再次肝移植治疗移植肝缺血型胆道损伤15例报告

目的探讨再次肝移植治疗缺血型胆道损伤的临床经验。方法回顾性分析15例因缺血型胆道损伤施行再次肝移植受者的临床资料。结果 15例移植受者术前均接受过介入治疗,再次肝移植全组无手术死亡。术后1个月存活率为67%,1年存活率为60%,3年存活率为53%。截止至2012年3月,有8例存活并返院随诊,存活时间超过5年的5例,其余3例存活时间分别为47个月、58个月、35个月,肝功能及生活情况良好。术后严重感染导致的多器官功能衰竭是再次肝移植患者死亡的主要原因。结论再次肝移植是治疗缺血型胆道损伤唯一有效的方法。对于缺血性胆道损伤,预防的意义远大于治疗。从供肝切取与保存、胆道重建、术后免疫抑制方案的选择、长期随访等等环节加以重视,有利于减少缺血型胆道损伤。     

Pediatric liver transplantation. A single center experience spanning 20 years

BACKGROUND: Survival after liver transplantation has improved significantly over the last decade with pediatric recipients faring better than adults. The 20-year experience of pediatric liver transplantation at Children's Hospital of Pittsburgh is reported in terms of patient survival; graft survival in relation to age, gender, and immunosuppressive protocols; causes of death; and indications for retransplantation. METHOD: From March 1981 to April 1998, 808 children received liver transplants at Children's Hospital of Pittsburgh. All patients were followed until March 2001, with a mean follow-up of 12.2+/-3.9 years (median=12.6; range=2.9-20). There were 405 female (50.2%) and 403 male (49.8%) pediatric recipients. Mean age at transplant was 5.3+/-4.9 years (mean=3.3; range 0.04-17.95), with 285 children (25.3%) being less than 2 years of age at transplant. Cyclosporine (CsA)-based immunosuppression was used before November 1989 in 482 children (50.7%), and the subsequent 326 recipients (40.3%) were treated with tacrolimus-based immunosuppression. Actuarial survival was calculated using the Kaplan-Meier statistical method. Differences in survival were calculated by log-rank analysis. RESULTS: Overall patient survival at 1, 5, 10, 15, and 20 years was 77.1%, 72.6%, 69.4%, 65.8%, and 64.4%, respectively. There was no difference in survival for male or female patients at any time point. At up to 10 years posttransplant, the survival for children greater than 2 years of age (79.5%, 75.7%, and 71.6% at 1, 5, and 10 years, respectively) was slightly higher than those at less than 2 years of age (72.6%, 66.9%, and 65.3% at 1, 5, and 10 years, respectively). However, at 15 and 20 years posttransplant, survival rates were similar (>2 years=67.3% and 65.8%; <2 years=64.1% and 64.1%). A significant difference in survival was seen in CsA-based immunosuppression (71.2%, 68.1%, 65.4%, and 61%) versus tacrolimus-based immunosuppression (85.8%, 84.7%, 83.3%, and 82.9%) at 1, 3, 5, and 10 years, respectively (P=0.0001). The maximum difference in survival was noted in the first 3 months between CsA and tacrolimus; thus, indicating there may have been other factors (nonimmunological factors) involved in terms of donor and recipient selection and technical issues. The mean annual death rate beyond 2 years posttransplant was 0.47%, with the mean annual death rate for patients who received tacrolimus-based immunosuppression being significantly lower than those who received CsA-based immunosuppression (0.14% vs. 0.8%; P=0.001). The most common etiologies of graft loss were hepatic artery thrombosis (33.4%), acute or chronic rejection (26.6%), and primary nonfunction (16.7%). Of note, retransplantation for graft loss because of acute or chronic rejection occurred only in those patients who received CsA-based immuno-suppression. CONCLUSION: The overall 20-year actuarial survival for pediatric liver transplantation is 64%. Survival has increased by 20% in the last 12 years with tacrolimus-based immunosuppression. Although this improvement may be the result of several factors, retransplantation as a result of acute or chronic rejection has been completely eliminated in patients treated with tacrolimus.     

Evolution of Causes and Risk Factors for Mortality Post‐Liver Transplant: Results of the NIDDK Long‐Term Follow‐Up Study

Although mortality rates following liver transplantation (LT) are well described, there is a lack of detailed, prospective studies determining patterns of and risk factors for long‐term mortality. We analyzed the multicenter, prospectively obtained The National Institute of Diabetes and Digestive and Kidney Diseases LT Database of 798 transplant recipients from 1990 to 1994 (follow‐up 2003). Overall, 327 recipients died. Causes of death >1 year: 28% hepatic, 22% malignancy, 11% cardiovascular, 9% infection, 6% renal failure. Renal‐related death increased dramatically over time. Risk factors for death >1 year (univariate): male gender, age/decade, pre‐LT diabetes, post‐LT diabetes, post‐LT hypertension, post‐LT renal insufficiency, retransplantation >1 year, pre‐LT malignancy, alcoholic disease (ALD) and metabolic liver disease, with similar risks noted for death >5 years. Hepatitis C, retransplantation, post‐LT diabetes, hypertension and renal insufficiency were significant risk factors for liver‐related death. Cardiac deaths associated with age, male gender, ALD, cryptogenic disease, pre‐LT hypertension and post‐LT renal insufficiency. In summary, the leading causes of late deaths after transplant were graft failure, malignancy, cardiovascular disease and renal failure. Older age, diabetes and renal insufficiency identified patients at highest risk of poor survival overall. Diligent management of modifiable post‐LT factors including diabetes, hypertension and renal insufficiency may impact long‐term mortality.     

Long-term survival after liver transplantation in 4,000 consecutive patients at a single center

OBJECTIVE: To evaluate the long-term survival outcomes of a large cohort of liver transplant recipients and to identify static and changing factors that influenced these outcomes over time. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, with continual improvements in patient survival as a result of advances in immunosuppression and medical management, technical achievements, and improvements in procurement and preservation. Although many reports, including registry data, have delineated short-term factors that influence survival, few reports have examined factors that affect long-term survival after liver transplantation. METHODS: Four thousand consecutive patients who underwent liver transplantation between February 1981 and April 1998 were included in this analysis and were followed up to March 2000. The effect of donor and recipient age at the time of transplantation, recipient gender, diagnosis, and year of transplantation were compared. Rates of retransplantation, causes of retransplantation, and cause of death were also examined. RESULTS: The overall patient survival for the entire cohort was 59%; the actuarial 18-year survival was 48%. Patient survival was significantly better in children, in female recipients, and in patients who received transplants after 1990. The rates of retransplantation for acute or chronic rejection were significantly lower with tacrolimus-based immunosuppression. The risk of graft failure and death was relatively stable after the first year, with recurrence of disease, malignancies, and age-related complications being the major factors for loss. CONCLUSION: Significantly improved patient and graft survival has been observed over time, and graft loss from acute or chronic rejection has emerged as a rarity. Age-related and disease-related causes of graft loss represent the greatest threat to long-term survival.     

单个移植中心连续4000例肝移植后长期生存情况回顾

目的：评价大样本肝移植病人长期生存情况和分析影响移植疗效的动静因素。背景回顾：自1983年以来肝移植被接受为治疗终末期肝病的主要选择之一，随着免疫抑制剂的发展，手术技术的不断完善，取肝及保存方法改进，生存期获不断延长。虽然报告影响近期生存因素的文章甚众，但分析影响长期生存因素者却不多见。方法：回顾性分析1981年2月至1998年4月连续施行的4000例肝移植资料（随访至2000年3月），并对移植时供，受体年龄，受体性别和诊断以及上份等因素进行比较；也统计了再移植率，再移植原因和死亡原因。结果：全组的总生存率为59％，统计18年生存率为48％；小儿，女性和1990年以后接受移植的病人生存情况产好。以FK506为基础的免疫抑制剂使因急，慢性排斥反应而施行的再移植率显著下降，手术一年后，移植肝脏丧失功能病人死亡的曲线相对趋于平稳，疾病复发，急性肿瘤和与年龄相关的并发症是移植物丧失功能的最主要因素。结论：随着年供的推移，病人和移植物的生存活情况获显著改善，由急性，慢性排斥反应所致的移植物失功已属十分罕见，与年龄相关和疾病相关的移植物失功，已构成肝移植患者长期生存的最大威胁。     

Long-term survival and late graft loss in pediatric liver transplant recipients—a 15-year single-center experience

Increasing numbers of children undergo successful liver transplantation. Limited data exist on long-term survival and late graft loss. Survival and graft loss were studied in 376 primary liver graft recipients who survived more than 3 months after transplantation (80.5% of all primary graft recipients). Patient records were reviewed retrospectively for causes of graft loss. Risk factors were identified by analyzing graft, recipient, and posttransplant variables using multivariate Cox regression. One-, 5-, and 10-year actuarial graft survival rates in the study population were 94.6%, 87.3%, and 86.3%, respectively. Corresponding patient survival rates were 95.7%, 91.4%, and 90.4%. Forty-seven (12.5%) grafts were lost subsequently, 15 by patient death with preserved graft function. Survival rate after late retransplantation was 63.3%. Causes of late graft loss were infection (21.2%), posttransplant lymphoproliferative disease (PTLD, 21.2%), chronic rejection (17%), biliary complications (14.8%), and recurrence of malignant disease (8.5%). Independent risk factors for late graft loss and patient death included liver malignancy as primary disease, steroid resistant rejection, and PTLD. Graft loss rate was significantly increased for reduced-size grafts. Patients undergoing transplantation after 1991 and recipients of full-size grafts were more likely to survive. In conclusion, the long-term outcome for pediatric primary liver graft recipients surviving the early postoperative period is excellent except for patients with liver malignancy. There is no increased risk of late graft loss with the use of split or living related donor grafts. Technical complications are only a minor factor in late graft loss, but complications related to immunosuppression and infection remain a major hazard and must be addressed. (Liver Transpl 2002;8:615-622.)     

Causes of mortality beyond 1 year after primary pediatric liver transplant under tacrolimus

BACKGROUND: Success of pediatric liver transplantation has improved significantly. Most posttransplant deaths occur early and are related to surgical complications or recipient status at the time of transplantation. The causes of mortality beyond the first year have not been well described. METHODS: Three hundred twenty-six pediatric liver transplants were performed between November 1989 and April 1998 using tacrolimus-based immunosuppression. Patients were followed until March 2002. Mean follow-up was 9.2+/-2.4 years. RESULTS: At 1 year, 279 patients (85.5%) were alive. In the subsequent 12.5 years, 10 of the remaining children died (3.58%) at a mean interval of 3.68+/-1.69 years after transplant. The mean age at transplant was 5.62+/-6.3 years. Six patients had infections as a major contributor to mortality, including two patients with posttransplant lymphoproliferative disorder (PTLD) and one patient that died after retransplantation for hepatitis. Two patients had recurrent malignancy. Other deaths were attributable to chronic rejection, liver failure after being lost to follow-up, and complications of cystic fibrosis. CONCLUSIONS: Pediatric liver transplantation using tacrolimus-based immunosuppression has demonstrated excellent success, with 1- and 10-year survival rates of 85.5% and 82.9%, respectively. Late mortality after pediatric liver transplantation overall remains low, with a rate of 0.32% per year. The most common cause of death was infection (60%), including PTLD-related disease (20%). However, in the recent cohort of patients who underwent transplantation after September 1995, there were no fatal cases of Epstein-Barr virus or PTLD or late mortality thus far, suggesting a benefit from improved infectious disease surveillance using currently available modalities. Mortality from chronic rejection and noncompliance under tacrolimus has been exceedingly rare.     

Liver Retransplantation in Children: A SPLIT Database Analysis of Outcome and Predictive Factors for Survival

To examine outcomes and identify prognostic factors affecting survival after pediatric liver transplantation, data from 246 children who underwent a second liver transplantation (rLT) between 1996 and 2004 were analyzed from the SPLIT registry, a multi-center database currently comprised of 45 North American pediatric liver transplant programs. The main causes for loss of primary graft necessitating rLT were primary nonfunction, vascular complications, chronic rejection and biliary complications. Three-month, 1- and 2-year patient survival rates were inferior after rLT (74%, 67% and 65%) compared with primary LT (92%, 88% and 85%, respectively). Multivariate analysis of pretransplant variables revealed donor age less than 1 year, use of a technical variant allograft and INR at time of rLT as independent predictive factors for survival after rLT. Survival of patients who underwent early rLT (ErLT, <30 days after LT) was poorer than those who received rLT >30 days after LT (late rLT, LrLT): 3-month, 1- and 2-year patient survival rates 66%, 59%, and 56% versus 80%, 74% and 61%, respectively, log-rank p = 0.0141. Liver retransplantation in children is associated with decreased survival compared with primary LT, particularly, in the clinical settings of those patients requiring ErLT.     

Late rejection episodes more than 1 year after pediatric heart transplantation: risk factors and outcomes.

BACKGROUND: Little is known about late rejection episodes after pediatric heart transplantation. We determined the frequency of late rejection episodes (>1 year) after pediatric heart transplantation, defined risk factors for its occurrence, and evaluated outcome after late rejection. METHODS: We analyzed data from 685 pediatric recipients (<18 years at transplantation) who underwent transplantation between January 1, 1993, and December 31, 1997, at 18 centers in the Pediatric Heart Transplant Study (PHTS). Probability of freedom from late rejection was determined and risk factors for late rejection and for death after late rejection were sought using univariate and multivariate analyses. RESULTS: We followed 431 patients for >1 year (median follow-up, 32.9 months) of whom 106 (24.6%) experienced 1 or more late rejection episodes (total of 178 episodes, 27 with severe hemodynamic compromise). Probability of freedom from first late rejection was 73% at 3 years and 66% at 4 years after transplantation. Risk factors (multivariate analysis) for first late rejection were >1 episode of rejection in the first year (p = 0.009), recipient black race (p = 0.0002), and older age at transplantation (p = 0.0003). Only 4 of 325 (1.2%) children who survived beyond 1 year without late rejection died compared with 26 of 106 (24.6%) with late rejection (p < 0.0001). Nine of these 26 died within 1 month of the first late rejection episode, and 17 died subsequently: 5 of acute rejection, 3 of sudden unexplained deaths, 3 of documented coronary artery disease, and 6 of other causes. Severe hemodynamic compromise with late rejection was identified as a risk factor for death among children with 1 or more episodes of late rejection. CONCLUSIONS: Approximately 25% of pediatric recipients in the PHTS who survived beyond 1 year experienced late rejection episodes. Late rejection is associated with poor survival, especially when associated with hemodynamic compromise. Absence of late rejection episodes is associated with very low risk of death during medium-term follow-up after pediatric heart transplantation. Determining the risk factors for late rejection will help to identify a cohort of patients who may benefit from enhanced rejection surveillance and treatment.     

Late mortality after orthotopic liver transplantation.

BACKGROUND: Mortality within the first year after orthotopic liver transplantation (OLTx) is usually due to infection or allograft failure. Late complications leading to death after OLTx have not been extensively evaluated. The aim of this study was to determine the incidence of late mortality and to identify the most common causes and risk factors associated with late mortality after OLTx. METHODS: A total of 479 OLTx were performed in 459 patients (320 males, 139 females; mean age 47 years, range 13 to 69) between September 1991 and April 2000. All patient deaths among liver transplant recipients who survived more than 1 year after transplantation (follow-up mean 3.4 years, median 3, range 1 to 8.6) were reviewed. RESULTS: In all, 122 allografts (24%) were lost in 109 patients during the study period (24%). Seventy-five allografts were lost in 69 patients by 1 year (15%). Forty-seven allografts were lost in 40 patients who survived at least 1 year (9.6%). Actuarial survivals at 2 years, 5 years, and 9 years were 95%, 85%, and 80%, respectively (based on 100% survival at 1 year). The causes of the late mortality were malignancy (9 patients), disease recurrence (8), late infection (6), renal failure complications (5), cardiovascular complications (4), chronic rejection (3), gastrointestinal hemorrhage (2), medication noncompliance (1), and unknown (2). CONCLUSIONS: Malignancy and disease recurrence are the major causes of late mortality among adult OLTx recipients. Pharmacologic immunosuppression is associated with many of the causes of late mortality. Advances in immunosuppression with less toxicity may improve long-term survival after OLTx.     

Pancreatitis after liver transplantation in children: a single-center experience

BACKGROUND AND METHOD: Posttransplantation acute pancreatitis (PTAP) is a rare but serious complication after pediatric liver transplantation (LTx). We performed a retrospective review in a large cohort of pediatric liver transplant recipients at a single institution to define the impact of this problem in children. RESULTS: Between January 1986 and December 1999, 634 pediatric LTx were performed. Twenty-six patients developed serious acute pancreatitis. The mean age at transplantation was 7.7 years (9 months to 19 years), and the indications for transplantation were biliary atresia in seven, fulminant hepatic failure in six, chronic rejection in seven, and other etiologies in six patients. PTAP was more likely to occur early after LTx (61% within the first week), was associated with the presence of an infrarenal aortic graft in 14 (54%) of 26 patients, was more likely to occur after retransplantation (11/26 patients), and was associated with blood loss and prolonged surgery in four cases. Acute renal failure occurred in 15 (58%) of 26 patients. Mortality was 42% (11/26); causes of death were sepsis or multiple organ failure in nine and hemorrhage in two patients. Management of PTAP included antibiotics, sphincterotomy, debridement with drainage, hepatic arterial revascularization, and arterial ligation. Of the 14 patients with complicated pancreatitis, 5 were treated conservatively and died. Nine patients had extensive operative interventions and four survived (45%). CONCLUSIONS: Several risk factors such as retransplantation, extensive dissection at the time of LTx, and use of infrarenal arterial graft contribute to development of PTAP in children. Early exploration and debridement in patients with complicated pancreatitis may result in a better outcome. Retransplantation in the presence of clinical pancreatitis has a high failure rate.     

Pediatric liver retransplantation: indications and outcome

INTRODUCTION: Liver transplantation is the only treatment for end-stage liver disease. Not all patients have a favorable outcome. Graft failure secondary to primary nonfunction, vascular complications, or chronic rejection among other problems may lead to retransplantation. Retransplantation represents 8% to 29% of liver transplantations in the pediatric population. The aim of this study was to present our experience with retransplanted children by analyzing the indications and the results. METHODS: All patients were prospectively included in our database, including 125 children. We included the indications for retransplantation, complications, and mortality. Kaplan-Meier curves were used for survival analysis. RESULTS: Since 1994, 125 patients were transplanted and 25 were retransplanted (20%), including 5 who received a third graft. Primary nonfunction represented 30% of the indications for retransplantation and hepatic artery thrombosis, 20%. Six of 25 patients who received a first retransplantation and 2 of 5 who received a second retransplantation died. The most frequent cause of death was multiorgans failure. The survivals at 1 and 5 years were 82% and 76% for children receiving a first retransplantation, and 60% at 1 and 5 years for those who received a second retransplantation. CONCLUSIONS: Organ failure after liver transplantation was a common event in pediatric transplantation. Survival was similar between patients transplanted once and those who received one retransplantation. Survival decreased among patients who received a third graft but was maintained at 60%, which is better than most published results for first retransplanted patients. Retransplantation is a valid option with good results for selected pediatric cases.     

Twenty‐eight years of intestinal transplantation in Paris: experience of the oldest European center

Our aim was to describe our achievements in pediatric intestinal transplantation (ITx) and define areas for improvement. After a period (1987–1990) of nine isolated small bowel transplants (SBTx) where only one patient survived with her graft, 110 ITx were performed on 101 children from 1994 to 2014: 60 SBTx, 45 liver–small bowel, four multivisceral (three with kidneys), and one modified multivisceral. Indications were short bowel syndrome (36), motility disorders (30), congenital enteropathies (34), and others (1). Induction treatment was introduced in 2000. Patient/graft survival with a liver‐containing graft or SBTx was, respectively, 60/41% and 46/11% at 18 years. Recently, graft survival at 5/10 years was 44% and 31% for liver‐containing graft and 57% and 44% for SBTx. Late graft loss occurred in 13 patients, and 7 of 10 retransplanted patients died. The main causes of death and graft loss were sepsis and rejection. Among the 55 currently living patients, 21 had a liver‐containing graft, 19 a SBTx (17 after induction), and 15 were on parenteral nutrition. ITx remains a difficult procedure, and retransplantation even more so. Over the long term, graft loss was due to rejection, over‐immunosuppression was not a significant problem. Multicenter studies on immunosuppression and microbiota are urgently needed.     

The Effect of Early Retransplantation on Early and Late Survival After Liver Transplantation

BackgroundEarly liver retransplantation after liver transplantation (LT) is the ultimate salvage procedure for irreversible graft failure. The aim of this study was to assess the impact of early retransplantation on 90-day and 5-year patient survival.MethodsThis retrospective cohort study included 2185 patients after LT in the period between 1997 and 2019. First, the patients undergoing first retransplantation within 6 months after initial LT were compared with naïve LT patients for early mortality (within 90 days). Second, to assess late survival, the patients who had retransplantation and survived at least 90 days post LT were compared with naïve LT patients for 5-year overall survival. The patients undergoing late retransplantation (>6 months) were excluded from analyses. Fisher's exact test was used to compare groups for early survival and log-rank test for late survival.ResultsThe cumulative 1-, 3-, and 5-year overall survival was 87.0%, 79.9%, 75.0%, respectively, and did not differ significantly between the groups. The patients undergoing early retransplantation had lower 90-day survival rate of 89.2% as compared to 95.7% for naïve LT patients (P < .001).ConclusionsThe early liver retransplantation has profound impact on post-LT 90-day survival; however, patients who survive that period can achieve long overall survival comparable with naïve LT patients.     

Long-term outcome of immunosuppression withdrawal after liver transplantation

Eighteen liver transplant recipients were followed up for 10 years after a trial of immunosuppression withdrawal. Three groups were identified according to the early outcome of complete (group A, n = 5), partial (group B, n = 9), and unsuccessful (group C, n = 4) withdrawal of immunosuppression. The indications for liver transplantation (LT) (August 1983-December 1988) were as follows: primary biliary cirrhosis (n = 3), primary sclerosing cholangitis (n = 3), Budd-Chiari syndrome (n = 3), acute liver failure (n = 3), hepatitis C virus (HCV) cirrhosis (n = 1), HCV and autoimmune hepatitis (n = 1), HCV and alcohol-related cirrhosis (n = 1), HCV and hepatocellular carcinoma (HCC) (n = 1), cystic fibrosis (n = 1), and liver metastases from testicular teratoma (n = 1). Immunosuppression was based on cyclosporine. All patients experienced 1 or more complications of prolonged immunosuppression (median, 7 years; range, 5-11). Thirteen patients (72%) are alive at a median interval of 17 years (range, 16-21) after LT. Of the 5 patients in group A, 2 currently have normal graft function with no rejection episodes, and 3 have restarted immunosuppression following late low-grade acute rejection (n = 1), retransplantation for chronic rejection (n = 1), and kidney transplantation (n = 1). Of the 9 patients in group B, 5 died. The deaths were due to ruptured arterial pseudoaneurysm following retransplantation, HCC recurrence, cardiac failure, renal failure, and posttransplant lymphoma at 5, 7, 7, 14, and 17 years after LT, respectively. All 4 patients in group C are alive on a full immunosuppressive regimen. Long-term follow-up of 18 LT recipients withdrawn from immunosuppression has shown that at a median of 17 years 10% of patients remain off all immunosuppression.     

Liver retransplantation in children. A 21‐year single‐center experience*

In this study, the epidemiology and outcome of graft loss following primary pediatric liver transplantation (LT) were analysed, with the hypothesis that early retransplantation (reLT) might be associated with lower immunologic risks when compared with late reLT. Between March 1984 and December 2005, 745 liver grafts were transplanted to 638 children at Saint‐Luc University Hospital, Brussels. Among them, a total of 90 children (14%) underwent 107 reLT, and were categorized into two groups (early reLT, n = 58; late reLT, n = 32), according to the interval between either transplant procedures (< or >30 days). Ten‐year patient survival rate was 85% in recipients with a single LT, vs. 61% in recipients requiring reLT (P < 0.001). Ten‐year patient survival rates were 59% and 66% for early and late reLT, respectively (P = 0.423), the corresponding graft survival rates being 51% and 63% (P = 0.231). Along the successive eras, the rate of reLT decreased from 17% to 10%, whereas progressive improvement of outcome post‐reLT was observed. No recurrence of chronic rejection (CR) was observed after reLT for CR (0 of 19). Two children developed a positive cross‐match at reLT (two of 10, 20%), both retransplanted lately for CR secondary to immunosuppression withdrawal following a post‐transplant lymphoproliferative disease. In summary, the results presented could not evidence better results for late reLT when compared with early reLT. The former did not seem to be associated with higher immunologic risk, except for children having withdrawal of immunosuppression following the first graft.     

成人良性终末期肝病肝移植术后中远期死亡的危险因素分析

目的 了解成人良性终末期肝病肝移植患者术后中远期的生存情况和导致中远期生存率下降的危险因素.方法 回顾性分析2003年10月至2007年6月行原位肝移植手术且术后存活时间超过1年的221例良性终末期肝病受者的资料,选取包括受者术前变量、供者变量、术中变量和受者术后变量共26个可能影响患者长期存活的危险因素,采用Cox回归分析筛选出影响肝移植受者术后长期存活的独立危险因素.结果 221例受者的随访率为97.3%(215/221),平均随访时间为(36.4±6.9)个月(12～56个月).其中28例在术后1年后死亡,主要死亡原因依次为感染(5.0%,11/221)、胆道并发症(3.6%,8/221)、乙型肝炎复发或再感染(1.4%,3/221).保留在Cox回归方程内的协变量为高龄(RR=2.325,P=0.009)、ABO血型(RR=2.206,P=0.015)、冷缺血时间(RR=3.001,P=0.000)、术后感染部位(RR=1.665,P=0.007)和胆道并发症(RR=2.655,P=0.004).结论 影响受者术后中远期存活的危险因素包括年龄≥60岁、ABO血型不符、冷缺血时间>12 h、术后肺部感染和移植肝胆管弥漫性狭窄.     

Rejection and Steroid Dependence: Unique Risk Factors in the Development of Pediatric Posttransplant De Novo Autoimmune Hepatitis

Posttransplant de novo autoimmune hepatitis (d-AIH) is increasingly described as a long-term complication after pediatric liver transplantation (LT). d-AIH is characterized by graft dysfunction, the development of autoimmune antibodies and histologic evidence of hepatitis in liver transplant recipients without previous history of autoimmune liver disease. This study is a matched case-control, univariate analysis aimed at identifying risk factors for the development of d-AIH and evaluating response to treatment. From 1984 to 2003, 619 children received 788 LTs at a single center. Forty-one patients developed d-AIH and were matched with controls for year of LT, age at time of LT and diagnosis. The following variables were insignificant in the development of d-AIH: age, gender, race, initial diagnosis, ischemia time, graft type, Epstein-Barr virus and cytomegalovirus status, HLA typing and primary immunosuppression. Compared to controls, d-AIH patients were less likely to be on monotherapy immunosuppression or weaned off prednisone at the time of diagnosis. The d-AIH group relative to the controls had statistically significant greater numbers of rejection episodes. d-AIH was treated with prednisone and/or MMF in 39 of 41 patients and lead to significant improvements in liver function tests. Thirty-nine patients are alive at a mean of 4.0 years follow-up after diagnosis. Three have required retransplantation.     

Hyperbaric oxygen therapy for hepatic artery thrombosis after liver transplantation in children.

Early hepatic artery thrombosis (HAT) after pediatric orthotopic liver transplantation (OLT) can cause significant morbidity and mortality, leading to liver failure or septic complications requiring urgent retransplantation. Experimental evidence that hyperbaric oxygen (HBO) may ameliorate hepatic ischemic-reperfusion injury led to this study of HBO in pediatric liver transplant recipients who developed HAT. Children undergoing OLT under primary tacrolimus immunosuppression and University of Wisconsin organ preservation between August 1, 1989, and December 31, 1998, who developed HAT were the basis for this study. Patients who developed HAT between March 1, 1994, and December 31, 1998, were treated with HBO therapy until signs of ischemia resolved (absence of fever, normalizing liver injury test results) or for 2 weeks. The pediatric OLTs performed from August 1, 1989, to February 28, 1994, who developed HAT served as a control group. Primary outcome measures were survival, retransplantation rate, time to retransplantation, incidence of hepatic gangrene, and days to collateral formation. Three hundred seventy-five consecutive pediatric patients underwent 416 OLTs between August 1, 1989, and December 31, 1998. Thirty-one patients (7.5%) developed HAT at a mean time of 8.2 days (range, 1 to 52 days) post-OLT. In 17 patients, HBO treatment was begun within 24 hours of HAT or immediately after the revascularization attempt and performed twice daily for 90 minutes at 2.4 atmospheres pressure. Fourteen patients were treated without HBO. None of the HBO-treated patients developed hepatic gangrene. Eight HBO patients (47%) were bridged to retransplantation at a mean time of 157 days (range, 3 to 952 days) after initial OLT and all survived. Mean time to retransplant in the control group was 12.7 days (range, 1 to 64 days). HBO was well tolerated without significant complications. Although there was no significant difference in survival or retransplantation rates, HBO significantly delayed retransplantation, potentially by hastening the development of hepatic artery collaterals.     

Retransplantation of the liver in children

BACKGROUND: Because of the poor outcome of hepatic retransplantation, it is still debated whether this procedure should be performed in an era of donor organ scarcity. The aim of this study was to analyze outcome of hepatic retransplantation in children, to identify risk factors influencing this outcome, and to assess morbidity and causes of death. METHODS: A series of 97 children after a single transplantation and 34 children with one retransplantation was analyzed. RESULTS: The 1-, 3-, and 5-year survival of children with a retransplantation was 70, 63, and 52%, respectively, compared with 85, 82, and 78%, respectively, for children after a single transplantation (P=0.009). Survival of children with a retransplantation within 1 month after primary transplantation was worse (P=0.007) and survival of children with a late retransplantation was comparable (P=0.66) with single transplantation. In early retransplantations, the Child-Pugh score was higher, donors were older and weighed more, and more technical variant liver grafts were used compared with single transplantations. Biliary atresia and a high Child-Pugh score were associated with decreased patient survival after retransplantation. Sepsis was the most important complication and cause of death after retransplantation. CONCLUSIONS: Retransplantation is a significant event after pediatric liver transplantation. Outcome after hepatic retransplantation in children is inferior compared with single transplantation. This difference is explained by low survival after early retransplantation and can be explained by the poor clinical condition of the children at time of retransplantation, especially in children with biliary atresia, and by the predominant use of technical variant liver grafts in retransplantations.