Orthotopic liver transplantation for congenital biliary atresia. An 11-year, single-center experience.

OBJECTIVE: The authors analyze a single center's 11-year experience with 190 orthotopic liver transplants for congenital biliary atresia. SUMMARY BACKGROUND DATA: Hepatic portoenterostomy generally is the initial treatment for children with congenital biliary atresia. Despite multiple modifications of the hepatic portoenterostomy, two thirds of treated patients still develop recurrent cholestasis, portal hypertension, cholangitis, and cirrhosis. Therefore, the only hope of long-term survival in the majority of children with congenital biliary atresia is definitive correction with orthotopic liver transplantation. METHODS: The medical records of 190 consecutive patients undergoing orthotopic liver transplantation for congenital biliary atresia from July 1, 1984 to February 29, 1996 were reviewed. Results were analyzed via Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival was determined at 1, 2, and 5 years. The type and incidence of post-transplant complications were determined, as was the quality of long-term graft function. The median follow-up period was 3.21 years. RESULTS: The liver grafts were comprised on 155 whole-organ, 24 reduced-size, and 11 living donor organs. Median pretransplant values for recipient age, weight, and total bilirubin were 1.4 years, 12.3 kg, and 13.8 mg/dL, respectively. One hundred sixty-four patients (86%) had undergone prior hepatic portoenterostomy. Eighty-seven patients (46%) were United Network for Organ Sharing (UNOS) status 1 or 2 at the time of liver transplantation. The majority (15/24, 62%) of reduced-size graft recipients were UNOS status I at the time of transplantation. One hundred fifty-nine patients (84%) received a single graft, whereas 31 patients required 37 retransplants. The 1, 2, and 5 year actuarial patient survival rates were 83%, 80% and 78% respectively, whereas graft survival rates were 81%, 77%, and 76%, respectively. Cox multivariate regression analysis demonstrated that pretransplant total bilirubin, UNOS status, and graft type significantly predicted patient survival, whereas recipient age, weight, and previous hepatic portoenterostomy did not. Current median follow-up values for total bilirubin and aspartate aminotransferase levels in the 154 surviving patients were 0.5 mg/dL and 34 international units/L, respectively. CONCLUSION: Long-term patient survival after orthotopic liver transplantation for congenital biliary atresia is excellent and is independent of recipient age, weight, or previous hepatic portoenterostomy. Optimal results are obtained in this patient population when liver transplantation is performed before marked hyperbilirubinemia, and when possible, using a living-donor graft.     

Orthotopic liver transplantation for biliary atresia

Biliary atresia (BA) represents the most frequent indication for liver transplantation (OLTX) in the pediatric population. The aim of this paper was to present a series collected over the last 7 years from October 1997 through July 2004, including 260 pediatric OLTX in 231 patients. BA was the indication in 137 patients. There were 69 boys and 68 girls of mean weight 10.68 kg and median age 0.9 years. As a primary transplant, 99 patients received a LLS graft; 27 a whole graft; four a I+IV-VIII segment, and two a I-IV segment. Mean follow up was 1047 days (range, 1-2496 day). Infections were diagnosed in 45 patients, vascular complications in 27 patients. Surgical complications that required reintervention occurred in 25 patients. In 41 cases biliary complications occurred, 11 requiring reintervention. 16 patients were retransplanted. In two cases another re-OLTx was performed. Currently 126 patients are alive, showing an actuarial 1 year survival of 92% and 5 year 91%, with actuarial graft survivals of 85% at 1 year and 82% at 3 and 5 years. Our results confirm the effectiveness of OLTx for the treatment of children with BA and a failed Kasai procedure. Split liver grafts represent an excellent organ supply for these patients, achieving optimal results with no mortality on the waiting list.     

Living-donor liver transplantation in 126 patients with biliary atresia: single-center experience

Objectives

To describe our experience with 126 consecutive living-donor liver transplantation (LDLT) procedures performed because of biliary atresia and to evaluate the optimal timing of the operation.

Patients and Methods

Between May 2001 and January 2010,126 patients with biliary atresia underwent 130 LDLT procedures. Mean (SD) patient age was 3.3 (4.2) years, and body weight was 13.8 (10.7) kg. Donors included 64 fathers, 63 mothers, and 3 other individuals. The left lateral segment was the most commonly used graft (75%). Patients were divided into 3 groups according to body weight: group 1, less than 8 kg (n = 40); group 2,8 to 20 kg (n = 63); and group 3, more than 20 kg (n = 23). Medical records were reviewed retrospectively. Follow up was 4.5 (2.7) years.

Results

All group 3 donors underwent left lobectomy, and all group 1 donors underwent left lateral segmentectomy. No donors required a second operation or died. Comparison of the 3 groups demonstrated that recipient Pediatric End-Stage Liver Disease score in group 1 was highest, operative blood loss in group 2 was lowest (78 mL/kg), and operative time in group 3 was longest (1201 minutes). Hepatic artery complications occurred more frequently in group 1 (17.9%), and biliary stenosis (43.5%) and gastrointestinal perforation (8.7%) occurred more frequently in group 3. The overall patient survival rates at 1, 5, and 9 years was 98%, 97%, and 97%, respectively. Five-year patient survival rate in groups 1,2, and 3 were 92.5%, 100%, and 95.7%, respectively. Gastrointestinal perforation (n = 2) was the primary cause of death.

Conclusions

Living-donor liver transplantation is an effective treatment of biliary atresia, with good long-term outcome. It seems that the most suitable time to perform LDLT to treat biliary atresia is when the patient weighs 8 to 20 kg.     

Timing for orthotopic liver transplantation in children with biliary atresia: a single-center experience

Introduction

Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in childhood. The purpose of this study was to determine predictive prognostic factors for children with biliary atresia related to the timing for OLT within 15 months after hepatoportoenterostomy (HPE).

Patients and methods

We retrospectively analyzed the medical records of 25 children (7 boys and 18 girls) who underwent HPE because of biliary atresia between January 1990 and December 2005 at our center. Data examined included age and pathologic findings at HPE, Pediatric End-Stage Liver Disease score at first admission, whether phototherapy was given, liver function test results and total bilirubin level before and 30 days after HPE, and number of cholangitis events.

Results

Twelve children were alive with their native liver, 8 had undergone living donor OLT (all children alive), and 5 had died without OLT. Five- and 10-year survival rates without OLT after HPE were 47.4% and 26.3%, respectively. At univariate analysis, the predictive prognostic factors for children with biliary atresia were total bilirubin level at 30 days after HPE and Pediatric End-Stage Liver Disease score before HPE. At multivariate analysis, the only prognostic factor was total bilirubin level at 30 days after HPE.

Conclusions

In this study, the predictive prognostic factor was total bilirubin level at 30 days after HPE. Orthotopic liver transplantation within 15 months after HPE is needed in children with biliary atresia with a high total bilirubin level at 30 days after HPE.     

Orthotopic liver transplantation for Wilson's disease: a single-center experience

BACKGROUND: Wilson's disease is an inherited disorder of copper metabolism characterized by reduced biliary copper excretion, which results in copper accumulation in tissues with liver injury and failure. Orthotopic liver transplantation (OLT) can be lifesaving for patients with Wilson's disease who present with fulminant liver failure and for patients unresponsive to medical therapy. The aim of this study is to review our experience with OLT for patients with Wilson's disease. METHODS: Between 1988 and 2000, 21 OLTs were performed in 17 patients with Wilson's disease. Patient demographics, pre-OLT laboratory data, operative data, and early and late postoperative complications were reviewed retrospectively. One-year patient and graft survival was calculated. RESULTS: Eleven patients had fulminant Wilson's disease; in six patients the presentation was chronic. Mean patient age at presentation was 28 years (range 4-51 years); mean follow-up was 5.27 years (range 0.4-11.4 years). Neurologic features of Wilson's disease were not prominent preoperatively and did not develop post-OLT except in one patient who developed acute neuropsychiatric illness and seizure. Renal failure, present in 45% of patients with fulminant Wilson's disease, resolved post-OLT with supportive care. One-year patient and graft survivals were 87.5% and 62.5%, respectively. Fifteen survivors have remained well with normal liver function and no disease recurrence. CONCLUSION: Liver transplantation for hepatic complications of Wilson's disease cures and corrects the underlying metabolic defect and leads to long-term survival in patients who present with either acute or chronic liver disease. Acute renal failure develops frequently in patients with fulminant Wilsonian hepatitis and typically resolves postoperatively.     

Orthotopic liver transplantation for biliary atresia: the U.S. experience.

Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in the pediatric population. The outcomes of liver transplantation for biliary atresia, however, have not been formally examined on a national scale. The objective of this study was to identify pretransplant variables that predict patient survival after primary liver transplantation for biliary atresia. A cohort of 1,976 pediatric patients undergoing primary liver transplantation for biliary atresia between 1/1988 to 12/2003 was enrolled from the United Network for Organ Sharing database after excluding patients with a history of multiorgan transplant or previous liver transplant. Follow-up data up to 16 years post-OLT was available. The 5- and 10-year actuarial survival rates of patients that underwent liver transplantation for biliary atresia in the United States are 87.2% and 85.8%, respectively, and the 5- and 10-year graft actuarial survival rates are 76.2% and 72.7%, respectively. Early deaths (< or =90 days post-OLT) were more often caused by graft failure (P = 0.01), whereas late deaths (>90 days post-OLT) were more often due to malignancy (P < 0.01). An analysis of outcomes over time demonstrated a decrease in post-OLT survival and an increase in the number of OLTs done for biliary atresia at an increasing number of centers. A multivariate analysis revealed that cadaveric partial/reduced liver grafts, a history of life support at the time of OLT, and decreased age were independent predictors of increased post-OLT mortality. In conclusion, OLT is an effective treatment for biliary atresia. Certain pretransplant variables may help predict patient survival following liver transplantation for biliary atresia.     

Orthotopic liver transplantation for biliary atresia. Evolution of management

Forty-five patients with biliary atresia were accepted for orthotopic liver transplantation. Nine patients died awaiting transplantation, and 36 underwent transplantation. A portoenterostomy had been performed in 28 of these 36 patients, and its presence did not significantly affect the intraoperative blood loss (5.6 vs 4.1 blood volumes), the need for retransplantation (21% vs 12%), biliary complications (21% vs 12%), postoperative infections (36% vs 25%), or survival (82% vs 63%). These results indicate that early portoenterostomy is appropriate early therapy for biliary atresia; however, prompt referral to a liver transplant center for evaluation at the first sign of cholestasis is needed to attain optimal results for transplantation. Revisions of the portoenterostomy prior to transplantation did not improve the longevity of the procedure but did substantially increase complications and death after orthotopic liver transplantation.     

Orthotopic liver transplantation in critically ill cirrhotic patients with multi-organ failure: a single-center experience

Due to the lack of donor organs for orthotopic liver transplantation (OLT) in Germany, a larger proportion of patients advance to multi-organ failure (MOF) before OLT. Twenty-three patients on the waiting list for OLT were admitted to our intensive care unit (ICU) from January 2007 until September 2009. They consisted of 16 men and 7 women of median (25th–75th percentile) age of 60 years (54–65). Acute Physiology and Chronic Health Evaluation (APACHE II) score upon ICU admission was 26 (19–34); Model of End-Stage Liver Disease (MELD) score was 29 (22–41); Sequential Organ Failure Assessment (SOFA) score was 12 (8–16). The 90-day mortality rate was 39%. A decrease in MELD score during the first 48 hours (−2 [−5–0] vs 2 [−1–4]; P = .019) was associated with survival. Thirteen patients underwent transplantation from the ICU. By the time of the OLT, the MELD scores had deteriorated to 38 (33–39) and SOFA scores to 19 (18–19). All patients were mechanically ventilated and received hemodynamic support with catecholamines. Ten of 13 patients (77%) received renal replacement therapy and/or single pass albumin dialysis. Eight of 13 patients (62%) had a SOFA score of 3 or 4 (organ failure) in each of the respective subscores for the cardiovascular, renal, and respiratory systems at the time of OLT. The 90-day mortality rate after OLT was 38% and the 1-year-mortality rate was 54%. Patients who did not survive 90 days post OLT showed lower MELD scores on admission (33 [18–35] vs 44 [32–46]; P = .045), an increased MELD during the first 48 hours (3 [1–4] vs −2 [−8–1]; P = .002), and a longer ICU stay before OLT (32 [18–37] vs 8 [2–15]; P = .006). In conclusion, OLT may be successful treatment for cirrhotic patients with MOF. Outcomes of MOF in cirrhotic patients may improve after OLT but are generally worse than acceptable. A shorter ICU waiting time seemed to be beneficial.     

Dermatologic complications after liver transplantation: a single-center experience

OBJECTIVE: To report our experience with dermatological complications after both deceased donor liver transplantation (DDLT) and living-donor liver transplantation (LDLT). PATIENTS AND METHODS: Between April 2001 and November 2006, a total of 116 liver transplantation (LT) procedures were performed (73 DDLTs and 43 LDLTs) in 112 patients (4 re-transplants). Posttransplant dermatological problems were recorded. RESULTS: Among 112 OLT recipients, 14 patients (12.5%) experienced dermatologic problems: epidermolysis bullosa acquisita in one patient, which was self-limiting; graft-versus-host-disease in one patient treated with high-dose steroids; Kaposi sarcoma in one patient treated with surgical excision and conversion to sirolimus-based immunosuppression; drug-induced cutaneous vasculitis with deep thigh ulcer formation treated by drug discontinuation and surgical excision of the ulcer; herpes zoster in one patient treated with intravenous antiviral therapy; herpes simplex in two patients treated with local antiviral cream; cyclosporine-induced gingival hyperplasia treated with conversion to FK506; cyclosporine-induced hypertrichosis treated with conversion to FK506; steroid-induced skin hyperpigmentation in one patient treated with steroid withdrawal; hypomagnesemia-induced hair loss treated with daily oral magnesium supplement; pressure-induced alopecia areata in two patients that was self-limiting; and finally, one patient with a pressure-induced heel ulcer that was treated conservatively. In 8 of 14 patients (57%) who suffered from dermatologic problems, the complication was primarily related to immunosuppressive drugs. CONCLUSIONS: In our experience, dermatologic complications following LT are not uncommon and usually related to immunosuppressive therapy. Most complications could be prevented by optimizing immunosuppression. The majority of complications were easily managed by simple adjustment of immunosuppression.     

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.     

Outcome of liver transplantation in septuagenarians: a single-center experience

HYPOTHESIS: We hypothesized that selected septuagenarians may do as well after transplantation as those of a younger group of older recipients. This work compares post-liver transplant survival in septuagenarians with that of patients aged 50 to 59 years. DESIGN: Review of a prospectively maintained database. SETTING: University transplant center. PATIENTS: First-time liver transplant recipients treated from January 1, 1988, to December 31, 2005. Group 1 consisted of liver transplant recipients aged 70 years or older at the time of transplant. Group 2 was a younger cohort of patients aged 50 to 59 years. INTERVENTIONS: Liver transplantation. MAIN OUTCOME MEASURES: Patient survival. Survival data were stratified, Kaplan-Meier survival was calculated, and a multivariate analysis was performed. RESULTS: Group 1 included 62 patients aged 70 years or older (average, 71.9 +/- 2.1 years). Group 2 included 864 patients aged 50 to 59 years (average, 54.3 +/- 2.9 years). Unadjusted patient survival of group 1 at 1, 3, 5, and 10 years was 73.3%, 65.8%, 47.1%, and 39.7%, respectively. Unadjusted patient survival of group 2 at 1, 3, 5, and 10 years was 79.4%, 71.5%, 65.3%, and 45.2%, respectively. The difference was not statistically significant (P = .14). Multivariate analysis for factors affecting survival demonstrated preoperative hospitalization, cold ischemia time, and hepatitis C/ethanol as risk factors for death. Age 70 years or more was not a strong risk factor (mortality ratio, 1.28; P = .27). CONCLUSIONS: When other risk factors for mortality are controlled in older recipients, risk of death due to age is reduced in well-selected recipients. Age by itself should not be used to limit liver transplantation.     

Advagraf de novo in liver transplantation: a single-center experience

Advagraf, a prolonged release formulation of tacrolimus, is administered once daily in the morning. The aim of this study was to show the results obtained in our center, analyzing the safety, efficacy, blood trough levels, and drug doses.

Methods

We analyzed 50 consecutive recipients of a first liver transplantation with 6 months follow-up. Efficacy and safety variables were collected as the incidence of acute rejection episodes, patient and graft survivals, kidney function as well as incidences of diabetes mellitus and arterial hypertension de novo.

Results

The incidence of biopsy proven acute rejection episodes was 10% (n = 5), none 7 of which were steroid resistant and all resolved favorably. The rate of diabetes mellitus de novo was 22% (n = 11), 7 of whom required insulin. Hypertension developed in 9 patients (18%), all of whom were treated with a single drug. The mean serum creatinine level was 1.08 ± 0.25 mg/dL, with 3 patients (6%) displaying a value ≥ 1.5 mg/dL. Patient and graft survivals were 100%.

Conclusion

Advagraf is an effective immunosuppressant in liver transplantation with a low incidence of biopsy-confirmed acute rejection episodes. The good results for patient and graft survival with few side effects make it a useful drug for de novo liver transplantation.     

Orthotopic transplantation of the liver in children with biliary atresia and polysplenia syndrome: report of two cases

Biliary atresia is the most common indication for liver transplantation in infants and children, despite the advent of the Kasai operation. Coexisting anomalies, which have been noted in up to 27% of patients with biliary atresia, may form an association known as the "polysplenia syndrome," which includes (1) polysplenia, (2) midgut malrotation, (3) preduodenal portal vein, (4) absent prerenal inferior vena cava with azygos continuation, (5) situs inversus, (6) symmetric liver, (7) hepatic arterial anomalies, and (8) bilobed right lung with hyparterial bronchus. Two of 31 patients undergoing orthotopic liver transplantation for biliary atresia following failed portoenterostomy over the past 11 years manifested the polysplenia syndrome with absent prerenal inferior vena cava. The clinical course of these patients, constellation of anomalies, and technical adjustments required to perform liver transplantation are described. We do not believe that these complex congenital anomalies preclude liver transplantation.     

儿童肝移植治疗Alagille综合征的单中心经验

目的  探讨儿童肝移植治疗Alagille综合征(ALGS)的疗效。方法  收集12例ALGS患儿的临床资料进行回顾性分析,分析ALGS患儿的临床特征和病肝组织病理学特点、肝移植的特点及其术后并发症和随访情况。结果  12例患儿均存在JAG1基因突变和典型面部特征,黄疸是最常见的首发症状,在出生后7(3,40)d出现。患儿行肝移植时身高和体质量Z评分分别为-2.14(-3.11,-1.83)分和-2.32(-3.12,-1.12)分,5例患儿严重发育迟缓,4例患儿严重营养不良。12例患儿中8例伴有心血管异常。病理学检查结果显示,4例患儿病肝的小叶结构基本保持,8例存在大小不等结节性肝硬化,其中1例病肝检测到单个早期中分化肝细胞癌。3例患儿因误诊为胆道闭锁行葛西手术治疗。8例患儿行活体肝移植,3例患儿行尸体供肝肝移植(包括2例劈离式肝移植和1例尸体全肝移植),1例患儿行多米诺肝移植(供肝来自枫糖尿病患者)。在随访30.0(24.5,41.7)个月时,患儿和移植物存活率均为100%。在随访过程中,患儿身高和体质量Z评分分别为-1.24(-2.11,0.60)分和-0.83(-1.65,-0.43)分,表明患儿术后生长和发育情况明显改善。结论  肝移植是治疗肝硬化失代偿期和严重瘙痒伴生活质量差的ALGS患儿的有效方法。伴随心血管异常的ALGS患儿,术前应进行详细评估,必要时联合儿科心脏病专家进行治疗。     

The marginal donor: a single-center experience in orthotopic liver transplantation

The use of marginal donors has become more common worldwide due to the sharp increase in recipients with a consequent shortage of suitable organs. The definition of "marginal donor" has not been reached by all centers. We herein analyzed our single-center experience over the last 3 years in liver transplantation (OLT) to evaluate the outcomes of using a high percentage of so-called "marginal donors", according to the current classification from the National (Italian) Center of Transplantation (CNT). Among the 78 OLT performed in 77 patients from January 1, 2003 to October 31, 2005, donor livers were divided into three groups according to the CNT classification. We evaluated donor variables, cold ischemia time (CIT), warm ischemia time (WIT), MELD score, and length of hospital stay. Histologic graft steatosis was correlated with estimated steatosis by ultrasound. There were no differences among the three graft recipient groups concerning CIT, WIT, MELD score, and the length of hospital stay. Steatosis is indicated in all series as a definite variable for a higher risk of postoperative mortality. CIT is necessarily related to donor retrieval policy and organization. Donor age seemed also to be related to a possible increase in postoperative mortality, but there are significant variations in the definition of the age limit. We failed to observe a correlation between a higher mortality rate and any of the variables currently listed to define a "marginal donor." A shorter CIT seemed to positively influence the role played by the other variables identifying a "marginal liver." Finally, the use of HCV(+) or HBV(+) grafts did not lead to an increased mortality.