on dialysis pre OLT (n = 3) were excluded from the study. Immunosuppression included steroids, calcineurin inhibitors (CNIs), with (n = 32) or without mycophenolate mofetil. A total of 85% of patients also received induction therapy with antithymocyte globulins (29%) or anti-CD25 monoclonal antibodies (56%). RESULTS: 39 patients (41.5%) and 21 (22.3%) patients developed injury, and failure, respectively. Of these, 10 (10.6%) underwent dialysis. Univariate analysis revealed that acute renal dysfunction with a RIFLE score > or = 3 was significantly associated with a pre-operative serum creatinine level of > 100 micromol/l, pre-operative creatinine clearance of < 75 ml/mn, need for a transfusion (> 10 red packed units), post-operative diuresis of < 100 ml/h, use of vasopressive drugs, times to aspartate (AST) and alanine (ALT) aminotransferase peaks of > 20 and > 24 hours, respectively, relaparotomy, CNIs transient discontinuation, and the use of lower daily dosage of CNIs at post-OLT Days 3, 5, 7 and 15. In multivariate analysis, failure was significantly associated with time to AST peak (> 20 h) (OR 6.35 (1.2 - 33.6), p = 0.029), post-operative diuresis (< 100 ml/h) (OR 9.8 (2.03 47.3), p = 0.004), post-operative use of vasopressive drugs (OR 9.91 (2.02 - 48.7), p = 0.004), and transient CNIs withdrawal (OR 51.08 (7.58-344.1), p < 0.0001). Finally, the occurrence of ARF was significantly associated with an increased number of days on mechanical ventilation, on stay-in intensive care unit (ICU), and on overall hospitalization time. CONCLUSION: ARF is quite common after OLT and significantly increases the post-operative time at the hospital, thereby increasing the OLT cost. Its independent predictive factors are mainly related to perioperative events.